propylthiouracil and Hyperthyroidism

The thionamide anti-thyroid drugs namely carbimazole, methimazole, and propylthiouracil, have been the predominant therapy modality for Graves' hyperthyroidism for over 60 years. Although these agents have proven efficacy and favorable side-effect profiles, non-thionamide alternatives are occasionally indicated in patients who are intolerant or unresponsive to thionamides alone. This review examines the available non-thionamide drug options for the control of Graves' hyperthyroidism and summarizes their clinical utility, efficacy, and limitations.. We reviewed existing literature on mechanisms, therapeutic utility, and side-effect profiles of non-thionamide anti-thyroid drugs. Established non-thionamide agents act on various phases of the synthesis, release, and metabolism of thyroid hormones and comprise historical agents such as iodine compounds and potassium perchlorate as well as drug repurposing candidates like lithium, glucocorticoids, beta-blockers, and cholestyramine. Novel experimental agents in development target key players in Graves' disease pathogenesis including B-cell depletors (Rituximab), CD40 blockers (Iscalimab), TSH-receptor antagonists, blocking antibodies, and immune-modifying peptides.. Non-thionamide anti-thyroid drugs are useful alternatives in Graves' hyperthyroidism and more clinical trials are needed to establish their safety and long-term efficacy in hyperthyroidism control. Ultimately, the promise for a cure will lie in novel approaches that target the well-established immunopathogenesis of Graves' disease.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Propylthiouracil

The purpose of this meta-analysis was to assess the safety of the anti-thyroid drugs (ATDs) propylthiouracil (PTU) and methimazole (MMI) in the treatment of hyperthyroidism during pregnancy.. From inception until June 2, 2022, all available studies were searched in PubMed, Web of Science, Cochrane, EBSCO, Embase, Scopus, and CNKI.. Thirteen articles satisfying the inclusion criteria were examined. Our meta-analysis indicated that pregnant women treated with MMI had a higher risk of congenital anomalies than those treated with PTU (OR 0.80, 95%CI 0.69-0.92, P = 0.002, I2 = 41.9%). Shifting between MMI and PTU during pregnancy did not reduce the risk of birth defects compared to PTU alone (OR 1.18, CI 1.00 to 1.40, P = 0.061, I2 = 0.0%). There were no statistically significant differences in hepatotoxicity (OR 1.54, 95%CI 0.77-3.09, P = 0.221, I2 = 0.0%) or miscarriage (OR 0.89, 95%CI 0.72-1.11, P = 0.310, I2 = 0.0%) between PTU and MMI exposure.. The study confirmed propylthiouracil is a safer alternative to methimazole for treating hyperthyroidism in pregnant women, and it is appropriate to treat maternal thyroid disease with PTU during the first trimester of pregnancy. However, it is not clear whether switching between propylthiouracil and methimazole is a better option than treating PTU alone during pregnancy. Further studies on this matter may be needed to develop new evidence-based guidelines for the treatment of pregnant women with hyperthyroidism.

Topics: Abortion, Spontaneous; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy.. We searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity.. We identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06-1.54) and PTU (RR, 1.16; 95% CI, 1.08-1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01-1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14-1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up.. ATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is generally treated with propylthiouracil (PTU). However, previous studies about the effects of propylthiouracil on maternal or foetal are contentious.. This meta-analysis was carried out to investigate the safety and efficacy of propylthiouracil during pregnancy.. PubMed, EBSCO, Embase, Scopus, Web of Science, Cochrane, CNKI, Wanfang and VIP database were searched from inception until August 31, 2021 for all available randomized controlled trials (RCTs) or cohort studies that evaluated the efficacy of propylthiouracil and its effects on pregnancy outcomes. Odds ratio (OR) and 95% confidence interval (CI) were used for binary variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used for continuous variables. RevMan5.4 and Stata 16.0 were used for performing the meta-analysis.. The researchers examined data from 13 randomized controlled trials and cohort studies involving 18948 infants. Congenital anomalies were not significantly associated with PTU in the pooled results (OR = 1.03, 95%CI: 0.84-1.25, P = 0.80, I2 = 40.3%). There were no statistically significant differences in neonatal hypothyroidism (OR = 0.55, 95%CI: 0.06-4.92, P = 0.593, I2 = 57.0%) or hepatotoxicity (OR = 0.34, 95%CI: 0.08-1.48, P = 0.151, I2 = 0.0%) exposed to PTU compared to the control group. The serum levels of FT3, FT4, TT3, and TT4 were significantly lower in the propylthiouracil group compared to the control group.. This meta-analysis confirmed the beneficial effects of propylthiouracil treatment, namely the risks of adverse pregnancy outcomes were not increased, and it also proved PTU's efficacy in the treatment of pregnant women with hyperthyroidism. The findings supported the use of propylthiouracil during pregnancy with hyperthyroidism in order to improve clinical pregnancy outcomes in patients with thyroid dysfunction.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been associated to thyroid tumours in rodents. According to a systematic review by the International Agency for Research on Cancer (IARC) published in 2000, evidence for the human carcinogenicity was inadequate.. We performed an up-to-date systematic review of human epidemiological studies on the association between such compounds and thyroid cancer incidence or mortality.. The literature research (1999-March 2020) identified four relevant articles. Considering also reports from the previous IARC review, this systematic review considered seven reports (five distinct studies) on antithyroid drugs and two on ethylenethiourea. As for antithyroid drugs, three reports based on different follow-ups gave results from a cohort of patients treated for hyperthyroidism in 1946-1964. In the earlier report, thyroid cancer incidence was higher in patients primarily treated with antithyroid drugs (3.2/1000) than in those originally treated with thyroidectomy (0.34/1000) or radioactive iodine (0.88/1000), which can be explained by the higher frequency of subsequent thyroidectomy, and hence the higher chance of cancer detection, in that group (30 vs. 0.5 and 1.2%). The two subsequent reports found no deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through 1990 and 2014. A nested case-control study found an odds ratio (OR) of thyroid cancer of 2.79 [95% confidence interval (CI), 0.78-10.02, from a 2-year lag analysis] for ≥3 vs. no propylthiouracil prescriptions. The increased risk can be attributed to advanced diagnosis of an underlying cancer, as suggested by the stronger association observed in a no-lag analysis (OR, 8.03). In a historical cohort of newly diagnosed hyperthyroid patients, the hazard ratio for treatment with radioactive iodine vs. thionamides only was 0.45 (95% CI, 0.21-0.99), possibly due to the closer surveillance of patients receiving thionamides only. Two case-control studies did not find any association with the use of antithyroid drugs. As for ethylenethiourea, no thyroid cancer cases were found in a historical cohort of 1929 workers occupationally exposed in a 15-year period and no association with proxies of mancozeb exposure (a fungicide whose main metabolite is ethylenethiourea) was detected in a cohort of >236 000 farmers.. There is no evidence for a relevant role of either antithyroid drugs or ethylenethiourea on thyroid cancer.

Topics: Antithyroid Agents; Case-Control Studies; Ethylenethiourea; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroid Neoplasms

Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies.. Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random-effects generic inverse variance method and absolute risk calculated.. Seven cohort studies and 1 case-control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08-1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06-1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16-1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02-1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism.. When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Case-Control Studies; Female; Humans; Hyperthyroidism; Methimazole; Observational Studies as Topic; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Fetal thyroid disorders while uncommon in general, have significant morbidity and profound effects in the neonate. Pregnancy provides the opportunity not only for the diagnosis of these conditions but also for therapeutic interventions. In careful balance, these disorders range from hypothyroidism to hyperthyroidism, both may manifest with fetal thyroid goiters as well. The intrauterine therapeutic approach of these must also weight the balance in this range as well as the maternal well being which may also express thyroid dysfunction. In this review we explore the different fetal manifestations of thyroid disease, describe the pathophysiology and therapeutic approaches both in practice and in development.

Topics: Antithyroid Agents; Female; Fetal Diseases; Gestational Age; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Neonatal Screening; Pregnancy; Pregnancy Complications; Prenatal Diagnosis; Propylthiouracil; Thyroid Diseases; Thyroxine; Ultrasonography, Prenatal

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy.

Topics: Abnormalities, Drug-Induced; Acetaminophen; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Analgesics, Non-Narcotic; Anti-Asthmatic Agents; Antidepressive Agents; Antiemetics; Antithyroid Agents; Asthma; Congenital Abnormalities; Depressive Disorder; Female; Humans; Hyperthyroidism; Leukotriene Antagonists; Maternal-Fetal Exchange; Methimazole; Morning Sickness; Ondansetron; Pregnancy; Pregnancy Complications; Propylthiouracil; Teratogens

Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications. The treatment of choice in pregnancy is antithyroidal medications (ATDs). The risk of embryopathies associated with the use of Methimazole (MMI) and Propylthiouracil (PTU) in early pregnancy is a matter of clinical attention and concern. This review describes current evidence and how scientific findings are reflected in current clinical guidelines.. Embryopathies after the use of ATDs were previously mainly described in case reports and considered rare. Recent large observational studies, including nonexposed control groups, have quantified an increased risk of embryopathies associated with use of ATDs during pregnancy. Findings suggest a risk of embryopathies with the use of both MMI and PTU, but the pattern of embryopathies differs, and embryopathies with the use of PTU appear less severe.. Current guidelines highlight the need for clinical attention on the use of ATDs in early pregnancy. Patients managed on ATDs for the treatment of hyperthyroidism should be counseled to report a pregnancy as early as possible. PTU is the recommended treatment in early pregnancy, but if the risk of relapse or worsening of hyperthyroidism is considered low, it is suggested that ATD treatment can be withdrawn followed by frequent monitoring of thyroid function.

Topics: Antithyroid Agents; Female; Fetal Diseases; Gestational Age; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk Factors

Thionamides, such as methimazole and propylthiouracil, are used for the management of hyperthyroidism. Agranulocytosis is a rare adverse effect of thionamides and elderly patients are especially vulnerable. Here we discuss a case of an 80-year-old woman who developed agranulocytosis and pneumonia approximately 4 weeks after starting low dose methimazole therapy. Despite aggressive treatment with broad-spectrum antibiotics and granulocyte colony stimulating factor, she developed multiorgan failure and died. Our goals are to identify risk factors common to elderly patients and hopefully improve outcomes in this population when prescribed thionamides.

Topics: Age Factors; Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Fatal Outcome; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Risk Factors

This review covers the current American Thyroid Association recommendations on diagnosis and management of thyroid disease during pregnancy and the postpartum period. It lists the recommendations in a reader-friendly way, and facilitates rational therapy of thyroid disorders, in relation to obstetric health, at the primary care level.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Disease Management; Female; Fluid Therapy; Humans; Hyperthyroidism; Hypothyroidism; Postnatal Care; Practice Guidelines as Topic; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Prenatal Care; Propylthiouracil; Thyroid Neoplasms; Thyroid Nodule; Thyrotropin; Thyroxine; Time Factors

Antithyroid drugs (ATDs) are widely used for the treatment of Graves' disease (GD) in the general population. Over the past decade, there has been an increasing awareness that several disturbances of thyroid function may occur in mothers after delivery which may be more prevalent than previously appreciated. Exacerbation of immune reactions occurs 3-12 month following delivery. Management of hyperthyroidism during lactation requires special considerations and should be implemented to prevent any adverse outcomes in mother and neonate. Continuation of breastfeeding is safe and should be encouraged in hyperthyroid mothers taking ATDs, whether these are ATDs being continued after gestation or indeed ATD treatment initiated in the postpartum period. Given PTU hepatotoxicity concerns, experts currently recommend using low-to-moderate MMI doses as a first-line therapy in lactating mothers. PTU should be reserved only as a second-line agent for cases of severe hyperthyroidism (thyroid storm) and allergic reactions to previous MMI treatment. ATD should be administered in divided doses immediately following each feeding. Evaluation of thyroid function tests is advisable at least 3-4 weeks after the initiation of breastfeeding.

Topics: Adult; Antithyroid Agents; Breast Feeding; Drug Hypersensitivity; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Mothers; Propylthiouracil

Hyperthyroidism can occur during pregnancy and the postpartum period, and the treatment of hyperthyroidism should be considered in the preconception phase. Pregnancy has multiple normal physiologic effects on thyroid hormone, which is a separate process distinct from syndromes such as transient hyperthyroidism of hyperemesis gravidarum. The rationale regarding antithyroid drug use during different stages of pregnancy is reviewed, including the literature regarding adverse neonatal outcomes such as aplasia cutis and methimazole embryopathy in the setting of first trimester maternal methimazole use. The use of treatment modalities for hyperthyroidism during pregnancy such as surgery is also discussed. Studies of maternal, fetal, and neonatal complications of hyperthyroidism are examined in this article. Moreover, the evidence regarding antithyroid drugs, specifically methimazole and propylthiouracil, during lactation is considered. Other disease conditions that can take place during pregnancy and the postpartum period such as hyperemesis gravidarum, subclinical hyperthyroidism, gestational trophoblastic disease, and postpartum thyroiditis and their treatments are also presented.

Topics: Antithyroid Agents; Birth Weight; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Postpartum Period; Preconception Care; Pregnancy; Pregnancy Complications; Premature Birth; Propylthiouracil; Risk; Thyroid Hormones

Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero.. Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests.. Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively.. The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Cohort Studies; Databases, Factual; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Prenatal Exposure Delayed Effects; Propylthiouracil; Risk

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Case-Control Studies; Cohort Studies; Confidence Intervals; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Odds Ratio; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk

The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis.. The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis.. ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

Topics: Age Factors; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Prevalence; Propylthiouracil; Time Factors

Functional thyropathies present significant health risks for patients. Advanced functional thyropathies are always treated while indications for therapy of subclinical thyropathies are individual and often controversial. It is widely agreed that these disorders should be diagnosed and individuals should be followed. The drug of choice in substitution therapy of hypothyroidism is levothyroxine, in the treatment of hyperthyroidism it is methimazole. Administration of propylthiouracil should be limited to the first trimester of pregnancy, because its serious hepatotoxicity has been described. Hyperthyroidism based on thyroid nodules and immunogenic hyperthyroidism not reaching long-term remission, need to be treated radically: by surgery or radioiodine treatment. When radiation protection requirements are met, radioiodine can also be administered on an outpatient basis. Exceptionally, small doses of methimazole can be administered over an extended period of time in individual cases.

Topics: Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroidectomy; Thyroxine

Topics: Amniotic Fluid; Diagnosis, Differential; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Pregnancy; Propylthiouracil; Thyroid Diseases; Thyroxine; Ultrasonography, Prenatal

Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.. This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.. PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.

Topics: Adult; Antithyroid Agents; Carbimazole; Chemical and Drug Induced Liver Injury; Child; Drug Labeling; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Propylthiouracil; Severity of Illness Index

Medical treatment of Graves' hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves' hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), β-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves' hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis.

Topics: Animals; Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Treatment Outcome

The treatment of choice for hyperthyroidism in pregnancy is antithyroid drugs, but the potential risk of birth defects is of major concern. For the use of thiamazole and carbimazole, there is consistent evidence of an increased risk of birth defects, which are often severe. For the use of propylthiouracil, the evidence is less clear. These birth defects may be less severe, and a Danish study which included all birth defects diagnosed before the age of two years showed an increased risk of birth defects in the face and neck region and in the urinary system after the use of propylthouracil.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil; Risk Factors

We report a case of neonatal thyrotoxicosis with concurrent respiratory failure in an infant born to a mother with Graves' disease and review the published literature describing neonatal hyperthyroidism. The male infant who was born by spontaneous delivery at 35 weeks of gestational age presented with fever, tachycardia and tachypnea at rest on day 11 after birth, and developed severe apnea on day 14. Thyroid function studies revealed hyperthyroidism in the infant, and his mother was confirmed to have Grave's disease during pregnancy. Literature review showed that among the 33 infants with similar conditions, tachycardia, tachypnea and poor weight gain were the most distinct clinical features of congenital hyperthyroidism. Accurate diagnosis of Graves' disease in the mother during pregnancy and awareness of the clinical presentations of neonatal hyperthyroidism are key to reducing missed diagnosis or misdiagnosis of neonatal hyperthyroidism.

Topics: Antithyroid Agents; Apnea; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Antithyroid drugs are relatively simple molecules known as thionamides, which contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure. Propylthiouracil (6- propyl 2- sulfanylidene 1,2,3,4- tetrahydropyrimidin4- one) and methimazole (1- metyl 2,3- dihydro1H imidazole 2- thione) are the antithyroid drugs used in the United States. Methimazole is used in most of Europe and Asia, and carbimazole -  methimazole analogue, is used in the United Kingdom and parts of the former British Commonwealth. Their primary effect is to inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin and is an important step in the synthesis of thyroxine and triiodothyronine. Propylthiouracil (but not methimazole or carbimazole), can block the conversion of thyroxine to triiodothyronine within the thyroid and in peripheral tissues. Antithyroid drugs may have clinically important immunosuppressive effects. Side effects of thionamides are usually mild, serious untoward effects are observed in < 5% of cases, more frequently during the initial phases of treatment, when the drug daily dose is higher.

Topics: Antithyroid Agents; Carbimazole; Europe; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Structure-Activity Relationship; Thyroglobulin; Thyroid Hormones; Thyroxine; Triiodothyronine

Clinical hyperthyroidism has been associated with an increased risk of maternal, fetal, and neonatal complications. The available antithyroid drugs are methimazole/carbimazole and propylthiouracil. Several case reports and some epidemiologic studies suggest that methimazole/carbimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations, including ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele. However, the absolute risk appears to be very small, and it remains unclear whether the association is driven by the maternal disease, the medication, or the combination of both factors. Propylthiouracil exposure has not been associated with an increased risk of congenital malformations and is the recommended drug during the first trimester of pregnancy. Since propylthiouracil-induced hepatotoxicity has been reported in approximately 0.1% of exposed adults and the number of case-reports of severe liver injury is increasing, treatment with low dose methimazole during the second and third trimesters should be considered. Until now, there has been no evidence that children prenatally exposed to methimazole/carbimazole or propylthiouracil have an increased risk of neurodevelopmental delay.

Topics: Antithyroid Agents; Carbimazole; Choanal Atresia; Drug Administration Schedule; Esophageal Atresia; Female; Hernia, Umbilical; Humans; Hyperthyroidism; Infant, Newborn; Maternal Exposure; Methimazole; Pregnancy; Pregnancy Trimester, First; Propylthiouracil

To bring to the attention of healthcare professionals the additional information on propylthiouracil (PTU)-related hepatotoxicity, based on a reanalysis of medical files reported to the Food and Drug Administration (1982-2008) for acute liver failure in PTU-treated hyperthyroid patients, and propose recommendations for the clinical use of PTU. Thirteen files of PTU-related severe liver adverse effects were analyzed for the pediatric population, seventeen for nonpregnant adults and two for pregnant women.. The recent findings showed that the daily PTU dose administered was high in the children, with a mean of 300 mg/day for an average 10-year-old individual. With regard to treatment duration, PTU administration lasted for at least 4 months in 75% of pediatric cases. Similarly, in a majority of adult cases (64%), PTU-induced liver injury occurred after a relatively long treatment period (4 months to >1 year).. PTU should not be used in children, in whom methimazole (MMI) represents the logical alternative. In adults, PTU should be restricted to those rare patients with Graves' disease for whom no better alternative can be offered and in patients with thyroid storm. For the special circumstance of pregnancy, PTU is the preferred choice during early gestation; switching back to MMI during later gestational stages remains a matter of clinical judgment. It is unknown whether liver function tests monitoring is worthwhile to prevent life-threatening, PTU-related hepatotoxicity.

Topics: Adult; Age Factors; Antithyroid Agents; Child; Drug Administration Schedule; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Patient Selection; Pregnancy; Pregnancy Complications; Propylthiouracil; United States; United States Food and Drug Administration

Hyperthyroidism is one of the most common endocrine disorders in pregnant women, and it can severely complicate the course and outcome of pregnancy. Methimazole (MMI) and propylthiouracil (PTU) are the standard anti-thyroid drugs used in the treatment of hyperthyroidism in pregnancy. Traditionally, MMI has been considered to have clearer evidence of teratogenicity than PTU. Recent studies suggest that PTU can be hepatotoxic, leading to a United States Food and Drug Administration "black box alert." We wished to systematically review the effects of PTU and MMI during pregnancy, and to compare maternal and fetal safety.. We conducted a systematic search of PubMed, EMBASE, TOXNET, TOXLINK, DART, Medscape, EBSCO, and Google. Both English and non-English publications were included. We excluded studies using anti-thyroid therapies other than PTU and MMI, studies not allowing interpretation of results, and abstracts of meetings.. Overall, insufficient statistical power precluded determination of accurate rates of either MMI teratogenicity or PTU hepatotoxicity in cohort studies. However, a case-control study helped identify the relative risk of MMI-induced choanal atresia. A second case-control study failed to show that aplasia cutis congenita is associated with MMI. PTU has been associated with a rare but serious form of hepatic failure.. MMI causes a specific pattern of rare teratogenic effects after first trimester exposure, while PTU therapy may be followed by rare but severe hepatotoxic sequelae. It is therefore appropriate to use PTU to treat maternal hyperthyroidism during the first trimester of pregnancy, and to switch to MMI for the remainder of the pregnancy.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Case-Control Studies; Chemical and Drug Induced Liver Injury; Female; Gestational Age; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).. The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Topics: Agranulocytosis; Animals; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Evidence-Based Medicine; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Randomized Controlled Trials as Topic; Thyrotoxicosis; Vasculitis

Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods.. To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation.. A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.'. Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation.. Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

Topics: Adult; Antithyroid Agents; Child Development; Female; Gestational Age; Humans; Hyperthyroidism; Infant, Low Birth Weight; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Methimazole; Postpartum Thyroiditis; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk; Thyroid Function Tests; Thyroid Gland

Advances in prenatal imaging techniques and in fetal hormonology now allow for identification of disorders of thyroid function in the fetus. These can potentially be treated in utero by giving drugs to the mother.. This review examines the feasibility of in utero treatment of fetal thyroid disorders, either indirectly by treating the mother or by giving the necessary drugs directly to the fetus.. In women with Graves' disease, autoimmune fetal hyperthyroidism can generally be treated in a noninvasive way by optimizing treatment of the mother, such as by increasing the dose of antithyroid drugs. For goitrous fetal hypothyroidism leading to hydramnios, repeated intra-amniotic injections of thyroxine have been reported to decrease the size of the fetal thyroid.. Experience with such procedures is limited but positive. The risk that direct in utero treatment of the fetus may provoke premature labor or cause infection should be carefully evaluated.. Follow-up of the efficacy and the possible long-term consequences of medical interventions to normalize thyroid function of the fetus are of great importance. Specialized care of the fetus should be provided by skilled teams with extensive experience in prenatal care.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Diseases; Thyroxine

To collect and assess clinical reports of a putative relationship between thyroid state and the biology of cancers of various types.. A number of prospective case-control studies reviewed here have suggested that subclinical hyperthyroidism increases risk of certain solid tumors and that spontaneous hypothyroidism may delay onset or reduce aggressiveness of cancers. Small case studies have reached similar conclusions. A controlled prospective trial of induced hypothyroidism beneficially affected the course of glioblastoma. A context in which to interpret such findings is the recent description of a plasma membrane receptor for thyroid hormone on cancer cells and dividing tumor-associated endothelial cells.. Accumulating clinical evidence may justify new, broadly-based controlled studies in cancer patients of the possible contribution of thyroid hormone to tumor behavior.

Topics: Animals; Antithyroid Agents; Cell Proliferation; Female; Humans; Hyperthyroidism; Hypothyroidism; Integrin alphaVbeta3; Neoplasms; Propylthiouracil; Rats; Receptors, Thyroid Hormone; Risk Factors; Thyroid Hormones

Hyperthyroidism is a common endocrine disorder affecting 2% of females and 0.5% of males worldwide and antithyroid drugs constitute the first line of treatment in the majority of cases. These agents may cause severe adverse effects and among them liver failure, although rare, is a potential lethal one. This case illustrates the sudden and abrupt deterioration of hepatic function due to antithyroid drug administration. This case along with a concise literature review is presented aiming to increase the awareness of endocrinologists of possible fatal complications from the everyday use of common agents such as antithyroid drugs.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Failure; Methimazole; Propylthiouracil; Thyroidectomy

Antithyroid drugs (ATD) are used as a first line treatment in thyrotoxicosis. Propylthiouracil (PTU), carbimazole (CMZ) and methimazole (MMI) are available. During absorption CMZ is bioactivated to MMI. Initially, mothers were not allowed to breastfeed during treatment with ATD. Newer studies minimized the risk for mother and infant. PTU should be preferred over MMI due to its lower milk concentration. Recent studies have shown severe hepatic dysfunction for both ATD, but especially for PTU, in hyperthyroid patients. Most of those cases were idiosyncratic, not-dose related and presented a latent period of occurrence. No biomarkers could predict hepatic damage. The American Thyroid Association (ATA) has recommended that PTU should not be prescribed as the first line agent in children and adolescents. Its use might be accepted in the first trimester of pregnancy for severe thyrotoxicosis or for patients with previous MMI adverse reactions. Considering the potential harmful effects of PTU, MMI should be used instead during lactation.

Topics: Adult; Antithyroid Agents; Breast Feeding; Carbimazole; Child Development; Female; Humans; Hyperthyroidism; Infant; Lactation; Methimazole; Milk, Human; Mothers; Propylthiouracil

I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was initially treated with propylthiouracil but was switched to methimazole owing to urticaria. I have heard about birth defects in infants whose mothers used methimazole during pregnancy. How safe is it?. In North America, propylthiouracil has been the drug of choice for hyperthyroidism during pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is an alternative for patients who cannot tolerate propylthiouracil. Some case reports raised concern about fetal toxicity from methimazole, which is reportedly characterized by aplasia cutis, esophageal atresia, choanal atresia, facial abnormalities, and mental retardation. However, causality is unclear and the overall risk of congenital abnormalities in infants exposed to methimazole in utero was not higher than in those exposed to nonteratogenic drugs in cohort studies. It is important for a pregnant woman to continue methimazole, if necessary, because uncontrolled hyperthyroidism increases the risk of complications such as preterm labour and low birth weight.

Topics: Antithyroid Agents; Female; Fetal Diseases; Humans; Hyperthyroidism; Infant, Newborn; Lactation; Pregnancy; Pregnancy Complications; Propylthiouracil; Treatment Outcome

Radioiodine is considered the treatment of choice for hyperthyroidism, but in some situations, methimazole therapy is preferred, such as in cats with pre-existing renal insufficiency. Methimazole blocks thyroid hormone synthesis, and controls hyperthyroidism in more than 90% of cats that tolerate the drug. Unfavorable outcomes are usually due to side effects such as gastrointestinal (GI) upset, facial excoriation, thrombocytopenia, neutropenia, or liver enzyme elevations; warfarin-like coagulopathy or myasthenia gravis have been reported but are rare. Because restoration of euthyroidism can lead to a drop in glomerular filtration rate, all cats treated with methimazole should be monitored with BUN and creatinine, in addition to serum T4, complete blood count, and liver enzymes. Transdermal methimazole is associated with fewer GI side effects, and can be used in cats with simple vomiting or inappetance from oral methimazole. Hypertension may not resolve immediately when serum T4 is normalized, and moderate to severe hypertension should be treated concurrently with-atenolol, amlodipine, or an ACE inhibitor. Alternatives to methimazole include carbimazole, propylthiouracil, or iodinated contrast agents.

Topics: Adrenergic beta-Antagonists; Animals; Antithyroid Agents; Carbimazole; Cat Diseases; Cats; Contrast Media; Hyperthyroidism; Iodine Radioisotopes; Iodobenzenes; Methimazole; Propylthiouracil; Treatment Outcome

Hyperthyroidism occurs in approximately 1 in every 1000 to 2000 pregnancies. Although the signs and symptoms of the disease are similar in the pregnant and nonpregnant patient, the complications of hyperthyroidism can have even more profound consequences for the mother and fetus during gestation. These include maternal heart failure, preeclampsia, miscarriage, and preterm labor; as well as fetal loss and low birth weight. Furthermore, thyroid function and laboratory testing for hyperthyroidism are altered in pregnancy. The gestational increase in thyroid size, increased thyroid-binding globulin levels, increased serum total T4 and total T3 levels, and decreased thyroid stimulating hormone levels often confuses the evaluation of the thyroid status in pregnancy. Worldwide, the thionamides-propylthiouracil, methimazole, and carbimazole-have been used in pregnancy for the treatment of hyperthyroidism. However, propylthiouracil has been the drug of choice in the United States because it is believed to have less potential to induce fetal/neonatal hypothyrodism, to cross the placenta and into breast milk to a lesser degree, and to be less teratogenic than methimazole or carbimazole. None of the above have been substantiated in more recent studies. The pharmacokinetics of the thionamides in the pregnant and nonpregnant states, as well as the pharmacotherapeutic recommendation for hyperthyroidism will be reviewed.

Topics: Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Sulfhydryl Compounds; Thiones

Topics: Abortion, Spontaneous; Adult; Antithyroid Agents; Autoantibodies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fertilization in Vitro; Gestational Age; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infertility, Female; Iodine; Male; Menstrual Cycle; Menstruation Disturbances; Pregnancy; Pregnancy Complications; Prevalence; Propylthiouracil; Puerperal Disorders; Risk Factors; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyroiditis; Thyrotropin; Thyroxine; Ultrasonography

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine Radioisotopes; Lithium Carbonate; Methimazole; Propylthiouracil; Treatment Outcome

In Graves' patients complicated by pregnancy, both maternal and fetal problems related to the disease can be reduced or avoided by controlling hyperthyroidism. However, optimal treatment for mothers may exert detrimental effects on fetuses. Methimazole may cause "methimazole embryopathy". Antithyroid drug doses that maintain mothers in euthyroid status are sometimes excessive fetuses. Furthermore, successful treatment with surgery or radioiodine occasionally may result in fetal hyperthyroidism due to TSH receptor antibody(TRAb). There are approaches to manage these problems. Propylthiouracil is chosen in treating Graves' disease in early pregnancy. In later pregnancy, maternal free thyroxine is maintained near or somewhat above normal. Ablative therapy is not recommended in women whose TRAb levels are extremely high from the standpoint of fetal thyroid state.

Topics: Antithyroid Agents; Autoantibodies; Congenital Abnormalities; Female; Fetal Diseases; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Infant; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Methimazole; Milk, Human; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Propylthiouracil

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Imaging, Three-Dimensional; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Propylthiouracil; Thyroid Gland; Thyroxine; Ultrasonography, Doppler; Ultrasonography, Prenatal

Topics: Agranulocytosis; Algorithms; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotoxicosis; Thyroxine; Triiodothyronine

The subject of thyroid disease in pregnancy is receiving increasing attention from many scientific disciplines. Thyroid function in pregnancy is characterised by a T4 surge at 12 weeks declining thereafter. Serum thyroid hormone concentrations fall in the second half of pregnancy but there are few data on normal reference ranges. Fetal brain development depends on T4 transport into the fetus which in turn depends on sufficient maternal iodine supply. There is current concern that adequate iodisation is not present in large parts of Europe. There is increasing evidence that thyroid autoimmunity is associated with fetal loss but the mechanism is unclear and therapy requires carefully conducted studies. While hyperthyroidism in pregnancy is uncommon, effects on both mother and child are critical if untreated. The use of propylthiouracil is recommended together with measurement of TSH receptor antibodies at 36 weeks gestation. Women receiving thyroxine therapy for hypothyroidism or as suppressive therapy should have their dose increased by up to 50% during pregnancy. There are now substantial data to show deleterious effects on child IQ resulting from low maternal T4 (or high TSH) during gestation. Major advances in molecular biology have contributed to elucidation of many genetic causes of congenital hypothyroidism. However, the aetiology of the majority of cases is still unclear and further research is required. The presence of TPO antibodies in about 10% of pregnant women in early gestation is a predictor of an increased incidence of subclinical hypothyroidism during pregnancy and also of postpartum thyroid dysfunction. The latter condition occurs in 5-9% of women and 25-30% progress to permanent hypothyroidism. This review suggests that screening for thyroid function in early pregnancy and levothyroxine intervention therapy for maternal subclinical hypothyroidism should be considered but evidence is awaited. Screening for both thyroid dysfunction and thyroid antibodies ideally at a preconception clinic but certainly in early gestation is recommended.

Topics: Antithyroid Agents; Autoantibodies; Congenital Hypothyroidism; Drug Combinations; Female; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Intelligence Tests; Mass Screening; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Receptors, Thyrotropin; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Thyroxine

To report 2 fatal cases of fulminant hepatic failure associated with propylthiouracil treatment against hyperthyroidism.. Two women, 30 and 32 years old with no previous liver disease, were treated with propylthiouracil against Graves' disease. Both patients developed jaundice after a 4- and 5-month treatment period, respectively. The disease was similar to viral hepatitis, with a progressive course to severe liver dysfunction and death, along with multisystem organ failure despite extensive therapeutic measures. One of the patients was pregnant and subsequently miscarried. Neither patient had a history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. A submassive necrosis was shown in a postmortem histologic study.. Naranjo probability scale criteria applied to both cases confirm the adverse reactions as probable. These cases fit the requirements of drug hepatotoxicity proposed by Hanson and the Council of the International Organization of Medical Sciences. Eight deaths associated to propylthiouracil were found in our review of the medical literature up to December 2000.. Despite the widespread use of propylthiouracil, fulminant hepatitis with death is exceptionally rare; these 2 cases could be added to the fatal outcomes published to date.

Topics: Adult; Chemical and Drug Induced Liver Injury; Fatal Outcome; Female; Humans; Hyperthyroidism; Propylthiouracil

Radioiodine therapy is now the most common definite treatment for persistent hyperthyroidism. The outcome of radioiodine therapy depends mainly on the absorbed energy dose in the diseased thyroid tissue. The administered activity and the resulting target dose in the thyroid depend on both the biokinetics of radioiodine and the actual therapeutic effect of radioiodine in the thyroid. Thyrostatic drugs have a major influence on the kinetics of radioiodine in the thyroid and may additionally have a radioprotective effect. Pre-treatment with thyrostatic medication lowers the effective half-life and uptake of radioiodine. This can reduce the target dose in the thyroid and have a negative influence on the outcome of the therapy. Discontinuation of medication shortly before radioiodine administration can increase the absorbed energy dose in the thyroid without increasing the whole-body exposure to radiation as much as would a higher or second radioiodine administration. Furthermore, administration of non-radioactive iodine-127 2-3 days after radioiodine administration can also increase the effective half-life of radioiodine in the thyroid. Thus, improving the biokinetics of radioiodine will allow lower activities to be administered with lower effective doses to the rest of the body, while achieving an equally effective target dose in the thyroid.

Topics: Antithyroid Agents; Carbimazole; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Graves Disease; Half-Life; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Methimazole; Propylthiouracil; Radiation-Protective Agents; Radiopharmaceuticals; Radiotherapy Dosage

Pregnancy is accompanied by changes in thyroid function. Due to the increased synthesis of thyroid binding globulin and the thyroid-stimulating effect of human chorionic gonadotrophin (hCG), serum concentrations of thyroid hormones will increase in the first trimester of pregnancy (total T4, T3). Free T4 levels decrease during the latter half of pregnancy. Hyperthyroidism during pregnancy is usually due to Graves' disease. Definitive therapy may be considered for cases prior to pregnancy, although a medical management as would be given during pregnancy is an equally good option. The medical management of hyperthyroidism consists of a monotherapy with thyreostatics in which the recommended dose needs to be adjusted on the basis of free T4 in the high-normal and thyroid stimulating hormone (TSH) in the low-normal area so as to minimise the risk of foetal hypothyroidism. The transplacental passage of maternal TSH receptor stimulating antibodies may cause foetal hyperthyroidism. Another cause of maternal hyperthyroidism during pregnancy is 'gestational transient thyrotoxicosis', which is associated with high hCG levels during the first trimester of pregnancy. It is nearly always accompanied by hyperemesis gravidarum. Hypothyroidism in pregnancy has negative consequences for the foetus. If the hypothyroidism is apparent prior to pregnancy, it should be corrected before conception (target TSH value of 1 mU/l). If discovered during pregnancy, treatment with levothyroxine should be started as soon as possible. In the case of a pre-existing hypothyroidism a 25-50% increase in the levothyroxine dosage is often needed during the first trimester of pregnancy. This is possibly due to an increased requirement. An adequate serum concentration of T4 is necessary for foetal brain development.

Topics: Adult; Antithyroid Agents; Disease Management; Dose-Response Relationship, Drug; Female; Fetal Diseases; Hormone Replacement Therapy; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Propylthiouracil; Thyroid Function Tests; Thyroxine

The development of hyperthyroidism after primary hypothyroidism is unusual. We report such a case in a 37-year old man and review the clinical and immunologic aspects of the previously published cases of 50 female and 19 male patients with a similar condition.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Thyrotropin; Thyroxine

Hyperthyroidism due to autoimmune Graves' disease is the leading cause of thyrotoxicosis in pregnant women. The peak incidence of the disease is in the second through the fourth decade of life, which encompasses the reproductive years for women. Although menstrual irregularity is frequent in women with mild to moderate hyperthyroidism, convincing evidence that fertility is impaired is lacking. In general, 2 of every 1000 pregnancies have been reported to be complicated by hyperthyroidism. Hyperthyroidism associated with pregnancy may pose a challenging diagnostic and therapeutic dilemma. The current review focuses on the discussion of symptomatology and diagnosis of the disease, on therapeutic options available to women presenting with hyperthyroidism during gestation, and on the controversy surrounding maternal and fetal outcome in pregnancies complicated by thyrotoxicosis.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Thyroidectomy; Thyrotoxicosis

A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and inflammation of the nose. Examination of a renal biopsy specimen showed focal segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti-leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody to be markedly elevated, we challenged this data by performing dot blot analysis. The patient's serum reacted with the native form, but not with denatured leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms abated within 2 weeks and all values of ANCA were reduced after the drug was withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently it was reported in association with ANCA. We present the findings of this patient and compare them with those described in 19 published cases of propylthiouracil-induced vasculitis associated with ANCA.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Hyperthyroidism; Leukocyte Elastase; Propylthiouracil; Vasculitis

We have experienced a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis induced by propylthiouracil (PTU). A 45-year-old female had been treated with PTU for 4 years after the diagnosis of hyperthyroidism. She was referred to out hospital because of abrupt macroscopic hematuria and moderate proteinuria after several days of upper respiratory tract infection. On admission, her laboratory findings showed deterioration of renal function. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes. Her serology was found to be MPO-ANCA-positive and cytoplasmic-ANCA-negative. Based of these findings, we diagnosed idiopathic crescentic glomerulonephritis. Following the initiation of steroid pulse therapy, her urinary protein excretion and renal function gradually improved in parallel with a decrease in the MPO-ANCA titer. Although steroid therapy effectively responded to their renal function without the withdrawal of PTU, it seems that PTU may be closely associated with the development of (MPO-ANCA)-related glomerulonephritis in this case. Therefore, hyperthyroidism patients treated with PTU should be paced under vigilant observation by monitoring their urinalysis and serum creatinine level.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Female; Glomerulonephritis; Humans; Hyperthyroidism; Middle Aged; Peroxidase; Propylthiouracil

Therapy of thyroid dysfunction needs a close cooperation between endocrinologist and gynecologist. In addition to a number of metabolic changes during pregnancy, the diaplacentar transfer of different substances (thionamides, antibodies) has to be considered. Pregnant women with overt and subclinical hypothyroidism should be treated using L-Thyroxine with the bTSH between 1 and 2 mU/l. Many of the women need an increase of the L-Thyroxine dose during pregnancy. Overt hyperthyroidism (mostly due to Graves' disease) has to be treated immediately after diagnosis using thionamides. Because thionamides cross the placenta, the dose should be as low as possible with the fT4 in upper level and bTSH in the lower level of normal range. Most studies show, that both methimazole (MI) and propylthiouracil (PTU) can be used in pregnancy. Although PTU is preferred especially in the USA, an advantage of PTU over MI is not proven. Surgery is necessary in only few cases of hyperthyroidism during pregnancy with the optimal time for surgery during the second trimester. In case of subclinical hyperthyroidism and HCG induced hyperthyroidism several controls of thyroid function should be performed to decide whether treatment is necessary.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk Factors; Thyroid Function Tests; Thyroxine

Topics: Adrenergic beta-Antagonists; Carbimazole; Female; Fetal Diseases; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Pregnancy; Pregnancy Complications; Propylthiouracil; Referral and Consultation; Thyroid Function Tests; Thyroidectomy; Thyroxine; Treatment Outcome

Thioamide therapy has improved the outcome of pregnancies complicated by maternal hyperthyroidism, without long-term effects on cognitive and somatic development. However, there remain questions concerning whether these drugs, especially methimazole (MMI), may be associated with aplasia cutis congenita (ACC) and how best to avoid impairment of fetal thyroid function during their use. We report an example of ACC and review the relevant literature. We conclude that there is insufficient evidence either to establish or eliminate a direct causal relationship between ACC and MMI use. Since propylthiouracil is an equally effective antithyroid agent and has not been associated with ACC, it is the preferred thioamide for hyperthyroidism during pregnancy. Our review also indicates that impairment of neonatal thyroid function may be minimized by using a thioamide dose that is just sufficient to maintain the maternal serum free thyroxine concentration in the high normal or slightly thyrotoxic range.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Child Development; Female; Humans; Hyperthyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Skin Abnormalities; Teratogens; Thyroid Diseases; Thyroxine

Topics: Agranulocytosis; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Liver Diseases; Middle Aged; Propylthiouracil

Propylthiouracil (PTU) is widely used to treat patients with hyperthyroidism. In rare cases, this drug has been found to have severe toxic effects on the liver. The case of a 14-year-old girl treated with PTU for hyperthyroidism who developed jaundice, severe hepatocellular dysfunction, and hepatomegaly is reported. Her condition gradually deteriorated, and she developed paranoid ideation, profound lethargy, and peripheral edema. After three weeks of prednisone therapy, clinical and laboratory signs of improvement were observed. This patient was one of only five pediatric cases among the 16 reported cases of PTU liver toxicity reported to date. Her history and the fatal outcome in some reported cases demonstrate the high degree of sensitivity required to recognize this potential complication in patients treated with PTU, particularly since its immediate discontinuance and steroid-therapy intervention may lead to recovery.

Topics: Adolescent; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Propylthiouracil

The authors review the current knowledge of fetus and woman thyroid physiology during pregnancy. They analyze the abnormalities related to hyperthyroidism, and clinical and therapeutic aspects of thyrotoxicosis; in detail possible fetal complications. They suggest the practical management of thyrotoxicosis during pregnancy.

Topics: Adolescent; Adult; Embryonic and Fetal Development; Female; Humans; Hyperthyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotoxicosis; Thyrotropin

Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful.

Topics: Adult; Agranulocytosis; Antibody Formation; Cross Reactions; Drug Hypersensitivity; Female; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Methimazole; Middle Aged; Propylthiouracil

Topics: Adrenergic beta-Antagonists; Bromocriptine; Humans; Hyperthyroidism; Iodides; Iodine Radioisotopes; Lithium; Propylthiouracil; Thyroidectomy

Topics: Animals; Ethanol; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Liver; Liver Cirrhosis, Alcoholic; Propylthiouracil; Rats; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Recent modifications of the radioimmunoassay systems for TSH have greatly extended the clinical utility of the measurement of this hormone, so that its use is no longer limited to the diagnosis of primary hypothyroidism. The newer assays provide improved sensitivity and specificity, such that it is now possible to distinguish TSH levels that are within the normal range from those that are suppressed, e.g., in thyrotoxicosis. New vistas of clinical applications are being revealed as we improve our understanding of human thyroid physiology and pathophysiology. It is the purpose of this communication to summarize information about the improved TSH radioimmunoassay, to demonstrate the new observations available regarding TSH concentrations in various normal and diseased conditions, and finally, to illustrate the various ways in which the assay provides more accurate guidance in the clinical diagnosis and management of thyroid and nonthyroid disease.

Topics: Adolescent; Adult; Aged; Aging; Child; Child, Preschool; Circadian Rhythm; Female; Goiter; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Male; Mass Screening; Middle Aged; Pregnancy; Propylthiouracil; Radioimmunoassay; Reference Values; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Calcium; Carbimazole; Congenital Hypothyroidism; Dihydrotachysterol; Female; Humans; Hyperparathyroidism; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Infant, Newborn; Parathyroid Diseases; Parathyroid Glands; Pregnancy; Pregnancy Complications; Propylthiouracil; Puerperal Disorders; Thyroid Diseases; Thyroxine

Topics: Animals; Cat Diseases; Cats; Clinical Enzyme Tests; Female; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy

Over the past four decades, a great deal has been learned about the pharmacology and mechanisms of action of antithyroid drugs. Their ability to inhibit hormone biosynthesis involves complex interactions with thyroid peroxidase and thyroglobulin, many of which are still poorly understood. Their spectrum of activity is much wider than previously thought, and a number of clinically important extrathyroidal actions have been identified. Despite a greater appreciation for the intricacies of antithyroid-drug pharmacology, controversies still surround the use of these agents in the treatment of thyrotoxicosis. These controversies are apt to continue until the pathophysiology of Graves' disease is fully elucidated.

Topics: Adult; Agranulocytosis; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Child; Female; Fetus; Graves Disease; Humans; Hyperthyroidism; Immunity; Immunoglobulins; Infant, Newborn; Insulin Antibodies; Leukopenia; Lupus Vulgaris; Methimazole; Milk, Human; Pregnancy; Pregnancy Complications; Propylthiouracil; Vascular Diseases

Topics: Adolescent; Adult; Antithyroid Agents; Carbimazole; Child; Female; Goiter; Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Lithium; Methimazole; Pregnancy; Propranolol; Propylthiouracil; Thyroidectomy

Topics: Adenocarcinoma; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Thyroid Neoplasms

Topics: Adult; Aminoglutethimide; Animals; Antithyroid Agents; Carbimazole; Cobalt; Ethionamide; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Iodides; Lithium; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Rats; Sulfonamides; Sulfonylurea Compounds; Vegetables

Topics: Female; Fetal Diseases; Fetus; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland

Topics: Aging; Animals; Dexamethasone; Fasting; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Kinetics; Liver Cirrhosis; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

There are two biologically active thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Most T3 is produced extrathyroidally, so that alterations in circulating thyroid hormone concentrations may occur as a result of both thyroidal and extrathyroidal abnormalities. Extrathyroidal T4 conversion to T3 is decreased in patients with different acute and chronic illnesses. When T4 conversion to T3 is impaired and serum T3 concentrations decline, serum concentrations of biologically inactive 3,3',5'-triiodothyronine (reverse T3) increase. In this review, we present current information on thyroidal and extrathyroidal T4 and T3 production in normal subjects and patients with various thyroid diseases and other illnesses, consider the physiologic significance of these changes, and discuss the value and interpretation of various iodothyronine measurements.

Topics: Chemical Phenomena; Chemistry; Glucocorticoids; Humans; Hyperthyroidism; Hypothyroidism; Prealbumin; Propylthiouracil; Protein Binding; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Acetaldehyde; Animals; Brain; Ethanol; Fasting; Hyperthyroidism; Hypothyroidism; Liver; Male; Oxygen Consumption; Propylthiouracil; Rats; Triiodothyronine

Topics: Congenital Hypothyroidism; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Prognosis; Propylthiouracil; Thyroid (USP); Thyroid Diseases; Thyroid Gland; Thyroxine

Topics: Animals; Antithyroid Agents; Dogs; Humans; Hyperthyroidism; Iodine; Methimazole; Methylthiouracil; Propylthiouracil; Radioimmunoassay; Rats; Thyroidectomy; Thyroxine; Triiodothyronine

Topics: Depression, Chemical; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Lithium; Methimazole; Propranolol; Propylthiouracil; Reserpine; Thyroid Hormones

Topics: Abortion, Spontaneous; Female; Fetal Diseases; Humans; Hyperthyroidism; Hypothyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine

Topics: Biological Transport; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodides; Kinetics; Methimazole; Pregnancy; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Umbilical Cord

Topics: Agranulocytosis; Antithyroid Agents; Carbimazole; Eye Manifestations; Female; Follow-Up Studies; Goiter; Humans; Hyperthyroidism; Imidazoles; Methimazole; Pregnancy; Propylthiouracil; Thyroxine; Time Factors; Triiodothyronine

Topics: Abortion, Spontaneous; Congenital Hypothyroidism; Female; Fetal Death; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Intellectual Disability; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy; Triiodothyronine

Topics: Basal Metabolism; Female; Fetal Death; Goiter; Humans; Hyperthyroidism; Infant; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Methylthiouracil; Pregnancy; Pregnancy Complications; Propylthiouracil; Research; Thiouracil; Thyroid Function Tests; Thyrotropin; Thyroxine; Toxicology

Topics: Desoxycorticosterone; Dogs; Epinephrine; Heart Diseases; Hyperthyroidism; Hypokalemia; Isoproterenol; Myocardial Infarction; Necrosis; Norepinephrine; Potassium Deficiency; Propylthiouracil; Rats; Research; Thyroidectomy; Toxicology

A hypothesis was tested that providing the breeder hens with exogenous thyroxine (T(4)) would help their offspring to better survive the ascites-inducing condition during the growing period. In total, 132 broiler breeder hens were randomly assigned to one of 3 treatments: control (CON), hypothyroid [HYPO; 6-N-propyl-2-thiouracil (PTU)-treated], and hyperthyroid (HYPER; T(4)-treated). The hens were artificially inseminated, and the hatching eggs (n = 1,320) were incubated. No eggs in the HYPO group hatched. The 1-d-old male chicks (n = 288) from other groups were reared for 42 d under standard or low ambient temperature to induce ascites. Blood samples were drawn from the hens, embryos, and broilers for determination of T(4) and triiodothyronine (T(3)). The hematocrit was also determined in broilers. The PTU-treated hens had an increased BW along with lower plasma T(3) and T(4) concentrations. Plasma T(4) was higher in the HYPER hens compared with CON hens, but T(3) concentration was not different between these groups. The fertility rate was not affected by either hypo- or hyperthyroidism. The embryos in the HYPO group had lower plasma T(3) and T(4) concentrations at d 18 of embryonic development and internal pipping. Higher plasma T(4) was recorded in the HYPER birds at internal pipping, although plasma T(3) concentration was not affected at this stage. Maternal hyperthyroidism decreased the overall incidence of ascites in the cold-exposed chickens (10.0 vs. 33.4% for HYPER and CON groups, respectively). Although the effect of maternal PTU or T(4) treatment on plasma thyroid hormones and on the right ventricle-to-total ventricular weight ratio in the broilers was not significant, the cold-exposed healthy CON chicks showed higher hematocrit values, compared with the HYPER birds. It was concluded that maternal hyperthyroidism could decrease the incidence of cold-induced ascites in broiler chickens; however, probable causal mechanisms remain to be elucidated.

Topics: Animals; Ascites; Chickens; Cold Temperature; Female; Hyperthyroidism; Hypothyroidism; Male; Poultry Diseases; Propylthiouracil; Thyroxine; Weight Gain

Alterations in thyroid function are associated with changes in body weight, metabolism, and low-grade inflammation. In several studies, plasma levels of visfatin were found to be associated with body mass index, diabetes, and metabolic syndrome. In our study we aimed to evaluate visfatin levels according to thyroid dysfunction. The study cohort comprised 56 Hashimoto thyroiditis patients with hypothyroidism (43.94+/-14.27 yr), 56 Graves patients with hyperthyroidism (45.87+/-13.28 yr), and 56 euthyroid healthy subjects (45.23+/-7.11 yr) as a control group. In addition, we evaluated the effect of therapy on plasma visfatin levels in 16 hypothyroid and in 25 hyperthyroid patients. Markedly low visfatin levels were found in hyperthyroid patients [9.44 (8.07- 10.8) ng/ml] compared with the hypothyroid [49.93 (40.72- 59.1) ng/ml] and control groups [38.6 (30.6-46.6) ng/ml] (p<0.001, p<0.001). Plasma visfatin levels in patients with hypothyroidism decreased significantly following treatment [58.58 (10.21-190.7) ng/ml vs 40.00 (10.01-102.6) ng/ml; p=0.001]. Plasma visfatin levels increased significantly after antithyroid therapy in patients with hyperthyroidism [7.86 (1.02-19.23) ng/ml vs 12.63 (3.48-110.9) ng/ml; p<0.001]. There were negative correlations between visfatin levels with free T3 (r=-0.719, p<0.001), and free T4 (r=-0.716, p<0.001) levels. There was a positive correlation between visfatin and TSH levels (r=0.701, p<0.001). There was a negative correlation between delta visfatin levels with delta free T3, delta free T4 (r=-0.686, p<0.001; r=-0.624, p<0.001). Visfatin thus seems to be regulated by thyroid hormones. While the influence of thyroid dysfunction on adipocytokine production and release is still poorly understood, the results of our study suggest that the effects of hyper- and hypothyroidism on various metabolic parameters may be partly mediated by visfatin.

Topics: Adult; Antithyroid Agents; Cross-Sectional Studies; Cytokines; Female; Hormone Replacement Therapy; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Osmolar Concentration; Propranolol; Propylthiouracil; Recovery of Function; Thyroid Gland; Thyroxine

A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved.. Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease.. Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels.. The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up.. SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability.. Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.

Topics: Action Potentials; Adult; Antithyroid Agents; Atrial Fibrillation; Carbimazole; Echocardiography; Electric Stimulation; Female; Heart Rate; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Tachycardia, Supraventricular

Graves' hyperthyroidism and multinodular toxic goiter lead to high serum T(3) compared with serum T(4). The source of this high T(3) has not been clarified.. Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T(3) production and to estimate the sources of T(3) in hyperthyroidism.. The study was a prospective, randomized, open-labeled study in a secondary care setting.. Consecutive patients with hyperthyroidism caused by Graves' disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T(3) and T(4) were measured in serum, and we estimated the sources of T(3).. PTU reduced the T(3)/T(4) in serum to 47.7 +/- 2.5% (mean +/- sem) of the initial value on d 4 of therapy in patients with Graves' disease. The addition of KI to PTU led to a greater fall in T(3) and T(4), but the balance was unaltered. After PTU plus ipodate, T(3)/T(4) on d 4 was lower, 34.1 +/- 1.2% of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T(3) was D1-catalyzed T(4) deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T(3) production takes place in the hyperactive thyroid gland.. Although thyroidal T(3) contributes only around 20% of total T(3) production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T(4) deiodinated in the thyroid.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Drug Therapy, Combination; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Ipodate; Male; Middle Aged; Propylthiouracil; Prospective Studies; Thyroxine; Treatment Outcome; Triiodothyronine

Although methimazole (MMI) and propylthiouracil (PTU) have long been used to treat hyperthyroidism caused by Graves' disease (GD), there is still no clear conclusion about the choice of drug or appropriate initial doses.. The aim of the study was to compare the MMI 30 mg/d treatment with the PTU 300 mg/d and MMI 15 mg/d treatment in terms of efficacy and adverse reactions.. Patients newly diagnosed with GD were randomly assigned to one of the three treatment regimens in a prospective study at four Japanese hospitals.. Percentages of patients with normal serum free T(4) (FT4) or free T(3) (FT3) and frequency of adverse effects were measured at 4, 8, and 12 wk.. MMI 30 mg/d normalized FT4 in more patients than PTU 300 mg/d and MMI 15 mg/d for the whole group (240 patients) at 12 wk (96.5 vs. 78.3%; P = 0.001; and 86.2%, P = 0.023, respectively). When patients were divided into two groups by initial FT4, in the group of the patients with severe hyperthyroidism (FT4, 7 ng/dl or more, 64 patients) MMI 30 mg/d normalized FT4 more effectively than PTU 300 mg/d at 8 and 12 wk and MMI 15 mg/d at 8 wk, respectively (P < 0.05). No remarkable difference between the treatments was observed in patients with initial FT4 less than 7 ng/dl. Adverse effects, especially mild hepatotoxicity, were higher with PTU and significantly lower with MMI 15 mg/d compared with MMI 30 mg/d.. MMI 15 mg/d is suitable for mild and moderate GD, whereas MMI 30 mg/d is advisable for severe cases. PTU is not recommended for initial use.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Propylthiouracil; Prospective Studies; Thyroxine; Treatment Outcome; Triiodothyronine

To observe the therapeutic effect of combined therapy of modified Kangjia Recipe (KR) and western medicine propylthiouracil (PTU) on hyperthyroidism and to assess its advantage.. Ninety patients with hyperthyroidism were divided into the treatment group (TG) and the control group (CG). The 60 patients in TG treated with KR and PTU, and the 30 patients in CG treated with PTU alone. The treatment course of both groups was 3 months. The serum thyroid hormone (TH) level, clinical symptoms and signs, and adverse reaction were observed before and after treatment.. The serum TH level, clinical symptoms and signs were significantly improved after treatment in both groups (all P < 0.01). The total effective rate was 93.3% in TG, which was higher than that in CG (83.3%, P < 0.01); and the efficacy in improving palpitation, fidget, aversion to heat, sweating and insomnia was better in the TG than that in the CG respectively (P < 0.05). As for the incidence of adverse reaction, it that was lower in the TG than in the CG.. KD has good efficacy in treating hyperthyroidism, and the combined treatment of Chinese and Western medicine shows obvious advantages.

Topics: Adult; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Hyperthyroidism; Male; Middle Aged; Phytotherapy; Propylthiouracil

Aiming at evaluating the effect of antithyroid drugs on the efficacy of radioiodine treatment (RAI) we retrospectively analyzed 226 patients with Graves disease hyperthyroidism submitted to RAI between 1990 and 2001: 58 patients without any antithyroid drug (ATD) prior to RAI, 119 patients using propylthiouracil (PTU) and 49 patients using methimazole (MMI) prior to RAI. Clinical and laboratory parameters 1 year after RAI defined their clinical status (cured or not cured). High serum free T4 and 131-iodine uptake were negatively related with cure as well as lower RAI doses (mCi) and larger goiters (p< 0.05). The percentage of cured patients on PTU prior to RAI was 70.2% (84/119), while those on MMI was 85.7% (42/49), and 84.5% (49/58) of those without ATD prior to RAI (p= 0.034). On logistic regression analysis, free T4 > 4 ng/dl, large goiter, RAI dose < 10 mCi and PTU prior to RAI were related to lower cure rates. Compared to patients with no ATD prior to RAI, we concluded that the previous use of PTU implies in higher failure rates after RAI (OR= 3.13), an effect not observed in patients on MMI (OR= 1.28).

Topics: Adult; Antithyroid Agents; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Logistic Models; Male; Methimazole; Propylthiouracil; Radiation-Protective Agents; Radiography; Retrospective Studies; Thyroid Function Tests; Thyroid Hormones; Treatment Outcome

The effects of intranasal calcitonin on bone metabolism were investigated in patients with hyperthyroidism. Urinary deoxypyridinoline (uDPD) levels were measured as a bone turnover marker and lumbar spine (L2) bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 7 patients who were given only antithyroid drug (group 1), in 10 patients who were given antithyroid drug plus intranasal calcitonin (group 2), and in 10 healthy subjects who were given placebo (group 3) at the beginning and at the end of the study. The study continued until the patients with hyperthyroidism became euthyroidic according to the laboratory values. This period was approximately 3 months in groups 1 and 2. At the beginning of the study, uDPD was 21.5 +/- 2.6 nM DPD/mM creatinine in group 1, 23.3 +/- 3.6 nM DPD/mM creatinine in group 2, and 4.3 +/- 1.2 nM DPD/mM creatinine in group 3. uDPD levels measured in groups 1 and 2 were significantly higher than those in group 3 ( P << 0.001). Area BMD Z scores of the patients in groups 1 and 2 were significantly lower than the healthy controls ( P << 0.01, for both). At the end of the study, uDPD was 11.5 +/- 1.6 nM DPD/mM creatinine in group 1, 5.3 +/- 0.6 nM DPD/mM creatinine in group 2, and 4.4 +/- 1.3 nM DPD/mM creatinine in group 3. The levels of uDPD obtained in group 1 were significantly higher than those obtained in groups 2 and 3 ( P << 0.05, for both). The difference between groups 2 and 3 was not significant. Area BMD Z scores measured at the end of the study were found to be increased in groups 1 and 2 compared to early values, but the values were slightly lower than the normal values. In comparison of early and late uDPD values, the decrease in late period was statistically significant in groups 1 ( P << 0.05) and 2 ( P << 0.001). We concluded that bone turnover is high in hyperthyroidism. The treatment of hyperthyroidism decreases the rate of bone turnover, but it is not sufficient to prevent the degradation of bone in hyperthyroidism. The addition of intranasal calcitonin to the treatment of hyperthyroidism prevents the degradation of bone.

Topics: Adult; Amino Acids; Antithyroid Agents; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Calcitonin; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Lumbar Vertebrae; Male; Placebos; Propylthiouracil; Thyroid Hormones

A randomized clinical trial was performed to clarify whether pretreatment with propylthiouracil (PTU) before radioiodine ((131)I) therapy influences the final outcome of this therapy, as has been indicated by retrospective studies. Untreated consecutive hyperthyroid patients with Graves' disease (n = 23) or a toxic nodular goiter (n = 57) were randomized to either PTU (+PTU; n = 39) or no pretreatment (-PTU; n = 41) before compensated (131)I therapy. The median PTU dose was 100 mg, which was discontinued 4 d before treatment. The median (131)I activity was 302 MBq (range, 87-600 MBq). After (131)I therapy, the serum free T(4) index increased in the +PTU group from 97.7 +/- 47.5(+/-sd) nmol/liter at the time of therapy to 152.3 +/- 77.6 nmol/liter at 3 wk (P < 0.001) and 140.4 +/- 75.9 nmol/liter at 6 wk (P < 0.001). In the -PTU group, the serum free T(4) index, which was initially 254.3 +/- 145.7 nmol/liter, decreased significantly to 212.0 +/- 113.0 nmol/liter at 3 wk (P < 0.05) and 165.8 +/- 110.0 nmol/liter at 6 wk (P < 0.005). After 1 yr of follow-up, the treatment failure rate in patients with a toxic nodular goiter was four times higher in the +PTU group than in the -PTU group (nine of 20 vs. three of 25 patients; P = 0.06), whereas the difference among patients with Graves' disease was less obvious (four of six vs. four of nine; P = 0.81). Patients in the +PTU group who were cured had higher serum TSH (s-TSH) levels at the time of (131)I therapy than those who were not cured. By adjusting for a possible interfactorial relationship through a regression analysis, including the s-TSH level and type of disease, only PTU pretreatment had a significant adverse effect on the cure rate (P = 0.03). In conclusion, this randomized trial demonstrates that PTU pretreatment reduces the cure rate of (131)I therapy in hyperthyroid diseases, although this adverse effect seems to be attenuated by the concomitant rise in s-TSH.

Topics: Adult; Aged; Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Thyrotropin; Thyroxine; Treatment Outcome

Previous studies have described the therapeutic effects of propylthiouracil (PTU) and methimazole in normal subjects after rectal suppositories. The goal of our study was to compare the pharmacokinetic and pharmacologic effects of a suppository and suspension form of PTU given per rectum. Fifteen newly diagnosed hyperthyroid patients of both genders (ages 21 to 55 years) were randomly given the drug as follows: group 1 (n = 7), a single enema (400 mg of PTU in 90 mL of sterile water) and group 2 (n = 8), two suppositories of polyethylene glycol base (200 mg of PTU in each). The pharmacokinetic study revealed earlier time to peak levels (T(max)) and significantly greater maximal peak levels (C(max)) in group 1 than in group 2, (85.71 +/- 12.12 minutes vs. 172.5 +/- 26.24 minutes for T(max) and 3.89 +/- 0.34 vs. 2.01 +/- 0.38 microg/mL, p < 0.05 for C(max), respectively). However, the area under the curve (635.16 +/- 105.71 vs. 377.87 +/- 68.09 microg x min/mL) was not statistically different between both groups. Both forms induced a significant decrease in serum free triiodothyronine (FT(3)) levels and an increase in serum rT(3) levels shortly after administration. Four subjects reported a bitter taste 5-10 minutes after receiving the drug. PTU can be effectively absorbed via the rectal route. The enema form appeared to provide better bioavailability than the suppository form. However, both preparations exhibited comparable therapeutic effect.

Topics: Administration, Rectal; Adult; Enema; Female; Humans; Hyperthyroidism; Male; Propylthiouracil; Suppositories; Thyroxine; Triiodothyronine

This study was planned to determine the effects of free-radical-induced damage on the Na+,K+-ATPase activity of erythrocytes during hyperthyroidism and 4 wk after propylthiouracil (PTU) therapy (400 mg/d). The levels of plasma thiobarbituric acid-reactive substances (TBARS) as a marker of lipid peroxidation, erythrocyte glutathione (GSH) concentration as an antioxidant, blood ATP concentration, and erythrocyte membrane Na+,K+-ATPase activity were determined in female hyperthyroid patients (n = 22, mean age 40.5 +/- 6.5 yr). Before the PTU therapy, plasma TBARS concentration was significantly higher and the levels of blood ATP and erythrocyte GSH and the activity of membrane Na+,K-+-ATPase were significantly lower in the hyperthyroid patients (n = 15 women, mean age 40.8 +/- 7.3 yr). Four weeks after PTU therapy, plasma TBARS concentration was decreased, and levels of erythrocyte GSH and blood ATP and of Na+,K+-ATPase activity of erythrocytes were elevated in the treated patients. There was a significant positive correlation between blood ATP concentration and Na+,K+-ATPase activity, and a negative correlation between plasma TBARS concentration and Na+,K+-ATPase activity before PTU. Our results might help to clarify the effects of the oxidative mechanisms on the erythrocyte membrane Na+,K+-ATPase activity in hyperthyroid patients.

Topics: Adenosine Triphosphate; Adult; Antithyroid Agents; Erythrocyte Membrane; Erythrocytes; Female; Humans; Hyperthyroidism; Oxidative Stress; Propylthiouracil; Sodium-Potassium-Exchanging ATPase; Thiobarbituric Acid Reactive Substances

Topics: Adult; Aged; Aged, 80 and over; Carbimazole; Female; Homocysteine; Hormone Replacement Therapy; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Thyroxine

This study was performed on 17 hyperthyroid patients and 15 healthy controls. The patients were under propylthiouracil (PTU) therapy at a dosage of 3 x 100 mg/day for one month. Blood samples, taken at the beginning and on the 30th day of therapy, were analyzed for hormonal parameters (T3, T4, TSH), lipid peroxidation endproduct [thiobarbituric acid reactive substances (TBARS)] and antioxidant status parameters: glutathione (GSH), glutathione peroxidase (GSH-Px) and CuZn superoxide dismutase (CuZn SOD). Hyperthyroid patients were observed to have significantly higher TBARS, GSH and CuZn SOD levels than controls (P < 0.05, P < 0.001, P < 0.001, respectively). PTU therapy caused a relief in oxidative stress as reflected by significantly decreased TBARS levels (P < 0.001) and a selective modification in the antioxidant status parameters: significant decreases in GSH and CuZn SOD levels (P < 0.001) and a significant increase in GSH Px (P < 0.01) activity. Our findings suggest a selective modification of the antioxidative profile in hyperthyroidism. PTU should also be considered as an in vivo antioxidant, in addition to its antithyroid action.

Topics: Adult; Antithyroid Agents; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Humans; Hyperthyroidism; Lipid Peroxides; Male; Middle Aged; Oxidoreductases; Propylthiouracil; Reference Values; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The purpose of this study was to examine lipid peroxidation and antioxidant states during hyperthyroidism states and after given different treatments.. We examined 44 hyperthyroid patients and 19 euthyroid healthy controls. Patients were divided into three groups according to the treatment: Propylthiouracil (PTU) group, PTU + propranolol (PRP) group, PTU + PRP + vitamin E (vitE) group.. In the hyperthyroid patients plasma malondialdehyde (MDA) levels were significantly high as compared to the control group (p < 0,001). There was a significant decrease in the MDA levels post-treatment (p < 0.001 in the PTU + PRP group and PTU + PRP + vitE group, p < 0.01 in the PTU group). In the hyperthyroidism, blood reduced glutathione (GSH) levels were lower, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities were higher than in the control group, but these changes were not significant. Post-treatment in each of the three groups the GSH levels were increased significantly as compared to the pretreatment levels (p < 0.001). There was significant decrease in the SOD activity post treatment (p < 0.01 in all three groups). Post-treatment CAT activity was decreased (p < 0.05 in the PTU group, p < 0.001 in the other two groups). The erythrocyte glutathione peroxidase (Gpx) activity was lower significantly in the hyperthyroidism as compared to the control group (p < 0.001). Post-treatment, in the three groups Gpx activity increased significantly as compared to the pretreatment levels (p < 0.05 in the PTU group, p < 0.001 in the PTU + PRP group and PTU + PRP + vitE group).. We considered that giving all three treatments would be useful to the prevention of oxidative stress in the hyperthyroidism states.

Topics: Adult; Antioxidants; Antithyroid Agents; Catalase; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Humans; Hyperthyroidism; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Propranolol; Propylthiouracil; Superoxide Dismutase; Thyroid Function Tests; Vitamin E

It is still debated which is the best treatment for Basedow-Graves' hyperthyroidism (BGH). We reviewed 195 patients treated and followed-up during the past 30 years: 88 treated with propylthiouracil (PTU), 70 with 131I and 37 thyroidectomized.. to analyze the efficacy of each therapy in terms of achieving euthyroidism and the search of possible indexes for success. Surgery attained euthyroidism in 70.2% but has disadvantages; 131I accounted for the highest hypothyroid rate (72.1%) irrespective of the dose administered; PTU alone was successful in only 26.4% but combined with T4, success rose to 62.5% (p < 0.025). Suppression test and/or TRAb measurements after 6 mo PTU therapy were used to decide if therapy continued or was changed to other form of treatment. Using this criteria, 87.5% of pts with positive results achieved longstanding euthyroidism. Pretreatment predictive indexes were goiter size, T4 levels and 24 h/RAI uptake.. As 131I induces hypothyroidism in over 2/3 of pts and surgery besides its cost is not devoid of serious complications, we advocate for the use of PTU as first line therapy; combined treatment (PTU + T4) seems promising. If after 6 mo on PTU, TRAb or Suppression test do not improve, we recommend 131I or surgery.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Thyroidectomy; Treatment Outcome

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Topics: Antithyroid Agents; Diltiazem; Humans; Hyperthyroidism; Immunoradiometric Assay; Placebos; Propylthiouracil; Prospective Studies; Reference Values; Reproducibility of Results; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine

This study to compare single-dose and multiple-dose antithyroid therapy was prompted by a perceived lack of compliance in our University Medical Clinics by those patients using multidose regimens. Twenty-two hyperthyroid patients were randomly assigned to two therapy groups. Twelve received methimazole (Tapazole) 30 mg once daily in the morning; 10 received propylthiouracil 100 mg every 8 hours. Patients were seen every 4 weeks for 3 months and assessed clinically, as well as having the appropriate thyroid tests done. Univariate analysis revealed no difference in the two groups at baseline. Posttreatment assessment revealed the once-a-day methimazole therapy to be just as effective as propylthiouracil in improving thyroid indices and clinical markers. Compliance with methimazole was 83.3% compared to 53.3% with propylthiouracil. In conclusion, once-a-day methimazole was just as effective as propylthiouracil every 8 hours in this population. Compliance was also improved with the once-a-day therapy.

Topics: Drug Administration Schedule; Female; Humans; Hyperthyroidism; Male; Methimazole; Patient Compliance; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Contrary to the usual inhibitory role of tumor necrosis factor-alpha (TNF-alpha) in thyroid metabolism, it also has specific stimulatory effects in autoimmune thyroid disorders, including induction of HLA class II antigen-presenting cell-T cell interaction. Despite high intrathyroidal concentrations, various studies were not able to demonstrate high serum levels of TNF-alpha in patients with Graves' disease. To investigate this discrepancy we determined TNF-alpha and interleukin 6 (IL-6) levels in 25 hyperthyroid patients who responded to propylthiouracil treatment (16 with Graves' disease and nine with toxic multinodular goiter) and compared them with the levels found in euthyroid patients with simple diffuse goiter (n = 15) and normal healthy controls (n = 15). Median IL-6 levels were high in both Graves' disease and toxic multinodular goiter patients before propylthiouracil treatment (23 and 26.5 pg/ml, respectively). After restoring euthyroidism there was a statistically significant decline to near-normal levels (3 and 10 pg/ml, respectively). On the other hand, median serum TNF-alpha levels were high only in Graves' disease patients (20 pg/ml) and could not be normalized with antithyroid medication (20 pg/ml) compared to that of controls (5 pg/ml). Tumor necrosis factor-alpha, but not IL-6, was found to be high in the sera of Graves' disease patients when euthyroid, which may be due to an ongoing antigen-antibody interaction, a feature of autoimmune attack. It remains to be determined whether the degree of TNF-alpha and/or IL-6 elevation will be a predictor of disease recurrence.

Topics: Adult; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Interleukin-6; Male; Middle Aged; Propylthiouracil; Thyrotoxicosis; Thyroxine; Triiodothyronine; Tumor Necrosis Factor-alpha

In 92,130 pregnancies followed between 1980 and 1987, 48 cases of hyperthyroidism were reported including 38 Grave's diseases, 5 toxic adenomas, 4 multinodules goiters. In comparing the results with those mentioned in the literature, a number of conclusions may be reached. In case of hyperthyroidism treated before the pregnancy or discovered at the beginning, there is, in every other case, an aggravation at the end of the first trimester, then a stabilization in the 2nd or 3rd trimester and finally an aggravation in the post-partum period. There is a high rate of abortions (35 p. cent), a delayed intra-uterine growth in half of the cases. The problem of the treatment is of paramount importance; there is no problem with Beta-blockers but the SAT are not without danger: risk of hypothyroidism and fetal goiter, but also risk of maternal hypothyroidism. From the 15th week, the doses should therefore be decreased, and sometimes the treatment discontinued and replaced with Beta-blockers. The best SAT drug during pregnancy is the propylthioracile which is the least likely to cross the fetal barrier. Surgery is only exceptionally indicated. In a woman who is cured from her Grave's disease, recurrences are always possible, and also fetal hyperthyroidism caused by crossing of thyreostimulins immunoglobins, even in case of maternal euthyroidism.

Topics: Adult; Carbimazole; Female; France; Humans; Hyperthyroidism; Multicenter Studies as Topic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Retrospective Studies

To assess the value of antithyroid drugs as an adjunct to radioactive iodine for the treatment of hyperthyroidism the incidence of relapse or hypothyroidism after a mean follow-up of 5 1/2 years (range 2-7 years) was reviewed retrospectively for 206 patients, some treated with and others without antithyroid drugs after radioiodine therapy. Allocation to treatment group had been random, and both groups were similar in all respects except for the adjunctive treatment with antithyroid drugs. All doses of 131I had been calculated by one physician. Compared with those who received 131I alone, those starting on antithyroid drugs within 8 days after 131I had a lower incidence of hypothyroidism but a higher incidence of early post-treatment recurrence or persistence of hyperthyroidism, and a considerably lower incidence of remission.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Retrospective Studies; Thyroid Hormones

A hyperthyroid symptom scale (HSS) was designed and administered to ten subjects with untreated Graves' disease. All subjects had clinical and chemical evidence of hyperthyroidism and reproducible HSS scores of 20 or more points. During sequential treatments with propranolol hydrochloride (phase 2) followed by propylthiouracil (phase 3) there was a significant decline in the HSS scores at each phase. Accompanying the decrease in HSS scores was a decrease in heart rate, but there was no change in thyroid function test results at phase 2 and a decrease in heart rate, thyroid function test results, and goiter size at phase 3. This new scale includes ten categories of symptoms, it is sensitive to changes in both the adrenergic and metabolic components of hyperthyroidism, and it is useful in the clinical assessment and management of patients with thyrotoxicosis.

Topics: Adult; Analysis of Variance; Clinical Trials as Topic; Diagnosis-Related Groups; Evaluation Studies as Topic; Female; Graves Disease; Humans; Hyperthyroidism; Male; Middle Aged; Propranolol; Propylthiouracil; Severity of Illness Index

Hyperthyroid patients in the postabsorptive state have elevated levels of blood glycerol and ketone bodies (KB): this is believed to be due to increased lipolysis and ketogenesis. These increased glycerol and KB levels return toward normal after oral propranolol administration. In order to investigate the mechanism of action of propranolol in hyperthyroid patients, we compared the effects of the oral administration of propranolol with those of timolol, propylthiouracil (PTU), and a placebo. The placebo had no effect. The free thyroxine index, immunoreactive insulin level and glucagon level were not modified by propranolol, timolol, or PTU. Propranolol decreased the pulse rate (P less than 0.01) and the levels of serum triiodothyronine (T3; P less than 0.05), blood glycerol (P less than 0.01), and KB (P less than 0.01). Like propranolol, timolol decreased the pulse rate (P less than 0.01) but had no effect on the T3, glycerol, or KB levels. Propylthiouracil did not modify the pulse rate, but like propranolol, it decreased the T3 (P less than 0.05), glycerol (P less than 0.01) and KB (P less than 0.01) levels. These results suggest that the metabolic actions of propranolol are not caused by its hemodynamic effects nor its beta-blocking properties but are mediated by the decrease of the T3 level.

Topics: Adolescent; Adult; Fatty Acids, Nonesterified; Female; Glycerol; Humans; Hyperthyroidism; Ketone Bodies; Male; Middle Aged; Propranolol; Propylthiouracil; Pulse; Timolol; Triiodothyronine

In order to investigate the mechanism whereby oral propranolol administration reduces the increased rate of urinary hydroxyproline excretion (UHxE) of patients with hyperthyroidism, a comparison was made of the effects of the oral administration of propranolol-timolol, propylthiouracil (PTU), and a placebo to patients with hyperthyroidism and to normal controls. Propranolol decreased the pulse rate (P less than 0.01), serum triiodothyronine (T3) level (P less than 0.05), and UHxE (P less than 0.01) without modifying the serum free thyroxine index (FT4I) or parathormone (PTH) level. Timolol decreased the pulse rate (P less than 0.01) to the same extent as propranolol, had no effect on T3, FT4I, or PTH, and failed to decrease UHxE. Administration of PTU decreased the T3 level (P less than 0.05) to a similar extent as propranolol without modifying the FT4I or PTH level and had no effect on UHxE. Placebo administration had no effect. These results suggest that the reduction of UHxE by propranolol is not due to the beta-receptor-blocking properties of propranolol nor mediated by the propranolol-induced decrease in the level of T3 but is probably due to the membrane-stabilizing properties of propranolol.

Topics: Adult; Female; Humans; Hydroxyproline; Hyperthyroidism; Male; Middle Aged; Propranolol; Propylthiouracil; Thyroxine; Timolol; Triiodothyronine

Serum propylthiouracil semi splitting occurs in 1.1 and 1.65 hours when administered in a single dose. In this work treatment for hyperthyroid patients is described; 350 mg were administered daily in divided doses, every two and eight hours. In group A fifteen patients received 50 mg every two hours from 8:00 to 20:00 hs. and in group B nine patients were administered 100, 100 and 150 mg at 8 hour intervals. The patients were hospitalized the first seven days and during this time circulating triiodothyronine and thyroxine concentrations were measured daily at 8:00 and 20:00 hrs. and then at 8:00 hrs. at days 8, 14, 21 and 28. After almost one week of treatment, in group "A", seven patients (46.6 per cent p 0.05) had normal concentration levels in both hormones. In group "B" only one patient reached normal levels in the first eight days. The administration of propylthiouracil every two hours is a useful procedure to attain the euthyroid state in less time than with other therapeutic patterns without undesirable side effects.

Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Tablets; Time Factors

In 28 patients with Graves' disease showing a wide range of thyroid function between the extremes of hypothyroidism and hyperthyroidism, the following parameters of peripheral thyroid function were measured: serum thyroxine concentration, serum-free thyroxine concentration, serum triiodothyronine concentration, and serum-free triiodothyronine concentration. In 25 patients, thyroxine turnover was also measured. Thyroxine turnover was found to be highly correlated with serum-free thyroxine concentration (r equals 0.9405) and serum-free triiodothyronine concentration (r equals 0.9184). Serum-free thyroxine fraction correlated with serum-free triiodothyronine fraction (r equals 0.8445), suggesting that similar factors in serum controlled the intensity of protein binding for both thyroxine and triiodothyronine. Thyroxine turnover calculated by a noncompartmental method agreed closely with values calculated by the compartmental method, suggesting that the former simpler method has general utility.

Topics: Adult; Aged; Clinical Trials as Topic; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Radioimmunoassay; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Adolescent; Adult; Birth Weight; Female; Fetal Death; Humans; Hyperthyroidism; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones

Topics: Animals; Calcinosis; Calcium; Calcium Chloride; Clinical Trials as Topic; Disease Models, Animal; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Parathyroid Glands; Phosphates; Propylthiouracil; Rats; Skin Diseases; Thyroid Function Tests; Thyroid Gland; Thyroidectomy

Topics: Adult; Aged; Carbimazole; Clinical Trials as Topic; Female; Guanethidine; Humans; Hyperthyroidism; Male; Middle Aged; Propranolol; Propylthiouracil

Topics: Antithyroid Agents; Clinical Trials as Topic; Follow-Up Studies; Humans; Hyperthyroidism; Imidazoles; Iodine Radioisotopes; Methimazole; Prognosis; Propylthiouracil; Thyroid Function Tests; Triiodothyronine

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroid Function Tests; Time Factors

Topics: Antithyroid Agents; Carbimazole; Clinical Trials as Topic; Follow-Up Studies; Humans; Hyperthyroidism; Imidazoles; Iodine Radioisotopes; Metabolic Clearance Rate; Prognosis; Propylthiouracil; Thyroid Gland

Topics: Antithyroid Agents; Clinical Trials as Topic; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Perchlorates; Potassium; Propylthiouracil; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Adult; Antithyroid Agents; Clinical Trials as Topic; Female; Follow-Up Studies; Goiter; Humans; Hyperthyroidism; Male; Middle Aged; Prognosis; Propylthiouracil; Thiouracil

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome.. A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later.. Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.

Topics: Adult; Drug Hypersensitivity Syndrome; Eosinophilia; Exanthema; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil

Topics: Antithyroid Agents; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; East Asian People; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil

Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.. We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.. We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.. Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.. The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.

Topics: Antithyroid Agents; Carbimazole; Cohort Studies; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Pregnancy; Propylthiouracil; Thyroid Function Tests; Thyrotropin; Thyroxine

Thionamides (methimazole and propylthiouracil) have been associated with common side effects, such as rash and pruritus, and rare but serious adverse effects, such as agranulocytosis and hepatotoxicity. Methimazole is usually the preferred thionamide for the treatment of hyperthyroidism if the patient is not planning to conceive or not in the first trimester of pregnancy, given the less frequent dosing and lower risk of hepatotoxicity. In patients who experience rash or itching when treated with methimazole, switching them to propylthiouracil is one treatment option. Here we report our experience regarding desensitization to methimazole to allow continued treatment with methimazole as an alternative management option.. We conducted a retrospective chart review of patients at a single institution who had side effects to methimazole and who were desensitized to methimazole under the supervision of an allergist. A total of 7 patients were included who experienced side effects to methimazole that did not include agranulocytosis or hepatotoxicity.. All 7 patients were able to take methimazole for treatment of their hyperthyroidism, either for continued medical therapy or as a bridge to definitive therapy, with either surgery or radioactive iodine treatment.. Under the supervision of an allergist, desensitization to methimazole is an option for treating patients who experience side effects to methimazole (excluding agranulocytosis and hepatotoxicity).

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms

Propylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis.. A 27-year-old woman diagnosed with Graves' disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover.. All synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Purpura

The aim of this study was to evaluate the efficiency and safety of methimazole (MMI) and propylthiouracil (PTU) in the treatment of hyperthyroidism.. Articles were searched through the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and QVIP. The primary outcomes were clinical efficacy and thyroid hormone levels in MMI and PTU groups. The secondary outcomes were liver function indexes and adverse reactions in MMI and PTU groups. Results were expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). The Begg test was applied to assess the publication bias.. Totally, 16 randomized controlled trials were retained in this meta-analysis with 973 patients receiving MMI and 933 receiving PTU. The levels of triiodothyronine (T3) (WMD = -1.321, 95% CI: -2.271 to -0.372, P = .006), thyroxine (T4) (WMD = -37.311, 95% CI: -61.012 to -13.610, P = .002), Free T3 (FT3) (WMD = -1.388, 95% CI: -2.543 to -0.233, P = .019), Free T4 (FT4) (WMD = -3.613, 95% CI: -5.972 to -1.255, P = .003), and the risk of liver function damage (OR = 0.208, 95% CI: 0.146-0.296, P < .001) in the MMI group were lower than those in the PTU group. The thyroid-stimulating hormone level (WMD = 0.787, 95% CI: 0.380-1.194, P < .001) and the risk of hypothyroidism (OR = 2.738, 95% CI: 1.444-5.193, P = .002) were higher in the MMI group than those in the PTU group.. Although MMI might have higher risk of hypothyroidism than PTU, the efficacy of MMI may be better than PTU in patients with hyperthyroidism regarding reducing T3, T4, FT3, and FT4 levels, decreasing the risk of liver function damage and increasing the level of thyroid-stimulating hormone.. osf.io/ds637 (https://osf.io/search/).

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Randomized Controlled Trials as Topic

Topics: Aged; Antithyroid Agents; Diagnosis, Differential; Female; Hemangioendothelioma; Humans; Hyperthyroidism; Livedo Reticularis; Lymphoma, B-Cell, Marginal Zone; Propylthiouracil; Skin Neoplasms

Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Case-Control Studies; Comorbidity; Databases, Factual; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatitis; Pharmacovigilance; Propylthiouracil; Retrospective Studies; Risk; Taiwan; Thioamides

This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism.. In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo.. sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004).. The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

Topics: E-Selectin; Humans; Hyperthyroidism; Intercellular Adhesion Molecule-1; Propylthiouracil; Vascular Cell Adhesion Molecule-1

Thyroid hormones have important roles in normal development and energy regulating mechanisms as well as signaling mechanisms that affect energy consumption through central and peripheral pathways. The aim of this study was to determine the effects of thyroid dysfunction on adropin, asprosin and preptin levels in rat.. The study was performed on the 38 male Wistar-albino rats. Experiment groups were designed as follows. 1-Control, 2-Hypothyroidism; To induce hypothyroidism PTU was applied by intraperitoneal as 10 mg/kg/day for 2 weeks. 3-Hypothyroidism + Thyroxine; Previously animals were made with hypothyroidism by 1 week PTU application and then 1 week l-thyroxine was given by intraperitoneal as 1.5 mg/kg/day. 4-Hyperthyroidism; Rats were made with hyperthyroidism by 3 weeks l-thyroxine (0.3 mg/kg/day). 5-Hyperthyroidism + PTU; Animals were made hyperthyroisim by l-thyroxine as groups 4, then 1 week PTU was applied to treatment of hiperthyrodism. At the end of supplementation animals were sacrificed and blood samples were collected for FT3, FT4, adropin, asprosin, preptin analysis.. FT3 ve FT4 levels were reduced significantly in hypothyroidism while increased in hyperthyroidism (p<0.001). Hipothyrodism led to reduces adropin, asprosin and preptin levels. And also hyperthyroidism reduced adropin and preptin levels (p<0.001).. The results of study show that experimental hypothyroidism and hyperthyroidism lead to significantly change to adropin, asprosin and preptin levels. However, correction of thyroid function caused to normals levels in asprosin and preptin.

Topics: Animals; Blood Proteins; Fibrillin-1; Hyperthyroidism; Hypothyroidism; Insulin-Like Growth Factor II; Peptide Fragments; Peptide Hormones; Peptides; Propylthiouracil; Rats; Thyroxine; Triiodothyronine

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Drug Administration Schedule; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia.. A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse.. The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP.. Withdrawal of PTU and the administration of methylprednisolone.. The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions.. Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Lung Diseases, Interstitial; Propylthiouracil; Tomography, X-Ray Computed

Topics: Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Drug Substitution; Emergencies; Female; Humans; Hyperthyroidism; Lung Abscess; Methimazole; Middle Aged; Propylthiouracil; Tomography, X-Ray Computed

High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition.. C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days. The mice were euthanized and proximal intestine was removed to study GLUT2, GLUT5, PEPT1, FAT-CD36, FATP4, NPC1L1 and NHE3 distribution by Western blotting. Since PPAR-a is activated by fatty acids, which is abundant in the HFD, we also evaluated whether PPAR-a affects nutrients transporters. Thus, mice were treated with fenofibrate, a PPAR-a agonist.. HFD decreased GLUT2, PEPT1, FAT-CD6 and NPC1L1, but increased NHE3, while GLUT5 and FATP4 remained unaltered. THs did not alter distribution of nutrients transporters neither in LFD nor in HFD groups, but they increased villi length and depth crypt in LFD and HFD, respectively. Fenofibrate did not affect content of nutrients transporters, excluding PPAR-a involvement on the HFD-induced changes.. We assume that chronic HFD consumption reduced most of the nutrients transporters content in the small intestine of mice, which might limit the entrance of nutrients and gain weight. Since NHE3 promotes sodium absorption, and it was increased in HFD group, this finding could contribute to explain the hypertension observed in obesity.

Topics: Animals; Antithyroid Agents; Diet, High-Fat; Fenofibrate; Glucose Tolerance Test; Hyperthyroidism; Hypolipidemic Agents; Hypothyroidism; Intestinal Mucosa; Intestine, Small; Intestines; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; PPAR alpha; Propylthiouracil; Sodium-Hydrogen Exchanger 3; Thyroid Hormones; Triiodothyronine

Thyroid hormones (THs) play a critical role in the development of ovarian cells. Although the\ effects of THs on female reproduction are of great interest, the mechanism remains unclear. We\ investigated the effects of TH dysregulation on reproductive hormones in rats. Propylthiouracil (PTU)\ and L-thyroxine were administered to rats to induce hypo- and hyperthyroidism, respectively, and the\ reproductive hormone profiles were analyzed by radioimmunoassay (RIA). Ovarian histology was\ evaluated with hematoxylin and eosin (H&E) staining, and gene protein level or mRNA content was\ analyzed by western blotting or reverse transcription polymerase chain reaction (RT-PCR). The serum\ levels of gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in both rat\ models were significantly decreased on day 21, although there were no significant changes at earlier\ time points. There were no significant differences in luteinizing hormone (LH) or progesterone (P4)\ levels between the treatment and the control groups. Both PTU and L-thyroxine treatments downregulated\ estradiol (E2) concentrations; however, the serum testosterone (T) level was increased only in\ hypothyroid rats at day 21. In addition, the expression levels of FSH receptor, cholesterol side-chain\ cleavage enzyme (P450scc), and steroidogenic acute regulatory protein (StAR) were decreased in both\ rat models. Moreover, the onset of puberty was significantly delayed in the hypothyroid group. These\ results provide evidence that TH dysregulation alters reproductive hormone profiles, and that the\ initiation of the estrous cycle is postponed in hypothyroidism.

Topics: Animals; Biomarkers; Cholesterol Side-Chain Cleavage Enzyme; Disease Models, Animal; Estradiol; Estrous Cycle; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hyperthyroidism; Hypothyroidism; Luteinizing Hormone; Ovary; Phosphoproteins; Progesterone; Propylthiouracil; Rats, Sprague-Dawley; Sexual Maturation; Testosterone; Thyroid Gland; Thyroid Hormones; Thyroxine; Time Factors

BACKGROUND Thyrotoxic periodic paralysis (TPP) is commonly observed in patients with acute paralysis and hyperthyroidism. However, there is a possibility of secondary causes of hypokalemia in such a setting. CASE REPORT Herein, we present the case of a 38-year-old woman with untreated hypertension and hyperthyroidism. She presented with muscle weakness, nausea, vomiting, and diarrhea since one week. The initial diagnosis was TPP. However, biochemistry tests showed hypokalemia with metabolic alkalosis and renal potassium wasting. Moreover, a suppressed plasma renin level and a high plasma aldosterone level were noted, which was suggestive of primary aldosteronism. Abdominal computed tomography confirmed this diagnosis. CONCLUSIONS Therefore, it is imperative to consider other causes of hypokalemia (apart from TPP) in a patient with hyperthyroidism but with renal potassium wasting and metabolic alkalosis. This can help avoid delay in diagnosis of the underlying disease.

Topics: Adrenergic beta-Antagonists; Adult; Aldosterone; Antithyroid Agents; Biomarkers; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Hyperaldosteronism; Hyperthyroidism; Hypokalemia; Paralysis; Potassium; Propranolol; Propylthiouracil; Renin; Treatment Outcome

Synthetic antithyroid drugs are often used in the treatment of hyperthyroidism, regardless of aetiology. They may cause various side effects, including the development of anti-neutrophil cytoplasmic antibodies (ANCA), ANCA-associated vasculitis, and neutrophilic dermatoses. Propylthiouracil (PTU) is the antithyroid drug most frequently implicated in ANCA-associated diseases specifically involving anti-myeloperoxidase ANCA (MPO-ANCA). To our knowledge, there are no clinical reports describing the association of pyoderma gangrenosum (PG) and anti-proteinase3-ANCA (PR3-ANCA) induced by PTU, with ANCA levels decreasing after antithyroid drug withdrawal.. A 68-year-old woman was treated with propylthiouracil (PTU) for toxic multinodular goitre. She presented necrotic ulceration of the lower abdomen. The patient's history, physical examination, and bacteriological and histological samples led to a diagnosis of pyoderma gangrenosum. This pyoderma involved ANCA with antigenic specificity for proteinase 3. Withdrawal of PTU and a short course of corticosteroids and cyclosporine resulted in rapid and complete resolution of the pyoderma gangrenosum as well as a decrease in ANCA. No relapse was observed one year after cessation of treatment.. We report a case of PG associated with PR3-ANCA induced by PTU, without any demonstrable vasculitis.

Topics: Abdomen; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hyperthyroidism; Propylthiouracil; Pyoderma Gangrenosum; Treatment Outcome

Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 μg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.

Topics: Adult; Amniotic Fluid; Female; Goiter; Humans; Hyperthyroidism; Pregnancy; Prenatal Injuries; Propylthiouracil; Thyroid Hormones; Thyroxine

The objective of this work is to report our experience with (131)I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.. Five patients with refractory severe hyperthyroidism were treated with (131)I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before (131)I treatment due to treatment failure or severe jaundice. Prior to (131)I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their (131)I treatment. The patients were followed for 4 to 9 years after (131)I therapy.. After (131)I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after (131)I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy.. (131)I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; China; Female; Humans; Hyperbilirubinemia; Hyperthyroidism; Iodine Radioisotopes; Jaundice; Liver Diseases; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Severity of Illness Index

Pancreatic progenitors derived from human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating diabetes and are currently being tested in clinical trials. Yet, how the milieu of pancreatic progenitor cells, including exposure to different factors after transplant, may influence their maturation remains unclear. Here, we examined the effect of thyroid dysregulation on the development of hESC-derived progenitor cells in vivo. Hypothyroidism was generated in SCID-beige mice using an iodine-deficient diet containing 0.15% propyl-2-thiouracil, and hyperthyroidism was generated by addition of L-thyroxine (T4) to drinking water. All mice received macroencapsulated hESC-derived progenitor cells, and thyroid dysfunction was maintained for the duration of the study ("chronic") or for 4 weeks posttransplant ("acute"). Acute hyperthyroidism did not affect graft function, but acute hypothyroidism transiently impaired human C-peptide secretion at 16 weeks posttransplant. Chronic hypothyroidism resulted in severely blunted basal human C-peptide secretion, impaired glucose-stimulated insulin secretion, and elevated plasma glucagon levels. Grafts from chronic hypothyroid mice contained fewer β-cells, heterogenous MAFA expression, and increased glucagon(+) and ghrelin(+) cells compared to grafts from euthyroid mice. Taken together, these data suggest that long-term thyroid hormone deficiency may drive the differentiation of human pancreatic progenitor cells toward α- and ε-cell lineages at the expense of β-cell formation.

Topics: Animals; Antithyroid Agents; Biomarkers; Cell Differentiation; Cell Line; Cells, Immobilized; Diabetes Mellitus, Type 1; Disease Models, Animal; Heterografts; Human Embryonic Stem Cells; Humans; Hyperthyroidism; Hypothyroidism; Insulin-Secreting Cells; Iodine; Male; Mice, SCID; Propylthiouracil; Random Allocation; Thyroxine; Transplantation, Heterologous; Transplantation, Heterotopic

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood.. Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000-2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed.. The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (±standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 ± 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 ± 8.0 mg/day and 253.6 ± 177.5 mg/day, respectively. ATD-induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and sore throat (72.8%) were the most common symptoms when agranulocytosis was diagnosed. The mean recovery time of agranulocytosis was 13.41 ± 7.14 days. Recovery time in the granulocyte colony-stimulating factor (G-CSF)-treated group (12.7 ± 6.0 days) did not differ from that in the group not treated with G-CSF (16.4 ± 10.6 days; p = 0.144). Treatment with (131)I was successful in 87/98 patients (88.8%). The success rate of (131)I was equivalent (p = 1.000) between the groups receiving methimazole (88.2%, 75/85) and propylthiouracil (92.3%, 12/13).. This largest single-institution study in China shows that ATD-induced agranulocytosis tends to occur within the first 12 weeks after the onset of ATD therapy. For patients with ATD-induced agranulocytosis, G-CSF does not improve the recovery time of agranulocytosis, and (131)I is an optimal treatment approach.

Topics: Adult; Agranulocytosis; Antithyroid Agents; China; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome

The present study is aimed at bringing out the information on the effect of berberine chloride in hyper and hypo thyroidal model with two dose levels.. The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms.. Sixty female wistar rats weighing between 150-250 gm were divided in to 10 groups. The animals were grouped in to solvent control; hypothyroid; hyperthyroid; prophylactic with two different doses of berberine chloride (50 and 100 mg/kg); treatment groups similar to that of the prophylactic and therapeutic group. To substantiate the dose dependent effect of berberine chloride in 6-n-propyL-2-thiouracil (PTU) induced hypothyroidism, lipid profile, thyroid profile, enzymes profiles and blood profiles, in addition to histopathological studies were also carried out. There was no any significant difference in the lipid profile among solvent control, treatment and prophylactic groups. However, there was a significant difference (***p<0.001) in serum triglycerides, LDL and VLDL of hypothyroid group when compound to that of the rest.. As far as thyroid profile is concerned, T3 level of berberine chloride (50 mg/kg) treated groups (prophylactic+ treatment) showed a significant rise compared to hypothyroid group. TSH level in prophylactic groups was far higher than the rest of the groups (3.002±0.0192, 1.051±0.0008 against the solvent control, 0.308±0.008). SGOT, SGPT levels were significantly higher with the therapeutic group than that of the normal and hypo-thyroidal group. Blood profile of berberine chloride (100 mg/kg) treated therapeutic group was comparable to that of the solvent control than all other groups. The probable mechanism underlying may be that inactivation of type I 5.-iodothyronine deiodinase (5.DI) enzyme by NF-kB pathway.. From the findings of the current study it can be concluded that berberine chloride possesses both thyroid stimulating and suppressing activities depending on its dose, especially berberine chloride 50 mg/kg supports thyroid stimulating property.

Topics: Animals; Antithyroid Agents; Berberine; Biomarkers; Chlorides; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hyperthyroidism; Hypothyroidism; Lipids; Patents as Topic; Propylthiouracil; Rats, Wistar; Thyroid Gland; Thyroid Hormones; Time Factors

The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Febrile Neutropenia; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thyroidectomy; Vasculitis

Preclinical Research The aim of the present study was to evaluate the effects of thyroid dysfunction on markers of oxidative stress in rat pancreas. Hypothyroidism and hyperthyroidism were, respectively, induced in rats via administration of propylthiouracil (PTU) and L-thyroxine sodium salt in drinking water for 45 days. The activities of superoxide dismutase (SOD), catalase (CAT), glutathioen peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), xanthine oxidase (XO), and nonenzymatic markers of oxidative stress including malondialdehyde (MDA), protein carbonyl (PC), reduced glutathione (GSH), and total thiols (T-SH) were determined in the rat pancreas. In hyperthyroid rats, pancreatic CAT, SOD, GPx, GR, XO, G6PD activities were increased compared with those in hypothyroid and control groups. There were no differences in activities of antioxidant enzymes between hypothyroid and control rats. Pancreatic MDA and PC in hyperthyroid rats increased compared with hypothyroid and the control animals. Whereas, hyperthyroid rats had decreased levels of tissue GSH and T-SH compared with hypothyroid and the control groups. The findings showed that only GSH level has decreased significantly in the hypothyroid group compared with control groups. In conclusion, our results showed that experimental hyperthyroidism induces oxidative stress in pancreas of rats, but hypothyroidism has no major impact on oxidative stress markers. Drug Dev Res 77 : 199-205, 2016.   © 2016 Wiley Periodicals, Inc.

Topics: Animals; Antioxidants; Biomarkers; Disease Models, Animal; Glutathione; Hyperthyroidism; Hypothyroidism; Male; Oxidative Stress; Pancreas; Propylthiouracil; Rats; Rats, Wistar; Sulfhydryl Compounds; Thyroxine

To report a rare case of maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of hCG.. A 36-year-old woman after successful intrauterine insemination and triplet pregnancy, developed hyperthyroidism with resistance to medical treatment.. All signs of hyperthyroidism resolved and the results of thyroid function tests returned to normal without any medication after embryo meiosis.. De novo maternal hyperthyroidism may develop during pregnancy as a result of pathological stimulation of the thyroid gland from the high levels of hCG hormone that can be seen in multiple pregnancies. The risk of hyperthyroidism is related to the number of fetuses. Reversibility of symptomatology can be seen after fetal reduction of multiple pregnancies.

Topics: Adult; Antithyroid Agents; Chorionic Gonadotropin; Female; Humans; Hyperthyroidism; Insemination, Artificial; Ovulation Induction; Pregnancy; Pregnancy Complications; Pregnancy Reduction, Multifetal; Pregnancy, Triplet; Propylthiouracil; Treatment Failure

The serum metabolomic profile and its relationship to physiological changes during hyperthyroidism and restoration to euthyroidism are not known. This study aimed to examine the physiological, adipokine, and metabolomic changes that occur when subjects with Graves' disease transition from hyperthyroidism to euthyroidism with medical treatment.. Chinese women between 21 and 50 years of age and with newly diagnosed Graves' disease attending the endocrine outpatient clinics in a single institution were recruited between July 2012 and September 2014. All subjects were treated with thioamides to achieve euthyroidism. Clinical parameters (body weight, body composition via bioelectrical impedance analysis, resting energy expenditure and respiratory quotient via indirect calorimetry, and reported total energy intake via 24 h food diary), biochemical parameters (thyroid hormones, lipid profile, fasting insulin and glucose levels), serum leptin, adiponectin, and metabolomics profiles were measured during hyperthyroidism and repeated in early euthyroidism.. Twenty four Chinese women with an average age of 36.3 ± 8.6 years were included in the study. The average duration of treatment that was required to reach euthyroidism for these subjects was 38 ± 16.3 weeks. There was a significant increase in body weight (52.6 ± 9.0 kg to 55.3 ± 9.4 kg; p < 0.001) and fat mass (14.3 ± 6.9 kg to 16.8 ± 6.5 kg; p = 0.005). There was a reduction in resting energy expenditure corrected for weight (28.7 ± 4.0 kcal/kg to 21.5 ± 4.1 kcal/kg; p < 0.001) and an increase in respiratory quotient (0.76 to 0.81; p = 0.037). Resting energy expenditure increased significantly with increasing free triiodothyronine levels (p = 0.007). Significant increases in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were noted. There was no significant change in leptin levels, but adiponectin levels increased significantly (p = 0.018). Significant reductions in fasting C2, medium-chain, long-chain, and total acylcarnitines were observed, but no changes in the fat-free mass, branched chain amino acid levels, or insulin sensitivity during recovery from hyperthyroidism were noted.. Serum metabolomics profile changes complemented the physiological changes observed during the transition from hyperthyroidism to euthyroidism. This study provides a comprehensive and integrated view of the changes in fuel metabolism and energy balance that occur following the treatment of hyperthyroidism.

Topics: Adiponectin; Adult; Antithyroid Agents; Asian People; Basal Metabolism; Biomarkers; Carbimazole; China; Energy Intake; Energy Metabolism; Female; Graves Disease; Hospitals, Urban; Humans; Hyperthyroidism; Metabolomics; Middle Aged; Outpatient Clinics, Hospital; Propylthiouracil; Thyroid Gland; Weight Gain; Young Adult

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure, Acute; Liver Transplantation; Methimazole; Propylthiouracil

Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients.. Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated.. The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31).. Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

Topics: Adult; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; China; Female; Graves Disease; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Thyroxine; Treatment Outcome; Triiodothyronine; Young Adult

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Ear, External; Female; Humans; Hyperthyroidism; Prednisone; Propylthiouracil; Purpura; Vasculitis, Leukocytoclastic, Cutaneous

A 43-year-old Chinese female had been diagnosed with hyperthyroidism 15 years ago. She was recently administered 150 mg/day propylthiouracil (PTU). After 3 weeks of PTU administration, she developed necrotizing stomatitis and osteonecrosis, most likely due to secondary effects from the PTU treatment. Her neutrophil count was reduced below normal to 0.24×10(9)/L but normalized after withdrawal of PTU therapy. About 1 month after onset, the patient came to our hospital and began to receive intravenous treatments of metronidazole and amoxicillin. Following review of her medical history and a series of clinical and laboratory examinations, the patient was diagnosed with secondary necrotizing gingivostomatitis and osteonecrosis possibly associated with PTU-induced agranulocytosis. One-year after treatment, the patient's oral manifestations remained unchanged. This case demonstrates the need for dental practitioners to more closely monitor oral symptoms in patients with hyperthyroidism treated with antithyroid drugs.

Topics: Adult; Antithyroid Agents; Biopsy; Combined Modality Therapy; Female; Gingivitis; Humans; Hyperthyroidism; Necrosis; Osteonecrosis; Propylthiouracil; Radiography, Panoramic; Stomatitis

Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy.

Topics: Aged; Antithyroid Agents; Diagnosis, Differential; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Propylthiouracil; Pulmonary Alveoli; Tomography, X-Ray Computed; Treatment Outcome; Vasculitis

Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy.. A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed.. The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy".. While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Prospective Studies; Retrospective Studies

Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 10(2) B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma.

Topics: Animals; Antithyroid Agents; Disease Models, Animal; Eye Neoplasms; Hyperthyroidism; Hypothyroidism; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred C57BL; Propylthiouracil; Survival Rate; Thyroxine

To study the role of deoxyribonuclease (DNase) I activity and ANCA in propylthiouracil (PTU)-induced lupus-like syndrome (LLS).. We compared 36 SLE patients with 17 PTU-induced LLS patients diagnosed from 2008 to 2014. We studied ANCA profile (MPO, PR3, lactoferrin, CTG, elastase, bactericidal/permeability-increasing protein), anti-dsDNA, anti-ENA, anti-nucleosome, anti-histone, anti-C1q, anti-aCL, complement components, cryoglobulins and serum DNase I activity. Healthy persons and patients without LLS treated with PTU comprised the control groups. Twelve LLS patients were serologically and clinically followed for 4.1 (S.D. 2.0) years.. PTU-induced LLS patients less frequently had arthritis, renal and neurological manifestations, but more frequently had fever, purpura, urticarial-like vasculitis and ulceration (P < 0.01). PTU-induced LLS patients more frequently had polyspecific ANCA (anti-MPO, anti-elastase and anti-PR3 were most commonly detected) (P < 0.01). SLE patients more frequently had anti-dsDNA, anti-ENA, anti-nucleosome, anti-C1q (P < 0.01) and anti-histone antibodies (P < 0.05). PTU-induced LLS patients had lower DNase I activity than SLE patients and controls (P < 0.01). Discontinuation of PTU increased DNase I activity, although it did not reach the levels of controls (P < 0.01). After remission, MPO-ANCA decreased (P < 0.01), but persisted for a long time.. PTU, as a trigger, and low DNase I activity, as a predisposing factor, may lead to LLS. Polyspecific ANCAs are useful markers for differentiating SLE from PTU-induced LLS. Low DNase I activity might be an important prognostic biomarker for PTU-induced LLS. Monitoring of ANCA and DNase I activity may prevent long-lasting exposure to causal drugs, unnecessary immunosuppressive therapy and severe complications of LLS.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Case-Control Studies; Deoxyribonucleases; Female; Humans; Hyperthyroidism; Lupus Erythematosus, Systemic; Male; Middle Aged; Prevalence; Prognosis; Propylthiouracil; Retrospective Studies; Syndrome; Young Adult

Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased-and hyperthyroid animals significantly decreased-ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.

Topics: Animals; Body Weight; Diet, High-Fat; Eating; Female; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Rats; Rats, Sprague-Dawley; Thrombophilia; Triiodothyronine

Pancytopenia in the first trimester is very rare. A 33-year-old multiparous woman presented with nausea, loss of appetite, and bodyweight loss of 7.4 kg at 9(1/7) weeks of gestation due to hyperemesis gravidarum. Her laboratory data demonstrated pancytopenia involving white blood cell count of 3500/μL, a hemoglobin level of 9.8 g/dL, and a platelet count of 10.5 × 10(4)/μL. An extensive investigation into the causes of the pancytopenia detected true hyperthyroidism: thyroid-stimulating hormone, <0.02 μU/mL; free triiodothyronine, 11.25 pg/mL; free thyroxine, 4.74 ng/dL; and anti-thyroid-stimulating hormone receptor antibodies, 12.2 IU/L. Propylthiouracil was started at a dose of 300 mg/day at 10(5/7) weeks of gestation, which resulted in the normalization of her blood parameters and concomitant improvements in her free triiodothyronine and free thyroxine levels at 12(0/7) weeks of gestation. Pancytopenia in the first trimester might be indicative of hidden hyperthyroidism.

Topics: Adult; Female; Humans; Hyperthyroidism; Pancytopenia; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Failure; Pregnancy; Pregnancy Complications; Propylthiouracil

This study was designed to show the effect of propylthiouracil treatment on sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels on subjects with subclinical hyperthyroidism. After checking sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels of 35 patients with subclinical hyperthyroidism, each was given 50 mg tablets of propylthiouracil three times daily. After 3 months, sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels were then compared to the levels before treatment. Although high-sensitivity C-reactive protein and sCD40L levels were normal in the subclinical hyperthyroidism patients compared to the healthy controls, fetuin-A levels were statistically significantly higher (*p = 0.022). After treatment, fetuin-A levels of subclinical hyperthyroidism patients decreased statistically significantly compared to the levels before treatment (**p = 0.026). sCD40L and high-sensitivity C-reactive protein levels did not have a statistically significant difference compared to the control group and post-propylthiouracil treatment. In subclinical hyperthyroidism patients, high fetuin-A levels before propylthiouracil treatment and decreases in these levels after treatment in cases with subclinical hyperthyroidism indicated the possibility of preventing long-term cardiac complications with propylthiouracil treatment.

Topics: Adult; alpha-2-HS-Glycoprotein; Antithyroid Agents; Biomarkers; C-Reactive Protein; Case-Control Studies; CD40 Ligand; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Male; Propylthiouracil; Retrospective Studies; Treatment Outcome

Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society have published guidelines for the management of thyroid diseases in pregnancy. We aimed to disclose the impact of these guidelines in current practices of Asian members of the Asia-Oceania Thyroid Association (AOTA) regarding the management of hyperthyroidism in pregnancy. Completed questionnaire survey, based on clinical case scenarios, was collected from 321 Asian physician members of AOTA from 21 Asian countries in 2013. For a woman with Graves' disease planning pregnancy, 92% of clinicians favored antithyroid treatment, 52% with propylthiouracil (PTU) while 40% preferred methimazole (MMI). For a pregnant woman with newly diagnosed overt hyperthyroidism, nearly all responders initiated PTU treatment. To monitor dosage of antithyroid drugs, approximately 73% of responders used TSH and free T4 (FT4) levels without free T3 (FT3) (53%) or with FT3 (20%). Majority of responders targeted achieving low serum TSH with FT4 (or total T4) in the upper end of the normal range. For management of gestational thyrotoxicosis, 40% chose to follow up and 52% treated patients with PTU. Although timing of TSH receptor antibodies measurement in pregnant hyperthyroid patients was variable, 53% of responders would check it at least once during pregnancy. Nearly 80% of responders do not treat subclinical hyperthyroidism in pregnancy. Therefore, despite wide variations in the management of hyperthyroidism during pregnancy in Asia, majority of Asian physicians practice within the recommendations of major professional societies.

Topics: Adult; Asia; Data Collection; Female; Humans; Hyperthyroidism; Postpartum Period; Pregnancy; Pregnancy Complications; Professional Practice; Propylthiouracil; Referral and Consultation; Surveys and Questionnaires; Thyroid Function Tests; Young Adult

Periodic paralysis is a muscle disorder that belongs to the family of diseases called channelopathies, manifested by episodes of painless muscle weakness. Periodic paralysis is classified as hypokalemic when episodes occur in association with low potassium levels. Most cases are hereditary. Acquired cases have been described in association with hyperthyroidism. Diagnosis is made on clinical and biochemical grounds. Patients may be markedly hypokalemic during the episode and respond well to potassium supplementation. Episodes can be prevented by achieving a euthyroid state. This report describes a young gentleman presenting with thyrotoxic hypokalemic paraparesis. The condition needs to be considered in the differential diagnosis of neuromuscular weakness in the context of hypokalemia by the treating physicians.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Hypokalemic Periodic Paralysis; Male; Muscle Weakness; Paraparesis; Potassium; Propranolol; Propylthiouracil; Thyroid Function Tests; Thyrotoxicosis; Treatment Outcome

Propylthiouracil (PTU) used in the treatment of maternal hyperthyroidism in early pregnancy may be associated with a higher prevalence of birth defects in the face and neck region and in the urinary system but the severity of these complications remains to be elucidated.. Review of hospital-registered cases of birth defects in the face and neck region and in the urinary system after PTU exposure in early pregnancy. We obtained information on maternal redeemed prescription of PTU and child diagnosis of birth defect from nationwide registers for all children born in Denmark between 1996 and 2008 (n=817,093). The children were followed until December 31, 2010 (median age, 8.3 years) and the Cox proportional hazards model was used to estimate adjusted hazard ratio (HR) with 95% confidence interval (CI) for having a birth defect after PTU exposure versus nonexposed children (n=811,730).. Fourteen cases of birth defects were identified in the face and neck region and in the urinary system after PTU exposure in early pregnancy; 11 children were exposed to PTU only (n=564), whereas 3 children were born to mothers who switched from methimazole (MMI)/carbimazole (CMZ) to PTU in early pregnancy (n=159). Among children exposed to PTU only, the adjusted HR for having a birth defect in the face and neck region was 4.92 (95% CI 2.04-11.86) and in the urinary system 2.73 (1.22-6.07). Looking into details of the 14 cases, 7 children were diagnosed with a birth defect in the face and neck region (preauricular and branchial sinus/fistula/cyst) and 7 children had a birth defect in the urinary system (single cyst of kidney and hydronephrosis). Surgical treatment was registered in 6 of the cases with a birth defect in the face and neck region and 3 of the cases with a birth defect in the urinary system. Two of the children with a birth defect in the urinary system also had other birth defects (genital organs).. We report details on possible PTU-associated birth defects. They tend to be less severe than the defects observed after MMI/CMZ exposure. Yet, the majority of affected children had to undergo surgery.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; Craniofacial Abnormalities; Denmark; Female; Humans; Hyperthyroidism; Infant; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Proportional Hazards Models; Propylthiouracil; Registries; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Urogenital Abnormalities

Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs.. We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20.. In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed.. We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy.

Topics: Animals; Antithyroid Agents; Female; Hyperthyroidism; Methimazole; Mice; Mice, Inbred C57BL; Pregnancy; Pregnancy Complications; Propylthiouracil; Rats; Rats, Sprague-Dawley; Teratogens

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

Topics: Animals; Animals, Newborn; Antithyroid Agents; Blood Pressure; Blotting, Northern; Gene Expression; Heart Rate; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Male; Muscle, Skeletal; Myocardium; Myoglobin; Organ Size; Propylthiouracil; Random Allocation; Rats, Wistar; Reactive Oxygen Species; RNA, Messenger; Triiodothyronine

The female C3H-A mice with agouty fur color were used to model hyper- and hypothyroidism in the long lasting experiment. The study was carried out for 44 weeks. Hyperthyroidism was induced by the administration of the L-thyroxine injections on alternate days during the whole period of the investigation. Hypothyroidism was achieved by adding propylthiouracil to the drinking water. The change of thyroid state was characterized by biphasic change in body weight. At the beginning of the experiment the hypothyroid animals were retarding by their weight. Otherwise the hyperthyroid animals were advancing by their weight. But since the 18th-21st week the initial trends changed, i. e. the hypothyroid mice body weight started ahead the hyperthyroid one. In the open field test both hypo- and hyperthyroid animals demonstrated the higher level of the investigating activity in comparison with the euthyroid mice. In the hyperthyroid mice the frequency of side-activity acts (grooming) increased significantly. Thus, the hyperthyroid animals appeared to be more anxious. To the 18th week of the experiment the animals of study groups started to demonstrate the apparent visual difference in their fur color. The hyperthyroid mice fur color became darker than one of the hypothyroid and the euthyroid mice. It is worthy of note that the hyperthyroid mice fur color was getting lighter than one of the euthyroid animals. The results are discussed in the context of hypothalamic-pituitary-thyroid axis functioning. The possible mechanisms of hormonal regulation of the fur color in mice are considered to include the hypothalamic-pituitary-thyroid axis hormones activities.

Topics: Animals; Female; Grooming; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Mice; Mice, Inbred C3H; Pigmentation; Propylthiouracil; Thyroxine; Time Factors

The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner.. We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively.. The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22).. MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Chemical and Drug Induced Liver Injury; Cohort Studies; Databases, Factual; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hyperthyroidism; Incidence; Male; Methimazole; Middle Aged; Proportional Hazards Models; Propylthiouracil; Retrospective Studies; Taiwan; Young Adult

A 28 year-old woman in her first pregnancy was referred to the department of obstetrics and gynecology at 24 weeks of gestation because of pregnancy-induced hypertension.. Thyroid stimulating hormone (TSH), free T3 and free T4 were elevated. Antibody screening did not show antithyroid peroxidase (anti-TPO) antibodies and TSH receptor antibodies. Clinical findings were suspicious of TSH secreting pituitary tumour (TSH-om) or thyroid hormone resistance (RTH). In absence of clinical sings of elevated intracranial pressure magnetic resonance imaging (MR) was discussed but not carried out and planned after delivery. A visual-field defect was ruled out by orbital field evaluation.. Treatment with 3 × 50 mg propylthiouracil daily was initiated. However, normal fT3/fT4 titers could not be achieved. Serum levels were in the high normal ranges and TSH remained increased. The clinical situation of the patient improved resulting in a normal delivery at term. The healthy newborn was breast feed and MR imaging of the mother revealed a 5×8 mm tumor of the pituitary gland.. In pregnant women with pregnancy-induced hypertension thyroid diseases have to be ruled out. Rare causes of hyperthyreoidism are TSH secreting pituitary tumors or thyroid hormone resistance (RTH). Treatment of choice for hyperthyreoidism in pregnancy is propylthiouracil. Normal vaginal delivery and breast feeding are possible. Following delivery it is mandatory to determine an individual treatment strategy.

Topics: Adenoma; Antithyroid Agents; Female; Humans; Hyperpituitarism; Hyperthyroidism; Infant, Newborn; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Trimester, Second; Propylthiouracil; Rare Diseases; Thyroid Function Tests; Thyrotropin

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Diagnosis, Differential; Glomerulonephritis, IGA; Humans; Hyperthyroidism; Male; Middle Aged; Peroxidase; Propylthiouracil

Agranulocytosis is known to be a rare side effect of thionamides. This complication puts pregnant patients at particular risk for infections. Obstetricians caring for such patients have the difficult task of deciding between conservative or surgical management.. The patient is a 37-year-old gravida 4 para 3 Hispanic woman at 11 weeks of gestation with recently diagnosed hyperthyroidism who presented with a neutropenic fever and ecthyma as a complication of thionamide use. She subsequently underwent a thyroidectomy and then had a spontaneous abortion on postoperative day 2.. This patient had life-threatening thyrotoxicosis complicated by neutropenic fever and infection, likely caused by a reaction to thionamides. She quickly recovered with broad-spectrum antibiotics. She could not be restarted on methimazole or propylthiouracil as a result of agranulocytosis and thus underwent thyroidectomy.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Antithyroid Agents; Atenolol; Drug Eruptions; Ecthyma; Female; Humans; Hyperthyroidism; Methimazole; Neutropenia; Pregnancy; Pregnancy Complications; Propylthiouracil; Staphylococcal Skin Infections; Staphylococcus aureus

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Topics: Ablation Techniques; Adult; Antithyroid Agents; Combined Modality Therapy; Dietary Supplements; Female; Goiter; Graves Disease; Heart Failure; Hormone Replacement Therapy; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Maternal Nutritional Physiological Phenomena; Potassium Iodide; Pregnancy; Pregnancy, High-Risk; Prenatal Care; Prenatal Diagnosis; Propylthiouracil; Recurrence; Thyroxine; Treatment Outcome; Ultrasonography

Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications, but teratogenic effects of antithyroid drug (ATD) treatment have been described. Evidence is still lacking in regard to the safety and choice of ATD in early pregnancy.. Our objective was to determine to which degree the use of methimazole (MMI)/carbimazole (CMZ) and propylthiouracil (PTU) in early pregnancy is associated with an increased prevalence of birth defects.. This Danish nationwide register-based cohort study included 817 093 children live-born from 1996 to 2008. Exposure groups were assigned according to maternal ATD use in early pregnancy: PTU (n = 564); MMI/CMZ (n = 1097); MMI/CMZ and PTU (shifted in early pregnancy [n = 159]); no ATD (ATD use, but not in pregnancy [n = 3543]); and nonexposed (never ATD use [n = 811 730]). Multivariate logistic regression was used to estimate adjusted odds ratio (OR) with 95% confidence interval (95% CI) for diagnosis of a birth defect before 2 years of age in exposed versus nonexposed children.. The prevalence of birth defects was high in children exposed to ATD in early pregnancy (PTU, 8.0%; MMI/CMZ, 9.1%; MMI/CMZ and PTU, 10.1%; no ATD, 5.4%; nonexposed, 5.7%; P < .001). Both maternal use of MMI/CMZ (adjusted OR = 1.66 [95% CI 1.35-2.04]) and PTU (1.41 [1.03-1.92]) and maternal shift between MMI/CMZ and PTU in early pregnancy (1.82 [1.08-3.07]) were associated with an increased OR of birth defects. MMI/CMZ and PTU were associated with urinary system malformation, and PTU with malformations in the face and neck region. Choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, and aplasia cutis were common in MMI/CMZ-exposed children (combined, adjusted OR = 21.8 [13.4-35.4]).. Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed. More studies are needed to corroborate results in regard to early pregnancy shift from MMI/CMZ to PTU. New ATD with fewer side effects should be developed.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Carbimazole; Denmark; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Prevalence; Propylthiouracil

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Male; Methimazole; Pregnancy; Propylthiouracil

Topics: Adult; Antithyroid Agents; Autoantibodies; Diagnosis, Differential; Humans; Hyperthyroidism; Male; Propylthiouracil; Thyroid Function Tests; Thyrotropin; Thyroxine

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are rare, but they can be triggered by chemicals, infections and drugs; among them, antithyroid drugs are common. Autoimmune disorders, such as vasculitis, are unusual, but serious complications of antithyroid therapy. Both propylthiouracil (PTU) and methimazole may induce ANCA-associated vasculitis. PTU-induced vasculitides may have different organ involvement patterns. Herein, we report four cases with ANCA-associated vasculitis with different clinical manifestations.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Female; Goiter; Humans; Hyperthyroidism; Immunosuppressive Agents; Male; Middle Aged; Propylthiouracil; Withholding Treatment; Young Adult

This study is aimed to explore the relationship between bone marrow characteristics and clinical prognosis of antithyroid drug (ATD) induced agranulocytosis. A retrospective study was conducted in the first affiliated hospital of the University of South China. A total of 33 hospitalized patients diagnosed with ATD-induced agranulocytosis were analyzed. The bone marrow characteristics were classified into two types. Type I was characterized by reduction or absence of granulocytic precursors and type II was recognized as hypercellular bone marrow with dysmaturity of granulocytic cells. Bone marrow of 20 cases (61%) were characterized with type I whereas 13 cases (39%) with type II. The median duration of neutrophil recovery and high-grade fever were 4.7 ± 1.0 days and 3.6 ± 2.5 days respectively for type II, compared to 8.0 ± 2.8 days and 8.6 ± 3.1 days for type I (p < 0.01 in both compared groups). However, there was no significant difference between the two types in terms of age, median duration of drug administration before the diagnosis of agranulocytosis, the amount of neutrophil count on admission and the total administration dose of granulocyte-colony stimulating factor (G-CSF) before bone marrow examination. Two cases of type I died of complications from infection. This study showed that the bone marrow characteristics of ATD-induced agranulocytosis could be classifed into two types. Also, the clinical prognosis was closely related to the bone marrow features. Type I is the dominant type which is usually associated with worse clinical prognosis compared to type II.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Cell Differentiation; China; Female; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte Precursor Cells; Hospitals, University; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Retrospective Studies; Young Adult

Although thyroid dysfunction occurs frequently in humans and some animal species, the mechanisms by which hypo- and hyperthyroidism affect the corpus luteum have not been thoroughly elucidated. This study evaluated the levels of proliferative activity, angiogenesis, apoptosis and expression of cyclooxygenase-2 in the corpus luteum of female rats with thyroid dysfunction. These processes may be important in understanding the reproductive changes caused by thyroid dysfunction. A total of 18 adult female rats were divided into three groups (control, hypothyroid and hyperthyroid) with six animals per group. Three months after treatment to induce thyroid dysfunction, the rats were euthanized in the dioestrus phase. The ovaries were collected and immunohistochemically analysed for expression of the cell proliferation marker CDC-47, vascular endothelial growth factor (VEGF), VEGF receptor Flk-1 and cyclooxygenase-2 (COX-2). Apoptosis was evaluated using the TUNEL assay. Hypothyroidism reduced the intensity and area of COX-2 expression in the corpus luteum (p < 0.05), while hyperthyroidism did not alter COX-2 expression in the dioestrus phase. Hypothyroidism significantly reduced the expression of CDC-47 in endothelial cells and pericytes in the corpus luteum, whereas hyperthyroidism did not induce a detectable change in CDC-47 expression (p > 0.05). Hypothyroidism reduced the level of apoptosis in luteal cells (p < 0.05) and increased VEGF expression in the corpus luteum. In contrast, hyperthyroidism increased the level of apoptosis in the corpus luteum (p < 0.05). In conclusion, thyroid dysfunction differentially affects the levels of proliferative activity, angiogenesis and apoptosis and COX-2 expression in the corpus luteum of female rats.

Topics: Animals; Apoptosis; Cell Proliferation; Corpus Luteum; Cyclooxygenase 2; Female; Hyperthyroidism; Hypothyroidism; Immunohistochemistry; In Situ Nick-End Labeling; Minichromosome Maintenance Complex Component 7; Neovascularization, Physiologic; Propylthiouracil; Rats; Rats, Wistar; Thyroxine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

One of the cardiovascular effects of hyperthyroidism is increased carotid intima media thickness (CIMT). The aim of this study is to investigate the CIMT in patients with Graves' hyperthyroidism and the effect of propylthiouracil (PTU) therapy on CIMT.. Twenty-six patients with Graves' hyperthyroidism and 33 healthy controls were included in the study. CIMT was measured at the right and left external carotid arteries in every patient in both groups. CIMT was measured before and after the PTU therapy in patients with Graves' hyperthyroidism.. There was a significant difference in CIMT between the group of Graves' hyperthyroid patients and the control group (0.72 versus 0.55 mm, P < 0.0001) at baseline. Twenty-five of 26 patients with Graves' disease were followed up for 18 months prospectively. Euthyroidism has been achieved in 21 patients. After 18 months of treatment, CIMT decreased significantly compared with the baseline values [0.84 (0.54-1.3) to 0.72 (0.50-1.2), change 0.12 mm, P < 0.001].. Graves' hyperthyroidism is associated with atherosclerosis as assessed by CIMT. Treatment of Graves' hyperthyroidism with PTU decreases the CIMT.

Topics: Adult; Carotid Intima-Media Thickness; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Prospective Studies; Remission Induction

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Microscopic Polyangiitis; Propylthiouracil; Pyoderma Gangrenosum; Treatment Outcome

A 30-year-old pregnant female was diagnosed to have thyrotoxicosis (TSH= 0.005 µU/ml) at 13th week of gestation. Propylthiouracil (PTU; 200 mg daily) was prescribed to her and four weekly follow ups by the endocrinologist and obstetrician were ensured. At each examination TSH, FT4 and FT3 levels were normal and she became symptom free. Repeated ultrasound examination throughout the pregnancy did not reveal any fetal abnormality. The lady normally delivered heterozygotic twins. Umbilical cord blood of the baby boy twin showed a high TSH (541 µU/ml; reference range 0.270 - 4.20 μU/ml). He was started on thyroxine therapy (50 µg once daily). Ultrasound reported the absence of the thyroid gland. One month later TSH was within normal range and thyroxine dose was adjusted to 25 µg once daily. Repeated ultrasound confirmed the absence of thyroid gland. TSH was repeatedly normal. The boy is currently doing well on thyroxine replacement therapy. The other non-identical twin was a healthy girl with normal thyroid function tests and always thereafter. This case report suggested that PTU could be a hazardous drug to the fetus, since the mother gave birth to a baby with thyroid aplasia.. PTU, Thyroid aplasia, Thyrotoxicosis, TSH.

Topics: Adult; Diseases in Twins; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Pregnancy, Twin; Prenatal Exposure Delayed Effects; Propylthiouracil; Thyroid Dysgenesis; Twins

  Propylthiouracil (PTU), one of the mainstays of antithyroid therapy drugs, can lead to antineutrophil cytoplasmic antibody (ANCA) positivity and skin lesions. PTU-induced ANCA-positive vasculitis is rare and even more rare is erythema nodosum.. To report a case of a 57-year-old woman with hyperthyroidism who developed myeloperoxidase (MPO)-ANCA erythema nodosum after PTU treatment for 11 months.. Skin biopsy demonstrated septal panniculitis without vasculitis. PTU-induced ANCA-positive erythema nodosum was made.. With discontinuation of PTU and initiation of thalidomide, skin lesions resolved completely in three weeks, and after three months, the titers of MPO-ANCA and perinuclear-ANCA (p-ANCA) had decreased remarkably. At 14-month follow-up, the patient was asymptomatic, but low levels of ANCA titers persisted.. This report indicated that ANCA positive erythema nodosum could develop following PTU treatment. Thalidomide has been proven to be helpful and averted the adverse effects from systemic corticosteroids and other immunosuppressive drugs in this patient.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Erythema Nodosum; Female; Humans; Hyperthyroidism; Immunologic Factors; Middle Aged; Propylthiouracil; Thalidomide

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Topics: Animals; Antithyroid Agents; Complement Factor B; Complement Pathway, Alternative; Hyperthyroidism; Hypothyroidism; Luminescent Measurements; Male; Propylthiouracil; Rats; Rats, Wistar; Thyroidectomy; Thyroxine; Triiodothyronine

Agranulocytosis is a life-threatening disorder characterised by a greatly decreased number of circulating neutrophils below 500/μL. This article presents two cases of agranulocytosis in patients treated with pegylated interferon and ribavirin due to chronic hepatitis C. Interferon induced hyperthyroidism, which required the use of a tyreostatic. Anti-thyroid drugs (ATD) used to treat hyperthyroidism can cause agranulocytosis. The synergistic reaction of ATD and interferon on bone marrow cannot be excluded.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Hyperthyroidism; Interferon alpha-2; Interferon-alpha; Methimazole; Middle Aged; Polyethylene Glycols; Propylthiouracil; Recombinant Proteins; Ribavirin; Time Factors; Viral Load

To report the first case of concomitant drug- and infection-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in a patient treated with propylthiouracil (PTU) and suffering from tuberculosis.. A 28-year-old woman with PTU-treated hyperthyroidism presented with fever, purpura, pulmonary cavitations and ANCA to myeloperoxidase, bactericidal/permeability-increasing protein (BPI), proteinase-3 and elastase. Skin histopathology confirmed vasculitis. However, sputum examination revealed Mycobacterium tuberculosis. Remission was achieved after PTU withdrawal and treatment with antituberculosis drugs.. Our case confirmed that BPI-ANCA are elevated in active tuberculosis. Multispecific ANCA were helpful for the diagnosis of concomitant PTU- and M. tuberculosis-induced AAV.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Antitubercular Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Tuberculosis, Pulmonary; Vasculitis

We describe herein a case of thyrotoxic crisis after esophagectomy in a 64-year-old woman with esophageal carcinoma and well-controlled hyperthyroidism. On the fourth postoperative day, she had palpitations, abdominal pain, fever, and tachycardia, which were similar to the symptoms of an anastomotic leak. There was no evidence to indicate the existence of an anastomotic leak after examination. We were confused at first. After turning to Burch and Wartofsky's scoring system, we finally diagnosed thyrotoxic crisis and then prescribed several agents for emergency treatment, including propylthiouracil, metoprolol tartrate, and hydrocortisone. Afterward, she recovered and was discharged safely.

Topics: Adrenergic beta-1 Receptor Antagonists; Anastomotic Leak; Anti-Inflammatory Agents; Antithyroid Agents; Carcinoma, Squamous Cell; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Esophageal Neoplasms; Esophagectomy; Female; Humans; Hydrocortisone; Hyperthyroidism; Metoprolol; Middle Aged; Neoplasm Staging; Postoperative Complications; Propylthiouracil; Thyroid Crisis

Topics: Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propylthiouracil

The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby influencing the functional development of this major sensory and motor structure. However, the neurochemical development of glia and other non-neuronal cells, where BuChE is mainly localized, is comparatively unaffected in these abnormal developmental conditions.

Topics: Acetylcholinesterase; Animals; Animals, Newborn; Antithyroid Agents; Body Weight; Butyrylcholinesterase; Female; Hyperthyroidism; Hypothyroidism; Pregnancy; Propylthiouracil; Rats; Rats, Sprague-Dawley; Spinal Cord; Thyroxine

Propylthiouracil (PTU) is a drug used to treat hyperthyroidism. A number of adverse effects have been reported with this drug, including fever, agranulocytosis, skin rash, and vasculitis. PTU-induced interstitial pneumonia is rare--only three cases have been reported--and PTU-induced nonspecific interstitial pneumonia (NSIP) has not been reported. We report a patient who developed NSIP after taking PTU for 1 year. She developed dyspnea, cough, and mild fever lasting 1 month, and a chest CT scan showed multifocal patchy consolidation in both lungs. She underwent a surgical lung biopsy, and NSIP was confirmed pathologically. The symptoms and abnormalities seen in the chest radiograph improved after withdrawal of PTU. To our knowledge, this is the first documented case of pathologically proven PTU-induced NSIP.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Lung Diseases, Interstitial; Methimazole; Middle Aged; Propylthiouracil; Radiography, Thoracic; Tomography, X-Ray Computed

Topics: Antithyroid Agents; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propylthiouracil

To date, there has been only one in vitro study of the relationship between neuropeptide EI (NEI) and the hypothalamic-pituitary-thyroid (HPT) axis. To investigate the possible relationship between NEI and the HPT axis, we developed a rat model of hypothyroidism and hyperthyroidism that allows us to determine whether NEI content is altered in selected brain areas after treatment, as well as whether such alterations are related to the time of day. Hypothyroidism and hyperthyroidism, induced in male rats, with 6-propyl-1-thiouracil and l-thyroxine, respectively, were confirmed by determination of triiodothyronine, total thyroxine, and thyrotropin levels. All groups were studied at the morning and the afternoon. In rats with hypothyroidism, NEI concentration, evaluated on postinduction days 7 and 24, was unchanged or slightly elevated on day 7 but was decreased on day 24. In rats with hyperthyroidism, NEI content, which was evaluated after 4 days of l-thyroxine administration, was slightly elevated, principally in the preoptic area in the morning and in the median eminence-arcuate nucleus and pineal gland in the afternoon, the morning and afternoon NEI contents being similar in the controls. These results provide the bases to pursue the study of the interaction between NEI and the HPT axis.

Topics: Animals; Brain; Hyperthyroidism; Hypothyroidism; Male; Median Eminence; Oligopeptides; Pituitary Gland; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

To compare, using two large nationwide population-based data sets, the risk of adverse pregnancy outcomes (low birthweight [LBW], preterm birth, small for gestational age [SGA] and congenital anomalies) among pregnant women with hyperthyroidism classified into three groups: receiving propylthiouracil (PTU) treatment during pregnancy, receiving methimazole/carbimazole (MMI) treatment, and no antithyroid treatment during pregnancy.. A matched case-control study.. Taiwan.. A total of 2830 mothers with hyperthyroidism and 14,150 age-matched randomly selected mothers without hyperthyroidism were included.. Conditional logistic regression analyses were performed to examine the risk of adverse pregnancy outcomes (LBW, preterm birth, SGA and major congenital anomalies) among these three groups.. LBW, preterm birth, SGA and major congenital anomalies.. Women receiving PTU treatment during pregnancy had a higher risk of giving birth to LBW infants than those not receiving antithyroid treatment (odds ratio = 1.40; 95% CI 1.00-1.96), after adjusting for maternal education, anaemia, hyperlipidaemia, pregestational diabetes, pregestational hypertension, hyperemesis gravidarum and infant's gender and birth order. However, children of women receiving MMI treatment did not have increased risks of any adverse fetal outcome relative to mothers not receiving antithyroid treatment.. Our study finds an increased risk of LBW among babies of mothers with hyperthyroidism receiving PTU treatment during pregnancy relative to untreated mothers with hyperthyroidism.

Topics: Adult; Antithyroid Agents; Carbimazole; Case-Control Studies; Congenital Abnormalities; Female; Humans; Hyperthyroidism; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Logistic Models; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prevalence; Propylthiouracil; Taiwan; Young Adult

Topics: Antithyroid Agents; Atenolol; Chorea; Dibenzothiazepines; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Patient Compliance; Prednisone; Propylthiouracil; Quetiapine Fumarate; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult

Subclinical hyperthyroidism is a difficult entity to diagnose because of silent clinical features and it may be easily underdiagnosed unless it is suspected and thyroid hormone levels are examined. Although atrioventricular (AV) conduction abnormalities such as complete heart block may occasionally be seen in hyperthyroidism, its association with subclinical hyperthyroidism has not been reported previously. We report on a 50-year-old female patient who did not have any systemic or cardiovascular disease or history of drug use that could affect AV conduction and presented with presyncope and complete heart block with narrow QRS complexes. Thyroid function tests showed subclinical hyperthyroidism and an electrophysiological study showed the supra-His level as the site of complete AV block. After initiation of antithyroid treatment (propylthiouracil), the patient's rhythm improved to second-degree AV block on the third day and returned to normal sinus rhythm on the fourth day.

Topics: Antithyroid Agents; Diagnosis, Differential; Electrocardiography; Female; Heart Block; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil

The mechano growth factor (MGF), a splice variant of the IGF-I gene, was first discovered in mechanically overloaded skeletal muscle and was shown to play an important role in proliferation of muscle stem cells. Since then, the presence and effects of MGF have been demonstrated in other tissues. MGF has been shown to act neuroprotectively during brain ischemia, and pretreatment with MGF before myocardial infarction improves cardiac function. Because MGF plays a permissive role in exercise-induced skeletal muscle hypertrophy, we hypothesize that MGF is commonly involved in cardiac hypertrophy. To investigate the regulation of MGF expression in heart, mice were treated with thyroid hormone (T(3)) for 12 d to induce physiological cardiac hypertrophy. MGF mRNA expression was specifically increased in midregions of the septum and left ventricular wall. Interestingly, MGF expression strongly correlated with the increased or decreased beating frequency of hyperthyroid and hypothyroid hearts. To further investigate the mechanically dependent induction of MGF, neonatal rat cardiomyocytes were isolated and exposed to T(3). Upon T(3) treatment, cardiomyocytes increased both contractile activity measured as beats per minute and MGF as well as IGF-IEa mRNA expression. Importantly, when cardiomyocytes were contractile arrested by KCl, simultaneous exposure to T(3) prevented the up-regulation of MGF, whereas IGF-IEa was still induced. These studies demonstrated that MGF but not IGF-IEa expression is dependent on beating activity. These findings suggest that MGF is specifically stimulated by mechanical loading of the heart to mediate the hypertrophic response to thyroid hormone.

Topics: Alternative Splicing; Animals; Animals, Newborn; Genetic Variation; Hyperthyroidism; Hypothyroidism; Insulin-Like Growth Factor I; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Myocytes, Cardiac; Physical Conditioning, Animal; Polymerase Chain Reaction; Propylthiouracil; Rats; Rats, Wistar; RNA; RNA, Messenger; Thyroid Gland; Triiodothyronine

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Biomarkers; Female; Hepatitis B; Hepatitis, Viral, Human; Humans; Hyperthyroidism; Liver Function Tests; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Severity of Illness Index; Thyroid Function Tests; Young Adult

The thionamide antithyroid drugs methimazole and propylthiouracil are the mainstay of pharmacologic therapy for Graves' disease. However, little is known about the rate of use of these drugs and the prescribing practices of physicians treating hyperthyroidism.. The objective of the study was to examine the frequency of methimazole and propylthiouracil use from years 1991 to 2008.. The data were acquired by the U.S. Food and Drug Administration's Division of Epidemiology through two databases: IMS National Sales Perspectives and the Surveillance Data, Inc. Vector One: National database.. There was a 9-fold increase in the annual number of methimazole prescriptions during the study period, from 158,000 to 1.36 million per year. There was a 19% increase in the annual number of propylthiouracil prescriptions, from 348,000 to 415,000 per year. Propylthiouracil, which held two thirds of the market from 1991 to 1995, was surpassed by methimazole in 1996. Patient demographic data indicated that although 72% of methimazole prescriptions were for females, males were more likely to be on methimazole (82%) than females (74%) (P < 0.001, two tailed chi(2) test). The only demographic group in which methimazole use decreased was women of child-bearing age (5% decrease, P < 0.001, two tailed chi(2)). The incidence of hyperthyroidism in 2008 was estimated based on the number of new prescriptions of thionamides by age group and data from the 2008 U.S. census: 0.44 per 1000 for ages 0-11 yr, 0.26 per 1000 for ages 12-17 yr, 0.59 per 1000 for ages 18-44 yr, 0.78 per 1000 for ages 45-64 yr, and 1.01 per 1000 for ages 65+ yr.. Methimazole has become the most frequently prescribed antithyroid drug. The remarkable increase in the total number of dispensed thionamide prescriptions over the last 18 yr may indicate a trend toward pharmacological treatment as primary treatment of Graves' disease in the United States.

Topics: Adolescent; Adult; Age Factors; Aged; Antithyroid Agents; Child; Child, Preschool; Drug Prescriptions; Female; Humans; Hyperthyroidism; Incidence; Male; Methimazole; Middle Aged; Prescription Drugs; Propylthiouracil; Sex Characteristics; United States; United States Food and Drug Administration

Hyperthyroidism is mainly caused by Graves' disease and toxic adenoma or multinodular goiter. In Europe, treatment of both disorders is usually started with antithyroidal drugs such as methimazole. Complications include agranulocytosis and the risk is dose-dependent. The starting dose of methimazole should not exceed 15-20 mg/d. Propylthiouracil can cause severe liver failure, leading to liver transplantation or death. Propylthiouracil, therefore, should not be used as first line agent and is only recommended when an antithyroid drug is to be started during the first trimester of pregnancy or in individuals who have experienced adverse responses to methimazole. Toxic adenoma is finally treated with radioioidine. To reduce the risk of treatment failure, antithyroidal drugs should be stopped at least one week prior to radioiodine. For Graves' disease, remission is unlikely if antibodies against the TSH-receptor remain above 10 mU/l after 6 months of antithyroidal treatment and radioiodine or thyroidectomy can be recommended. Thyroidectomy should be performed as (near) total thyreoidectomy.

Topics: Adenoma; Agranulocytosis; Antithyroid Agents; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy

Topics: Antithyroid Agents; Delayed Graft Function; Fatal Outcome; Female; Graft Rejection; Hepatorenal Syndrome; Humans; Hyperthyroidism; Immunosuppressive Agents; Kidney Transplantation; Liver Failure; Male; Middle Aged; Propylthiouracil; Renal Insufficiency; Tissue Donors; Treatment Outcome; Young Adult

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Carbimazole; Female; France; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Product Surveillance, Postmarketing; Propylthiouracil

The role of thyroid hormones in testis structure and function has been fairly well studied in laboratory rodents. However, there are no comprehensive data in the literature for mice regarding the effects of transiently induced neonatal hypo- and hyperthyroidism on testis and spermatogonial cell development from birth to adulthood. Our goals were to evaluate the effects of propylthiouracil (PTU) and triidothyronine (T3) on Sertoli cell proliferation/differentiation and to correlate these events with the evolution of the spermatogenic process, tubular lumen formation, blood vessel volume density, and size and number of different spermatogonial types. Although Sertoli cell maturation was accelerated or delayed, respectively, in T3- and PTU-treated mice, the pace of the germ cell maturation was only slightly altered before puberty and the period of Sertoli cell proliferation was apparently not affected by the treatments. However, compared with controls, the total number of Sertoli cells per testis from 10 days of age to adulthood was significantly increased and decreased in PTU- and T3-treated mice, respectively. In comparison to all other spermatogonia, type A(2) was the largest cell in all ages and groups investigated. The PTU-treated mice had a significantly increased total number of undifferentiated spermatogonia as well as volume and percentage of vessels/capillaries, probably due to the higher number of Sertoli cells, particularly at 10 days of age. Taken together, our results suggest that neonatal hypothyroidism may be a valuable tool for studying spermatogonial biology as well as a means for providing more spermatogonial stem cells that could potentially be used for spermatogonial transplantation, thereby optimizing the efficiency of this technique when young mice are used as donors.

Topics: Analysis of Variance; Animals; Animals, Newborn; Antithyroid Agents; Cell Differentiation; Cell Proliferation; Hyperthyroidism; Hypothyroidism; Male; Mice; Mice, Inbred C57BL; Propylthiouracil; Sertoli Cells; Spermatogenesis; Testis; Time Factors; Triiodothyronine

A 19-year-old female diagnosed with Graves' disease had treatment initiated with propylthiouracil (PTU). Pretreatment complete blood count and liver-associated enzymes (LAEs) were normal, but no further LAEs were obtained, reflecting U.S. guidelines written in 1995. Three months later, she presented with nausea, vomiting, abdominal pain, and jaundice. LAEs were markedly elevated with: total bilirubin, 6.5 mg/dl; aspartate aminotransferase (AST), 1747 IU/L; and alanine aminotransferase (ALT) 1589 UL/L. After 6 days at an outside hospital, she was transferred to our tertiary care center in acute liver failure with coagulopathy and stage II encephalopathy. Liver transplant evaluation was promptly initiated and she was listed as status 1. PTU was the only medication she had taken; and all serologic, autoimmune, and metabolic studies were negative. She demonstrated rapid clinical deterioration, and on hospital day 7 she underwent orthotopic liver transplant but succumbed to tonsillar herniation immediately after surgery. Pathology from her explanted liver revealed marked necrosis and collapse, consistent with her acute liver failure. PTU-associated hepatotoxicity and myelotoxicity have been well-recognized serious adverse effects for more than 50 years. However, as deaths related to hepatic injury from PTU are rare, American Thyroid Association guidelines do not call for routine monitoring of LAEs, although monitoring of white blood cell count levels is advised. Given the wide spectrum of PTU-related liver injury, ranging from asymptomatic elevations in ALT to fatal acute liver failure, we urge consideration of an LAE monitoring program to prevent irreversible liver damage and call for a reappraisal of monitoring guidelines in the United States.

Topics: Antithyroid Agents; Diagnosis, Differential; Fatal Outcome; Female; Follow-Up Studies; Humans; Hyperthyroidism; Liver Failure; Liver Function Tests; Propylthiouracil; Young Adult

Clinical hyperthyroidism is not uncommon in pregnancy, with a reported prevalence of 0.1 to 0.4%. The available antithyroid drugs are propylthiouracil and methimazole/carbimazole.. In this report we examined the association of both drugs with congenital malformations using data from the International Clearinghouse for Birth Defects Surveillance and Research.. The study used a case-affected control analysis and included 18,131 cases with malformations and reported first-trimester exposure to medication. A total of 127 subjects were born to mothers with known first-trimester antithyroid drug exposure.. Among the 52 groups of malformations that were analyzed, situs inversus ± dextrocardia, isolated unilateral kidney a/dysgenesis, and cardiac outflow tract defects were associated with prenatal exposure to propylthiouracil based on three, two, and five cases, respectively. Prenatal exposure to methimazole/carbimazole was significantly associated with choanal atresia, omphalocele, and total situs inversus ± dextrocardia (P < 0.01).. Further studies are required to exhaustively evaluate the associations between propylthiouracil and birth defects because of the low number, the lack of biological plausibility, and the possibility of underdiagnosis. Association between methimazole/carbimazole exposure and omphalocele and choanal atresia is consistent with previous reports and definitely suggests that these malformations could be part of a specific, even if rare, embryopathy.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Case-Control Studies; Female; Humans; Hyperthyroidism; Incidence; Methimazole; Odds Ratio; Pregnancy; Pregnancy Complications; Propylthiouracil

The antithetical regulation of cardiac α- and β-myosin heavy chain (MHC) genes by thyroid hormone (T(3)) is not well understood but appears to involve thyroid hormone interaction with its nuclear receptor and MHC promoters as well as cis-acting noncoding regulatory RNA (ncRNA). Both of these phenomena involve epigenetic regulations. This study investigated the extent that altered thyroid state induces histone modifications in the chromatin associated with the cardiac MHC genes. We hypothesized that specific epigenetic events could be identified and linked to cardiac MHC gene switching in response to a hypothyroid or hyperthyroid state. A hypothyroid state was induced in rats by propylthiouracil treatment (PTU), whereas a hyperthyroid (T(3)) was induced by T(3) treatment. The left ventricle was analyzed after 7 days for MHC pre-mRNA expression, and the chromatin was assessed for enrichment in specific histone modifications using chromatin immunoprecipitation quantitative PCR assays. At both the α-MHC promoter and the intergenic region, the enrichment in acetyl histone H3 at K9/14 (H3K9/14ac) and trimethyl histone H3 at K4 (H3K4me3) changed in a similar fashion. They were both decreased with PTU treatment but did not change under T(3), except at a location situated 5' to the antisense intergenic transcription start site. These same marks varied differently on the β-MHC promoter. For example, H3K4me3 enrichment correlated with the β-promoter activity in PTU and T(3) groups, whereas H3K9/14ac was repressed in the T(3) group but did not change under PTU. Histone H3K9me was enriched in chromatin of both the intergenic and α-MHC promoters in the PTU group, whereas histone H4K20me1 was enriched in chromatin of β-MHC promoter in the normal control and T(3) groups. Collectively, these findings provide evidence that specific epigenetic phenomena modulate MHC gene expression in altered thyroid states.

Topics: Acetylation; Animals; Binding Sites; Chromatin Assembly and Disassembly; Chromatin Immunoprecipitation; Disease Models, Animal; DNA, Intergenic; Epigenesis, Genetic; Female; Gene Expression Regulation; Histones; Hyperthyroidism; Hypothyroidism; Methylation; Myocardium; Myosin Heavy Chains; Polymerase Chain Reaction; Promoter Regions, Genetic; Propylthiouracil; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; RNA Precursors; RNA, Messenger; Time Factors; Transcription, Genetic; Triiodothyronine; Ventricular Myosins

We aimed to compare the prevalence of antineutrophil cytoplasmic antibody (ANCA) and its subgroups between on-treatment (with anti-thyroid drugs; propylthiouracil, methimazole) and untreated patients with hyperthyroidism in our unit. Overall 78 consecutive patients were enrolled in the study; 45 patients were on-treatment (female/male 31:14) and 33 were newly diagnosed (female/male 20:13). We have studied ANCA, perinuclear-ANCA (p-ANCA), cytoplasmic-ANCA (c-ANCA), myeloperoxidase-ANCA (mpo-ANCA), and proteinase 3-ANCA (pr3-ANCA) in sera of all the patients. The data about clinical status, laboratory tests, and physical examination and mean duration of treatment in treated group were recorded. There was no statistically significant difference between the two groups for ANCA, c-ANCA, and pr3-ANCA (P=0.13, P=0.07, and P=0.63 respectively). p-ANCA and mpo-ANCA prevalences were significantly higher in on-treatment group than in untreated group (P=0.04 and P=0.01, respectively). The mean duration of treatment was 17 months in on-treatment group. The use of antithyroid drugs (propylthiouracil, methimazole) seems to be correlated with increased prevalence of ANCA. These drugs may especially increase p-ANCA and mpo-ANCA positivity.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Myeloblastin; Peroxidase; Propylthiouracil; Seroepidemiologic Studies

Neonatal hyperthyroidism is a rare disorder and occurs in two forms. An autoimmune form is associated with maternal Graves' disease, resulting from transplacental passage of maternal thyroid-stimulating antibodies and a nonautoimmune form is caused by gain of function mutations in the thyrotropin receptor (TSHR) gene. Thyrotoxicosis caused by germline mutations in the TSHR gene may lead to a variety of clinical consequences. To date, 55 activating mutations of the TSHR gene have been documented. Fourteen cases with sporadic activating TSHR germline mutations have been described. Here we report a male infant with nonautoimmune hyperthyroidism due to an activating germline TSHR mutation (A623V), whose clinical picture started in the newborn period with severe hyperthyroidism. His parents did not have the same mutation. This mutation had been previously detected as a somatic mutation in patients with toxic adenomas. This is the first report of a sporadic case of nonautoimmune congenital hyperthyroidism associated with A623V mutation.

Topics: Germ-Line Mutation; Goiter; Humans; Hyperthyroidism; Infant; Male; Propylthiouracil; Receptors, Thyrotropin; Thyroid Gland

Topics: Adult; Antithyroid Agents; Atrioventricular Block; Electrocardiography; Female; Humans; Hyperthyroidism; Propylthiouracil

A 34-year-old woman who had been treated with propylthiouracil (PTU) for hyperthyroidism, was admitted because of bloody sputum and pyrexia. The chest CT scan showed some nodules in both lung fields. The serum level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high, but proteinase-3 antineutrophil cytoplasmic antibody (PR-3 ANCA) was negative. A limited form of Wegener's granulomatosis without PR-3 ANCA was ruled out, because of the absence of abnormalities in the upper airway and kidney. No lesions other than the multiple pulmonary nodules of the lung were detected. We diagnosed MPO-ANCA associated vasculitis induced by PTU. After the termination of PTU, bloody sputum, pyrexia, and pulmonary nodules improved spontaneously and the serum level of MPO-ANCA returned to normal gradually. The case of MPO-ANCA positive vasculitis associated with multiple pulmonary nodules following propylthiouracil treatment is very rare.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Hyperthyroidism; Multiple Pulmonary Nodules; Peroxidase; Propylthiouracil; Vasculitis

Topics: Aged; Antithyroid Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Pyoderma Gangrenosum; Remission, Spontaneous

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Incidence; Liver Diseases; Liver Transplantation; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; United States

6-Mercaptopurine (6-MP), although an effective immunosuppressive when used in the treatment of certain cancers, can have devastating effects when ingested accidentally or used in excessive amounts. We report here the case of an unintentional ingestion of a large amount of 6-MP by a woman with hypothyroidism who was erroneously given this antimetabolic agent by her pharmacist instead the propylthiouracil (PTU) she was actually prescribed. This is one of several documented cases in which 6-MP has been dispensed instead of PTU. Because of the myelosuppressive and hepatotoxic effects of 6-MP, this case reinforces the need for both physicians and patients to understand the importance of examining their medications before ingestion.

Topics: Adult; Antimetabolites, Antineoplastic; Antithyroid Agents; Blepharoptosis; Drug Overdose; Female; Humans; Hyperthyroidism; Medication Errors; Mercaptopurine; Propylthiouracil

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Propylthiouracil; Thyroid Crisis

I have a patient who has hyperthyroidism due to Graves disease. She was taking methimazole but discontinued when she found out she was pregnant. She is currently close to delivery and might require antithyroid therapy in the postpartum period. Can methimazole cross into human milk, and is breastfeeding safe for her infant?. The exposure of infants to methimazole or propylthiouracil through breast milk is minimal and not clinically significant. Women with hyperthyroidism using methimazole or propylthiouracil should not be discouraged from breastfeeding, as the benefits of breastfeeding largely outweigh the theoretical minimal risks.

Topics: Antithyroid Agents; Breast Feeding; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Infant; Infant, Newborn; Lactation; Maternal Exposure; Methimazole; Milk, Human; Pregnancy; Propylthiouracil; Thyroid Gland; Treatment Outcome

Topics: Agranulocytosis; Animals; Anura; History, 20th Century; Humans; Hyperthyroidism; Iodine; Larva; Physical Examination; Propylthiouracil; Receptors, Thyrotropin; Thyroid Diseases

Propylthiouracil (PTU) is presently considered to be the treatment of choice for hyperthyroidism in pregnancy. It is known to cross the human placenta, and therefore may affect the fetus. The major aims of this study were to evaluate the rate of major anomalies and to report the rate of fetal goitre, accompanied by hypothyroidism, in fetuses/ newborns of mothers after in utero exposure to PTU.. Prospective observational controlled cohort study of PTU-exposed pregnancies of women counselled by the Israeli Teratology Information Service between the years 1994 and 2004 compared with women exposed to nonteratogens.. We followed up 115 PTU-exposed pregnancies and 1141 controls. The rate of major anomalies was comparable between the groups [PTU 1/80 (1.3%), control 34/1066 (3.2%), P= 0.507]. Hypothyroidism was found in 9.5% of fetuses/neonates (56.8% of whom with goitre). Hyperthyroidism, possibly resulting from maternal disease, was found in 10.3%. Goitres prenatally diagnosed by ultrasound were successfully treated in utero by maternal dose adjustment. In most cases neonatal thyroid functions normalized during the first month of life without any treatment. Median neonatal birth weight was lower [PTU 3145 g (2655-3537) vs. control 3300 g (2968-3600), P= 0.018].. PTU does not seem to be a major human teratogen. However, it could cause fetal/neonatal hypothyroidism with or without goitre. Fetal thyroid size monitoring and neonatal thyroid function tests are important for appropriate prevention and treatment.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Birth Weight; Case-Control Studies; Cohort Studies; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Propylthiouracil; Ultrasonography, Prenatal

We report a 36 year-old pregnant woman who presented with acute pulmonary edema in the absence of preexisting cardiac disease. On admission she was on sinus rhythm and her blood pressure was mildly elevated. No cardiac abnormalities were detected by color Doppler echocardiography and no ischemic changes were seen on the electrocardiogram. Cardiac enzymes were normal. Thyroid function tests were diagnostic for hyperthyroidism. She was treated with propylthiouracil and propranolol and discharged in good conditions seven days after admission. This case emphasizes the need to consider hyperthyroidism as the cause of unexplained pulmonary edema in young patients with no history of heart disease who present with heart failure.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Pulmonary Edema

Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. Also, there is growing evidence supporting the role of reactive oxygen species in the pathogenesis of thyroid disorders. The aim of this study was to investigate the influence of hypothyroidism, hyperthyroidism, and their treatments on the metabolic state of oxidative stress, and antioxidant status markers.. A total of 20 newly diagnosed patients with overt hypothyroidism due to Hashimoto's thyroiditis, 20 patients with overt hyperthyroidism due to Graves' disease, and 20 healthy subjects as the control group were enrolled in the study. Fasting blood samples (12 h), taken at the initiation, after the 30th and 60th day of therapy were analyzed for malondialdehyde, nitrite, vitamin E, vitamin A, beta-carotene, ascorbate, and myeloperoxidase and superoxide dismutase activity. No patient presented additional risk factors for increased reactive oxygen species levels.. Malondialdehyde, nitrite, vitamin E, and myeloperoxidase activity increased in patients with hypothyroidism. After 2 months, the levels of nitrite and vitamin E were reduced to control levels by treatment. The patients with hyperthyroidism had increased levels of malondialdehyde and myeloperoxidase activity in comparison with the controls. Treatment with propylthiouracil attenuated these increments after 1 month.. Our results reveal an increased generation of reactive oxygen species and impairment of the antioxidant system in patients with hyperthyroidism, and particularly in patients with hypothyroidism. These findings indicate that thyroid hormones have a strong impact on oxidative stress and the antioxidant system.

Topics: Adult; Antioxidants; Antithyroid Agents; beta Carotene; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Malondialdehyde; Middle Aged; Nitrites; Oxidative Stress; Peroxidase; Propylthiouracil; Reactive Oxygen Species; Superoxide Dismutase; Thyroxine; Vitamin A; Vitamin E

Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in skeletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB1. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB1, along with binding partner proteins. LKB1, MO25, and downstream targets were determined in muscle extracts in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 wk, and in rats given 0.01% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB1 and MO25 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB1 responses were variable, but MO25 increased in all. In soleus, MO25 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC were elevated in soleus and gastrocnemius of hyperthyroid rats. Thyroid hormone treatment also increased the amount of phospho-cAMP response element binding protein (CREB) in the soleus, heart, and red quadriceps. Four proteins having CREB response elements (CRE) in promoter regions of their genes (peroxisome proliferator-activated receptor-gamma coactivator-1alpha, uncoupling protein 3, cytochrome c, and hexokinase II) were all increased in soleus in response to thyroid hormones. These data provide evidence that thyroid hormones increase soleus muscle LKB1 and MO25 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters.

Topics: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Animals; Antithyroid Agents; Blotting, Western; Calcium-Binding Proteins; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Electric Stimulation; Hyperthyroidism; Hypothyroidism; Male; Mitochondrial Proteins; Multienzyme Complexes; Muscle, Skeletal; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphoprotein Phosphatases; Phosphorylation; Promoter Regions, Genetic; Propylthiouracil; Protein Phosphatase 2C; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; RNA-Binding Proteins; RNA, Messenger; Signal Transduction; Thyroxine; Transcription Factors; Triiodothyronine

It was well known that propylthiouracil (PTU) could induce ANCA-associated vasculitis (AAV) and clinical evident vasculitis could resolve after cessation of PTU with or without immunosuppressive therapy. However, the treatment strategy for patients with PTU-induced AAV remained inconclusive and their long-term outcomes were lacking. The aim of our study was to summarize these data.. Fifteen patients with PTU-induced AAV, receiving immunosuppressive agents for <12 months and following over 24 months, were selected in the current study. The clinical and pathological data, including treatment protocols and outcomes, were retrospectively investigated.. All the patients were followed for a mean of 55.0 (25-98) months. PTU was discontinued upon diagnosis of PTU-induced AAV. Immunosuppressive therapy was administrated only for patients with vital organ involvements, such as lung and kidney, and lasted only 7.9 +/- 3.3 (0.27-12) months. No relapse of vasculitis occurred during follow-up, even after withdrawal of immunosuppressive therapy. Twelve (80%) patients remained in complete remission and one patient remained in partial remission at the latest follow-up. Two patients were treatment resistant due to late referral and late withdrawal of PTU, both of them progressed to end-stage renal disease. For uncontrolled hyperthyroidism on presentation, six patients switched to methimazole and none of them experienced relapse of vasculitis.. The long-term outcomes of patients with PTU-induced AAV were relatively good. PTU should be discontinued immediately after diagnosis. Immunosuppressive therapy may be only used in patients with vital organ involvements, and a long-term maintenance therapy may not be necessary.

Topics: Adolescent; Adult; Algorithms; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmune Diseases; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Hyperthyroidism; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Propylthiouracil; Retrospective Studies; Treatment Outcome; Vasculitis

This study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease.. A total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved.. Relief from hyperthyroidism was achieved in 96% of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p = 0.22).. Thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Retrospective Studies; Treatment Outcome

To retrospectively review health records in two general practices in Hamilton, New Zealand (NZ) linking three data sources to estimate the prevalence of diagnosed thyroid dysfunction (TD).. A record-linkage study using computerised searches to find cases of diagnosed TD by diagnostic codes, prescribing data, and laboratory data. Data was verified against computerised and written records.. The prevalence of diagnosed TD was 3.1%. Overt hypothyroidism was diagnosed in 2.5%, overt hyperthyroidism in 0.2% and 'other' conditions such as goitres, nodules and thyroiditis in 0.4% of the study population.. This study provides a representation of TD in the community prior to mandatory iodine fortification. Our prevalence data is similar to national and international literature with the burden of TD being greater in women and in the older population.. A national study with a sufficient sample of Māori and Pacific patients is needed before supplementation with iodine is introduced.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Family Practice; Female; Food, Fortified; Humans; Hyperthyroidism; Hypothyroidism; International Classification of Diseases; Iodine; Male; Medical Records, Problem-Oriented; Middle Aged; New Zealand; Prevalence; Propylthiouracil; Sex Distribution; Thyroid Diseases; Thyroxine; Young Adult

Topics: Antithyroid Agents; Bradycardia; Female; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Syncope

Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. The aim of this study is to investigate whether PTU has a beneficial effect on endothelial function.. Ninety patients with a history of hyperthyroidism receiving either PTU (n=45) or methimazole (MMI) (n=45) during the euthyroid status were enrolled in this study. Brachial artery endothelium-dependent (flow-mediated dilatation [FMD]) and endothelium-independent (nitroglycerin-mediated dilatation) responses were assessed by high-resolution ultrasound image. Data for these two groups were compared with those of 41 healthy control subjects. The FMD values were significantly increased in patients maintained on PTU versus those in the MMI and control groups (9.3+/-4.4%, 3.4+/-2.5%, and 3.6+/-3.4%, respectively; P<0.01). Nitroglycerin-mediated dilatation had no significant difference between the PTU, MMI, and control groups (17.4+/-7.5%, 15.9+/-6.1%, and 17.5+/-6.8%, respectively; P=0.455). On multivariate analysis, no significant relationship was found between the FMD and thyroid hormone index levels. To further elucidate whether PTU has a direct effect on endothelial function, the effect of PTU on isolated segments of Sprague-Dawley rat aorta was studied. Vasodilatation induced by PTU was endothelium-dependent and could be blocked by pretreatment with nitric oxide (NO) inhibitors. PTU also increased NO formation in aortic segments.. This study demonstrated that PTU produced endothelium-dependent vasodilatation through thyroid-independent and NO-mediated mechanisms that may contribute to its beneficial effect on atherosclerosis.

Topics: Adult; Animals; Antithyroid Agents; Aorta, Thoracic; Brachial Artery; Case-Control Studies; Cohort Studies; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Nitric Oxide; Propylthiouracil; Rats; Rats, Sprague-Dawley; Ultrasonography; Vasodilation

Although low thyroid function is known to have detrimental effects on the cardiovascular system, including microvascular impairment, little is known about the pathophysiologic consequences of hypothyroidism in the background of hypertension.. Hypothyroidism was induced in female spontaneously hypertensive heart failure (SHHF) rats by treatment with propylthiouracil (PTU) for 6 months. Untreated SHHF and normotensive Wistar Furth (WF) rats served as controls. In terminal experiments, heart weight, echocardiographic measurements, hemodynamics, and arteriolar morphometry were performed. Left ventricular internal diameter in systole and diastole were increased and wall thickness, ejection fraction, heart rate, systolic blood pressure, and +/-dP/dt were significantly decreased in the treatment group. Surprisingly, there were no observed differences in arteriolar density among the 3 groups.. As expected, PTU treatment of SHHF rats led to systolic dysfunction and chamber dilation. However, PTU treatment did not lead to arteriolar loss as previously observed in normotensive rats treated with PTU. These finding suggest that induced hypothyroidism leads to detrimental changes in SHHF rats, but the overall effects were no worse than those previously observed in normotensive rats treated with PTU.

Topics: Animals; Female; Heart Failure; Hemodynamics; Hypertension; Hyperthyroidism; Microcirculation; Myocardium; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland; Time Factors

We characterized the enzymes that catalyze the deiodination of T(4) to T(3) in the male reproductive tract. Testis, epididymis (EPI), seminal vesicles, prostate, bulbourethral glands, spermatozoa, and semen were taken from sexually mature rats (300 g). Iodothyronine 5'-deiodinase (5'-D) activity was quantified by the radiolabeled-iodide-release method. 5'-D activity was 10-fold higher in EPI and semen than in the rest of the tissues. In EPI, semen, and prostate, the enzymatic activity was completely inhibited by 1 mm 6-n-propyl-2-thiouracil, whereas in the other tissues the inhibition was partial (50%). The high susceptibility to 6-n-propyl-2-thiouracil inhibition, a ping-pong kinetic pattern, and low cofactor (Michaelis Menten constant for dithiothreitol=0.7 mm) and high substrate (Michaelis Menten constant for reverse T(3)=0.4 microm) requirements indicate that EPI 5'-D corresponds to type 1 deiodinase (D1). Real-time RT-PCR amplification of D1 mRNA in this tissue confirms this conclusion. The highest EPI D1 expression occurred at the onset of puberty and sexual maturity, and in the adult, this activity was more abundant in corpus and caput than in the caudal region. EPI D1 expression was elevated under conditions of hyperthyroidism and with addition of 17beta-estradiol. Our data also showed a direct association between D1 and a functional epididymis marker, the neutral alpha-glucosidase enzyme, suggesting that local generation of T(3) could be associated with the development and function of EPI and/or spermatozoa maturation. Further studies are necessary to analyze the possible physiological relevance of 5'-D in the male reproductive system.

Topics: Animals; Antithyroid Agents; Epididymis; Gene Expression Regulation, Enzymologic; Genitalia, Male; Gonadal Steroid Hormones; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Male; Propylthiouracil; Rats; Rats, Wistar; Sexual Maturation

This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy.. Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality.. A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm.. A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months.. Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Prevalence; Propylthiouracil; Prospective Studies

Two genes encoding cardiac myosin heavy chain (MHC) isoforms, beta and alpha, are arranged in tandem 4.5 kb apart. We examined pre-mRNA and mature mRNA levels of beta and alpha genes in control, diabetic (streptozotocin), hypothyroid (propylthiouracil), and hyperthyroid rat hearts and analyzed the naturally occurring antisense (AS) beta RNA species that starts in the middle of the 4.5-kb intergenic region and extends upstream to the beta-gene promoter. The beta and alpha genes are expressed antithetically in control, diabetic, hypothyroid, and hyperthyroid hearts. Expression of AS beta-RNA was positively correlated with alpha-mRNA and negatively correlated with sense beta mRNA. These results support the novel idea of common promoter-regulatory elements situated in the intergenic region that likely control transcription of both sense alpha and AS beta genes and that AS beta transcription negatively regulates beta-MHC gene expression. To test whether an intergenic promoter drives transcription of AS beta RNA, a 1340-bp sequence of the intergenic region was inserted into a luciferase plasmid in the 3'-to-5' AS direction and was injected into rat ventricle. This promoter was activated in control heart and decreased greatly in response to propylthiouracil and streptozotocin and increased in hyperthyroid rats, similar in pattern to the endogenous AS beta RNA. When a putative retinoic acid receptor (RAR) site (a known thyroid hormone receptor cofactor) in this promoter was mutated, the reporter activity was almost abolished in control, propylthiouracil, and streptozotocin hearts. We conclude that there is an intergenic promoter that is active in the AS direction and that the putative RAR element is a vital regulatory site.

Topics: Animals; Diabetes Mellitus, Experimental; DNA, Intergenic; Female; Genes, Reporter; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Luciferases; Mutation; Myosin Heavy Chains; Promoter Regions, Genetic; Propylthiouracil; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; Response Elements; RNA; RNA Precursors; RNA, Antisense; RNA, Messenger; Transcription, Genetic; Triiodothyronine; Ventricular Myosins

Recent reports suggest an association between hyperthyroidism and pulmonary hypertension (PHT), although the potential mechanisms and clinical implications remain unclear.. Our objective was to determine the prevalence of PHT related to hyperthyroidism and the associated hemodynamic changes and outcome.. We performed serial echocardiographic examinations in 75 consecutive patients with hyperthyroidism (43 +/- 2 yr, 47 women) to estimate pulmonary artery systolic pressure (PASP), cardiac output (CO), total vascular resistance (TVR), and left ventricular (LV) filling pressure. Examinations were performed at baseline and 6 months after initiation of antithyroid treatment. Results were compared with 35 age- and sex-matched healthy controls. All hyperthyroid patients had normal LV systolic function, and 35 patients (47%) had PHT with PASP of at least 35 mm Hg. There were no significant differences in the clinical characteristics of hyperthyroid patients with or without PHT (all P > 0.05). Nonetheless, those with PHT had significantly higher CO, PASP, peak transmitral early diastolic flow velocity (E), and ratio of E to early diastolic mitral annular velocity (E') compared with those without PHT and controls (all P < 0.05). Hyperthyroid patients with PHT also had significantly lower TVR than controls (P < 0.05). Among the 35 hyperthyroid patients with PHT, 25 (71%) had pulmonary arterial hypertension (PAH) with normal E/E', and 10 (29%) had pulmonary venous hypertension (PVH) with elevated E/E'. Hyperthyroid patients with PAH had a significantly higher CO and a lower TVR compared with those with PVH. In contrast, hyperthyroid patients with PVH had lower E' and a higher E/E' ratio compared with those with PAH. These hemodynamic abnormalities and PHT were reversible in patients with PAH or PVH after restoration to a euthyroid state.. In patients with hyperthyroidism and normal LV systolic function, up to 47% had PHT due to either PAH with increased CO (70%) or PVH with elevated LV filling pressure (30%). Most importantly, hyperthyroidism-related PHT was largely asymptomatic and reversible after restoration to a euthyroid state.

Topics: Adult; Antithyroid Agents; Blood Pressure; Carbimazole; Cardiac Output; Echocardiography; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Prospective Studies; Treatment Outcome; Vascular Resistance; Ventricular Function, Left

Propylthiouracil is a drug used in the treatment of hyperthyroidism for more than 60 years. Adverse side effects are seen in 1-5% of patients. Renal complications of the drug including glomerulonephritis and vasculitis are rarely seen. Cases of propylthiouracil-induced rapidly progressive glomerulonephritis and vasculitis are reported in association with antineutrophil cytoplasmic autoantibodies. Here we report a case of positive antineutrophil cytoplasmic autoantibodies rapidly progressive glomerulonephritis (RPGN) associated with propylthiouracil treatment.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Antineutrophil Cytoplasmic; Atrophy; Humans; Hyperthyroidism; Kidney; Kidney Glomerulus; Male; Propranolol; Propylthiouracil; Ramipril; Vasculitis

Topics: Antithyroid Agents; Child; Female; Humans; Hyperthyroidism; Liver Failure, Acute; Propylthiouracil

This study evaluated antibody production against sheep red blood cells (SRBC) in hyperthyroid rats during treatment with triiodothyronine (T(3)). The immune response was evaluated by measuring plaque forming cells (PFC) in the spleen and by enzyme-linked immunosorbent assay (ELISA) in serum of male Wistar rats (180+/-10 g) treated with 25 mug/day of triiodotironine (T(3)) during 7-12 days and immunized with SRBC at the 8th day of treatment. The results showed that anti-SRBC antibody production was significantly decreased in animals treated for 12 days when compared to normal rats immunized with the same antigen, as evaluated by the two assays. These results show that in this experimental model hyperthyroidism decreases antibody response. We previously observed the opposite effect, that is, an increase in this response in hypothyroid rats resulting from the treatment with propylthyouracil, a blocker of thyroid hormone biosynthesis. It is suggested that antibody production is affected by thyroid hormone levels.

Topics: Animals; Antibody Formation; Antibody-Producing Cells; Antithyroid Agents; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Hemolytic Plaque Technique; Hyperthyroidism; Immunoglobulin M; Injections, Intraperitoneal; Male; Propylthiouracil; Rats; Rats, Wistar; Sheep, Domestic; Thyrotropin; Triiodothyronine

The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

Topics: Acetylcholinesterase; Animals; Antithyroid Agents; Ca(2+) Mg(2+)-ATPase; Hippocampus; Hyperthyroidism; Hypothyroidism; Male; Prefrontal Cortex; Propylthiouracil; Rats; Sodium-Potassium-Exchanging ATPase; Thyroxine

Vascular responsiveness changes in hyperthyroid patients remains controversial. This study attempts to determine whether the vasomotor activity can be influenced by hyperthyroid conditions, and, if so, whether changes induced by hyperthyroidism may be restored to normal during the euthyroid state after treatment.. A case-control clinical study.. Forty-five pretreated hyperthyroid patients (mean age 36.62 +/- 10.12 years, 36 female) were compared with 45 gender- and age-matched control subjects (mean age 38.98 +/- 11.17 years, 40 female). Brachial artery endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD) responses were assessed noninvasively by high-resolution ultrasound imaging. Among the 45 hyperthyroid patients, 27 patients underwent the same procedures prospectively in the post-treatment euthyroid state.. The FMD values were significantly increased in hyperthyroid patients vs. those of controls (8.94 +/- 5.65%vs. 3.77 +/- 3.42%, P < 0.001), whereas NMD levels were not significantly different (18.17 +/- 7.76%vs. 17.28 +/- 6.63%, P = 0.560). Multiple regression analysis revealed that the presence of hyperthyroidism was the only significant factor associated with FMD. In the follow-up study of 27 hyperthyroid patients, the FMD values were significantly decreased in the post-treatment euthyroid state compared with those in the pretreated hyperthyroid state (6.40 +/- 4.27%vs. 8.83 +/- 4.61%, P = 0.021), although these values were still higher than those of controls.. This study demonstrated that endothelium-dependent FMD was increased in the hyperthyroid patients, and could be partially restored by treatment with antithyroid agents.

Topics: Adult; Antithyroid Agents; Brachial Artery; Case-Control Studies; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Hyperthyroidism; Methimazole; Middle Aged; Nitroglycerin; Propylthiouracil; Prospective Studies; Regional Blood Flow; Regression Analysis; Ultrasonography; Vasodilation; Vasodilator Agents

We reported the case of pulmonary alveolar hemorrhage caused by propylthiouracil (PTU) with severe respiratory failure and anemia, who improved with PTU discontinuance and steroid therapy. A 35-year-old woman presented with pyrexia, shortness of breath, and arthralgia. Her chest radiograph and CT showed diffuse ground-glass opacities, and her arterial blood gas analysis revealed severe respiratory failure. Laboratory results included a hemoglobin level of 5.2 g/dl, and a myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) level of 203 EU (normal range <9.0 EU). As bronchoalveolar lavage (BAL) fluid showed fresh blood-like fluid containing hemosiderin-laden macrophages, pulmonary alveolar hemorrhage was diagnosed. Since she had been taking PTU for 4 years, PTU was immediately discontinued. Steroid pulse therapy was performed, followed by oral prednisolone 30 mg per day, and her symptoms and chest radiograph findings rapidly improved. Based on the time-course changes, MPO-ANCA may have been involved in the development of pulmonary alveolar hemorrhage.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Methylprednisolone; Peroxidase; Prednisolone; Propylthiouracil; Pulmonary Alveoli; Pulse Therapy, Drug; Respiratory Insufficiency; Treatment Outcome

A twin pregnancy with a coexisting complete hydatiform mole and a healthy fetus is rare. Associated with this condition are potentially serious maternal and fetal complications. We describe a case of a woman, 23/40 pregnant, who was diagnosed with a twin pregnancy complicated by a hydatiform mole, vaginal bleeding, hyperthyroidism and preterm labour at 26/40. Her hyperthyroidism was successfully treated with propylthiouracil. The preterm labour resulted in the livebirth of a healthy male infant. The baby developed biochemical hypothyroidism post-natally. The baby's thyroid function tests were unexpected, revealing a low T4 and a low-normal thyroid stimulating hormone. This is the first case reported in the literature to describe an infant's clinical and biochemical thyroid status after gestational trophoblastic disease complicated by hyperthyroidism.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Female; Humans; Hydatidiform Mole; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Live Birth; Male; Pregnancy; Propranolol; Propylthiouracil; Thyroid Function Tests; Treatment Outcome; Twins

Involvement of thyroid gland in the hepatotoxic manifestations of arsenic trioxide (As(III)) has been studied in rat. The effects of n-propylthiouracil (PTU) (a thyrotoxic compound) and L-thyroxine (a thyroid hormone) have been studied with reference to T(3) and T(4) values in the serum, arsenic concentration in the liver, Ca(2+) accumulation in the liver, aspartate transaminase, alanine transaminase and bilirubin values as the indicators of liver function, histopathological observations and finally the ultrastructural studies. It is concluded that hypothyroid condition protects against As(III) toxicity. Scavenging of reactive oxygen species (ROS) that significantly contribute in As(III) toxicity, by high intracellular concentration of reduced glutathione, as a consequence of PTU treatment is proposed as the plausible protective mechanism.

Topics: Animals; Arsenic Poisoning; Arsenic Trioxide; Arsenicals; Calcium; Hyperthyroidism; Hypothyroidism; Liver; Male; Oxides; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland; Thyroxine; Triiodothyronine

We experienced a case of fetal goitrous hypothyroidism in an infant delivered by a 33-year-old woman receiving 300 mg/day of propylthiouracil (PTU) for hyperthyroidism due to Graves' disease. A large fetal goiter (maximum diameter, 60 mm) was detected by magnetic resonance imaging (MRI) at 36 weeks of gestation. Initial fetal blood sampling revealed hypothyroidism with a serum thyroid-stimulating hormone (TSH) of 99 microIU/mL, free triiodothyronine (T(3)) of 1.97 pg/mL, and free thyroxine (T(4)) of 0.29 ng/dL. Consequently, a diagnosis of fetal goitrous hypothyroidism due to transplacental passage of maternal PTU was made. To reduce the risk of perinatal complications, 300 microg of levothyroxine sodium (L-T(4)) was administered into the maternal amniotic fluid twice between 37 and 38 weeks of gestation. Subsequent fetal MRI showed that the size of goiter had decreased. At 38 weeks and 5 days of gestation, a 3042-g male infant was born by cesarean section. There were no severe complications at delivery, although mild tachypnea was observed and the infant's thyroid gland was slightly enlarged. He was treated with L-T(4) for two weeks. At present, his growth and neurological development are normal. This case indicates that intrauterine therapy by the intraamniotic administration of L-T(4) can be effective in treating fetal goitrous hypothyroidism even during late gestation.

Topics: Adult; Amniotic Fluid; Antithyroid Agents; Congenital Hypothyroidism; Female; Fetal Diseases; Fetal Therapies; Gestational Age; Goiter; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Trimester, Third; Propylthiouracil; Thyroxine; Treatment Outcome

Topics: Adult; Antithyroid Agents; Atrial Fibrillation; Atrioventricular Block; Diagnosis, Differential; Electrocardiography; Humans; Hyperthyroidism; Male; Propylthiouracil; Syncope; Thyroid Function Tests

Subclinical form of hypothyroidism was not associated with considerable changes in Ca(2+) content in osteoblasts and blood plasma and in the content of ATP and prostaglandin E2. Activation of prostaglandin E2 synthesis in response to binding of extracellular Ca(2+) in osteoblasts in the absence of ATP was less pronounced (by 11%) compared to the control. Progression of hypothyroidism and development of clinical signs of the disease were accompanied by a decrease in Ca(2+) content in osteoblasts and plasma by 45 and 12%, respectively, and ATP content in osteoblasts by 30%, and by activation of prostaglandin E2 synthesis by 117%. Moreover, the synthesis of prostaglandins in response to binding of extra- and intracellular Ca(2+) also considerably changed. Hyperthyroidism (2 months) was characterized by a moderate decrease in plasma content of Ca(2+) by 15% and ATP by 25%, together with an increase in prostaglandin E2 level by 55.5%. The release of prostaglandin E2 in response to chelation of extracellular Ca(2+) increased even more markedly, but somewhat decreased in response to addition of 5 mM ATP due to compensation of metabolic acidosis.

Topics: Animals; Calcium; Dinoprostone; Female; Femur; Homeostasis; Hyperthyroidism; Hypothyroidism; Male; Osteoblasts; Propylthiouracil; Rats; Thyroxine

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Female; Follow-Up Studies; Glomerulonephritis; Humans; Hyperthyroidism; Necrosis; Plasmapheresis; Propylthiouracil; Radiography, Thoracic; Time Factors; Treatment Outcome; Vasculitis

The effect of hyper or hypoactive thyroid on the renal toxicity of arsenic trioxide has been studied in rats. It was observed that pre-treatment of rats with thyroxine stimulates arsenic excretion in urine. The anti-thyroid drug n-propylthiouracil (PTU), inhibits the accumulation of arsenic in renal tissue. Both treatments affect the renal pathology. Histopathological lesions are less severe in PTU and arsenic-treated rats in comparison to thyroxine and arsenic-treated rats. Ultrastructural studies support light microscopical observations. An adaptive response was noticed against arsenic in PTU pre-treated rats. We attribute this response to decreased glutathione-S-transferase (GSH) activity and increased GSH synthesis in the kidney. A relationship between thyroidal activity and arsenic toxicity is suggested by present observations.

Topics: Animals; Antithyroid Agents; Apoptosis; Arsenic Trioxide; Arsenicals; Creatinine; Glomerulonephritis; Glutathione; Glutathione Transferase; Hyperthyroidism; Hypothyroidism; Kidney; Male; Necrosis; Oxides; Propylthiouracil; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is an uncommon complication of the use of propylthiouracil. When it occurs, it affects multiple organs as any systemic vasculitis. We report three females and one male, aged 30, 40, 43 and 41 years respectively, that after a lapse of 12 to 28 months of propylthiouracil use, presented clinical signs of vasculitis. All had high titers of ANCA against myeloperoxidase. In three patients, a skin biopsy confirmed the diagnosis. The condition subsided when propylthiouracil was discontinued, but one female patient required the use of prednisone.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Biopsy; Female; Humans; Hyperthyroidism; Male; Propylthiouracil; Vasculitis

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arm; Diagnosis, Differential; Drug Eruptions; Ear, External; Female; Heel; Humans; Hyperthyroidism; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy.

Topics: Adult; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Thyroxine; Treatment Outcome; Withholding Treatment

We describe a case of pulmonary hypertension and high-output heart failure in a 61-year-old woman suffering from relapsing Graves disease. The patient experienced prompt hemodynamic and symptomatic recovery after normal thyroid function was restored. Possible mechanisms for the development of pulmonary arterial hypertension due to hyperthyroidism include damage to pulmonary vascular endothelium due to high cardiac output or an autoimmune process or increased metabolism of intrinsic pulmonary vasodilators. Another possible mechanism is vascular vasoconstriction due to decreased cholinergic output.

Topics: Antihypertensive Agents; Antithyroid Agents; Female; Humans; Hypertension, Pulmonary; Hyperthyroidism; Middle Aged; Propranolol; Propylthiouracil

Terminalia arjuna bark extract is believed to exhibit cardio-protective effects. In the present study we investigated the possible involvement of thyroid hormones in the amelioration of cardiac and hepatic lipid peroxidation (LPO) by a bark extract of the plant in albino rats. While L-thyroxine (L-T4) treatment increased the level of thyroid hormones, heart/body weight ratio as well as cardiac and hepatic lipid peroxidation, simultaneous administration of 21.42 and 42.84 mg/kg of the plant extract decreased the level of thyroid hormones and also the cardiac LPO, suggesting the possible mediation of the drug action through an inhibition in thyroid function. These effects were comparable to a standard antithyroid drug, propyl thiouracil (PTU). When the drug was administered to euthyroid animals, serum concentrations of thyroid hormones were decreased, whereas the hepatic LPO increased indicating a drug induced toxicity in euthyroid subjects. Although a suboptimal dose of the drug was found to be non-toxic to the liver, it appeared to be of no use, as it could neither affect the thyroid functions nor the cardiac lipid peroxidation. Since in euthyroid animals, thyroid hormones were decreased and hepatic LPO was increased, it is suggested that high amounts of this plant extract should not be consumed, as hepatotoxicity as well as hypothyroidism may be caused.

Topics: Animals; Antithyroid Agents; Body Weight; Cardiotonic Agents; Female; Hyperthyroidism; Lipid Peroxidation; Liver; Malondialdehyde; Organ Size; Plant Bark; Propylthiouracil; Radioimmunoassay; Rats; Rats, Wistar; Terminalia; Thiobarbituric Acid Reactive Substances; Thyroid Hormones; Thyroxine; Triiodothyronine

Scopoletin (7-hydroxy-6-methoxy coumarin) was isolated from the leaves of Aegle marmelos and evaluated for its potential to regulate hyperthyroidism, lipid peroxidation and hyperglycemia in levo-thyroxine-induced hyperthyroid rats. Scopoletin (1.00 mg/kg, p.o.) administered daily for 7 days to levo-thyroxine-treated animals decreased the levels of serum thyroid hormones and glucose as well as hepatic glucose-6-phosphatase activity, demonstrating its potential to regulate hyperthyroidism and hyperglycemia. Scopoletin also inhibited hepatic lipid peroxidation and increased the activity of antioxidants, superoxide dismutase and catalase. Compared with the standard antithyroid drug, propylthiouracil, scopoletin exhibited a superior therapeutic activity, since unlike propylthiouracil, it also inhibited hepatic lipid peroxidation. These findings indicate that scopoletin has the potential to inhibit thyroid function and hyperglycemia without hepatotoxicity.

Topics: Aegle; Animals; Antioxidants; Antithyroid Agents; Blood Glucose; Female; Hyperglycemia; Hyperthyroidism; Hypoglycemic Agents; Lipid Peroxidation; Plant Extracts; Plant Leaves; Propylthiouracil; Rats; Rats, Wistar; Scopoletin; Thyroxine

Propylthiouracil (PTU) is known to be a potential cause of antineutrophil cytoplasmic antibody (ANCA) positive small vessel vasculitis, resulting in glomerulonephritis and diffuse alveolar hemorrhage (DAH). Herein, we describe a 25-year-old pregnant woman who developed a perinulcear ANCA (p-ANCA) and myeloperoxidase ANCA (MPO-ANCA) positive DAH during PTU therapy. The patient improved after corticosteroid therapy and discontinuation of the PTU. Methimazole was prescribed in spite of the risk of recurrence of DAH because of the pregnancy. The patient is currently free from pulmonary problems. Our case shows that the alternative agent, methimazole, can be used to treat hyperthyroidism in a pregnant patient with PTU associated DAH.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Bronchoscopy; Diagnosis, Differential; Female; Hemoptysis; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications, Hematologic; Propylthiouracil; Pulmonary Alveoli; Tomography, X-Ray Computed

We report on a case of pulmonary capillaritis with diffuse alveolar hemorrhage in a child due to propylthiouracil (PTU). PTU treatment is a rare cause of pulmonary capillaritis in adults; we report on the first case in a pediatric patient. The treatment of pulmonary capillaritis often requires corticosteroid therapy, other immunosuppressive medications, or withdrawal of the causative agent. Our patient recovered completely after treatment with a limited course of corticosteroids and removal of PTU.

Topics: Adrenal Cortex Hormones; Antithyroid Agents; Capillaries; Child; Female; Hemorrhage; Humans; Hyperthyroidism; Inflammation; Lung; Lung Diseases; Propylthiouracil

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil

To report a case of acute mesenteric ischemia associated with the use of oral propranolol.. A 59-year-old white man was admitted to the hospital with chronic diarrhea and weight loss. The patient was diagnosed as having hyperthyroidism. Therapy with propylthiouracil 100 mg 3 times daily and propranolol 20 mg twice daily was initiated on an outpatient basis. The following day, the patient was readmitted to our hospital with increased abdominal pain and bloody diarrhea. Angiography revealed superior mesenteric artery occlusion. Antegrade aorta-mesenteric bypass surgery was performed for revascularization, and the patient was discharged 10 days after the surgery. The patient was well both clinically and endoscopically at a follow-up visit 8 months later.. Although mesenteric ischemia is a devastating illness of varied causes, drug-associated mesenteric ischemia is rarely seen. By decreasing cardiac output and selective vasodilatory receptor inhibition in the splanchnic circulation, propranolol can cause a decline in splanchnic blood flow. An objective causality assessment indicated that propranolol was the possible cause of the arterial occlusion.. Propranolol may rarely be associated with mesenteric ischemia. In cases of newly developed acute abdomen undergoing propranolol therapy, physicians should be aware of this rare and serious adverse reaction to this drug.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Humans; Hyperthyroidism; Male; Mesenteric Vascular Occlusion; Middle Aged; Propranolol; Propylthiouracil

We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far.. A 40 year-old woman was treated with propylthiouracil for Graves'disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks.. Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves'disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet's syndrome, have been described in patients with propylthiouracil-induced ANCA. One case-report described a 44 year-old woman who developed pyoderma gangrenosum associated with propylthiouracil-induced p-ANCA. These manifestations usually appear within 2 years, as our patient. The data in the literature, allows us to report the polymorphic expressions of neutrophilic dermatosis in this patient with p-ANCA which could be related to propylthiouracil. Such association of Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum with p-ANCA has never been described in this endocrinologic context so far. Furthermore we propose that neutrophilic dermatosis should be inscribed in the list of side effects induced by propylthiouracil therapy.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Antineutrophil Cytoplasmic; Antibody Formation; Antithyroid Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Pyoderma Gangrenosum; Skin Diseases, Vesiculobullous

The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect.. Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-D-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects.. Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content.. Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.

Topics: Adipose Tissue; Animals; Blood Glucose; Carnitine O-Palmitoyltransferase; Energy Metabolism; Fatty Acids, Nonesterified; Gene Expression; Glucose; Glucose Clamp Technique; Hormones, Ectopic; Hyperthyroidism; Insulin; Insulin Resistance; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Muscle, Skeletal; Propylthiouracil; Rats; Rats, Wistar; Resistin; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

The aim of this work was to analyze beta-adrenergic receptor (betaAR) regulation of T-lymphocyte proliferation in mice according to different thyroid hormone statuses.. T cells from eu-, hypo- (by propylthiouracil treatment) and hyperthyroid (by thyroxine, T4 administration) mice were purified and specific radioligand binding assays were performed. The effects of the beta-agonist isoproterenol (ISO) on intracellular levels of cyclic AMP (cAMP) were determined. Mitogen-induced T-cell proliferation was measured by [(3)H]-thymidine incorporation. Finally, protein kinase C (PKC) activity in cytosol and membrane fractions were determined using radiolabelled enzymatic substrates.. Adecrease or a non-significant increase in betaAR number was found on T lymphocytes from hypo- and hyperthyroid mice compared to euthyroid controls. ISO stimulation of cAMP levels was lower in hypothyroid and higher in hyperthyroid T lymphocytes compared to controls. T-selective mitogen-induced proliferation was increased in T4-treated animals, but decreased in hypothyroid mice. During the peak of proliferation, downregulation of betaAR was observed in all animals. However, a higher or a lower decrease was observed in hyper- and hypothyroid T cells, respectively. In parallel, a higher translocation of PKC activity was observed in hyperthyroid cells, and a lower one was found in hypothyroid lymphocytes with respect to controls.. These results indicate that intracellular signals triggered by mitogen activation, namely PKC, would be related to differential betaAR downregulation in T lymphocytes depending on the thyroid hormone status, contributing to the distinct proliferative responses found in hypo- or hyperthyroidism compared to the euthyroid state.

Topics: Adrenergic beta-Agonists; Animals; Cell Proliferation; Cyclic AMP; Down-Regulation; Female; Hyperthyroidism; Hypothyroidism; Isoproterenol; Mice; Mice, Inbred BALB C; Mitogens; Neuroimmunomodulation; Propylthiouracil; Protein Kinase C; Protein Transport; Receptor Aggregation; Receptors, Adrenergic, beta; T-Lymphocytes; Thymidine; Thyroid Gland; Thyroxine

Topics: Antibodies, Antineutrophil Cytoplasmic; Antiphospholipid Syndrome; Biopsy, Needle; Dose-Response Relationship, Drug; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastric Mucosa; Humans; Hyperthyroidism; Immunohistochemistry; Intestinal Diseases; Methylprednisolone; Middle Aged; Propylthiouracil; Severity of Illness Index; Treatment Outcome; Ulcer; Vasculitis, Leukocytoclastic, Cutaneous

A 48 year old white woman was admitted to the hospital because of several bouts of migratory polyarthritis, weight loss, fever, and abdominal pain over a period of 15 months. She had been taking propylthiouracil 100 mg daily for three years for hyperthyroidism treatment. A test for antineutrophil cytoplasmic autoantibodies (ANCA) was positive with a perinuclear pattern of staining. Antiphospholipid antibodies were also detected. Colonoscopy showed several ulcers on intestinal mucosa and the biopsy specimen showed intense microscopic vasculitis. The patient is well after methylprednisolone pulse therapy and eight months of oral azathioprine. A surveillance colonoscopy showed complete healing of intestinal ulcers. No recurrence of symptoms has occurred and autoantibodies are negative, 10 months after treatment finished. The sequence of events suggests a propylthiouracil induced vasculitis p-ANCA positive and an antiphospholipid syndrome. This is the first report of colonic ulcers diagnosed and successfully treated in such circumstances.

Topics: Antiphospholipid Syndrome; Antithyroid Agents; Colonic Diseases; Female; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Ulcer; Vasculitis

To perform a case note review of pregnancies complicated by thyroid dysfunction to determine management and therapeutic intervention in relation to pregnancy outcome.. A retrospective case note analysis of 81 ongoing pregnancies in 70 pregnant women with a history of thyroid dysfunction over a period of 5 years at the Glasgow Royal Maternity Hospital (GRMH), Glasgow, Scotland, United Kingdom. The results of thyroid function tests and whether a change in treatment was instituted were recorded. Thyroid function was assessed by standard laboratory reference ranges for free thyroxine (FT4) and thyroid stimulating hormone (TSH) in all trimesters. Other parameters were also noted.. Medication levels needed to be increased in the hypothyroid group (45%), and decreased (38%) in the hyperthyroid group.. Pregnancy outcome was good in majority of cases given appropriate replacement therapy for stated reference values.

Topics: Antithyroid Agents; Carbimazole; Female; Gestational Age; Humans; Hyperthyroidism; Hypothyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Retrospective Studies; Risk Factors; Thyroid Function Tests; Thyroxine

It is a common knowledge that metabolic reactions increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how the metabolic reactions could affect the total antioxidant status (TAS), protein concentration (PC) and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+ -ATPase in the brain of hyper- and hypothyroid adult male rats. Hyperthyroidism was induced in rats by subcutaneous administration of thyroxine (25 microg/l00 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. TAS, PC, and enzyme activities were evaluated spectrophotometrically in the homogenated brain of each animal. TAS, PC, and Mg2+ -ATPase activity were found unaffected in hyperthyroidism, while AChE and Na+,K+ -ATPase activities were reduced by 25% (p < 0.01). In contrast, TAS, (Na+,K+)-ATPase and Mg2+-ATPase activities were found to be increased (approx. 23-30%, p < 0.001) in the hypothyroid brain, while AChE activity and PC were shown to be inhibited (approx. 23-30%, p < 0.001). These changes on brain enzyme activities may reflect the different metabolic effects of hyper- and hypothyroidism. Such changes of the enzyme activities may differentially modulate the brain intracellular Mg2+, neural excitability, as well as the uptake and release of biogenic amines.

Topics: Acetylcholine; Acetylcholinesterase; Animals; Antioxidants; Brain; Brain Diseases, Metabolic; Ca(2+) Mg(2+)-ATPase; Energy Metabolism; Hyperthyroidism; Hypothyroidism; Male; Nerve Tissue Proteins; Propylthiouracil; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Thyroxine; Up-Regulation

Thyroid hormones have pronounced effects on the cardiovascular system. Thyrotoxicosis affects blood pressure (BP), modifying both diastolic (DBP) and systolic (SBP) pressures. There are no studies examining BP with ambulatory blood pressure monitoring (ABPM) in hyperthyroidism before and after control of thyroid function. Our aims were (1) to analyse ABPM in a group of normotensive hyperthyroid patients before and after normalizing circulating thyroid hormones and (2) to compare these results with those obtained in a group of euthyroid subjects.. We studied 20 normotensive hyperthyroid subjects [18 women; age (mean +/- SEM) 49.0 +/- 3.0 years] and 15 healthy subjects. Patients were evaluated by ABPM over 24 h, at diagnosis and after therapy (n = 18).. The average 24-h, daytime and night-time SBP was significantly greater in hyperthyroid patients than in controls with no significant differences in DBP. Circadian BP rhythm, estimated by the difference between mean values of SBP, DBP and mean BP during daytime and night-time, was unchanged. The average 24-h and daytime SBP significantly decreased after normalizing thyroid function in the 18 hyperthyroid evaluated patients. Daytime SBP and DBP were higher than night-time values both before and after control of thyroid function. However, no differences in circadian BP rhythm were observed.. Normotensive hyperthyroid patients exhibit higher ambulatory SBP throughout 24 h than normotensive euthyroid subjects. Control of hyperthyroidism decreases ambulatory SBP values. Mean nocturnal fall in BP is comparable in normotensive hyperthyroid patients and control subjects.

Topics: Antithyroid Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Female; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Regression Analysis; Thyroid Gland; Thyroid Hormones

Substantial evidences suggested that propylthiouracil (PTU) could induced anti-myeloperoxidase (MPO) antibodies in sera from patients with hyperthyroidism, however, only a subgroup of the PTU-induced anti-MPO antibody positive patients developed clinical evident vasculitis. The aim of this study is to compare the titres and affinities of PTU induced anti-MPO antibodies in sera from patients with hyperthyroidism with and without clinical vasculitis. Anti-MPO antibody positive sera from patients diagnosed hyperthyroidism with (n = 13) and without (n = 14) clinical evident vasculitis were collected. The titre was determined by MPO-ELISA and expressed as logarithm value (lgT). The affinity constant (aK) of anti-MPO IgG was measured by antigen inhibition assay. The titre and aK values were compared between patients with and without vasculitis. In patients with vasculitis, the mean lgT of anti-MPO antibodies was 3.62 +/- 0.66; the median aK was 4.47 x 10(7)M(-1). In patients without vasculitis, the mean lgT was 2.54 +/- 0.29; the median aK was 0.14 x 10(7)M(-1), and both were significant lower than those in patients with vasculitis (t = 5.464; P = 0.000 & z = -4.373; P = 0.000, respectively). We concluded that the titre and affinity of anti-MPO antibodies might be associated with the development of clinical vasculitis in patients with PTU-induced ANCA.

Topics: Adolescent; Adult; Antibodies; Antibody Affinity; Child; Female; Humans; Hyperthyroidism; Immunoglobulin G; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

To evaluate the relationship between the incidence of congenital malformations of newborns and maternal hyperthyroidism with antithyroid drug (ATD) therapy during pregnancy.. The clinical data of 100 cases of pregnant women with hyperthyroidism and their 101 offsprings born in Peking Union Medical College Hospital during 1983-2003 were analyzed retrospectively. According to the maternal thyroid function, and antithyroid drugs taken during the first trimester of pregnancy, subjects were divided into different groups. The incidence of congenital malformations of newborns and risk factors, especially the effects of maternal hyperthyroidism with antithyroid drug therapy were analysed.. The prevalence of congenital malformation in infants born to mothers who had hyperthyroidism during pregnancy (6.9%, 7/101) was significantly higher than that of all the infants born in the same hospital during the same period (0.9%, 212/22 765, P < 0.01). The difference of the incidence of malformed infants born to mothers with hyperthyroidism (9.6%, 5/52) or euthyroidism (4.1%, 2/49) during the first trimester was not significant (P > 0.05). The incidence of malformed infants whose mothers received methimazole (MMI; 41.7%, 5/12) was significantly higher than that of mothers treated with propylthiouracil (PTU) (3.6%, 1/28) and without ATDs (1.6%, 1/61), respectively (P < 0.01). The Loglinear model analyses showed that mothers receiving MMI during the first trimester of pregnancy was independent risk factor for the increased incidence of malformation of their infants (L.R. square = 15.668, P = 0.0003).. The risk of congenital malformation in infants whose mothers take MMI during the first trimester may be increased. Therefore, we suggest that MMI should not be used as a choice of drug in treatment of pregnant women with hyperthyroidism.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Incidence; Infant, Newborn; Methimazole; Mothers; Pregnancy; Pregnancy Complications; Prevalence; Propylthiouracil; Thyroid Function Tests; Thyrotropin; Thyroxine

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Antithyroid Agents; Autoantigens; Autoimmune Diseases; Churg-Strauss Syndrome; Cyclophosphamide; Female; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Granulomatosis with Polyangiitis; Graves Disease; Hashimoto Disease; Humans; Hyperthyroidism; Immunoprecipitation; Kidney; Lung; Male; Methimazole; Middle Aged; Myeloblastin; Nephelometry and Turbidimetry; Peroxidase; Polyarteritis Nodosa; Prednisone; Pregnancy; Pregnancy Complications; Propylthiouracil; Retrospective Studies; Serine Endopeptidases; Skin; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous

The rat model of N-methyl-N-nitrosourea (MNU)-induced mammary carcinomas is well-established animal model for breast cancer. This study was carried out to investigate whether hypothyroid (thyroidectomy or PTU treatment) or hyperthyroid status of female rats would affect MNU-induced mammary carcinogenesis with specific focus on both retinoid and rexinoid receptor expression in mammary tumours. Application of PTU before and during MNU-induced mammary gland carcinogenesis yielded in a marked decrease of the number and volume of tumours per animal, however, there was no effect of hypothyroid state in thyroidectomized rats as well as hyperthyroid state concerning the number and volume of tumours. Mammary tumours of in euthyroid group of MNU animals showed that there was no tumour, in which all of subtypes of retinoid and rexinoid receptors were expressed. A different pattern of expression of retinoid or rexinoid receptors was found either in MNU-induced mammary carcinomas in both hypothyroid and hyperthyroid rats.

Topics: Animals; Carcinogens; Female; Gene Expression; Hyperthyroidism; Hypothyroidism; Mammary Neoplasms, Experimental; Methylnitrosourea; Propylthiouracil; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; RNA, Messenger; Thyroid Hormones; Thyroidectomy

Liver biochemical test (LBT) changes can be commonly observed in hyperthyroid patients. Those kinds of changes could also be observed because of propylthiouracil (PTU) therapy. We prospectively evaluated LBT changes because of PTU use for 1 year in patients who had been diagnosed with hyperthyroidism first. We studied 64 patients who had been diagnosed with hyperthyroidism. These patients took at least 1-year PTU treatment. We analysed LBT at diagnosis and after 2 and 12 months of treatment with PTU. Prior to PTU treatment, 30 (46.8%) of the 64 patients had at least one LBT abnormality. We observed at least one LBT abnormality in 11 (32%) patients after 2 months and nine (26%) patients after 12 months of treatment with PTU in 34 patients whose CBT were normal before treatment. We did not observe any deterioration in clinical picture and bilirubin levels. Elevated serum LBT during the pretreatment and PTU treatment period is common and usually transient and asymptomatic. PTU could be used for long times by lowering the dose and close follow-up in patients who have elevated LBT during the pretreatment and after PTU treatment period.

Topics: Adult; Antithyroid Agents; Biomarkers; Female; Humans; Hyperthyroidism; Liver; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Prospective Studies

It is claimed in a limited number of studies carried out on human beings that plasma homocysteine levels increased in hypothyroid patients and decreased in hyperthyroid patients.. The aim of this study is to determine total plasma homocysteine, thyroid function tests, vitamin B12, folic acid and lipid levels and to explore the relations among them in rat models with induced hypothyroidism and hyperthyroidism with a view to investigating whether hypothyroid and hyperthyroid rat models could represent human hypothyroidism and hyperthyroidism models.. The study included 30 male Wistar Albino species rats with a mean weight of 200 - 250 g. Rats were randomly divided into 3 groups as 1) hypothyroid group, 2) hyperthyroid group and 3) control group. Hypothyroidism was induced by adding 10 mg/kg/day propylthiouracil to rats' drinking water for 30 days. In order to induce hyperthyroidism, rats were administered 10 microg/100 g L-thyroxin ampule via intraperitoneal route for 10 days.. We found that total plasma homocysteine level of the hypothyroid group was significantly lower than those of the control group (p<0.05) and the hyperthyroid group (p<0.001). Total plasma homocysteine level of the hypothyroid group was found insignificantly higher than that of the control group (p>0.05) and significantly higher than that of the hyperthyroid group (p<0.001). We established a significant and positive correlation between total plasma homocysteine level and thyroid hormone levels. We did not identify a significant relation between total plasma homocysteine level and serum folic acid and serum vitamin B12 levels.. Our findings are different from the findings reported in human hypothyroidism and hyperthyroidism studies. We believe that hypothyroid and hyperthyroid rat models cannot represent human hypothyroidism and hyperthyroidism models.

Topics: Animals; Antithyroid Agents; Cholesterol; Folic Acid; Homocysteine; Hyperthyroidism; Hypothyroidism; Lipids; Male; Propylthiouracil; Rats; Rats, Wistar; Thyroid Function Tests; Thyroxine; Vitamin B 12

Hyperhomocysteinemia is a risk factor for premature atherosclerotic vascular diseases. It is known that plasma homocysteine levels are higher in hypothyroid patients compared to healthy subjects. The aim of our study was to assess plasma total homocysteine concentrations in hyperthyroid patients before and after treatment when euthyroid status was reached and compare them with control group. Thirteen hyperthyroid patients (age, 42.9 +/- 15.6 year) and eleven healthy subjects (age, 39.9 +/- 12.5 year) were involved in the study. Plasma levels of homocysteine and serum cholesterol, triglyceride, HDL cholesterol, urea, creatinine, vitamin B12, folate were measured before and after treatment. LDL cholesterol and creatinine clearances were calculated. Pretreatment homocycteine levels of the hyperthyroid patients were significantly lower than healthy controls (11.5 +/- 3.6 micromol/L vs. 15.1 +/- 4.5 micromol/L, respectively, p<0.05). Posttreatment homocysteine levels were significantly higher than pretreatment levels (13.9 +/- 6.3 micromol/L vs. 11.5 +/- 3.6 micromol/L, respectively, p<0.05) and posttreatment creatinine clearance were lower than pretreatment level (103.5 +/- 12.7 ml/min vs. 114.2 +/- 9.3 ml/min, respectively, p<0.01). Lower homocysteine levels in hyperthyroidism can be partially explained with the changes in creatinine clearance.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Creatinine; Female; Homocysteine; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Osmolar Concentration; Propylthiouracil

A 50-year-old woman had been treated with propylthiouracil (PTU) for hyperthyroidism. She was admitted to our hospital because of hemosputum, and severe hypoxemia developed. The CT scan showed diffuse infiltration in both lung fields, bronchoalveolar lavage fluid revealed diffuse alveolar hemorrhage, and the level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high; and therefore diffuse alveolar hemorrhage associated with MPO-ANCA positive vasculitis induced by PTU was diagnosed. Following corticosteroid therapy initiated after the termination of PTU, the pulmonary infiltration rapidly improved and the patient's MPO-ANCA level returned to normal. Recrudescence of diffuse alveolar hemorrhage occurred following a reduction in steroids, but no recurrence was found after cyclophosphamide therapy was combined with steroid therapy. During the course of therapy, various cardiac conducting system abnormalities which correlate with the course of steroid therapy were found, indicating that cardiac conducting system abnormalities may be associated with MPO-ANCA-positive vasculitis.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Bundle-Branch Block; Female; Heart Block; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Middle Aged; Peroxidase; Propylthiouracil; Pulmonary Alveoli; Vasculitis

To study the incidence, clinical features and related factors of propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.. A prospective study were carried out in 70 patients of hyperthyroidism with normal liver function. Every patient was treated with PTU 300 mg/d until the thyroid functions recovered to normal, following by decease and maintenance PTU dose in period of six months. Liver function, including serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL), thyroid function (serum thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine and thyrotropin) and blood routine items were measured before therapy and once a month for six months after PTU therapy was begun.. Sixty-four cases of 70 patients completed the therapy for 6 months. Hepatic injury developed in 33 patients (51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients (34.4%). Slight symptomatic hepatic injury occured in 6 cases (9.4%) and overt hepatic injury in 5 patients (7.8%) after PTU administration. However, all the patients who developed overt hepatic injury did not stop PTU. Hepatic function returned normal one month after stopping PTU. No one finally suffered from viral hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic injury.. PTU-induced symptomatic hepatic injury is not rare and usually develops within the first few months of PTU administration. Its clinical course is relatively benign. However, it may be difficult to predict its development, so all patients should be monitored for liver function test during the administration in early stage.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Follow-Up Studies; Humans; Hyperthyroidism; Liver; Liver Diseases; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Prospective Studies

Propylthiouracil (PTU) as a drug used during the treatment of hyperthyroidism could induce antineutrophil cytoplasmic autoantibody-positive vasculitis. Here the author reported a childhood case of antineutrophil cytoplasmic autoantibody-positive vasculitis induced by PTU, which is rarely described.. The diagnosis was made according to the symptoms, signs, serum markers and renal biopsy, and the relevant literature was reviewed.. The 12-year-old girl presented with gross hematuria, proteinuria, renal function damage [Ccr 52.46 ml/(min. 1.73 m(2))], positive antineutrophil cytoplasmic autoantibody (ANCA-MPO) (MPO ELISA 140%) and a vasculitis lesion in the renal biopsy sample. She had been treated with PTU for 5 years because of Graves disease. After the diagnosis, the PTU was withdrawn, and prednisone (40 mg/d) and cyclophosphamide (25 mg, Bid) were applied. Three weeks after the therapy with prednisone and cyclophosphamide the gross hematuria disappeared. Three months after the treatment the renal function returned to normal [Ccr 124 mg/(min.1.73 m(2))], and the titer of ANCA-MPO decreased from 140% to 57%.. PTU may induce antineutrophil cytoplasmic autoantibody positive vasculitis. A right diagnosis and treatment can improve its prognosis of the disease.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Prognosis; Propylthiouracil; Treatment Outcome; Vasculitis

Topics: Adult; Asthma; Drug Hypersensitivity; Female; Humans; Hyperthyroidism; Propylthiouracil

To study the clinical characteristics and factors of symptomatic propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.. A retrospective study of the patients diagnosed with symptomatic PTU-induced hepatic injury, admitted to Peking Union Medical College (PUMC) Hospital from January 1993 to December 2002, were carried out with regard to clinical characteristics, laboratory findings and management. In addition, a comparative study was carried out in hyperthyroidism with symptomatic, asymptomatic and without PTU-induced hepatic injury at the same time. Symptomatic PTU induced hepatic injury was defined as the development of hepatitis symptoms or jaundice with at least 3-times elevation of liver function test without other causes.. Nine hundred fourteen patients were admitted to PUMC Hospital from January 1993 to December 2002. Clinically overt symptomatic hepatic injury developed in twelve patients [1.3%, age (30 +/- 9) yr, male:female ratio, 1:11] between 7 and 77days after PTU administration. Abdominal distention and fatigue developed in all patients. Serum level of ALT and total bilirubin (TBil) increased to (531.7 +/- 352.0) 113 - 1425 U/L and 67.6 (17.1 - 567.7) micro mol/L, respectively. Prothrombin time prolonged in three cases and plasma ammonia elevated in one case. The types of hepatic injury were hepatocellular in eight, cholestatic in one and mixed in two. None resulted from viral hepatitis and autoimmune hepatitis. There was significant difference in history of side effects of antithyroid agents, PTU dose and abnormal ratio of serum ALT among patients with symptomatic, asymptomatic and without hepatic injury (P < 0.05). However, there were no statistic differences in age, sex, serum levels of T(4), T(3), and increased thyroglobulin antibody, thyroid peroxidase antibody and thyrotrophin receptor antibody at initial diagnosis. The liver function test normalized in all patients from 14 to 140 days after the PTU withdrawal.. Symptomatic hepatic injury usually develops with PTU administration in the first few months, though it is unusual. It may be difficult to predict its development and the patient should be monitored for the liver function in the early stage of PTU administration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Liver Diseases; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Retrospective Studies

This prospective study was designed to evaluate the effects of hyperthyroidism on flow-volume loops in nonasthmatic 20 patients with hyperthyroidism. Thyroid related hormones (Total T3, Total T4 and TSH), thyroid gland volumes with ultrasonography, circumference of neck values and flow-volume loops were obtained at the beginning and after three months of antithyroid treatment. Propylthiouracil treatment was followed by a statistically significant decrease in thyroid gland volume and circumference of neck (p< 0.001 and p< 0.001, respectively). The most significant result was improvement of maximum midexpiratory flow rate (MMEFR) after propylthiouracil therapy for three months (p= 0.003). Increases in mean forced expiratory flow after 25% of FVC has been exhaled (FEF25), mean forced expiratory flow after 75% of FVC has been exhaled (FEF75) values were found consistent with the overall improvement in expiratory flow parameters (p= 0.044, p= 0.012 respectively). In conclusion, we speculated that improvement of expiratory flow parameters might be the earlier changes in flow volume loops of patients who were treated with propylthiouracil for hyperthyroidism.

Topics: Administration, Oral; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Middle Aged; Neck; Propylthiouracil; Prospective Studies; Respiratory Function Tests; Thyroid Gland; Thyroid Hormones; Ultrasonography

Antithyroid drugs such as propylthiouracil (PTU) and methimazole (MMI) are common medications in Chinese patients with hyperthyroidism and PTU-induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis has been reported. The current cross-sectional study aimed to investigate the prevalence and the target antigens of ANCA in Chinese patients with hyperthyroidism pre- and post-antithyroid medication therapy.. Sera from 216 patients with hyperthyroidism in our hospital were collected from January to July in 2002. Patients were divided into four groups: untreated (n = 34); treated with PTU (n = 62); treated with MMI (n = 77); and treated with both PTU and MMI (n = 43). Indirect immunofluorescence (IIF) assay was used to detect ANCA and ANA. Antigen-specific ELISAs were used to detect antigen specificities. The known antigens included myeloperoxidase (MPO), proteinase 3 (PR3), human leukocyte elastase (HLE), lactoferrin, bactericidal/permeability-increasing protein (BPI), cathepsin G and azurocidin.. 33/216 sera were IIF positive, 20 of the 33 samples were ANCA positive, 11 samples were ANA positive, and two samples were both P-ANCA and ANA positive. The prevalence of positive ANCA in patients receiving PTU (14/62, 22.6%) was significantly higher than that of untreated patients (1/34, 2.9%) and patients treated with MMI (0/77, 0), P < 0.017. Of the 22 IIF-ANCA positive samples, 12 (54.5%) sera recognized lactoferrin, seven (31.8%) sera recognized HLE, four sera recognized MPO and azurocidin respectively, three sera recognized PR3 and cathepsin G respectively, and one serum recognized BPI. Six of the 22 (27.3%) patients with ANCA positive had clinical evidence of vasculitis. All patients with MPO-ANCA and two of the three patients with PR3-ANCA had clinical vasculitis.. PTU is associated with the production of ANCA in patients with hyperthyroidism. PTU-induced ANCA are due to polyclonal activation of B cells. Anti-MPO and anti-PR3 antibodies may associate the occurrence of clinical vasculitis.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Asian People; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fluorescent Antibody Technique, Indirect; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil

Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.. Twenty patients with hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age- and sex-matched healthy controls were enrolled in the study. Insulin sensitivity index, PON activity and lipid peroxidation were measured at baseline and 2 months after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients.. Insulin sensitivity was determined by an oral glucose tolerance test (OGTT) based on the insulin sensitivity index (ISI) formula, serum paraoxonase activity was determined with a spectrophotometric method. Lipid peroxidation was measured by the formation of thiobarbituric acid reactive substances (TBARs).. ISI was significantly lower in the hyperthyroid group than baseline levels in MNG patients and controls (P < 0.001). While ISI increased after treatment in the hyperthyroid group (P < 0.01), it significantly decreased with L-T4 treatment in the MNG group (P < 0.01). Serum paraoxonase activity was significantly lower in the hyperthyroid group before treatment than baseline and final measurements of other groups (P < 0.05). While PON activity increased after restoration of the euthyroid state in the hyperthyroid group (P < 0.05), it decreased with L-T4 treatment in the MNG group (P < 0.05). Lipid peroxidation was significantly higher in hyperthyroid group compared to baseline levels of other groups (P < 0.05). It decreased after treatment in the hyperthyroid group (P < 0.05) but a significant increase was observed following L-T4 treatment in the MNG group (P < 0.05). Serum paraoxonase activity was found to be negatively correlated with serum TT4 (r = -0.32, P = 0.003), TT3 levels (r = -0.31, P = 0.004), TBARs levels (r = 0.32, P = 0.003) and positively correlated with ISI (r = 0.35, P = 0.001) and high-density lipoprotein (HDL) cholesterol levels (r = 0.35, P = 0.0011) in the hyperthyroid and MNG groups.. Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative stress. These findings suggest that TSH suppression with levothyroxine may increase oxidative stress and LDL oxidation and thereby promote atherogenesis.

Topics: Adult; Analysis of Variance; Antithyroid Agents; Arteriosclerosis; Aryldialkylphosphatase; Case-Control Studies; Female; Goiter, Nodular; Humans; Hyperthyroidism; Insulin Resistance; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Propylthiouracil; Thyroid Function Tests

Plasmapheresis, also known as therapeutic plasma exchange, is used in the treatment of several disorders. Temporary improvement after plasmapheresis in cases with thyrotoxicosis has been reported. A 55-year-old woman presented with agranulocytosis induced by propylthiouracil and clinical signs of heart failure. Three sessions of plasmapheresis were performed. We observed an improvement of thyroid hormone levels and clinical findings as well. Plasmapheresis can be an option when drug treatment of thyrotoxicosis fails.

Topics: Agranulocytosis; Antithyroid Agents; Female; Humans; Hyperthyroidism; Middle Aged; Plasmapheresis; Propylthiouracil

A 32-year-old woman presented with persistent vomiting, epigastric pain and weight loss. A sinus tachycardia was the clue to the diagnosis of hyperthyroidism due to Graves' disease. On treatment with propylthiouracil and a beta-blocking agent, her symptoms resolved within one day, even though her free thyroxine level was still high. Hyperthyroidism is an uncommon, but previously reported cause of persistent vomiting.

Topics: Abdominal Pain; Adrenergic beta-Antagonists; Adult; Chronic Disease; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Metoprolol; Propylthiouracil; Thyrotoxicosis; Vomiting; Weight Loss

Acute hepatic failure is a rare and potentially lethal complication of propylthiouracil (PTU) use for hyperthyroidism. We present a 20-year-old woman with Basedow-Graves' disease who developed PTU-induced fulminant hepatitis, which progressed to acute hepatic failure with grade III hepatic encephalopathy. Laboratory evaluation ruled out the most common causes of fulminant hepatitis. We treated her hyperthyroidism with amiodarone (average daily dose, 200 mg) for 3 weeks, achieving rapid and persistent euthyroidism, (triiodothyronine [T(3)] levels ranged between 64 and 109 ng/dL) without side effects. Amiodarone treatment did not abolish the thyroid radioactive iodine uptake (RAIU), allowing for subsequent treatment with radioactive iodine. The clinical course was favorable and the patient achieved full hepatic recovery 3 months after the hepatic failure was detected. After an extensive review of the literature, we believe that this is the first communication of the successful use of amiodarone to control hyperthyroidism in a patient with PTU-induced fulminant hepatitis.

Topics: Adult; Amiodarone; Female; Humans; Hyperthyroidism; Liver Failure, Acute; Propylthiouracil; Triiodothyronine

To study the clinical characteristics of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibodies (ANCA) positive cases and increase the awareness of PTU induced ANCA positive vasculitis (APV).. The clinical data of nine cases with positive ANCA induced by PTU in Peking Union hospital since 2000 were analyzed and literature review was conducted.. (1) Nine patients with hyperthyroidism, at a mean age of 33.1 (16 approximately 51), who were treated with PTU for a mean period of 32.4 months (3 approximately 84); (2) Sera from nine cases were ANCA positive, and autoantibodies from six tested cases could recognize not only MPO, but also PR3, HLE, BPI and LF; (3) Six cases with high titer perinuclear ANGA (pANCA) (> or = 1:1280) were diagnosed APV and all had renal involvement (five confirmed by renal biopsies), three cases with low titer pANCA (< or = 1:320) had little clinical manifestations of vasculitis; (4) Eight patients stopped taking PTU when positive ANCA were noted. One case with APV got remission after stopping PTU, the other three APV were treated with glucocorticosteroid and immunosuppressive agents at meanwhile. Only one patient kept taking PTU for eighteen months without an increased titer of ANCA.. PTU could induce production of ANCA. High titer of ANCA might suggest existence of APV and the titer would be associated with status of APV. Early withdrawal of PTU and administration of glucocorticosteroid and immunosuppressive agents based on renal pathology will greatly improve the prognosis.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Humans; Hyperthyroidism; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Propylthiouracil; Vasculitis

The ethanolic extract from the fruits of Emblica officinalis Gaertn (Euphorbiaceae) was investigated to evaluate its possible ameliorating effects, on the L-thyroxine (L-T4) induced hyperthyroidism and on hepatic lipid peroxidation in mice. While an increase in serum T3 (triiodothyronine) and T4 (thyroxine) concentrations, and in a thyroid dependent parameter, hepatic glucose 6-phospatase (glu-6-pase) activity was observed in L-T4 (0.5 mg/kg/d) treated animals, simultaneous oral administration of the plant extract at a dose of 250 mg/kg/d (p.o.) for 30 days in hyperthyroid mice reduced T3 and T4 concentrations by 64 and 70% respectively as compared to a standard antithyroid drug, propyl thiouracil (PTU) that decreased the levels of the thyroid hormones by 59 and 40% respectively. The plant extract also maintained nearly normal value of glu-6-pase activity in hyperthyroid mice. The plant extract also decreased hepatic lipid peroxidation (LPO) and increased the superoxide dismutase (SOD) and catalase (CAT) activities in hyperthyroid mice, exhibiting its hepatoprotective nature. Our findings suggest that the test material may potentially ameliorate the hyperthyroidism with an additional hepatoprotective benefit.

Topics: Animals; Antithyroid Agents; Catalase; Euphorbiaceae; Fruit; Glucose-6-Phosphatase; Hyperthyroidism; Lipid Peroxidation; Liver; Male; Mice; Plant Extracts; Propylthiouracil; Radioimmunoassay; Superoxide Dismutase; Thyroid Hormones

In thyrotoxicosis there is an impaired GH response to GHRH, normal GH responsiveness to GHRP-6 and lack of synergistic GH response after simultaneous administration of both peptides. We have previously shown that the GHRH-induced GH release in these patients increases after an acute reduction of circulating T3 values with administration of iopanoic acid, a compound that inhibits peripheral conversion of T4 to T3. We have now studied the effect of a decrease in serum T3 levels on the GH response to GHRP-6 (1 microg/kg) plus GHRH (100 microg) in 9 hyperthyroid patients before and after 15 days of treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (600 mg/day). Nine normal subjects were also studied. In all hyperthyroid patients iopanoic acid induced a rapid decrease and normalisation of serum T3 levels. In these subjects peak GH (microg/l; mean +/- SE) and AUC (microg/l x 120 min) values after GHRP-6 plus GHRH were significantly higher on day 15 compared to pretreatment values (peak, 18.3 +/- 3.0 vs 13.4 +/- 1.9; AUC, 1227.9 +/- 212.9 vs 968.5 +/- 160.4; p<0.05). Despite the significant enhancement of the GH responsiveness to GHRP-6 plus GHRH after treatment with iopanoic acid, this response remained significantly blunted when compared to controls both in terms of peak GH (18.3 +/- 3.0 vs 83.7 +/- 15.2; p<0.05) and AUC values (1227.9 +/- 212.9 vs 4956.5 +/- 889.3; p<0.05). In conclusion, our results show that an acute decrease of circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. This could suggest that circulating T3 does not have a major role in the mechanisms involved in the synergistic effect of these peptides.

Topics: Adolescent; Adult; Antithyroid Agents; Area Under Curve; Female; Fluorescent Antibody Technique; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hyperthyroidism; Iopanoic Acid; Male; Oligopeptides; Propylthiouracil; Thyrotoxicosis; Triiodothyronine

Recently, propylthiouracil (PTU) has been thought to be one of the possible causes of antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis syndrome, resulting in glomerulonephritis and, infrequently, diffuse alveolar haemorrhage (DAH). The mechanism of ANCA-positive vasculitis during PTU therapy is still unknown. Herein, we describe the case of a 59-year-old woman who developed myeloperoxidase (MPO)- and proteinase 3 (PR3)-ANCA positive DAH, without any other organ system involvement, during PTU therapy. Diminution and discontinuation of PTU resulted in a positive response. To our knowledge, this is the first documentation of both MPO- and PR3-ANCA-positive DAH, without systemic manifestations, developing during PTU therapy.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Methylophilaceae; Middle Aged; Myeloblastin; Propylthiouracil; Pulmonary Alveoli; Serine Endopeptidases

Sudden sensorineural hearing loss (SSNHL) is one of the autoimmune diseases of the inner ear (AIED), which is characterized by a hearing loss of above 30 decibels in at least three contiguous audiometric frequencies over a time course of 72 hours or shorter. Its cause can be found in only 10% to 15% of patients. Histopathologic findings have reported retrograde neuronal degeneration and atrophy of Corti's organ and of the vascular stria. This paper describes a case of a middle-aged female patient undergoing a treatment for hyperthyroidism who developed bilateral SSNHL. The patient was treated with methylprednisone (1 mg/kg/day) for three days with considerable hearing improvement. This treatment was followed by lung and kidney tuberculosis. The immune mechanism of this entity and the possibility of interconnected participation of the antigen type, of an autoimmune disease and of bacterial infection are discussed.

Topics: Anti-Inflammatory Agents; Antithyroid Agents; Autoimmune Diseases; Cross Reactions; Female; Hearing Loss, Sensorineural; Humans; Hyperthyroidism; Methylprednisolone; Middle Aged; Propylthiouracil

To investigate the liver function tests during antithyroid treatment in the patients with hyperthyroidism.. Four hundred sixty five patients with hyperthyroidism (285 Graves' disease and 180 toxic nodular/multinodular goiter) and fifty healthy subjects were included in the study. The patients who had abnormal liver function tests were excluded from the study. Blood levels of thyrotropin (TSH), free thyroxine (FT4), alanine transaminase (ALT) and aspartate transaminase (AST) were detected at the beginning of the treatment (basal levels), and at the third and sixth months of the treatment. The patients were treated with propylthiouracil (PTU).. Average of age was 40.1 +/- 5.8 years in the patient group and was 37.3 +/- 4.5 years in the control group. TSH, FT4, ALT and AST levels measured in the patient and control group are shown in Table 1. Basal levels of TSH were lower in the study group than in the control group (p<0.001), and basal levels of FT4 were higher in the study group than in the control group (p<0.001). Basal levels of ALT and AST, and the levels of TSH, FT4, ALT and AST measured at the third and sixth months were similar in both groups.. We did not find abnormal liver function tests during the antithyroid treatment in the patients with hyperthyroidism.

Topics: Adult; Alanine Transaminase; Antithyroid Agents; Aspartate Aminotransferases; Case-Control Studies; Humans; Hyperthyroidism; Liver Function Tests; Propylthiouracil; Thyrotropin; Thyroxine

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arthritis; Diagnosis, Differential; Food Hypersensitivity; Foot Diseases; Hematologic Tests; Humans; Hyperthyroidism; Male; Propylthiouracil; Vasculitis

The ascites syndrome in broiler chickens is attributed to the progress in genetic selection for rapid growth, coupled with the metabolic burden imposed by exposure to a relatively low-ambient temperature (T(a)). The syndrome is mainly characterized by hematocrit elevation, decline in blood oxygen saturation, accumulation of fluid in the abdominal cavity, and finally, death. Ascitic chickens have demonstrated hypothyroidism coupled with a marked stress response (high corticosterone concentration) and reduction in the hemoglobin content. The objective of the present study was to examine the role of thyroid and corticosterone hormones in the development of the syndrome. Ascites was induced by exposure to a gradually declining T(a) and supplementation of a pellet-form diet. Exogenous thyroxin (T(4)) and propylthiouracil (PTU) (in Experiments 1 and 2, respectively) were supplemented in drinking water to induce hyper- or hypothyroidism, respectively. Ascites syndrome was developed in 21.5% and 23% of the birds exposed to ascites-induced conditions (Exps. 1 and 2, respectively). Excess T(4) (Exp. 1) significantly reduced the percentage of ascites (down to 7%), whereas PTU (Exp. 2) significantly increased the appearance of the syndrome (35%). In the T(4)-treated chickens, although the T(4) concentration reached pharmacological levels, the triiodothyronine (T(3)) concentration remained within physiological levels, whereas T(3) in the ascitic birds exhibited a reduction pattern similar to that observed in the ascitic non-supplemented ones. In the PTU-treated chickens, however, both ascitic and non-ascitic birds demonstrated significant reductions in both T(4) and T(3) concentrations. In both experiments, ascitic chickens exhibited a considerable stress response, characterized by a significant and persisted elevation in plasma corticosterone concentration, which was in accordance with a similar elevation of hematocrit, and the PTU-treated non-ascitic birds exhibited a similar stress response. At 5 weeks of age, ascitic birds and the PTU-treated non-ascitic ones exhibited significant reductions in the hemoglobin content of their red blood cells. It may be concluded that deficiency in the thyroid hormones and elevated corticosterone may play a key deleterious role in the development of the ascites syndrome.

Topics: Aging; Animals; Ascites; Chickens; Corticosterone; Hematocrit; Hemoglobins; Hyperthyroidism; Hypothyroidism; Male; Poultry Diseases; Propylthiouracil; Syndrome; Thyroxine; Triiodothyronine

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Propylthiouracil; Pulmonary Alveoli; Vasculitis

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

We report the case of a 27-year-old woman with hyperthyroidism during pregnancy. Antithyroid treatment with propylthiouracil (PTU) resulted in elevated hepatic enzymes and after the 12th week of pregnancy treatment was changed to carbimazole (CBZ). The remaining pregnancy, delivery and follow-up period were uneventful for the mother and her offspring. Antithyroid treatment during pregnancy should allow the use not only of PTU but also of CBZ and methimazole.

Topics: Adult; Antithyroid Agents; Carbimazole; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Prenatal Care; Propylthiouracil

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Treatment Failure

Thyroid status is crucial in energy homeostasis, but despite extensive studies the actual mechanism by which it regulates mitochondrial respiration and ATP synthesis is still unclear. We studied oxidative phosphorylation in both intact liver cells and isolated mitochondria from in vivo models of severe not life threatening hyper- and hypothyroidism. Thyroid status correlated with cellular and mitochondrial oxygen consumption rates as well as with maximal mitochondrial ATP production. Addition of a protonophoric uncoupler, 2,4-dinitrophenol, to hepatocytes did not mimic the cellular energetic change linked to hyperthyroidism. Mitochondrial content of cytochrome oxidase, ATP synthase, phosphate and adenine nucleotide carriers were increased in hyperthyroidism and decreased in hypothyroidism as compared to controls. As a result of these complex changes, the maximal rate of ATP synthesis increased in hyperthyroidism despite a decrease in ATP/O ratio, while in hypothyroidism ATP/O ratio increased but did not compensate for the flux limitation of oxidative phosphorylation. We conclude that energy homeostasis depends on a compromise between rate and efficiency, which is mainly regulated by thyroid hormones.

Topics: Adenosine Triphosphate; Animals; Disease Models, Animal; Electron Transport Complex IV; Hepatocytes; Hyperthyroidism; Hypothyroidism; Mitochondria, Liver; Oxidative Phosphorylation; Oxygen Consumption; Propylthiouracil; Proton Pumps; Rats; Rats, Wistar; Thyroid Gland

We describe the ANCA profile of two monozygotic triplets (A and B) treated with propylthiouracil (PTU) for hyperthyroidism who developed LE-like manifestations. Triplet C also developed hyperthyroidism but was not treated with PTU and never experienced LE-like symptoms. Triplet A and B showed a marked rise in P-ANCA titer to 1:1280 after PTU was introduced whereas triplet C never had a titer higher than 1:80. Consecutive sera were investigated for ANCA to six different neutrophil granule proteins. Triplet A and B, but not C, both developed a strongly positive elastase-ANCA. Our results confirm the importance of a genetic factor influencing the susceptibility to drug-induced LE.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Histocompatibility Testing; Humans; Hyperthyroidism; Lupus Erythematosus, Systemic; Propylthiouracil; Triplets

The effects of thyroid hormone depletion and enhancement on litter size, survival, body mass, ambulation, quadrant crossing, home orientation, day of eye opening, and free serum T3 and T4 levels were examined in Study 1. In Study 2, the effects of the timing of prenatal insult and the level of thyroid hormone depletion on litter size, survival, body mass, and free serum T3 and T4 levels were examined. Upon the completion of Study 1, randomly selected pups were maintained on ad-libitum water and food for 2 years, and performance was evaluated on fixed and variable ratio schedules, fixed and variable interval schedules, and probability and reversal learning tasks (Study 3). In Study 4, human subjects diagnosed with and treated for either congenital hypothyroidism or congenital hyperthyroidism were tested on the operant procedures used in Study 3, as well as on a series of simple reaction time, serial timing, and conjunctive and disjunctive search tasks. Dose-dependent decreases in survival and delays in the presentation of early motor and exploratory skills were observed following thyroid hormone depletion; dose-dependent accelerations in the presentation of early motor and exploratory skills were observed following thyroid hormone enhancement. Pups that had been prenatally exposed to propylthiouracil (PTU) 1-2 years after the return of thyroid hormones to baseline levels were significantly less accurate at timing on fixed and variable interval schedules, demonstrated an inability to allocate responding on probability tasks, and committed more errors during original learning (OL) and on each reversal problem. Similar deficits were observed in follow-up tests with humans diagnosed with congenital hypothyroidism, as were deficits in serial timing and visual searching. Collectively, the present results demonstrate that the pervasive and negative effects of prenatal thyroid deficiency on early behavior are also expressed during adult operant performance.

Topics: Analysis of Variance; Animals; Antithyroid Agents; Body Mass Index; Conditioning, Operant; Dose-Response Relationship, Drug; Exploratory Behavior; Female; Hyperthyroidism; Hypothyroidism; Litter Size; Motor Activity; Pregnancy; Prenatal Exposure Delayed Effects; Propylthiouracil; Random Allocation; Rats; Reaction Time; Reinforcement, Psychology; Survival Rate; Thyroid Function Tests; Thyroid Hormones; Thyroxine

To describe a patient with eyelash loss as the presenting feature of hyperthyroidism.. Case report.. A 19-year-old woman presented with right upper eyelid eyelash loss. Thyroid function studies confirmed hyperthyroidism. She subsequently lost further eyelashes and a patch of scalp hair. Once the hyperthyroidism was treated, the eyelashes and scalp hair regrew.. Eyelash loss may be an early sign of the hyperthyroid state.

Topics: Adult; Antithyroid Agents; Eyelashes; Eyelid Diseases; Female; Hair Diseases; Humans; Hyperthyroidism; Propylthiouracil

Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course.. Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes.. Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal, < 117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 +/- 46.4) days after the PTU withdrawal.. Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

Topics: Adult; Age Distribution; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Incidence; Korea; Liver; Liver Diseases; Liver Function Tests; Male; Middle Aged; Probability; Propylthiouracil; Retrospective Studies; Risk Factors; Sex Distribution

The thyroid function and sexual development of eight 6-week-old Suffolk ram lambs were studied. The lambs were divided into either control or treatment groups and housed indoors. From 6 to 12 weeks of age, four lambs in the treatment group received 15 mg kg(-1) body weight per day of 6-propyl 2-thiouracil orally to suppress normal thyroid function. During the same period, thyroxine and tri-iodothyronine were injected s.c. at the rate of 8 and 16 microg kg(-1) body weight per day, respectively, to induce a hyperthyroid state. Four control lambs received sham injection and oral excipient. Concentrations of thyroxine, tri-iodothyronine, FSH, testosterone and insulin-like growth factor I were determined in blood collected by indwelling jugular catheters once a week, every 20 min from 09:00 to 15:20 h. Scrotal circumference was recorded each week. Semen collection was attempted by electro-ejaculation between weeks 17 and 36. Lambs were castrated at week 36 and testicular histology was examined. During the treatment period only, the concentration of thyroid hormones was higher in treated lambs than in controls (P < 0.05). From week 6 to week 9 only, concentrations of FSH in treated lambs were lower than in controls (P < 0.05). Insulin-like growth factor I concentrations were lower in treated lambs than in controls from week 10 to week 13 (P < 0.05). Frequency of testosterone pulses was higher (P < 0.01) in the treated lambs but concentrations were similar in the control and treated lambs throughout the experiment. Scrotal circumference was greater in treated lambs from week 26 to week 36 (P < 0.05). Treated lambs produced viable spermatozoa earlier than did control lambs. At week 36, sperm concentration in treated lambs was higher than in controls (P < 0.01) but semen volumes were similar (P > 0.1). Diameter of the seminiferous tubules in treated lambs was larger than in controls (P < 0.05). In conclusion, transient neonatal hyperthyroidism decreased FSH and insulin-like growth factor I concentrations temporarily, increased testosterone pulses and sperm production and advanced puberty in Suffolk ram lambs.

Topics: Aging; Animals; Follicle Stimulating Hormone; Hyperthyroidism; Insulin-Like Growth Factor I; Male; Orchiectomy; Propylthiouracil; Sexual Maturation; Sheep; Sheep Diseases; Spermatogenesis; Testis; Testosterone; Thyroxine; Triiodothyronine

The effect of thyroid status on arterial baroreflex function and autonomic contributions to resting blood pressure and heart rate (HR) were evaluated in conscious rats. Rats were rendered hyperthyroid (Hyper) or hypothyroid (Hypo) with triiodothyronine and propylthiouracil treatments, respectively. Euthyroid (Eut), Hyper, and Hypo rats were chronically instrumented to measure mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Baroreflex function was evaluated with the use of a logistic function that relates LSNA or HR to MAP during infusion of phenylephrine and sodium nitroprusside. Contributions of the autonomic nervous system to resting MAP and HR were assessed by blocking autonomic outflow with trimethaphan. In Hypo rats, the arterial baroreflex curve for both LSNA and HR was shifted downward. Hypo animals exhibited blunted sympathoexcitatory and tachycardic responses to decreases in MAP. Furthermore, the data suggest that in Hypo rats, the sympathetic influence on HR was predominant and the autonomic contribution to resting MAP was greater than in Eut rats. In Hyper rats, arterial baroreflex function generally was similar to that in Eut rats. The autonomic contribution to resting MAP was not different between Hyper and Eut rats, but predominant parasympathetic influence on HR was exhibited in Hyper rats. The results demonstrate baroreflex control of LSNA and HR is attenuated in Hypo but not Hyper rats. Thyroid status alters the balance of sympathetic to parasympathetic tone in the heart, and the Hypo state increases the autonomic contributions to resting blood pressure.

Topics: Animals; Antithyroid Agents; Baroreflex; Blood Pressure; Consciousness; Ganglionic Blockers; Heart Rate; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System; Thyroid Gland; Triiodothyronine; Trimethaphan

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis, Membranous; Humans; Hyperthyroidism; Nephritis; Propylthiouracil

Thyroid dysfunction produces multiple alterations in plasma lipoprotein levels, including high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are important proteins that modulate the metabolism of HDL. Thus, the effect of thyroid hormone on the activities of CETP and of HL was investigated using hypothyroid and hyperthyroid CETP transgenic (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP) profile analysis showed a significant increase in the very-low-density lipoprotein (VLDL) fraction (P <.001) and decrease in the HDL fraction (P <.005), whereas in the hypothyroid Tg mice an increase in low-density lipoprotein (LDL) was observed (P <.02). CETP activity was measured as the transfer of (14)C-cholesteryl ester (CE) from labeled HDL to LDL by an isotopic assay indicative of mass. Hyperthyroid Tg mice had twice as much plasma CETP activity as compared with their controls, while in hypothyroid Tg mice plasma CETP activity did not change. The role of CETP in determining the changes in LP profile of hyperthyroid animals was confirmed by showing that nTg wild-type hyperthyroid and euthyroid mice exhibited the same percent cholesterol distribution in LP. Postheparin HL activity measured in hyperthyroid Tg mice was significantly reduced (P <.05). (3)H-cholesteryl oleoyl ether ((3)H-Cet)-HDL plasma fractional removal rate (FRR) was approximately 2-fold faster in the hyperthyroid Tg mice than in controls, but was not modified in hypothyroid animals. Tissue uptake of (3)H-Cet was examined in 10 tissue samples: levels were significantly increased in skeletal muscle and decreased in small intestine in hyperthyroid Tg mice, and decreased in the small intestine of hypothyroid Tg mice. In conclusion, the excess of thyroid hormone accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in plasma CETP activity and independently from the HL activity. Hypothyroid status did not change CETP activity and HDL metabolism.

Topics: Animals; Carrier Proteins; Cholesterol; Cholesterol Ester Transfer Proteins; Chromatography, High Pressure Liquid; Female; Glycoproteins; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Lipase; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Propylthiouracil; Triiodothyronine; Tritium

Thyroid disease commonly presents in women in their reproductive years. Maternal, fetal and neonatal outcomes are very good if the diagnosis is made early and appropriate management pathways are established. In the uncommon situation of concurrent maternal and fetal disease, the key management issues involve recognition of the involvement of the fetus and close intensive surveillance of both mother and fetus/neonate using a multi-disciplinary approach. This approach, utilising a combination of serial ultrasound of the fetus and serial biochemical testing for the mother, allows for the accurate titration of medical therapy to both patients.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Humans; Hyperthyroidism; Pregnancy; Propylthiouracil; Thyroidectomy; Thyrotoxicosis; Ultrasonography, Prenatal

A 45 year-old man had a typical episode of subacute thyroiditis with tender goiter, depressed radioiodine uptake (RAIU) and elevated erythrocyte sedimentation rate. The titer of TSH binding inhibitor immunoglobulin (TBII), which had been 8.6% at initial presentation, rose to 14.9% in 2 weeks. TBII consisted of high titers (94%) of TSH stimulation-blocking antibodies (TBAb) and negative thyroid stimulating antibodies (TSAb). About 2 months after the first visit, TBII titers had risen to 48.9% and were persistently elevated for 5 months with high TBAb activity. The patient developed hypothyroidism with a maximum serum TSH level of 54.5 microU/ml. TBII and TBAb titers then gradually decreased, and the patient spontaneously recovered from hypothyroidism. Eighteen months after the episode of subacute thyroiditis, he became hyperthyroid with elevated TSAb and negative TBAb values. Doppler ultrasonography showed increased blood flow in the thyroid, and RAIU at 24 h was 53%. He was treated with antithyroid drugs, and soon became euthyroid. This case indicates that subacute thyroiditis can induce thyroid autoimmunity, and that the character of TSH receptor antibodies (TSHRAb) in these patients can change thereby modifying their thyroid function.

Topics: Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroid Gland; Thyroiditis; Thyrotropin; Thyroxine; Triiodothyronine; Ultrasonography

Membrane and cytosolic fractions prepared from ventricular myocardium of young (21-day-old) hypo- or hyperthyroid rats and adult (84-day-old) previously hypo- or hyperthyroid rats were analyzed by immunoblotting with specific anti-G-protein antibodies for the relative content of Gs alpha, Gi alpha/Go alpha, Gq alpha/G11 alpha, and G beta. All tested G protein subunits were present not only in myocardial membranes but were at least partially distributed in the cytosol, except for Go alpha2, and G11 alpha. Cytosolic forms of the individual G proteins represented about 5-60% of total cellular amounts of these proteins. The long (Gs alpha-L) isoform of Gs alpha prevailed over the short (Gs alpha-S) isoform in both crude myocardial membranes and cytosol. The Gs alpha-L/Gs alpha-S ratio in membranes as well as in cytosol increased during maturation due to a substantial increase in Gs alpha-L. Interestingly, whereas the amount of membrane-bound Gi alpha/Go alpha and Gq alpha/G11 alpha proteins tend to lower during postnatal development, cytosolic forms of these G proteins mostly rise. Neonatal hypothyroidism reduced the amount of myocardial Gs alpha and increased that of Gi alpha/Go alpha proteins. By contrast, neonatal hyperthyroidism increased expression of Gs alpha and decreased that of Gi alpha and G11 alpha in young myocardium. Changes in G protein content induced by neonatal hypo- and hyperthyroidism in young rat myocardium were restored in adulthood. Alterations in the membrane-cytosol balance of G protein subunits associated with maturation or induced by altered thyroid status indicate physiological importance of cytosolic forms of these proteins in the rat myocardium.

Topics: Age Factors; Animals; Animals, Newborn; Cytosol; Heterotrimeric GTP-Binding Proteins; Hyperthyroidism; Hypothyroidism; Isoenzymes; Male; Membrane Proteins; Myocardium; Organ Size; Propylthiouracil; Protein Subunits; Rats; Rats, Wistar; Subcellular Fractions; Triiodothyronine

Mitochondrial heat shock protein 70 (mtHsp70), an important mitochondrial chaperone, is increased in cardiac muscle mitochondria of hyperthyroid rats. To determine the mechanism(s) underlying this increase, we used variations in thyroid status. In Series I, rats were made hyperthyroid by injecting them with 3,3', 5-triiodo-l-thyronine (T(3)) for 5 days, or by treating them with vehicle. In Series II, animals were given 6-n-propyl-2-thiouracil in their drinking water (0.05% w/v) for a period of 32-42 days to make them hypothyroid. During the last 5 days of treatment these animals received injections of either T(3) or vehicle. T(3) treatment resulted in parallel increases in mtHsp70 protein and mRNA levels in a variety of tissues, suggesting transcriptional regulation. However, evidence of tissue-specific post-transcriptional regulation was also apparent. In isolated heart mitochondria, T(3) treatment resulted in a 1.8-fold increase in mtHsp70. This was due to the 1. 6-fold greater import of mtHsp70 into mitochondria in T(3), compared with hypothyroid animals, and it could not be attributed to an altered rate of intramitochondrial mtHsp70 degradation. The rate of processing of mtHsp70 to its mature form, reflecting mitochondrial processing peptidase activity, was unaffected by T(3), but was more rapid than mtHsp70 import. These data indicate a novel mechanism by which T(3) modifies the mitochondrial phenotype via the adaptations in the protein import pathway.

Topics: Animals; HSP70 Heat-Shock Proteins; Hyperthyroidism; Hypothyroidism; Male; Mitochondria, Heart; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transcription, Genetic; Triiodothyronine

A 62-year-old woman had been treated with propylthiouracil(PTU) for hyperthyroidism. Because bloody sputum, dyspnea, and severe hypoxemia developed, the patient was admitted to our hospital. Chest X-ray and chest computed tomographic (CT) films disclosed diffuse infiltrative shadows in both lung fields. Bronchoalveolar lavage revealed abundant hemosiderin-laden macrophages. Alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis syndrome was diagnosed because of the high serum level of MPO-ANCA. After the initiation of steroid therapy and termination of PTU, the infiltrative shadows in both lung fields disappeared, PaO2 improved, and MPO-ANCA decreased. There have been some reports of MPO-ANCA positive vasculitis syndrome developing during PTU therapy, but most were concerned with renal disease. We concluded that PTU and similar agents should be given consideration as one of the possible causes of MPO-ANCA-induced alveolar hemorrhage.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Middle Aged; Peroxidase; Propylthiouracil; Pulmonary Alveoli; Syndrome; Vasculitis

We have previously reported that changes in thyroid status are associated with significant alterations in skeletal muscle blood flow during exercise and that changes in endothelium-dependent vasodilation may contribute to these blood flow abnormalities. The purpose of this study was to test the hypothesis that altered endothelium-dependent vasoconstriction is also associated with changes in thyroid status. To test this hypothesis, rats were rendered hypothyroid with propylthiouracil (Hypo, n = 14) or hyperthyroid with triiodothyronine (Hyper, n = 14) over approximately 3 mo. Treatment efficacy was confirmed by altered (P < 0.05) citrate synthase activity in several hindlimb skeletal muscles from Hypo and Hyper, compared with that in muscles from euthyroid rats (Eut, n = 12). Vascular rings were prepared from abdominal aortae, and responses to several vasoactive agents were determined in vitro. As found previously, maximal acetylcholine-induced vasorelaxation was modulated by thyroid status (Eut, 47 +/- 9; Hypo, 28 +/- 6; Hyper, 68 +/- 5%; P < 0.05). Contractile responses of vascular rings with intact endothelium to the endothelium-derived constrictor endothelin-1 (ET-1), however, were similar among groups across a range of ET-1 concentrations. In addition, maximal responses [Eut, 3.75 +/- 0.47; Hypo, 2.72 +/- 0.25; Hyper, 3.22 +/- 0.42 g; not significant (NS)] and sensitivities (Eut, 8.12 +/- 0.09; Hypo, 8.10 +/- 0.06; Hyper, 8.28 +/- 0.09 -log M; NS) to ET-1 were similar among groups. If these findings from the conduit-type abdominal aorta extend into resistance vasculature, it appears that changes in endothelium-dependent vasoconstriction do not contribute to skeletal muscle blood flow abnormalities associated with thyroid disease states.

Topics: Acetylcholine; Animals; Aorta, Abdominal; Citrate (si)-Synthase; Dose-Response Relationship, Drug; Endothelin-1; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Male; Muscle, Skeletal; Muscle, Smooth, Vascular; Nitroprusside; Norepinephrine; Propylthiouracil; Rats; Triiodothyronine; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

We tested the effects of thyroid hormone on Leydig cell (LC) regeneration in the adult rat testis after ethane dimethyl sulphonate (EDS) treatment. Ninety-day-old, thyroid-intact (n = 96) and thyroidectomized (n = 5) male Sprague-Dawley rats were injected intraperitoneally (single injection) with EDS (75 mg/kg) to destroy LC. Thyroid-intact, EDS-treated rats were equally divided into three groups (n = 32 per group) and treated as follows: control (saline-injected), hypothyroid (provided 0.1% propyl thiouracil in drinking water), and hyperthyroid (received daily subcutaneous injections of tri-iodothyronine, 100 microg/kg). Testing was done at Days 2, 7, 14, and 21 for thyroid-intact rats and at Day 21 for thyroidectomized rats after the EDS treatment. Leydig cells were absent in control and hyperthyroid rats at Days 2, 7, and 14; in hypothyroid rats at all ages; and in thyroidectomized rats at Day 21. The LC number per testis in hyperthyroid rats was twice as those of controls at Day 21. 3beta-Hydroxysteroid dehydrogenase (LC marker) immunocytochemistry results agreed with these findings. Mesenchymal cell number per testis was similar in the three treatment groups of thyroid-intact rats on Days 2 and 7, but it was different on Days 14 and 21. The highest number was in the hypothyroid rats, and the lowest was in the hyperthyroid rats. Serum testosterone levels could be measured in control rats only on Day 21, were undetectable in hypothyroid rats at all stages, and were detected in hyperthyroid rats on Days 14 and 21. These levels in hyperthyroid rats were twofold greater than those of controls on Day 21. Serum androstenedione levels could be measured only in the hyperthyroid rats on Day 21. Testosterone and androstenedione levels in the incubation media showed similar patterns to those in serum, but with larger values. These findings indicate that hypothyroidism inhibits LC regeneration and hyperthyroidism results in accelerated differentiation of more mesenchymal cells into LC following the EDS treatment. The observations of the EDS-treated, thyroidectomized rats confirmed that the findings in hypothyroid rats were, indeed, due to the deficiency of thyroid hormone.

Topics: Androstenedione; Animals; Antithyroid Agents; Body Weight; Cell Differentiation; Hydroxysteroid Dehydrogenases; Hyperthyroidism; Hypothyroidism; Leydig Cells; Luteinizing Hormone; Male; Mesoderm; Mesylates; Organ Size; Propylthiouracil; Rats; Rats, Sprague-Dawley; Regeneration; Testis; Testosterone; Thyroid Hormones; Thyroidectomy

Mitochondria seem to be involved in oxygen radical damage and aging. However, the possible relationships between oxygen consumption and oxygen radical production by functional mitochondria, and oxidative DNA damage, have not been studied previously. In order to analyze these relationships, male Wistar rats of 12 weeks of age were rendered hyper- and hypothyroid by chronic T(3) and 6-n-propyl-2-thiouracil treatments, respectively. Hypothyroidism decreased heart mitochondrial H(2)O(2) production in States 4 (to 51% of controls; P<0.05) and 3 (to 21% of controls; P<0.05). In agreement with this, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) decreased in the heart genomic DNA of hypothyroid animals to 40% of controls (P<0.001). Studies with respiratory inhibitors showed that the decrease in oxygen radical generation observed in hypothyroidism occurred at Complex III (mainly) and at Complex I; that decrease was due to the presence of a lower free radical leak in the respiratory chain (P<0.05). Hyperthyroidism did not significantly change heart mitochondrial H(2)O(2) production since the increase in State 4 oxygen consumption in comparison with control and hypothyroid animals (P<0.05) was compensated by a decrease in the free radical leak in relation to control animals (P<0.05). In agreement with this, heart 8-oxodG was not changed in hyperthyroid animals. The lack of increase in H(2)O(2) production per unit of mitochondrial protein will protect mitochondria themselves against self-inflicted damage during hyperthyroidism.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Fractionation; Deoxyguanosine; DNA Damage; Free Radicals; Hydrogen Peroxide; Hyperthyroidism; Hypothyroidism; Male; Mitochondria, Heart; Myocardium; Oxidation-Reduction; Oxygen Consumption; Propylthiouracil; Rats; Rats, Wistar; Rotenone; Thyroid Gland; Thyroid Hormones; Triiodothyronine; Uncoupling Agents

This case report describes the management of a breastfeeding mother who had been given radioactive iodine and technetium for diagnosis of thyroid disease. The mother requested to submit weekly milk samples for monitoring of radioactivity. Once activity fell below measurable counts, the mother resumed lactation.

Topics: Adult; Breast Feeding; Female; Humans; Hyperthyroidism; Infant; Iodine Radioisotopes; Metabolic Clearance Rate; Milk, Human; Propylthiouracil; Puerperal Disorders; Radiation Monitoring; Thyrotropin

The abundance of Na,K-ATPase and its alpha and beta subunit mRNAs is upregulated in cardiac and other target tissue by thyroid hormone (T3). Multiple Na,K-ATPase mRNA beta 1 species encoding an identical beta 1 polypeptide are expressed in the heart. The different mRNA beta 1 species result from utilization of two transcription start-sites in the first exon and multiple (five) poly(A) signals in the terminal exon of the beta 1 gene. In the present study we identify the mRNA beta 1 species that are expressed in rat ventricular myocardium under basal conditions, and determine whether they are differentially regulated by T3. mRNA beta 1 species were identified by 3'-RACE followed by DNA sequencing, and by Northern blotting using probes derived from different regions of rat cDNA beta 1. Five mRNA beta 1 species are expressed in rat heart: mRNA beta 1 species that are initiated at the first transcription start-site and end at the first, second and fifth poly(A) sites (resulting in mRNAs of 1630, 1810, and 2780 nucleotides), and mRNA beta 1 species initiated at the second transcription start-site and ending at the second and fifth poly(A) sites (resulting in mRNAs of 1500 and 2490 nucleotides); in order of increasing length, the five mRNAs constitute 0.04, 0.15, 0.38, 0.11 and 0.32 of total mRNA beta 1 content. In hypothyroid rats (induced by addition of propyl-thiouracil to the drinking water for 3 weeks), total mRNA beta 1 content decreased to 0.18 euthyroid levels, which was associated with a disproportionate 7.5-fold decrease in the abundance of the longest transcript (P < 0.05); transcripts initiating at the first transcription start-site and ending at the second poly(A) signal in hypothyroid hearts were 0.26 euthyroid levels (P < 0.05). Hyperthyroidism induced by injection of normal rats with three doses of 100 micrograms T3/100 g body weight every 48 h resulted in an overall approximately 2-fold increase in mRNA beta 1 content with no change in the fractional contribution of any of the mRNA beta 1 species. The results indicate a complex heterogeneity in the expression of mRNA beta 1 in myocardium.

Topics: Animals; Base Sequence; Blotting, Northern; Gene Expression Regulation; Hyperthyroidism; Hypothyroidism; Male; Molecular Sequence Data; Myocardium; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sequence Alignment; Sodium-Potassium-Exchanging ATPase; Thyroid Gland; Transcription, Genetic; Triiodothyronine

Cardiac beta-myosin heavy chain (beta-MHC) gene expression is mainly regulated through transcriptional processes. Although these results are based primarily on in vitro cell culture models, relatively little information is available concerning the interaction of key regulatory factors thought to modulate MHC expression in the intact rodent heart. Using a direct gene transfer approach, we studied the in vivo transcriptional activity of different-length beta-MHC promoter fragments in normal control and in altered thyroid states. The test beta-MHC promoter was fused to a firefly luciferase reporter gene, whereas the control alpha-MHC promoter was fused to the Renilla luciferase reporter gene and was used to account for variations in transfection efficiency. Absolute reporter gene activities showed that beta- and alpha-MHC genes were individually and reciprocally regulated by thyroid hormone. The beta-to-alpha ratios of reporter gene expression demonstrated an almost threefold larger beta-MHC gene expression in the longest than in the shorter promoter fragments in normal control animals, implying the existence of an upstream enhancer. A mutation in the putative thyroid response element of the -408-bp beta-MHC promoter construct caused transcriptional activity to drop to null. When studied in the -3, 500-bp beta-MHC promoter, construct activity was reduced ( approximately 100-fold) while thyroid hormone responsiveness was retained. These findings suggest that, even though the bulk of the thyroid hormone responsiveness of the gene is contained within the first 215 bp of the beta-MHC promoter sequence, the exact mechanism of triiodothyronine (T3) action remains to be elucidated.

Topics: Animals; Coleoptera; Enhancer Elements, Genetic; Female; Gene Expression Regulation; Heart; Hyperthyroidism; Hypothyroidism; Luciferases; Myocardium; Myosin Heavy Chains; Promoter Regions, Genetic; Propylthiouracil; Rats; Rats, Sprague-Dawley; Thyroid Gland; Transcription, Genetic; Triiodothyronine

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Nephritis, Interstitial; Propylthiouracil; Sjogren's Syndrome; Time Factors

Propylthiouracil (PTU) has recently been observed to be associated with antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis, resulting in crescentic glomerulonephritis and, infrequently, diffuse alveolar hemorrhage (DAH). We describe a case of a 23-year-old pregnant woman who developed a perinuclear ANCA and antimyeloperoxidase-positive small vessel vasculitis manifesting as DAH and crescentic glomerulonephritis after she began taking PTU. An open lung biopsy was consistent with pulmonary capillaritis. She responded to corticosteroid therapy and discontinuation of PTU. DAH can be caused by pulmonary capillaritis, bland hemorrhage, or diffuse alveolar damage. To our knowledge, this represents the first documentation of an underlying pulmonary capillaritis in a case of PTU-induced DAH.

Topics: Adult; Antimetabolites; Biopsy; Capillaries; Female; Glucocorticoids; Hemorrhage; Humans; Hyperthyroidism; Lung; Lung Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Propylthiouracil; Pulmonary Alveoli; Radiography, Thoracic; Vasculitis

We report the case of a Caucasian patient with insulin autoimmune syndrome (IAS), defined as the association of hypoglycaemic attacks with insulin autoantibodies in individuals not previously treated with exogenous insulin. This rare syndrome (more than 200 published cases) has been reported mainly in Japan. Most affected patients present with other autoimmune disorders, most often Graves' disease. In most cases, insulin autoantibodies appear a few weeks after the beginning of treatment with a drug containing a sulphyldryl group. A significant increase in insulin and C-peptide plasma concentrations and the presence of other antiorgan antibodies are observed. The susceptibility haplotype is present in the Japanese population, which may account for the high frequency of IAS. Spontaneous remission is observed in 80% of cases, with cessation of hypoglycaemic attacks and disappearance of insulin autoantibodies some months after withdrawal of the drug. This rare cause of hypoglycaemia in Caucasian subjects should be considered in aetiologic investigation of spontaneous hypoglycaemia.

Topics: Antithyroid Agents; Autoantibodies; Autoimmune Diseases; C-Peptide; Carbimazole; Humans; Hyperthyroidism; Hypoglycemia; Insulin; Japan; Male; Middle Aged; Morocco; Paris; Propylthiouracil; Syndrome; White People

We report three patients with Down syndrome that developed a hyperthyroidism. A 25 years old female and a 18 years old male had Basedow Graves disease and were treated with radioiodine. A 19 years old male had a Hashitoxicosis and is presently being treated with propylthiouracyl. Clinical and subclinical thyroid dysfunction is frequent in patients with Down syndrome and the risk increases with age. Therefore a surveillance with yearly TSH measurements should be done in these patients, since signs and symptoms of thyroid disease are barely detected in them. Hypothyroidism is the most frequent dysfunction but hyperthyroidism is also associated to Down syndrome.

Topics: Adolescent; Adult; Age of Onset; Down Syndrome; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Male; Propylthiouracil

Ninety-three hyperthyroid patients were treated with 1 dose of iodine-131 (131I) during the past 10 years. Thirty-three were pretreated with propylthiouracil (PTU), 22 with methimazole (MMI), and 38 received no antithyroid drugs (ATD). ATD were discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months before therapy in one fourth of the cases. The frequency of cures in the 3 groups, 6-8 months after radioiodine therapy, was retrospectively studied. The cure rate among those who discontinued PTU for 5-55 days before 131I was significantly reduced (24%), compared with those who discontinued MMI for the same duration (61%) or those who received no ATD (66%). When PTU was discontinued for more than 4 months, the cure rate was similar to those who received no ATD. It is concluded that if ATD are used as initial therapy for hyperthyroidism, then PTU (but not MMI) may reduce the therapeutic efficacy of subsequent 131I. The reduction in cure rate was observed even when PTU was discontinued for as long as 55 days before 131I therapy. To our knowledge, this is the first report to compare, in one study, the effects of pretreatment with PTU and MMI on 131I therapy.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Premedication; Propylthiouracil; Retrospective Studies; Treatment Outcome

Multiparous Brahman cows (n = 21) were randomly assigned during late fall within BW and body condition score (BCS) to receive either 3.0 mL of corn oil (C; n = 7), 3.0 mg/(cow x d) triiodothyronine (T3) s.c. in 3.0 mL of corn oil (HYPER; n = 7), or 4.0 mg/(kg x d) 6-n-propyl-2-thiouracil (PTU; fed with concentrate) plus 3.0 mL/d corn oil (HYPO; n = 7). Water, minerals, and Coastal bermudagrass hay were available free choice, and all cows received 3.2 kg x cow(-1) x d(-1) of 5:1 corn:soybean meal concentrate. The feeding period extended through three normal estrous cycles. Blood samples were collected weekly during the first and second estrous cycle, or until d 42 for anestrous cows, and daily throughout the third cycle. Also, between d 9 and 14 of the third cycle, or after d 35 in anestrous cows, intensive samples were collected at 2-h intervals for 24 h. Serum T3, thyroxine (T4), and progesterone (P4) were measured in weekly and intensive samples, and cortisol, insulin, GH, and thyroid-stimulating hormone (TSH) were measured in intensive samples. The altered thyroid status of HYPER and HYPO cows was evident (P < .001) during the third estrous cycle in mean daily T3, T4, and intensive TSH (P < .001) concentrations. Changes in BW and BCS were influenced by treatment (P < .001). A greater (P < .001) proportion of HYPER cows exhibited abnormal cycle length, and three of seven cows became anestrous. For cows that continued normal cycles, treatment did not affect (P > .05) the number of follicular waves, diameter of the dominant follicle, diameter of the ovulatory follicle, or P4 profiles during the third cycle. Insulin and GH concentrations did not differ (P > .05) among treatments in intensive samples, but, mean cortisol was greatest (P < .02) in HYPER cows. For Brahman cows that maintained normal estrous cycles, induced hyper-or hypothyroid status did not influence ovarian function.

Topics: Animal Feed; Animals; Cattle; Corpus Luteum; Estrus; Female; Hormones; Hyperthyroidism; Hypothyroidism; Ovarian Follicle; Ovary; Progesterone; Propylthiouracil; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

Topics: Acute Kidney Injury; Adult; Anti-Inflammatory Agents; Antithyroid Agents; Female; Humans; Hyperthyroidism; Kidney Function Tests; Male; Nephritis, Interstitial; Prednisolone; Propylthiouracil; Renal Dialysis

The neonatal proximal tubule has a lower rate of bicarbonate absorption than that of adults. This is due, in part, to a lower rate of apical membrane Na+/H+ antiporter activity. The purpose of these studies was to examine if thyroid hormone could be a factor in the maturational increase in Na+/H+ antiporter activity. Hypothyroid (0.01% propylthiouracil in drinking water starting at day 14 gestation and throughout the postnatal period), euthyroid, and hyperthyroid (intraperitoneal triiodothyronine, 10 micrograms/100 g body wt, once daily on days 17 to 20 of postnatal life) rats were all studied at 21 days of life. Renal cortical brush border Na+/H+ antiporter activity was 453 +/- 24, 527 +/- 30 and 608 +/- 25 pmol/mg protein in the hypothyroid, euthyroid and hyperthyroid groups, respectively (P < 0.001). Hyperthyroid neonates had approximately twofold greater renal cortical NHE-3 mRNA abundance than euthyroid and hypothyroid neonates (P < 0.05). Brush border membrane NHE-3 protein abundance in hypothyroid and hyperthyroid neonates was one-third and twofold that of euthyroid 21-day-old rats, respectively (P < 0.001). These data are consistent with a potential role of thyroid hormone in the postnatal increase in Na+/H+ antiporter activity.

Topics: Animals; Animals, Newborn; Antithyroid Agents; Female; Hyperthyroidism; Hypothyroidism; Kidney Cortex; Kidney Tubules, Proximal; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase; Triiodothyronine

The importance of local formation of T3 in the feedback effect of the thyroid gland on hypothalamic TRH-producing cells has been established. Primary failure of the thyroid gland results in a fall in circulating T4 and T3 levels, leading to an elevation in the production and release of TRH in the hypothalamic paraventricular nucleus. In contrast, during short term fasting, declining plasma levels of thyroid hormones coincide with suppressed TRH production and release. In the brain, the prevalent enzyme that converts T4 to T3 is type II iodothyronine deiodinase (DII). The present study was undertaken to determine whether a differential hypothalamic expression of type II deiodinase may exist in fasted rats and in animals that are hypothyroid due to the failure of the thyroid gland. Using in situ hybridization, we assessed type II deiodinase messenger RNA (mRNA) levels in the hypothalamus of rats that were control euthyroid, hyperthyroid (T4), hypothyroid induced by propylthiouracil (PTU), and fasted. A group of fasted rats also received exogenous T4. DII mRNA was detected around the third ventricle, including the ependymal layer and adjacent periventricular regions as well as in the arcuate nucleus and the external layer of the median eminence. Quantitative in situ hybridization analysis demonstrated that PTU treatment and short term fasting resulted in significant elevations in DII messenger levels compared with those in euthyroid controls. Three weeks of PTU administration induced a consistent decline in circulating T3 and undetectable T4 levels, whereas 3 days of fasting resulted in only a 50% fall in the concentration of serum thyroid hormones. Interestingly, however, the expression of the DII mRNA was more than 2-fold higher in fasted animals compared with the values in PTU-treated rats. Furthermore, although T4 administration repressed DII mRNA expression in euthyroid animals, the same treatment had no effect on the fasting-induced elevations of DII message. To assess whether DII enzymatic activity is also affected during food deprivation, hypothalami were dissected out, and DII activity was measured in control euthyroid, fasted, and fasted plus T4-treated rats. To determine whether comparable changes in plasma thyroid hormone levels induced by fasting and PTU treatment could have affected DII enzymatic activity in a similar manner, animals were injected ip with PTU for 5 days to decrease plasma thyroid hormones to levels similar to those caused by fa

Topics: Animals; Antithyroid Agents; Fasting; Histocytochemistry; Hyperthyroidism; Hypothalamus; Hypothyroidism; In Situ Hybridization; Iodide Peroxidase; Isoenzymes; Male; Propylthiouracil; Rats; Rats, Sprague-Dawley; Reference Values; RNA, Messenger; Thyroxine

Thyroid hormone (TH) levels increase in the postnatal life and are essential for maturation of myocardial Ca2+ handling. During this time, the sarcolemmal (SL) Na+/Ca2+ exchanger (NCX) function decreases and the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) function increases. We examined the effects of postnatal hypo- or hyperthyroidism on NCX and SERCA2 in rat hearts. Animals were rendered hypothyroid by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from days 2 to 21 postpartum. Hyperthyroidism was induced by daily injections of 10 microg/100 g body weight of 3,3',5-triiodo-L-thyronine during this period. Ventricular steady-state mRNA and protein levels of NCX and SERCA2 were analyzed by Northern and Western blotting. These were compared with SL Na+ gradient-induced and SR oxalate-supported Ca2+ transports in isolated membranes. In hypothyroidism, NCX mRNA and protein were elevated by 66 and 80%, respectively, and SERCA2 mRNA and protein were reduced to 55 and 70%, respectively (P < 0.05 vs. euthyroid). Corresponding differences were observed in the respective Ca2+ transports. Conversely, reduced NCX (by 50%) and elevated SERCA2 (by 150%) activities were found in hyperthyroidism (P < 0.05). The levels of NCX and SERCA2 mRNA and protein were, however, unchanged in hyperthyroidism, indicating that functional changes are not due to altered NCX and SERCA2 expression. In this case, a decline in noninhibitory phosphorylated phospholamban is a likely explanation for the elevated SR Ca2+ transport. In conclusion, physiological TH levels appear to be essential for normal reciprocal changes in the expression and function of myocardial NCX and SERCA2 during postnatal development.

Topics: Animals; Animals, Newborn; Calcium-Binding Proteins; Calcium-Transporting ATPases; Gene Expression Regulation, Developmental; Heart; Hyperthyroidism; Hypothyroidism; Membrane Proteins; Myocardium; Propylthiouracil; Rats; Rats, Wistar; Regression Analysis; RNA, Messenger; Sarcolemma; Sarcoplasmic Reticulum; Sodium-Calcium Exchanger; Thyroid Gland; Transcription, Genetic; Triiodothyronine

A teenage girl with crescentic glomerulonephritis had antineutrophil cytoplasmic antibody (ANCA) detected after she had received propylthiouracil (PTU) for hyperthyroidism without cutaneous vasculitis. ANCA was detected on admission; renal biopsy showed crescentic glomerulonephritis with focal necrotizing glomerulonephritis but no immune deposits. Administration of steroid and decreasing the dose of PTU produced a good clinical response and the ANCA disappeared. It was concluded that ANCA is closely related to the pathogenesis of crescentic glomerulonephritis and that treatment with PTU appeared to induce ANCA.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Hyperthyroidism; Necrosis; Propylthiouracil

Leptin, the product of the adipose specific ob gene, regulates food intake and energy expenditure. However, little is known about the effects of thyroid status on plasma leptin levels in women. We determined fasting plasma leptin levels before and 1 month after restoration of euthyroidism in 20 female patients with hypothyroidism, 20 female patients with hyperthyroidism and 20 age and BMI-matched female controls. To restore the normal thyroid function patients with hypothyroidism were treated with levothyroxine, whereas patients with hyperthyroidism were treated with propylthiouracil. Plasma leptin levels were measured by a RIA method with a sensitivity of 0.5 microgram/l. Leptin levels were significantly lower in patients with hypothyroidism before treatment (4.17 +/- 2.58 micrograms/l) than in patients with hyperthyroidism (6.80 +/- 4.3 micrograms/l; z = -2.06, p = 0.037). Leptin levels were significantly higher in hyperthyroid patients than in the control group (3.71 +/- 1.69 micrograms/l, z = -2.44, p = 0.014) whereas leptin levels in the hypothyroid patients were not significantly different from those in control subjects (z = -0.16, p = 0.87). Restoration of euthyroid state was not associated with a significant change in leptin levels either in the hypothyroid (from 4.17 +/- 2.58 to 5.22 +/- 3.4 micrograms/l; z = -1.74, p = 0.08) or in the hyperthyroid group (from 6.80 +/- 4.37 micrograms/l to 7.93 +/- 6.25 micrograms/l z = -0.89, p = 0.37), although a tendency for leptin to increase was observed in both groups. There was no correlation between plasma leptin and FT3, FT4, TSH, or BMI either before or after therapy in both groups. Leptin levels were significantly correlated with BMI in the control group (r = -0.53, p = 0.018). We conclude that plasma leptin levels are increased in hyperthyroidism and unchanged in hypothyroidism. Furthermore, our study demonstrates that mean plasma leptin levels are not influenced by short term restoration of euthyroidism in both hypothyroidism and hyperthyroidism, although an effect of long-term treatment may not be excluded.

Topics: Adult; Body Mass Index; Fasting; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Propylthiouracil; Proteins; Thyroid Hormones; Thyroxine

A patient with known hyperthyroidism was seen at 25 weeks' gestation with a rapidly growing neck mass. She was initially in thyroid storm and received aggressive medical therapy. Two subsequent episodes of thyrotoxicosis occurred during pregnancy in spite of large doses of propylthiouracil. Post partum the patient was diagnosed with a locally advanced thyroid malignancy.

Topics: Adenocarcinoma, Papillary; Adult; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Propylthiouracil; Thyroid Crisis; Thyroid Neoplasms

In this study the impact of vitamin C supplementation on oxidative damage as assessed by thiobarbituric acid reactive substances and markers of antioxidant status: namely Cu/Zn superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione were investigated in 24 hyperthyroid patients under propylthiouracil therapy (3x100 mg/day) for five days and in 15 healthy controls. Ascorbic acid (1000 mg/day) was given as a supplement for 1 month to both the patients and controls during the study period. Heparinised blood samples were taken at the beginning and the end of one month ascorbic acid supplementation. Comparison of the hyperthyroid patients with the controls revealed higher lipid peroxidation (p<0.001), higher Cu/Zn superoxide dismutase activity (p<0.001), higher glutathione level (p<0.001) and lower glutathione reductase activity (p<0.001). Vitamin C supplementation to hyperthyroid patients caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase activity (p<0.001), whereas there were significant decreases in glutathione reductase (p<0.001) and Cu/Zn superoxide dismutase activities (p<0.01). Thiobarbituric acid reactive substances and thiobarbituric acid reactive substances/glutathione ratio were significantly decreased (p<0.01). Vitamin C supplementation to euthyroid controls caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase and Cu/Zn superoxide dismutase activities (p<0.001), whereas there was a significant decrease in glutathione reductase (p<0.001). The thiobarbituric acid reactive substances/glutathione ratio was significantly decreased (p<0.05). Our findings reveal the potentiation of antioxidant status and a relief in oxidative stress in both propylthiouracil treated hyperthyroid patients and controls in response to vitamin C supplementation.

Topics: Adult; Antithyroid Agents; Ascorbic Acid; Case-Control Studies; Female; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Humans; Hyperthyroidism; Male; Middle Aged; Oxidative Stress; Propylthiouracil; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory polypeptide (GIP) and insulin was studied. Male rats were thyroidectomized (Tx) or sham Tx. Sham Tx rats were injected with either propylthiouracil ([PTU] 20 mg/kg intraperitoneally) or saline for 2 weeks. In addition, thyroid-intact rats were injected intravenously with triiodothyronine ([T3]5 microg/kg) or saline 10 minutes before an oral glucose load (3.2 g/kg). Blood samples were collected from each animal via a jugular catheter at 0, 10, 20, 30,45, 60, and 90 minutes following glucose ingestion. Plasma levels of GIP and insulin were measured by specific radioimmunoassays (RIAs). Thyroidectomy-induced hypothyroidism increased the basal level of plasma GIP, but decreased that of insulin. Insulin levels at 10, 20, and 30 minutes following oral glucose were lower in hypothyroid rats than in euthyroid rats. Conversely, GIP levels at 60 and 90 minutes following glucose ingestion in PTU-induced hypothyroid rats were higher than those in euthyroid rats. Furthermore, glucose-stimulated insulin secretion was unaltered by pretreatment with T3, whereas the glucose-induced increase in plasma GIP was completely abolished by preinjection of T3 in thyroid-intact rats. These results suggest that thyroid functions are involved in the regulation of insulin and GIP secretion in rats.

Topics: Animals; Blood Glucose; Calcium; Gastric Inhibitory Polypeptide; Hyperthyroidism; Hypothyroidism; Injections, Intravenous; Insulin; Insulin Secretion; Male; Propylthiouracil; Rats; Thyroid Hormones; Thyroidectomy; Thyrotropin; Triiodothyronine

Administration of streptococcal cell wall (SCW) preparation induces an inflammatory response in susceptible animals that is a model frequently used for rheumatoid arthritis. The degree of inflammation produced by SCW is greatly enhanced by low endogenous levels of glucocorticoids due to diminished hypothalamic-pituitary-adrenal activity. Because decreased glucocorticoid production is known to occur in the hypothyroid state, we tested whether hypothyroidism would increase, and conversely, whether hyperthyroidism would decrease, the inflammatory responses to SCW. Adult female Sprague Dawley rats were fed a regular diet (control), L-T4 (T4; hyperthyroid), or 6-propyl-thiouracil (hypothyroid) in drinking water for 7 weeks. Hypothyroidism resulted in elevated plasma levels of TSH and hypothalamic preproTRH messenger RNA (mRNA) while reducing anterior pituitary POMC mRNA and plasma ACTH and corticosterone levels. In contrast, hyperthyroid rats produced opposite results: decreased measures of central thyroid function but increased pituitary-adrenal function. Three days after administration of SCW, macrophage inflammatory protein-1alpha and interleukin-1beta mRNA expression increased dramatically in controls and even further in hypothyroid animals, as measured by Northern blot analysis. In contrast, T4-treated rats showed significant inhibition of these inflammatory markers. Thus, the hyperthyroid state combined with increased endogenous glucocorticoid levels is protective against inflammatory challenges. The inverse relationship between preproTRH expression and pituitary-adrenal function suggests the possibility of a direct inhibitory link connecting the hypothalamic-pituitary-adrenal and thyroid axes, and suggests alternative sites of therapeutic intervention for rheumatoid arthritis and other inflammatory associated disorders.

Topics: Animals; Arthritis, Infectious; Blotting, Northern; Cell Wall; Chemokine CCL4; Female; Hyperthyroidism; Hypothyroidism; Interleukin-1; Macrophage Inflammatory Proteins; Macrophages; Propylthiouracil; Rats; RNA, Messenger; Streptococcal Infections; Thyroxine

During a period of 7 years at our institution, four girls and one boy with Down's syndrome, ages 9 to 16 years, were examined and treated for hyperthyroidism. Two patients had Graves' disease and they responded to propylthiouracil (PTU) with a predictable clinical course resulting in remission within 4 years. The remaining three patients included in this report had hyperthyroid profiles similar to those of the two with Graves' disease except for their antibody panels. These patients, in addition to the elevated thyroid-stimulating immunoglobulin (TSI) level observed in Graves' disease, also had significantly elevated antimicrosomal antibody (AMA) and antithyroglobulin antibody (ATGA) at the time of diagnosis. Elevated TSI level was again present in two patients who had a recurrence of hyperthyroidism after PTU therapy was discontinued. Treatment of these three patients was best done with the continuation of PTU therapy at a lower dose and the addition of thyroxine as soon as mild hypothyroidism developed. Treatment with PTU and thyroxine was continued until the TSI level was no longer elevated. Levels of AMA and ATGA remained elevated long after the TSI level became normal. All three patients eventually had hypothyroidism and continue to require thyroxine replacement.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Child; Down Syndrome; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Microsomes; Propylthiouracil; Recurrence; Remission Induction; Thyroglobulin; Thyroxine

Changes in liver biochemical test results have been described in hyperthyroid patients before and after antithyroid therapy. In the present study, we analyzed liver tests at diagnosis and after 6 weeks of treatment with propylthiouracil (PTU) in 43 patients with hyperthyroidism. At diagnosis, 60.5% of the patients had at least one liver abnormality. Elevations of alkaline phosphatase, alanine and aspartate aminotransferase, and gamma-glutamyl transpeptidase levels were observed in 19 (44.2%), 10 (23.3%), six (14%), and six (14%) of the patients, respectively. At the end of the 6-week treatment with PTU, elevations in liver test values, possibly induced by PTU, were found in seven (16.3%) patients. Age, sex, type of goiter (either diffuse or multinodular), and presence or absence of abnormal liver biochemical tests at diagnosis were not significant in determining the possibility of PTU-induced elevations in liver tests. These data suggest that liver test abnormalities are frequently found at the time of diagnosis of hyperthyroidism. However, the presence or absence of these abnormalities does not predict elevations in liver test results, which are possibly induced by PTU during therapy.

Topics: Adult; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Risk Factors; Thyroid Function Tests; Thyrotoxicosis

We present a case study of a 52-year-old female patient with hyperthyroidism which had been diagnosed at the age of 35. However, the malfunction of thyroid had been poorly controlled. Thyroid function was returning to normal after the administration of propylthiouracil (PTU) 300 mg/day, however purpura appeared in both lower extremities. Renal function deteriorated rapidly, and the patient was admitted to our hospital. According to the biopsies, leukocytoclastic vasculitis in the skin was apparent, and crescent formation was observed in the glomerulus. Serological examination revealed positive antineutrophil cytoplasmic autoantibodies (ANCA) against proteinase 3 (Pr3) and myeloperoxidase (MPO). Antinuclear autoantibody was positive. After cessation of PTU and administration of prednisolone, the purpura disappeared and ANCA were becoming negative. Renal function recovered gradually. Thyroid function was kept within normal range using iodine solution. Thus, it is strongly suggested that PTU-induced rapidly progressive glomerulonephritis associated with ANCA.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil

We described here three individual pregnancies in a euthyroid mother with a past history of Graves disease and high levels of thyrotropin receptor stimulating antibodies. Ten years prior to her first pregnancy the mother underwent a partial thyroidectomy for Graves disease and remained euthyroid since, but still produced high levels of thyrotropin receptor stimulating antibodies. Fetal and postnatal hyperthyroidism was not recognized for the first child who was referred to us at one year of age for craniostenosis. During the two next pregnancies fetal hyperthyroidism was suspected on the basis of fetal tachycardia, growth retardation, fetal goiter and fetal cord blood sampling confirmed high levels of free T3, free T4, suppressed fetal TSH levels, and high levels of fetal TRAb. The mother received propylthiouracil to control fetal hyperthyroidism. Neither baby was premature and each had a more favorable outcome than the first. Fetal cord blood sampling proved to be useful during these two pregnancies to ascertain the diagnosis of fetal hyperthyroidism and to monitor the dose of PTU administered to this euthyroid mother.

Topics: Adult; Antithyroid Agents; Female; Fetal Blood; Fetal Diseases; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Hormone Resistance Syndrome; Thyroidectomy

It has previously been demonstrated that thyrotropin-releasing hormone (TRH) mRNA expression is dramatically increased in limbic structures including dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. Since thyroid hormone regulates TRH mRNA in the paraventricular nucleus of the hypothalamus (PVN), we investigated whether basal or kindling-induced TRH mRNA expression in limbic regions is also regulated by thyroid hormone. Hypo- and hyperthyroidism was induced by treating rats with 0.05% 6-n-propyl-2-thiouracil (PTU) (equivalent to approximately 30 mg/kg/day) or 0.9 microM 3,5,3'-triiodo-L-thyronine (T3) (equivalent to approximately 50 micrograms/kg/day), respectively, in their drinking water for 10 days before kindling and throughout the kindling procedure. Rats were sacrificed 4 h after their first stage 5 seizure. None of the thyroid hormone manipulations altered kindling development, or behavioral and electrographic after-discharge seizure durations. Pituitary TSH beta mRNA levels were significantly increased by PTU and suppressed by T3, but unaffected by kindling. In addition, in situ hybridization showed that PTU administration increased and T3 administration decreased TRH mRNA levels in the PVN, consistent with thyroid hormone's negative feedback effects. At the same time, kindling had no effect on TRH mRNA in the PVN. In contrast, kindling dramatically increased TRH mRNA in the dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices, but thyroid hormone manipulations did not affect either basal or kindling-induced TRH mRNA expression in limbic structures. These findings demonstrate that TRH mRNA expression is differentially regulated in the hypothalamic PVN and limbic structures.

Topics: Amygdala; Animals; Base Sequence; Gene Expression; Hyperthyroidism; Hypothalamus; Hypothyroidism; Kindling, Neurologic; Limbic System; Male; Molecular Sequence Data; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine

Non-immune fetal hydrops is a heterogeneous disorder with a mortality rate of 50-98%. Resolution of non-immune fetal hydrops is rare but has been reported to occur spontaneously or after targeted therapeutic measures.. A euthyroid gravida with Graves disease presented with a history of three prior perinatal deaths between 26 and 28 weeks' gestation, all associated with fetal hydrops. In the current pregnancy, the fetus developed hydrops at 24 weeks' gestation. Fetal hyperthyroidism, with high-output cardiac failure, was diagnosed with fetal blood sampling. After maternal therapy with propylthiouracil, resolution of the non-immune hydrops were documented and a healthy neonate subsequently delivered to term. The neonate developed transient hyperthyroidism after delivery, which required treatment for 10 weeks.. Non-immune hydrops occurring as a result of fetal hyperthyroidism with high output cardiac failure is treatable with propylthiouracil.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Heart Failure; Humans; Hydrops Fetalis; Hyperthyroidism; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Recurrence

To define the relationship between renal epidermal growth factor (EGF) expression and thyroid hormones in acute renal failure, we performed an analysis of the renal thyroid hormone-EGF axis following acute ischemic renal injury in rats. Levels of mature EGF extractable from kidney were elevated 24 h postinjury, and levels of membrane-associated EGF precursor were reduced. Administration of triodothyronine (T3) to rats, either prior to or immediately following the induction of injury, did not further increase levels of extractable EGF. Levels of EGF mRNA in kidneys were reduced 24 h following acute ischemic damage and not affected by administration of T3. Enhanced production of mature EGF from EGF precursor occurred in membranes isolated from kidneys of rats 24 h postinjury compared with production in membranes from kidneys of normal rats. In addition, levels of thyroxine 5'-deiodinase activity in renal membranes were increased 24 h following injury. Levels of circulating total thyroxine (T4), free T4, and free T3 were reduced postischemic injury. Total T3 was unchanged. The administration of T3 to normal rats increased renal 5'-deiodinase activity and EGF precursor cleavage. Administration of propylthiouracil to rats inhibited renal 5'-deiodinase activity and prevented the increase in extractable EGF postischemic injury. We conclude that the increase in levels of mature EGF extractable from kidneys of rats postischemic injury results from enhanced activity of the serine protease that cleaves the EGF precursor. This activity may be stimulated by T3 produced in kidney. These alterations in renal T4 metabolism and EGF expression could serve to facilitate recovery of renal function following ischemia.

Topics: Acute Disease; Acute Kidney Injury; Animals; Epidermal Growth Factor; Hyperthyroidism; Iodide Peroxidase; Ischemia; Kidney; Male; Propylthiouracil; Rats; Rats, Sprague-Dawley; Renal Circulation; RNA, Messenger; Serine Endopeptidases; Thyroxine; Time Factors; Triiodothyronine

We investigated the effect of hyper- and hypothyroidism on tyrosine hydroxylase protein concentration in the locus coeruleus (divided into anterior and posterior parts), the substantia nigra and the adrenals of adult rats. Rats were made hypothyroid with propylthiouracile (PTU, 0.02% in drinking water for 21 days) or hyperthyroid by thyroxine injection (100 or 250 micrograms/kg/day), for 3 or 17 days. PTU treatment resulted in statistically significant decrease of tyrosine hydroxylase in the anterior locus coeruleus (-13%) and the adrenals (-14%). After thyroxine treatment, in the anterior locus coeruleus, tyrosine hydroxylase was significantly higher (2 way ANOVA) after the 3 day treatment than after the 17 day treatment: tyrosine hydroxylase showed a trend to increase the 3 day treatment (+20% with the 250 micrograms/kg dose) and to decrease after the 17 day treatment (-15% with the 250 micrograms/kg dose). In the adrenals, tyrosine hydroxylase was increased by the 3 day treatment (+42% after the 250 micrograms/kg dose), but this increase was not observed after 17 days of treatment. Tyrosine hydroxylase was not altered in the posterior locus coeruleus and the substantia nigra, whatever the treatment. Together, our results support the hypothesis that in the anterior locus coeruleus and in the adrenals tyrosine hydroxylase level is positively modulated by thyroid hormones. After long-term treatment (17 days) this effect is not observed.

Topics: Adrenal Glands; Animals; Antithyroid Agents; Brain; Catecholamines; Hyperthyroidism; Hypothyroidism; Immunoblotting; Locus Coeruleus; Male; Nerve Tissue Proteins; Propylthiouracil; Rats; Rats, Sprague-Dawley; Substantia Nigra; Thyroid Hormones; Thyroxine; Tyrosine 3-Monooxygenase

Following the diagnosis of fetal goitre at 22 and 24 weeks' gestation in two hyperthyroid pregnant women who underwent treatment with 400-500 mg of propylthiouracil in the first weeks of pregnancy, a total of seven fetal blood samplings were performed to evaluate thyroid function before and after the initiation of two different treatment regimens. L-Thyroxine (600 micrograms) was injected five times intra-amniotically in one woman and continuous maternal administration of the thyroid analogue 3, 5, 3'-triiodothyroacetic acid (Triac) was attempted in the other. Normalization of fetal thyroid function and reduction of fetal goitre were achieved in both fetuses and transplacental passage of Triac was indirectly demonstrated by high levels of free triiodothyronine in fetal blood. In cases of fetal hypothyroidism, direct or indirect prenatal therapy can be adopted successfully and safely.

Topics: Adult; Amniotic Fluid; Female; Fetal Blood; Gestational Age; Humans; Hyperthyroidism; Hypothyroidism; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy. Although its pathogenesis remains to be established, detection of antineutrophil cytoplasmic antibodies (ANCA) in association with this type of vasculitis has recently been described. We report here 2 patients who developed ANCA-associated crescentic glomerulonephritis without evidence of cutaneous vasculitis during propylthiouracil treatment of hyperthyroidism. Improvement of the renal function and the disappearance of ANCA were correlately found after discontinuation of propylthiouracil and by corticosteroid therapy in both patients.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil

A case of a pregnant woman who underwent urgent cesarean section is presented. The patient had severe hyperthyroidism, preeclampsia, and congestive heart failure, which had not been treated until 36 weeks of gestational age. At 38 weeks, fetal distress occurred and an urgent cesarean section was performed successfully under epidural anesthesia with preoperative treatments using iodide, hydrocortisone and propylthiouracil. The patient required postoperative intensive care for heart failure. Thyroid function of the neonate was almost normal. No abnormality was observed except low birth weight.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Cesarean Section; Female; Heart Failure; Humans; Hydrocortisone; Hyperthyroidism; Iodides; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Propylthiouracil

To report a case of propylthiouracil-induced hepatic damage.. A 64-year-old white woman with hyperthyroidism received propylthiouracil 250 mg/d for 1 year. She developed hepatitis after 1 year of therapy. Alcohol and drug abuse were ruled out and all serologic tests for hepatitis A, B, and C were negative. Cytomegalovirus and Epstein-Barr virus infection were also ruled out. Antinuclear antibody, antimitochondrial antibody, and antismooth muscle antibody were negative. The clinical picture was similar to that of viral hepatitis characterized by nausea, vomiting, and jaundice. Histologic examination of a liver biopsy specimen showed chronic active hepatitis. The patient developed cirrhosis during follow-up.. Propylthiouracil is widely used in the treatment of hyperthyroidism. Despite its widespread use, there have been only a few reported cases of propylthiouracil-induced hepatotoxicity. The precise mechanism of the injury is unknown, although immunologic factors are suggested.. Hepatic damage induced by propylthiouracil is a rare complication. However, the danger of permanent hepatic damage should be kept in mind. The best way of preventing propylthiouracil hepatotoxicity is careful screening of patients considered for treatment.

Topics: Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Liver; Liver Cirrhosis; Middle Aged; Propylthiouracil

We present a 15-year-old girl with an unusual clinical course of intractable thyrotoxicosis that was resistant to thiocarbamide therapy and propranolol. Although the latter beta-adrenergic blocking agent has been used as the sole drug in the preparation of thyrotoxicosis patients for thyroidectomy, it was unsatisfactory for control of our case. In contrast, the patient's clinical response to lithium carbonate 900-1500 mg/d for 10 days was very good and no side effects were observed. This demonstrates the importance of lithium as the drug of choice in thyrotoxic emergencies and uncontrolled preoperative patients when rapid and safe inhibition of thyroid hormone secretion is required.

Topics: Adolescent; Antithyroid Agents; Drug Resistance, Multiple; Female; Humans; Hyperthyroidism; Lithium Carbonate; Methimazole; Premedication; Propranolol; Propylthiouracil; Thyroidectomy

Width of the external plexiform layer in olfactory bulbs and mean area of mitral and granule cell dendritic and glial processes were measured of normal, hypo- and hyperthyroid rat pups at the age of 24 days. Hypothyroidism was induced by treating the rats with a reversible goitrogen 6-n-propyl-2-thiouracil dissolved in their drinking water, while the hyperthyroid group was given water containing thyroxine. The 6-n-propyl-2-thiouracil treatment was begun on gestational day 18 and on the day of birth. Thyroxine treatment started on the day of birth. Both treatments were continued till the day of sacrifice. A significant decrease in the width of the external plexiform layer of the olfactory bulb in the prenatally 6-n-propyl-2-thiouracil treated group and a significant increase in the width of the external plexiform layer of the hyperthyroid group was shown by the Student's paired t-test. The areas of neuronal and glial processes were measured at electron microscopic level by using an IBAS image analysing system. A significant decrease was found by the Kruskal-Wallis test and Dunn's range test in the mean area of (1) mitral cell dendrites in the prenatal 6-n-propyl-2-thiouracil treated group, (2) granule cell dendrites in both the postnatally 6-n-propyl-2-thiouracil treated and in the hyperthyroid groups and (3) glial processes in the thyroxine treated group comparing to controls.

Topics: Animals; Dendrites; Female; Hyperthyroidism; Hypothyroidism; Neuroglia; Olfactory Bulb; Pregnancy; Prenatal Exposure Delayed Effects; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; Thyroxine

Untreated hyperthyroidism during pregnancy is associated with increased maternal and perinatal morbidity. Some features of this disease simulate preeclampsia, which may encourage delivery of the fetus. We report a case of poorly controlled hyperthyroidism associated with generalized seizures, where patient management was directed at a diagnosis of preeclampsia-eclampsia. Although the presence of eclampsia and marked hyperthyroidism is very rare, this case illustrates the importance of aggressive medical management of hyperthyroidism. A 17-year-old gravida was diagnosed with hyperthyroidism at 15 weeks' gestation. At 26 weeks' gestation, she was admitted to the hospital after noting edema of the upper and lower extremities, nausea, vomiting, shortness of breath, and a cough. At admission, she was hypertensive, tachycardic, and dyspneic. The patient was believed to have preeclampsia with pulmonary edema complicated by hyperthyroidism. We initiated magnesium sulfate therapy and administered several bolus doses of hydralazine, with little effect on blood pressure. Oliguria was noted, and a pulmonary artery catheter was inserted. Hours later, generalized seizure activity occurred, and a decision was made for abdominal delivery. Postoperatively, cardiovascular function stabilized. On postoperative day 3, we received the results of the thyroid function tests obtained at admission, which suggested a markedly hyperthyroid condition. Untreated or poorly treated hyperthyroidism may present a clinical picture similar to preeclampsia. In our case, both disease processes coexisted in their severest forms. It is possible, although completely unproven, that a relationship exists between poorly controlled hyperthyroidism and preeclampsia-eclampsia. More importantly, accurate diagnosis of hyperthyroidism should lead to prompt medical or surgical management, thereby decreasing maternal and perinatal morbidity.

Topics: Adolescent; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Propylthiouracil; Seizures

In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is decreased, resulting in a decreased serum T3 concentration. We investigated whether factors in serum of NTI patients may play a role in this energy-saving adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary culture was measured in the presence of 10% serum of normal subjects or of patients with NTI and related to the severity of disease. Patients with NTI were grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased in the presence of serum of patients of groups I-IV. A decreased net deiodination of T4 and T3 (corrected for differences in free hormone concentration) without an increase in conjugated T4 and T3 (corrected for differences in free hormone concentration) was observed, similar to results in experiments with compounds inhibiting transport into the cells and not the metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3 concentration of the patient (r = 0.69). Serum of patients with NTI influences thyroid hormone handling by hepatocytes comparable to the effect of transport inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport over the cell membrane may play a role in lowered T3 production in NTI.

Topics: Animals; Cells, Cultured; Culture Media; Disease; Humans; Hyperthyroidism; Hypothyroidism; Liver; Male; Monensin; Ouabain; Propylthiouracil; Rats; Rats, Wistar; Reference Values; Regression Analysis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Clinical studies in thyrotoxicosis reveal a state of high bone turnover leading, eventually, to osteoporosis. Recently there has been concern that thyroxine (T4) treatment may have a similar effect on bone. Rat models have been used to study the effects of T4 on bone, but the majority of studies have looked at the effects of T4 after only 3 weeks of treatment. The aim of this study was to evaluate histomorphometric changes in rats after 12 weeks of thyroxine overtreatment or 12 weeks of hypothyroidism compared with untreated control animals. Animals received either T4 200 micrograms/kg per day, 0.1% propylthiouracil, or vehicle for 12 weeks. Tetracycline was administered 1 week and 3 weeks prior to killing. Iliac crest bone was used for histomorphometry. Serum T4 measurements (taken at killing) confirmed hyper- and hypothyroidism in the appropriate animal groups (between group difference p < 0.001 by ANOVA). In hyperthyroid animals there was an increase in mineral apposition rate (MAR; 0.94 vs. 0.59 microns/day, p < 0.001) and mineral formation rate (MFR/BS; 0.24 vs. 0.12 x 10(-2) micron3/micron2 per day, p < 0.001) and a slight increase in eroded surfaces (ES/BS%; 1.54 vs. 1.36, p < 0.05) compared with controls, consistent with previous in vitro and in vivo observations. In hypothyroid rats there was a marked reduction in osteoid surfaces (OS/BS%; 1.7 vs. 24.8, p < 0.001) and MAR (0.3 vs. 0.59 micrograms/day, p < 0.001), a reduction in ES/BS% (0.51 vs. 1.36, p < 0.05), and an increase in cancellous bone volume (BV/TV%; 30.29 vs. 19.6, p < 0.05), suggesting that thyroid hormones are a requirement for normal bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Body Weight; Calcinosis; Disease Models, Animal; Drug Overdose; Hyperthyroidism; Hypothyroidism; Ilium; Male; Propylthiouracil; Radioimmunoassay; Rats; Rats, Wistar; Tetracycline; Thyroid Function Tests; Thyroxine

During hepatic development, beta-adrenergic receptors are replaced by alpha 1-receptors, an important event in the switchover from neonatal to adult glucose metabolism. In mature tissues, expression of adrenergic receptor subtypes is regulated, in part, by thyroid hormones; the current study examines whether they also participate in the transition of hepatic receptors. When triiodothyronine (T3) was given to rat pups on postnatal days 11-15, just before the receptor transition period, the developmental increase of alpha 1-receptors was accelerated but there was no change in the ontogenetic decline of beta-receptors. When propylthiouracil (PTU) was given over the same period to induce hypothyroidism, neither alpha 1- nor beta-receptor development were affected, thus, despite the selective promotion of alpha 1-receptor sites by exogenous thyroid hormone, endogenous hormone is not obligatory for receptor switching to take place. Finally, to distinguish whether the receptor transition is a function of general growth and cell differentiation, which are also impacted by thyroid status, animals were given PTU from gestational day 17 through postnatal day 5, a treatment that reproduces the growth defects of congenital cretinism, but that allows hormone levels to return to normal during the receptor transition period; the appropriate switchover still occurred. These studies indicate that thyroid hormone selectively promotes hepatic alpha 1-receptor expression during development, but is not itself responsible for the ontogenetic switchover in adrenergic receptor subtypes. Because other factors, such as glucocorticoids, have similar modulatory effects, the timing of hepatic adrenergic receptor development may be governed by multiple factors, no one of which is absolutely sufficient or essential.

Topics: Animals; Animals, Newborn; Female; Hyperthyroidism; Hypothyroidism; Liver; Membranes; Pregnancy; Propylthiouracil; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta; Thyroid Hormones; Triiodothyronine

Hypopotassaemic periodic paralysis as the sole manifestation of hyperthyroidism. Hypopotassaemic periodic paralysis is a rare disorder that is found in certain families, sporadically or in association with certain diseases. The association with hyperthyroidism is almost wholly restricted to south-east Asian males. It is characterized by attacks of subacute paralysis, starting most often early in the morning and lasting some hours to a few days. We present a 42-year-old patient of Indonesian origin, who experienced four attacks of paralysis before underlying hyperthyroidism was diagnosed. The mechanism is based on potassium shift into the muscle cell due to higher activity of the Na-K-ATP-ase pump, under the influence of beta-adrenergic stimulation and thyroid hormone. Treatment with antithyroidal medication and beta-blockers led to the complete abolition of attacks.

Topics: Adult; Humans; Hyperthyroidism; Hypokalemia; Male; Paralyses, Familial Periodic; Propylthiouracil

TSH initiates its action by binding to specific membrane receptors' thyroid cells and induces activation of the adenylate cyclase-cAMP cascade. The factors involved in the regulation of TSH receptors are poorly known, except for the TSH dose-dependent regulatory effect. The fact that the thyroid gland of Graves' patients has a normal density of TSH receptors with suppressed TSH and high T4 and T3 levels suggests a modulatory role of thyroid hormones on TSH receptors. To evaluate this hypothesis, the density of TSH receptors and the activity of adenylate cyclase were determined in the thyroid membranes from hyperthyroid and hypothyroid adult male rats; they were rendered hyperthyroid either with bovine TSH, TRH, or T3 for 7 days and hypothyroid by propylthiouracil treatment or by hypophysectomy. NaCl was given to the control group. Plasma T4, T3, and TSH were also quantified. Bovine TSH and TRH treatments induced mild hyperthyroidism with a small goiter and a 50% reduction in the density of TSH receptors due to hyperstimulation of the gland by either exogenous or endogenous high TSH levels. Severe hyperthyroidism caused by T3 treatment resulted in low T4, high T3, and suppressed TSH thyrocyte stimulation; it was associated with a significant increase in the number of TSH receptors (29.6 +/- 2.3 vs. control 17.9 +/- 1.7 mU TSH/mg protein). These last results suggest a putative positive effect of T3 on TSH receptors. To confirm this effect, hypothyroid rats were investigated. Severe primary hypothyroidism due to propylthiouracil treatment was associated with a large goiter, high plasma TSH levels (11.8 +/- 1.2 vs. control 1.5 +/- 0.1 mU TSH/ml), low plasma T4 and T3, and a 70% reduction in TSH receptors, confirming the down-regulatory effect of high TSH on the thyroid cell. However, in hypophysectomized rats, a 45% reduction in the density of TSH receptors was also observed in the absence of TSH. Injections of either TSH or T3 to these hypophysectomized rats restored a normal number of TSH-binding sites, and simultaneous TSH and T3 treatments resulted in a mildly additive effect in the number of TSH receptors, which was slightly greater than that of the controls. No important changes were found in the adenylate cyclase activity in the thyroid membrane preparations from hyperthyroid and hypothyroid rats despite variations in the density of TSH receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adenylyl Cyclases; Animals; Cattle; Graves Disease; Hyperthyroidism; Hypophysectomy; Hypothyroidism; Male; Propylthiouracil; Rats; Rats, Wistar; Receptors, Thyrotropin; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Two cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis following treatment with propylthiouracil and carbimazole are described. Both patients had crescentic glomerulonephritis proven by renal biopsy and responded to immunosuppressive therapy and withdrawal of the anti-thyroid drugs. Though systemic vasculitis associated with propylthiouracil is reported, this is the first report to our knowledge of renal biopsy-proven vasculitis associated with either of these drugs.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Carbimazole; Glomerulonephritis; Humans; Hyperthyroidism; Kidney; Male; Middle Aged; Propylthiouracil; Thyrotoxicosis; Vasculitis

The effects of altered thyroid states on the heart rate and ventricular electrophysiological properties of the frog were examined. Hypothyroidism was induced by a 10-day treatment with propylthiouracil and produced decreased serum-free and total triiodothyronine levels below detectable concentrations. Hyperthyroidism, elicited by a 5-day treatment with triiodothyronine, was associated with increased serum thyroid hormone levels. The hypothyroid state was associated with a significantly decreased heart rate measured in vivo and an increased duration of the action potential recorded in vitro from ventricular fibers. Hyperthyroidism was associated with an increased heart rate and a decreased ventricular action potential duration (APD). The dependence of APD on temperature was affected by thyroid status. An increase from 25 to 30 degrees barely shortened the repolarization phase in hyperthyroids, minimally (13.3%) shortened that in euthyroids, and greatly (43.7%) shortened that in hypothyroids; the APD was similar in euthyroid and hypothyroid frogs. The shortening of the repolarization phase, by increased stimulation frequency, was also greater for hypothyroid frogs. In this case, however, the differences in APD among groups remained significant at all the frequencies tested.

Topics: Action Potentials; Animals; Antithyroid Agents; Electric Stimulation; Electrophysiology; Heart; Heart Rate; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rana esculenta; Thyroid Gland; Triiodothyronine; Ventricular Function

Changes in thyroid status have a major effect on the GH/IGF-I axis. In the rat, there is a single gene for the growth hormone receptor (GHR), that is transcribed into two different sized mRNA transcripts following alternative splicing, one transcript codes for the GHR (4.0-4.5 kb) and the other growth hormone binding protein (GHBP) (1.2-1.3 kb). We have studied the regulation of hepatic GHR gene expression by thyroid hormones in male Wistar rats rendered hypothyroid (n = 6) and hyperthyroid (n = 6) compared to controls (n = 6). By northern blot analysis, two transcripts with an estimated size of 4.2 and 1.2 kb, respectively, were detected in all groups. Hyperthyroidism was associated with a significant increase in the 4.2 kb transcript compared to hypothyroidism (P < 0.05), but no changes were observed in the 1.2 kb transcript. Thus, our results suggest that in the rat hyperthyroidism is associated with either increased hepatic gene transcription or decreased clearance of the 4.2 kb transcript for the GHR compared with hypothyroidism.

Topics: Alternative Splicing; Analysis of Variance; Animals; Gene Expression Regulation; Hyperthyroidism; Hypothyroidism; Liver; Male; Propylthiouracil; Rats; Rats, Wistar; Receptors, Somatotropin; Reference Values; RNA, Messenger; Thyroid Gland; Thyroxine; Transcription, Genetic

Coronary capillary geometry was studied in male rats treated with 3,3',5-triiodo-L-thyronine (T3; Hyper), 6-N-propyl-2-thiouracil (PTU; Hypo), or a sequence of PTU and T3 (Hypo/Hyper). Ventricular mass and heart-to-body mass ratios revealed myocardial hypertrophy in Hyper, atrophy in Hypo, and a return of ventricular mass to control (Con) values in Hypo/Hyper rats. From cross-sectional analysis, capillary densities for Hyper and Hypo/Hyper were comparable with Con, despite increased left ventricular mass. Hypo rats demonstrated increased capillary density. In Hyper and Hypo rats, tissue area surrounding individual capillaries (capillary domain) decreased, compared with Con, for capillaries close to the feeding arteriole. In Hyper and Hypo/Hyper, capillaries distal to the feeding arteriole had similar domain areas as Con; in Hypo, this area was smaller. From longitudinal analysis, capillary segment lengths were significantly shorter in all groups compared with Con. Our data suggest that while hypothyroidism induced myocardial atrophy and hyperthyroidism induced myocardial hypertrophy, both thyroid states stimulated capillary proliferation.

Topics: Alkaline Phosphatase; Animals; Capillaries; Cardiomegaly; Coronary Circulation; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Histocytochemistry; Hyperthyroidism; Hypothyroidism; Male; Mathematics; Myocardium; Propylthiouracil; Rats; Rats, Sprague-Dawley; Silver; Staining and Labeling; Triiodothyronine

Topics: Antithyroid Agents; Dexamethasone; Emergencies; Humans; Hyperthyroidism; Iodides; Plasmapheresis; Propranolol; Propylthiouracil

Radioiodine therapy has become a cornerstone of treatment of hyperthyroidism. However, the timing of its administration varies between 1) the time of initial diagnosis with concurrent therapy with beta adrenergic blocking drugs or 2) following induction of euthyroidism with thioamide, Propylthiouracil or Methimazole. This study assessed 24-HR 131I uptake values and the thyroid scan in 24 subjects with hyperthyroidism at the time of diagnosis and again after attaining the euthyroid state with Propylthiouracil or Methimazole. Propylthiouracil of Methimazole was withdrawn seven days prior to the second 24-HR 131I uptake and scan. In all subjects, as a group, 24-HR 131I uptake increased following antithyroid therapy as compared to the time of initial of diagnosis [76 + 5% Vs. 54 + 4%; p < 0.01]. The thyroid gland size decreased in nine of twenty-four subjects, but remained unchanged in the remaining subjects. Since 24-HR 131I uptake and the gland size are the major factors influencing the therapeutic radioiodine dosage, it is possible that initial therapy with thioamide drugs may reduce the therapeutic dose of 131I in subjects with hyperthyroidism belonging to both groups, i.e., Graves' disease and Multinodular toxic goiter by inducing a rise in 24-HR 131I uptake. Furthermore, the shrinkage of thyroid glands may further decrease the radioiodine dosage in patients with Graves' disease.

Topics: Adult; Aged; Combined Modality Therapy; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland

Topics: Acromegaly; Adrenocorticotropic Hormone; Aminoglutethimide; Bromocriptine; Calcitonin; Cushing Syndrome; Diazoxide; Diphosphonates; Estrogens; Fluid Therapy; Hemangiopericytoma; Humans; Hypercalcemia; Hyperthyroidism; Hypoglycemia; Inappropriate ADH Syndrome; Ketoconazole; Mifepristone; Mineralocorticoids; Mitotane; Octreotide; Osteomalacia; Pamidronate; Paraneoplastic Endocrine Syndromes; Phosphorus; Plicamycin; Propylthiouracil; Saline Solution, Hypertonic; Somatostatin; Thyroid Neoplasms

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Drug Monitoring; Humans; Hydrocortisone; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Radioisotopes; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyroxine

Topics: Adenoma; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms

To reexamine the prevalence and sequential changes of liver and bone biochemical abnormalities in patients with hyperthyroidism.. A consecutive series of 95 patients with hyperthyroidism and 66 controls with euthyroid goiter seen during same period were studied. The patients were treated with propylthiouracil (PTU) 300 mg/day for 2 months, followed by 100-150 mg/day for 3 months and a subsequent maintenance dose of 100 mg/day. Serum aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin, ALP isoenzymes, and hepatitis markers were studied before therapy and at 2 and 5 months after PTU therapy was begun.. Seventy-two [75.8%, confidence interval (CI) 67.2-84.4%] of the 95 patients had at least one biochemical abnormality. AST, ALT, ALP, GGT, and bilirubin were elevated in 27.4%, 36.8%, 64.2%, 16.8%, and 5.3%, respectively. Of the 34 patients with ALT elevation, 62% showed gradual normalization of ALT, whereas 38% (CI 21.9-54.5%) showed transient, asymptomatic, but significant (p < 0.025) further elevation of ALT during PTU therapy. Overt hepatitis developed in one patient. None of these changes was due to hepatitis A, B, C, or delta virus infection or autoimmune hepatitis. Changes of serum GGT parallel those of ALT. In contrast, serum ALP (primarily bone isoenzyme) rose significantly (p < 0.01) as T4 and T3 levels declined at 2 months after therapy.. The results suggest that hyperthyroidism is often associated with abnormal biochemical tests, particularly ALP elevation, and thus may pose diagnostic confusion. The increase of bone isoenzyme accounts for the elevations in total ALP level before and during therapy. Serum ALT and GGT abnormalities usually subside during PTU therapy, but transient asymptomatic PTU hepatotoxicity occurs in one-third of the patients. Discontinuation of PTU is not required unless overt hepatitis develops.

Topics: Adolescent; Adult; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Bone and Bones; Female; Follow-Up Studies; gamma-Glutamyltransferase; Goiter; Hepatitis B Surface Antigens; Humans; Hyperthyroidism; Isoenzymes; Liver; Male; Middle Aged; Propylthiouracil; Prospective Studies

A male preterm infant (born at 34 weeks, birth weight 2130 g) developed jaundice (total bilirubin 7.4 mg/dl), hepatosplenomegaly, thrombocytopenia (82,000/microliters) and a raised C-reactive protein (1.2 mg/dl). Although sepsis was suspected, no organism was demonstrated. When the mother visited the child for the first time after 2 weeks, she had florid hyperthyroidism. This explained many of the child's clinical features (poor weight gain, tachycardia, exophthalmos). Both mother and child had raised TSH receptor antibodies (mother: 684.6 U/l; 54.1 U/l, normal < 15 U/l), an increased free T4 and a suppressed TSH. Because of the tachycardia, the child was treated with propranolol (1 mg/kg.d for 5 weeks). He was also initially given Lugol's solution (25 mg iodide/kg.d for 1 week) and then propylthiouracil (7 mg/kg.d) because of the increasing total T3. L-Thyroxine replacement was subsequently required for a period of 2.5 weeks because of treatment-related hypothyroidism. Since stopping treatment (at 12 weeks of age), the child has developed normally.--Neonatal hyperthyroidism due to transplacental transfer of TSH receptor antibodies associated with maternal Graves' disease is a rare self-limiting condition. However, it may pose considerable danger to the child both in utero and postnatally (with a mortality if untreated of up to 20%). Interdisciplinary cooperation is essential.

Topics: Adult; Bilirubin; C-Reactive Protein; Drug Therapy, Combination; Female; Graves Disease; Hepatomegaly; Humans; Hyperthyroidism; Infant, Newborn; Iodides; Jaundice, Neonatal; Male; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Receptors, Thyrotropin; Solutions; Splenomegaly; Thrombocytopenia; Thyroid Hormones; Thyrotropin; Thyroxine

Topics: Aged; Agranulocytosis; Bone Marrow; Heart Failure; Humans; Hyperthyroidism; Leukocyte Count; Male; Propylthiouracil

To study the regulation of carnitine palmitoyltransferase-I by thyroid hormone, a cDNA was obtained by PCR amplification of DNA obtained by reverse transcription of rat liver RNA. CPT-I mRNA abundance was measured in livers of hyperthyroid, euthyroid and hypothyroid rats. In hypothyroid rats, the CPT-I mRNA levels decreased 40-fold relative to that of the hyperthyroid animals. These changes paralleled alterations in enzyme activity. These data suggest that CPT-I is regulated at the transcriptional level by thyroid hormone.

Topics: Animals; Blotting, Northern; Carnitine O-Palmitoyltransferase; Gene Expression; Gene Expression Regulation, Enzymologic; Hyperthyroidism; Hypothyroidism; Kinetics; Liver; Male; Mitochondria, Liver; Polymerase Chain Reaction; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Substrate Specificity; Thyroid Hormones; Transcription, Genetic

The soluble CD antigens sCD8, sCD23, and sCD25 are increased in untreated Graves' hyperthyroidism. These levels remain elevated when euthyroidism is established in response to propylthiouracil (PTU) therapy but decrease to control values after PTU treatment is discontinued, when euthyroidism has been established and maintained. Neither sCD8 nor sCD23 are elevated in patients with euthyroid Graves' ophthalmopathy nor in the hyperthyroid phase of subacute thyroiditis. sCD25 is increased to an intermediate degree in these disorders. Soluble CD8 > or = 450 U/ml is sensitive, specific, and predictive of PTU success as sole therapy or need for definitive therapy in untreated and PTU-treated Graves' hyperthyroidism, exceeding the predictive values of thyroid-stimulating hormone receptor antibody, thyroid peroxidase antibody, and T3 radioimmunoassay.

Topics: Adult; Aged; Antibodies; Antigens, CD; CD8 Antigens; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Hyperthyroidism; Iodide Peroxidase; Iodine Radioisotopes; Male; Middle Aged; Predictive Value of Tests; Propylthiouracil; Radioimmunoassay; Receptors, IgE; Receptors, Interleukin-2; Receptors, Thyrotropin; Thyroiditis

Propylthiouracil, which is commonly used in the treatment of hyperthyroidism, has been associated in adults with antineutrophil cytoplasmic autoantibody, a serologic marker of vasculitis. Severe renal disease has not been reported as a complication of therapy with this drug. We report severe antineutrophil cytoplasmic autoantibody-positive vasculitis in children receiving propylthiouracil, as well as rapidly progressive crescentic glomerulonephritis after administration of this drug.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Child; Female; Glomerulonephritis; Humans; Hyperthyroidism; Male; Propylthiouracil

Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy.. Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism.. The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery.. Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Topics: Chi-Square Distribution; Cohort Studies; Congenital Abnormalities; Female; Follow-Up Studies; Humans; Hyperthyroidism; Incidence; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Prospective Studies; Radioimmunoassay; Retrospective Studies; Thyroxine; Triiodothyronine

In propylthiouracil (PTU)-fed (g/kg feed) hypothyroid cockerels, serum levels of growth hormone (GH), but not insulin-like growth factor (IGF)-1, tended to rise and those of IGF-binding activity to fall. Thyroxine (T4) supplement (200 micrograms/kg/day) to PTU-fed cockerels for 8 days produced a hyperthyroid state and reversed these serum parameters. A chromatographic analysis of serum proteins revealed that T4 supplement markedly enhanced the IGF-binding activity of a 30 kDa protein and slightly lowered that of a 150 kDa protein, suggesting that T4 increases unsaturated IGF-binding proteins by reducing circulating IGF-1 concentrations.

Topics: Animals; Animals, Newborn; Blood Proteins; Body Weight; Carrier Proteins; Chickens; Hyperthyroidism; Hypothyroidism; Insulin-Like Growth Factor Binding Proteins; Iodine Radioisotopes; Male; Organ Size; Propylthiouracil; Protein Binding; Somatomedins; Thyroid Gland; Thyroxine; Triiodothyronine

Vasculitis is a rare complication of propylthiouracil therapy. Antineutrophil cytoplasmic antibodies (ANCA) have been described in association with several vasculitic disorders. We report detection of ANCA against human neutrophil elastase, proteinase 3, and myeloperoxidase in serum from six patients who developed evidence of vasculitis during propylthiouracil treatment of hyperthyroidism. On withdrawal of the drug ANCA concentrations fell and clinical symptoms resolved completely.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Female; Humans; Hyperthyroidism; Immunoglobulin G; Middle Aged; Propylthiouracil; Vasculitis

To further elucidate the mechanism of increased serum ferritin levels in hyperthyroidism, the changes in erythrocytes and serum iron and total iron-binding capacity levels were examined in addition to serum ferritin levels in 13 hyperthyroid patients. The mean values of hemoglobin, red blood cells, and packed cell volume were increased by antithyroid therapy. While the serum levels of iron did not change, those of total iron-binding capacity increased significantly after achieving a euthyroid state. Increased serum ferritin levels returned to normal through antithyroid therapy. Furthermore, the serum ferritin levels of four anemic patients were significantly higher than those of nine nonanemic patients. Thus it is concluded that the increase in serum ferritin levels in patients with hyperthyroidism may be due to the direct action of thyroid hormones on its synthesis, while in some cases complicated with anemia impaired iron utilization by erythropoietic cells may also be involved.

Topics: Adult; Anemia; Erythrocyte Count; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Hyperthyroidism; Iron; Male; Methimazole; Middle Aged; Propylthiouracil

Aiming to know the incidence and evolution of major adverse reactions to propylthiouracil in patients with hyperthyroidism, we performed a retrospective analysis of 586 patients treated between 1982 and 1992. All known complications associated to the use of propylthiouracil were considered major adverse reactions, when other causes were discarded. Eight patients (1.4% of the sample) had major adverse reactions: three had agranulocytosis, 3 hepatitis, 1 cholestasis and 1 vasculitis. All had a good evolution after discontinuing the drug. The patients with agranulocytosis were treated with antibiotics and the patient with cholestasis received prednisone. We conclude that major adverse reactions to propylthiouracil are infrequent, that they occur preferentially during the first months of treatment, earlier after reexposure and that there was no associated mortality.

Topics: Adolescent; Adult; Agranulocytosis; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Vasculitis

Autoimmune thyroid disease has multiple manifestations and its presentation may change with time. We report two patients with primary hypothyroidism due to Hashimoto's disease that unexpectedly, developed a hyperthyroidism due to Basedow-Graves disease. This phenomenon may be explained by variations in the types and proportions of anti TSH receptor antibodies, that can stimulate or block thyroid gland function and growth. It is deducted that the hypothyroidism of these patients was not due to a definitive gland destruction, but to the action of function blocking antibodies.

Topics: Adult; Autoimmune Diseases; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine

The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30 cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after normalization of the thyroid state. Treatment of hyperthyroidism increased the mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P < 0.002); at the same time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to 3.7 mmol/L, P < 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17 g/L, P < 0.0005). In hypothyroidism, the opposite changes were observed: mean Lp(a) decreased from 136 to 114 mg/L (10%, P < 0.02), LDL-C from 4.6 to 3.9 mmol/L (13%, P < 0.01), and apo B from 1.51 to 1.20 g/L (14%, P < 0.01). Although the changes in Lp(a) concentrations did correlate with changes of LDL-C during treatment of hyperthyroidism (r = 0.43, P < 0.05), and with changes in apo B during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P < 0.05), we observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state. These data cannot rule out the possibility that the thyroid hormone-induced increase in LDL-C receptor activity was responsible for the decreased concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30% of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C-receptor-independent pathway, the present data suggest a direct effect of thyroid hormones on Lp(a) synthesis.

Topics: Adult; Aged; Apolipoproteins B; Cholesterol, LDL; Female; Humans; Hyperthyroidism; Hypothyroidism; Lipoprotein(a); Male; Methimazole; Pregnancy; Propylthiouracil; Thyroxine

The rat pituitary pars tuberalis (pt) is a functional and morphological unique component of the adenohypophysis. It mainly consists of specific secretory cells whose morphological and functional characterization is far from being complete. In this study the ultrastructure of fetal secretory pt cells developing under hypo- and hyperthyroid conditions was examined. Besides controls, young mature pregnant Wistar rats were treated with propylthiouracil (PTU) or thyroxine (T4). Areas of pt cells and of their nuclei were measured. Different cell organelles per cell were counted, and area densities of these organelles were determined. While the number of dictyosomes per cell area did not change, the area densities of long ribbons increased significantly in the experimental groups. Lysosomes and secretory granules, however, were found to be significantly diminished in pt cells of T4- and PTU-treated animals. The latter finding corresponds to earlier investigations when changes of the thyroid-stimulating-hormone-like immunoreactivity of fetal pt-specific cells were observed under the same experimental conditions. Results indicate that fetal pt-specific cells respond to changes of thyroid status in a manner different from pars distalis thyrotrophs. An interaction of pt-specific cells in thyroid regulation mechanisms is assumed.

Topics: Animals; Cytoplasmic Granules; Female; Hyperthyroidism; Hypothyroidism; Lysosomes; Microscopy, Electron; Pituitary Gland; Propylthiouracil; Rats; Rats, Wistar; Thyroxine

This study was designed to examine the involvement of thyroid hormone in the release of brain natriuretic peptide (BNP) from the heart. We measured plasma immunoreactive BNP (ir-BNP) concentrations in patients with untreated hyperthyroidism. We also measured BNP values in experimental rats with hyperthyroidism induced by thyroxine (T4) and in rats with hypothyroidism induced by propylthiouracil (PTU). The in vitro effects of triiodothyronine (T3) and T4 on the release of BNP were examined in newborn rat atrial and ventricular myocytes in primary culture. Plasma BNP levels were increased in hyperthyroid patients compared with normal control subjects. Plasma BNP levels were increased in hyperthyroid rats and decreased in hypothyroid rats compared with euthyroid rats. Plasma BNP level was correlated with serum T4 level in hyperthyroid patients and hyperthyroid rats. A major component of ir-BNP in plasma from hyperthyroid patients was human BNP-32 and that in plasma from hyperthyroid rats was rat BNP-45. T4 and T3 stimulated release of ir-BNP from both cultured atrial and ventricular myocytes in a dose-dependent manner. Plasma BNP concentration is frequently increased in hyperthyroidism, and thyroid hormone may regulate BNP release from both atrial and ventricular myocytes.

Topics: Adult; Animals; Atrial Natriuretic Factor; Brain Chemistry; Cells, Cultured; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Myocardium; Propylthiouracil; Radioimmunoassay; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

We have used in situ hybridization histochemistry to determine the effect of hippocampal-hypothalamic disconnection on hypothalamic thyrotrophin-releasing hormone (TRH) and anterior pituitary thyrotrophin beta subunit (TSH beta) transcripts in adult male CFY rats. Electrothermal lesions of the fornix pathway significantly increased TRH and TSH transcripts and increased circulating levels of triiodothyronine (T3). Fornix transection did not, however, prevent feedback regulation of TRH and TSH transcripts during exogenous T3-induced hyperthyroidism or propylthiouracil-induced hypothyroidism. Hippocampal inputs to the hypothalamus contribute to setting the basal activity of the thyroid axis, but do not mediate the feedback effects of T3.

Topics: Animals; Base Sequence; Gene Expression; Hippocampus; Hyperthyroidism; Hypothalamus; Hypothyroidism; In Situ Hybridization; Male; Molecular Sequence Data; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Anterior; Propylthiouracil; Rats; RNA, Messenger; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine

The genes coding for apolipoproteins A-I, C-III, and A-IV are closely linked to one another in the rat genome. Thyroid hormone stimulates apoA-I expression in rat liver by an unusual mechanism that enhances the maturation of mRNA. This hormone also increases apoA-IV mRNA abundance by a mechanism not yet studied, and its role in the expression of apoC-III has not been defined but may be of relevance to the metabolism of triglyceride-rich lipoproteins. We therefore measured the transcriptional activity of the apoA-IV and apoC-III genes and the abundance of their nuclear RNA and total cellular mRNA in livers of control rats and rats made hyper- and hypothyroid. After a single receptor-saturating dose of triiodothyronine (3 mg/100 g body weight), apoA-IV gene transcription increased at 20 min and reached a maximum of 260% of control at 6 h. Increases of transcription were reflected in increases of nuclear and total apoA-IV mRNA levels. ApoC-III gene transcription was temporarily increased to 160% at 2 h without changes in the abundance of its nuclear or total mRNA over 24 h. Lower hormone doses (20-500 micrograms/100 g body weight) stimulated apoA-IV mRNA transcription as well, but tended to reduce transcription from the apoC-III gene. Upon chronic administration of thyroid hormone, apoA-IV transcription decreased to 55% and nuclear apoA-IV RNA levels to 87% of control. However, total cellular apoA-IV mRNA levels increased to 279% of control, implying stabilization of mRNA in the cytoplasm. ApoC-III transcription decreased to 28% of control, but abundance of nuclear and total cellular apoC-III mRNA was reduced to a lesser extent. In hypothyroid rats, apoA-IV gene expression was decreased fourfold at the transcriptional level. In contrast, apoC-III gene transcription increased to 178% of control, but the abundance of nuclear and total cellular apoC-III mRNA did not differ from control rats. Thus, thyroid hormone affects the abundance of apoA-IV mRNA by changing its synthesis and its rate of degradation and enhances the efficiency of apoC-III mRNA maturation, thereby blunting the net effect of altered mRNA synthesis on mRNA abundance.

Topics: Animals; Apolipoprotein C-III; Apolipoproteins A; Apolipoproteins C; Base Sequence; Blotting, Northern; Gene Expression; Hyperthyroidism; Hypothyroidism; Kinetics; Liver; Male; Molecular Sequence Data; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transcription, Genetic; Triiodothyronine

To evaluate the incidence, severity, and course of propylthiouracil-induced hepatic injury in patients with hyperthyroidism.. Cohort study.. Outpatient clinic of a university-based hospital.. Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism.. Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d.. Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate.. Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill-defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/- 0.39 nmol/L, P = 0.048).. Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia.

Topics: Adult; Alanine Transaminase; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Cohort Studies; Female; Hepatitis, Viral, Human; Humans; Hyperthyroidism; Incidence; Liver; Liver Diseases; Male; Propylthiouracil; Severity of Illness Index

Thyroid hormone status has profound effects on signal transduction in various tissues throughout the body. Therefore, we quantified the signal transducing G-proteins in the rat heart, cerebral cortex, vas deferens and liver by immunoblotting and pertussis toxin labeling in response to chemically induced hypothyroidism (treatment with propylthiouracil) and hyperthyroidism (treatment with triiodothyronine). Levels of the pertussis toxin (PTX) substrates Gi alpha and Go alpha in the heart and vas deferens were inversely correlated with thyroid hormone levels, i.e. Gi alpha and Go alpha were decreased or unchanged in hyperthyroid rats and increased in hypothyroid rats compared to control animals. The cerebral cortex and liver expression of PTX substrates Gi alpha and Go alpha was not affected by changes in thyroid hormone. Regulation of Gs alpha protein was more complex in that Gs alpha was unaffected in the other tissues tested. Expression of G-protein beta-subunits was not affected by thyroid status in the heart, liver, or cerebral cortex. Our results suggest that tissue- and G-protein-specific factors are involved in the regulation of G-protein subunits by thyroid hormone. Moreover, cardiac expression of Gs alpha is upregulated by increases or decreases in the normal level of thyroid hormone.

Topics: Animals; Cerebral Cortex; Gene Expression Regulation; GTP-Binding Proteins; Hyperthyroidism; Hypothyroidism; Liver; Male; Muscle, Smooth; Myocardium; Propylthiouracil; Rats; Rats, Wistar; Thyroid Hormones; Triiodothyronine

The chance of permanent remission after prolonged drug therapy was investigated in 41 patients with toxic multinodular goiter. For purposes of comparison a group of 41 patients with Graves' disease was also studied. After euthyroidism was achieved all patients received a combination of thionamide and thyroxine for at least 12 months. The minimum follow-up period was 2 yr. Relapse of thyrotoxicosis occurred in 95.1% of patients with toxic multinodular goiter and 34.1% of patients with Graves' disease (p < 0.001). It is concluded that for patients with toxic multinodular goiter early radioiodine therapy or surgery is preferred since prolonged drug therapy seldom produces permanent remission.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Drug Therapy, Combination; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Radionuclide Imaging; Recurrence; Thyroid Gland; Thyroxine

Rats were made hypo and 'hyperthyroid' with propylthiouracil (PTU) and L-Thyroxine (L-T) respectively. The hypo and hyperthyroid status in these rats were confirmed by serum level of T4 and T3. Liver iron was significantly increased in both the hypo and hyperthyroid animals. However, liver ferritin synthesis rate was reduced by 36% in hypothyroid rats, and elevated by 38% in hyperthyroid ones. A similar trend was seen in liver ferritin concentration. Further, serum transaminases were elevated only in animals of the hyperthyroid group. It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron. Thus, the raised serum ferritin in hyperthyroid patients may be partially attributed to increased ferritin synthesis in the liver and its possible leakage into circulation.

Topics: Albumins; Animals; Ferritins; Hyperthyroidism; Hypothyroidism; Iron; Kinetics; Liver; Male; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland; Thyroid Hormones; Thyroxine; Triiodothyronine

5'-Nucleotidase was measured in isolated fat cells from normal, hypothyroid and hyperthyroid rats. This was done to find out whether thyroid hormones had an effect on the production of adenosine by the fat cell. The results showed that 5'-nucleotidase is modified when the rats received injections of 3,3',5-triiodo-L-thyronine (T3). There was no change in the enzyme in hypothyroidism or when T3 was added to incubation of cells.

Topics: 5'-Nucleotidase; Adipose Tissue; Animals; Cells, Cultured; Hyperthyroidism; Hypothyroidism; Inosine Monophosphate; Kinetics; Male; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland; Triiodothyronine

To evaluate the role of perinatal thyroid status in the development of pituitary-thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.

Topics: Aging; Animals; Animals, Newborn; Fetus; Hyperthyroidism; Hypothyroidism; Pituitary Gland; Propylthiouracil; Rats; Rats, Sprague-Dawley; Reference Values; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

We undertook this study to investigate respiratory muscle strength in relation to thyroid function in 20 thyrotoxic patients and in a group of 20 normal subjects matched for age and sex. Global respiratory muscle strength was assessed by measuring mouth pressure during maximal static inspiratory (PImax) and expiratory (PEmax) efforts. We also measured VC, FVC, and FEV1 as well as thyroid-related hormones (T3, T4, TSH). Measurements were made once in normal subjects and twice in thyrotoxic patients, before and 3 months after medical treatment. Our results showed that both maximal pressures were significantly reduced (p less than 0.0001) before treatment in thyrotoxic patients in relation to the mean values of the normal subjects (p less than 0.0001), and they increased significantly (p less than 0.0003) after treatment. Lung volumes were significantly reduced (p less than 0.0001) before and increased significantly (p less than 0.008) after treatment. The ratio FEV1/FVC did not change. A statistically significant linear relationship was found when PImax of patients with thyrotoxicosis before treatment and of normal subjects were plotted against thyroid hormones (T3, T4) (r = -0.746 and r = -0.745, respectively, p less than 0.001). Similarly, a statistically significant linear relationship was found between PEmax and T3 and T4 (r = -0.837 and r = -0.838, respectively, p less than 0.001). No relationship was found between maximal pressures and TSH. Finally, a significant linear relationship was found between PImax and PEmax (r = 0.872, p less than 0.001). Our results confirm that in thyrotoxicosis respiratory muscle weakness occurs that affects both inspiratory and expiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Humans; Hyperthyroidism; Lung Volume Measurements; Male; Methimazole; Propylthiouracil; Respiratory Function Tests; Respiratory Muscles; Thyroid Gland; Thyroid Hormones; Time Factors

A highly sensitive, specific, and reproducible RIA has been developed to measure rat type I iodothyronine 5'-monodeiodinase (5'-MD). A 16-amino acid peptide (LAP-744) corresponding to a portion of the carboxy-terminal region of the rat liver 5'-MD, as predicted from its cDNA, was synthesized, and rabbits were immunized with the peptide-BSA conjugate. In a final dilution of 1:15,000, our anti-5'-MD antibody bound about 30-35% of a tracer amount of [125I]LAP-744. The detection threshold of the RIA approximated 0.08 pmol LAP-744 or an equivalent amount of 0.08 pmol 5'-MD. Rat liver and kidney microsomes produced dose-response curves that were essentially parallel to that of LAP-744. No inhibition of binding of [125I]LAP-744 to antibody was produced by 0.3 mg or less rat microsomal proteins from testes, heart, brain, muscle, spleen, intestine, lung, placenta, or fetal liver. Recovery of nonradioactive LAP-744 added to spleen microsomes averaged 103%. The coefficient of variation averaged 4% within an assay and 11% between assays. In 16 normal rats studied, the mean (+/- SD) 5'-MD content was 2.4 +/- 0.22 pmol/mg protein in liver microsomes and 2.5 +/- 0.27 pmol/mg protein in kidney microsomes. Fasting of the rat for 2-4 days was associated with a significant reduction in both the activity and the content of the 5'-MD in liver and kidney. Hypothyroidism was also associated with a significant decrease in the activity and content of 5'-MD in both tissues. Significant opposite changes were observed in these parameters in hyperthyroidism. Treatment of the rat with sodium ipodate for 3 days was associated with a significant decrease in both the activity and the content of 5'-MD in liver and kidney. A similar treatment of the rat with propylthiouracil induced a clear reduction in the activity of 5'-MD in liver and kidney, but the content of the enzyme was significantly increased in both tissues. Rats treated with aurothioglucose for 3 days exhibited a significant decrease in 5'-MD activity in liver and kidney microsomes, whereas the tissue content of 5'-MD was not affected. A similar treatment of the rat with methimazole had no significant effect on either the activity or the content of 5'-MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Amino Acid Sequence; Animals; Fasting; Female; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Ipodate; Kidney; Liver; Male; Methimazole; Microsomes; Microsomes, Liver; Molecular Sequence Data; Organ Specificity; Peptide Fragments; Propylthiouracil; Radioimmunoassay; Rats; Rats, Sprague-Dawley

The microheterogeneity of pituitary thyroid-stimulating hormone (TSH) is dependent on variations in the hormone's carbohydrate moieties. In this study, changes in the pattern of heterogeneity have been assessed by chromatofocusing, which separates the isospecies on the basis of their isoelectric points (pI). Rats (n = 6 per group) were either untreated or rendered hypo- or hyperthyroid by including in the drinking water either propylthiouracil (0.05% for 8 weeks) or thyroxine (T4; 4 mg/l for 6 weeks) before they were killed at 16 weeks. On autopsy, serum TSH and total T4 were (means +/- S.E.M.): 2 +/- 0.3 micrograms TSH/l and 64 +/- 5 nmol T4/l (control); < 1 microgram TSH/l and 133 +/- 6 nmol T4/l (hyperthyroid); 58 +/- 6 micrograms TSH/l and 32 +/- 6 nmol T4/l (hypothyroid). The pituitaries were individually homogenized and the TSH isoforms separated by chromatofocusing over a pH range of 7-4. Fractions were assayed for TSH by radioimmunoassay. TSH from the control group was distributed into seven major peaks with pI values of (means +/- S.E.M., n = 6) 6.9 +/- 0.1, 6.6 +/- 0.1, 6.2 +/- 0.1, 5.8 +/- 0.1, 5.5 +/- 0.1, 5.2 +/- 0.1 and 4.8 +/- 0.1; 7 +/- 3% of the TSH had a pI of < 4.0. Six peaks of TSH were conserved in the hypothyroid group (with pI values of 6.8 +/- 0.1, 6.5 +/- 0.1, 6.2 +/- 0.1, 5.8 +/- 0.1, 5.4 +/- 0.1 and 5.2 +/- 0.1), and 11 +/- 4% of the hormone had a pI of < 4.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Hyperthyroidism; Hypothyroidism; Isoelectric Point; Male; Pituitary Gland; Propylthiouracil; Rats; Rats, Sprague-Dawley; Thyrotropin; Thyroxine

We report on a 74-year-old female patient with primary hemochromatosis complicated by hyperthyroidism. The serum ferritin level was reduced throughout a 217 day administration of deferoxamine (1 g/day). At the same time, the thyroid gland was changed from hyper- to hypo- functional proportionally.

Topics: Aged; Deferoxamine; Female; Hemochromatosis; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Function Tests

Based on the characteristics of the visible spontaneous luminiscence of human urine, we propose that this luminescence is due to the dark decomposition of long-lived luminescent intermediates produced by oxidations at the cellular level, and that it might reflect the development of oxidative stress conditions in vivo. This hypothesis is consistent with the higher emission levels monitored in the urine of hyperthyroid patients and the correlation observed between urinary thiobarbituric acid reactive substances (TBARS) levels and urinary chemiluminescence.

Topics: Free Radicals; Humans; Hydrogen-Ion Concentration; Hyperthyroidism; Lipid Peroxidation; Luminescent Measurements; Models, Biological; Oxidation-Reduction; Propylthiouracil; Urine

We report a patient who underwent, over a mere 3-year period, three successive cycles of oscillation from hypo to hyper-thyroidism and back to hypothyroidism. This unusual sequence of events originated in a rare passage of primary hypothyroidism to hyper-thyroidism. The hyperthyroidism seemed typical of the autoimmune subgroup of toxic multinodular goitre. Stimulating and blocking TSH receptor antibody activities were measured (by cAMP functional bioassays using cultured human thyrocytes) during the course of the fluctuating phases of hypo and hyper-thyroidism. Measurement of such antibody activities revealed the coexistence of both stimulatory and blocking types of antibody in several serum samples from the patient. Throughout the whole course of alterations in thyroid function, thyroid stimulating antibodies were present. This was not the case with thyrotrophin receptor antibodies exhibiting TSH antagonist activity which seemed to appear and disappear. Monitoring such activity indicated that the emergence of blocking antibody seems to herald the onset of hypothyroidism.

Topics: Autoantibodies; Autoimmune Diseases; Biological Assay; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Recurrence; Thyroid Function Tests; Thyroxine

Twenty-nine patients (22 female) aged 2 to 17 years were followed with serial measurements of serum triiodothyronine, thyroxine, and thyrotropin during medical therapy for Graves disease. Fourteen patients had 17 instances of hypothalamic-pituitary-thyroid suppression with inappropriately low thyrotropin levels. Five patients had six episodes of low thyroxine and triiodothyronine levels with normal levels of thyrotropin, and 10 patients had 11 episodes of normal thyroxine and triiodothyronine levels with subnormal levels of thyrotropin. We conclude that thyrotropin values may not be reliable for diagnosing either mild hypothyroidism or persistent hyperthyroidism during the medical treatment of Graves disease.

Topics: Adolescent; Child; Child, Preschool; Female; Graves Disease; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Methimazole; Propylthiouracil; Retrospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

While angina is not uncommonly seen in association with hyperthyroidism, only rare case reports have suggested that myocardial ischemia in this state may be due to coronary artery spasm. The authors review the literature and describe a case in which the repetitive occurrence of episodes of myocardial ischemia due to coronary spasm correlated with repeated transient elevations in thyroid hormone levels, thus clarifying this relationship. The importance of defining thyroid status in patients presenting with coronary vasospasm is emphasized and the effects of thyroid hormone on the heart are reviewed.

Topics: Coronary Vasospasm; Electrocardiography; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Middle Aged; Nitroglycerin; Propylthiouracil; Thyroxine; Triiodothyronine

Neonatal hyperthyroidism is only seen in children whose mothers had an autoimmune thyroid disease. In these women, thyroid stimulating immunoglobulins (TSI) must be assayed during pregnancy, so that the newborn can be taken care of immediately. Contrary to thyroid hormones, TSI cross the placental barrier and are responsible for thyrotoxicosis; regular monitoring of their decrease in the newborn indicates that these antibodies are of maternal origin. In both mother and child, the treatment of choice is a synthetic antithyroid drug.

Topics: Autoantibodies; Carbimazole; Female; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Male; Pregnancy; Propranolol; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Beta-blockers and calcium antagonists have been advocated for thyrotoxicosis induced tachyarrhythmias. Amiodarone is generally considered as contraindicated because of its high iodine content. Since amiodarone combined with propylthiouracil induced a greater fall in serum thyroid hormone concentrations than propylthiouracil alone, we treated 2 hyperthyroid patients with supraventricular arrhythmias by radioiodine (day 0) followed after 24 h by amiodarone and propylthiouracil. Serum T3 was normalized on day 2 (patient 1) and 3 (patient 2). Effective t1/2 of intrathyroidal 131I were 6.6 and 4.3 days (versus 5.9 days for 131I given alone). In patient 1, atrial fibrillation, reverted to sinus rhythm after verapamil and digoxin, and did not recur. In patient 2, conversion of atrial fibrillation to sinus rhythm occurred on day 11; from day 0 to day 11, ventricular rate decreased and was significantly correlated to T3 (r = 0.82; p < 0.05). In conclusion, amiodarone may be beneficial in thyrotoxicosis associated tachyarrhythmias, given with propylthiouracil 24 h after radioiodine, it did not decrease thyroid irradiation and rapidly decreased serum T3.

Topics: Adult; Aged; Amiodarone; Combined Modality Therapy; Female; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Male; Propylthiouracil; Tachycardia, Supraventricular; Thyroxine; Triiodothyronine

Topics: Chelation Therapy; Edetic Acid; Humans; Hyperthyroidism; Male; Mercury Poisoning; Middle Aged; Propylthiouracil

To study quantitatively actions of thyroid hormones on maturation of olfactory receptor neurons (ORN), surface density and total number of receptor knobs (1 knob/ORN) were measured in 1 mu sections from septal olfactory epithelium of newborn, 12- and 25 day normal, hypo- and hyperthyroid rats. Hypothyroidism was induced by adding to drinking water n-propylthiouracil (0.1% w/v) from birth. Hyperthyroidism was induced by daily injection of pups with T4 (1-thyroxine, 0.3 microgram/g b.w., s.c.). Experimental pups showed all the signs of hypo- and hyperthyroidism. Between days 1-25, normal pups showed marked increase in surface area of septal olfactory epithelium (6x), total number (12x) and surface density (#/mm2, 2x) of mature ORNs. Thyroid deficient rats showed, by day 12, marked reductions in epithelial surface area and total number of mature ORNs; these and the surface density deficits became very pronounced by 25 day (30% area, 27% density, 47% # mature ORNs). Hyperthyroid rats, however, did not show an increase in any of these parameters over controls. Although total number of ORNs (mature and immature), as measured by number of nuclei, was also reduced in hypothyroid pups, surface density was not altered, indicating that maturation of ORNs, but not their local accretion is altered in thyroid deficiency. The results indicate that thyroid hormones are essential for normal proliferative expansion of olfactory epithelium and for maturation of ORNs postnatally. These actions of thyroid hormones are not increased or accelerated by excess T4 suggesting saturation of the hormone receptor system at the normal plasma level.

Topics: Animals; Animals, Newborn; Cell Division; Cell Nucleus; Dendrites; Female; Hyperthyroidism; Hypothyroidism; Nasal Mucosa; Neurons, Afferent; Pregnancy; Propylthiouracil; Rats; Rats, Inbred Strains; Smell; Thyroid Hormones; Thyroxine

Previous studies have demonstrated that in different cardiac preparations action potential duration (APD) increases with age. As in various species, thyroid hormone levels increase developmentally, and since hyperthyroidism shortens APD while hypothyroidism prolongs it, we hypothesized that developmental changes in APD result from age-related variations in the thyroid state. The hypothesis was tested by analysing ventricular action potentials and total T4 (TT4) levels in guinea-pigs in the age range of 0 days to 3 months (adult), and in hyperthyroid and hypothyroid newborns (0-5 days old). We found that APD50 increased exponentially with age with a time constant of 6.7 days, from 100.6 +/- 3.4 ms in newborns (0-5 days old) to 147.4 +/- 5.2 ms in adults (P less than 0.001). TT4 decreased exponentially with age with a time constant of 4.8 days, from 3.9 +/- 0.4 micrograms/dl in newborns to less than 1.0 microgram/dl in adults. In the age range studied, APD50 and TT4 were linearly correlated: Y = -12.13X + 142, r - 0.865. In contrast to the marked changes in APD, resting potential and action potential amplitude were age-independent, and Vmax only slightly increased with age. Alterations in the thyroid state in newborns affected ventricular action potentials as predicted by the hypothesis. In euthyroid (TT4 = 3.9 +/- 0.4 micrograms/dl), hypothyroid (TT4 = 1.6 +/- 0.4 micrograms/dl) and hyperthyroid (TT4 = 39.8 +/- 10.8 micrograms/dl) newborns, APD50 was: 100.6 +/- 3.4 ms, 117.7 +/- 4.2 ms and 63.7 +/- 7.4 ms, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Aging; Animals; Animals, Newborn; Guinea Pigs; Hyperthyroidism; Hypothyroidism; Papillary Muscles; Propylthiouracil; Thyroxine; Triiodothyronine; Ventricular Function

Amiodarone (Cordarone) has been proven to be useful in the management of atrial fibrillation. However, because of a large iodine content, this drug is not used in this complication of thyrotoxicosis. We previously have observed a greater fall in serum T3 and T4 concentrations in hyperthyroid patients treated with amiodarone and methimazole than with methimazole alone. In the present study, we determined whether the addition of amiodarone to propylthiouracil (PTU) could improve the levels of circulating thyroid hormones in hyperthyroid patients, and we assessed the release of iodide from amiodarone by measuring the 24 h urinary iodine excretion. Twelve hyperthyroid patients were treated either with PTU, 600 mg daily for 10 days (group PTU), or with amiodarone (A), 1200 mg daily for 3 days in addition to PTU (group A-PTU). Basal serum T4, T3, and rT3 concentrations (mean +/- SEM) were respectively 206 +/- 13 nmol/L, 5.13 +/- 0.8 nmol/L, and 81 +/- 7 ng/dL for group PTU and 238 +/- 39 nmol/L, 4.73 +/- 1.06 nmol/L, and 84 +/- 12 ng/dL for group A-PTU (NS). In group A-PTU, plasma amiodarone peaked on day 3 (mean +/- SEM: 0.48 +/- 0.11 mg/L), and urinary iodine reached 5.27 +/- 1.28 mg/day on day 5. The fall in serum T3 and the increase in serum rT3 concentrations were significantly greater in group A-PTU than in group PTU (ANOVA, p less than 0.05). In group A-PTU, the minimal serum T3 concentration was observed on day 5 of treatment (28 +/- 6% of the pretreatment values).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amiodarone; Analysis of Variance; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodine; Male; Middle Aged; Propylthiouracil; Thyroxine; Triiodothyronine

The effects of a chronic treatment with L-triiodothyronine (T3; 100 mg/rat/day s.c. for 7 days) or with propylthiouracil (PTU; 50 mg/rat/day for 35 days by stomach tube) on the characteristics of alpha 1, alpha 2, beta, imipramine and GABA binding sites in different brain areas of the adult rat have been studied. T3-treatment caused an increase in the number of [3H]dihydroalprenolol and a decrease in the number of [3H]muscimol binding sites in the cerebral cortex. PTU-treatment caused a decrease in the number of [3H]prazosin, [3H]yohimbine and [3H]dihydroalprenolol binding sites in the cerebral cortex, while the number of [3H]imipramine binding sites was reduced in the cerebral cortex and hypothalamus, and increased in the hippocampus. Affinity constants were never modified. Concurrent experiments showed that the "in vitro" addition of T3 and PTU did not influence the binding of any of the ligands employed to control rat brain membranes. The present data further support the view that neurotransmission in the CNS is influenced by the thyroid status.

Topics: Animals; Brain; Dihydroalprenolol; Hyperthyroidism; Hypothyroidism; Imipramine; Kinetics; Male; Muscimol; Organ Specificity; Prazosin; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Receptors, GABA-A; Reference Values; Thyroid Gland; Triiodothyronine; Yohimbine

The photoreactive compound p-nitrophenyl-2-diazo-3,3,3-trifluoropropionate (PAL) was coupled to [125I]rT3, T4, or T3 and incubated with liver and kidney microsomes of hypo-, hyper-, or euthyroid rats to identify the type I iodothyronine deiodinase. Various substrates or inhibitors of the enzyme, including rT3, T4, T3, 6-n-propylthiouracil (PTU), and iopanoic acid, were used as competitors to establish the specificity of protein labeling. The PAL derivatization enhanced the behavior of T4 and T3 as substrates for the type I enzyme. No specific labeling of microsomal proteins was observed with either rT3 or T4-PAL, presumably due to deiodination of the labeled compound. In contrast, T3-PAL labeled a 27-kDa band, the presence of which paralleled thyroid status. The labeling of only this protein was blocked by either substrates or enzyme inhibitors in a dose-dependent fashion, with a rank order of potency predicted by the activity of such compounds in type I enzyme assays. The specific nature of these competitions provides further evidence that this 27-kDa protein, identified in previous studies using N-bromoacetyl [125I]T3 or -T4, contains the active site of the rat type I deiodinase. This is in agreement with the mol wt of the rat type I deiodinase deduced from the recently identified cDNA coding for this protein.

Topics: Affinity Labels; Animals; Binding, Competitive; Diazonium Compounds; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Iopanoic Acid; Male; Molecular Weight; Photochemistry; Propionates; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The hemodynamics of six pregnant women with hyperthyroidism were studied before and after therapy. Cardiac output was measured by Doppler technique, and blood pressure by automated cuff. When compared with values in euthyroid pregnant women, blood pressure (83.6 mmHg, P less than .001), heart rate (89.2 beats per minute, P less than .001), cardiac output (11.2 L/minute, P less than .001), and stroke volume (123 mL, P less than .001) were significantly elevated. Total peripheral resistance was significantly reduced (609 dyne.second.cm-5, P less than .001). Despite normalization of thyroid indices after therapy, cardiac output remained markedly elevated (9.7 L/minute, P less than .001) and vascular resistance remained reduced (708 dyne.second.cm-5, P = .01). Although the hemodynamics of pregnant thyrotoxic women normalize with therapy, they remain significantly hyperdynamic.

Topics: Echocardiography, Doppler; Female; Hemodynamics; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Thyroid Function Tests

The effects of calmodulin antagonists on the capacity of hydrogen-translocating shuttles were studied in the perfused rat liver. The capacity was estimated by measuring the changes in the rate of production of glucose from sorbitol during the oxidation of ethanol [T. Sugano, T. Ohta, A. Tarui, and Y. Miyamae. Am. J. Physiol. 251 (Endocrinol. Metab. 14): E385-E392, 1986]. Thyroxine given to intact rats increased the activity of alpha-glycerophosphate dehydrogenase (alpha-GPD). Glucocorticoid replacement in adrenalectomized rats decreased the activity of the alpha-GPD to values obtained after treatment with PTU. In either thyroxine-treated or steroid-replaced rats, the capacity of hydrogen-translocating shuttles increased markedly. However, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), trifluoperazine, and chlorpromazine inhibited the increased capacity in steroid-replaced rats and had no effect on the increased capacity in thyroxine-treated rats. W-7 inhibited the stimulatory effects of norepinephrine on the capacity of the malate-aspartate shuttle without inhibition of efflux of intracellular Ca2+. The stimulatory effects of vasopressin on the malate-aspartate shuttle were also inhibited by W-7, trifluoperazine, and chlorpromazine. The results suggest that the malate-aspartate shuttle may be regulated by Ca(2+)-calmodulin.

Topics: Adrenalectomy; Alanine; Aminooxyacetic Acid; Animals; Asparagine; Calcium; Calmodulin; Chlorpromazine; Glycerolphosphate Dehydrogenase; Hyperthyroidism; Hypothyroidism; Liver; Male; Mitochondria, Liver; NAD; Oxidation-Reduction; Perfusion; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; Sorbitol; Sulfonamides; Thyroxine; Trifluoperazine; Triiodothyronine; Vasopressins

Topics: Amiodarone; Drug Therapy, Combination; Humans; Hyperthyroidism; Propylthiouracil

The possibility of inducing long-term or permanent remission of Graves disease with hyperthyroidism from combination therapy with glucocorticoids and antithyroid drugs is considered. A case report is presented in support of this hypothesis.

Topics: Drug Therapy, Combination; Female; Graves Disease; Humans; Hyperthyroidism; Middle Aged; Prednisone; Propranolol; Propylthiouracil

Topics: Adult; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Ultrasonography

Rat liver contains two topologically different TRH-degrading pyroglutamate aminopeptidases. The particulate pyroglutamate aminopeptidase, unlike the soluble one, was highly specific for TRH and shared many physico-chemical properties with serum thyroliberinase, which is controlled by thyroid hormones. Both enzymes convert pGlu His Pro NH2 into His Pro NH2; the latter may be cyclized to cyclo His Pro known to possess several biological activities and specific binding sites in liver. The aim of the present study was to determine the effects of thyroid status on the particulate and soluble enzymes activity and gain more insight into their biological role. The regulatory pathway for the particulate pyroglutamate aminopeptidase was found similar to that of serum thyroliberinase: their specific activities decrease in hypothyroid rats and increase in hyperthyroid rats, whereas that of soluble enzyme remains unchanged. We postulate that the particulate pyroglutamate aminopeptidase may be a determining factor in the concentrations of TRH and/or cyclo His Pro reaching liver cells and a possible source for serum thyroliberinase. Taken together, these data suggest that this "converting enzyme" acts as a physiological regulator.

Topics: Aminopeptidases; Animals; Dipeptides; Hyperthyroidism; Hypothyroidism; Isoflurophate; Kinetics; Liver; Male; Propylthiouracil; Pyroglutamyl-Peptidase I; Pyrrolidonecarboxylic Acid; Rats; Rats, Inbred Strains; Serine Endopeptidases; Thyrotropin-Releasing Hormone; Triiodothyronine

Adrenal tyrosine hydroxylase activation was elicited in developing control, hypo- and hyperthyroid rats by insulin-hypoglycaemia. Rats were deeply anaesthetized with chloroform at a low concentration, since intrinsic tyrosine hydroxylase activation was very low with this technique, as compared to Ketamine injection or chloroform at a high concentration. The study of time-course of tyrosine hydroxylase activation showed that the maximum value was observed 2 h after insulin administration. In control animals, tyrosine hydroxylase activation increased between 4 and 20 days, and then decreased. Hypothyroidism is associated with a decreased tyrosine hydroxylase activation between 4 and 50 days, as compared to controls and hyperthyroidism with an increased activation between 6 and 30 days. While tyrosine hydroxylase from saline-treated rats exhibits two different forms (with two apparent Km values for the cofactor), enzyme from insulin-treated animals was present in a single form with a Km corresponding to the low Km value of the saline-injected rats. At 6 and 14 days, hypothyroidism increases tyrosine hydroxylase Km values as compared to euthyroid animals.

Topics: Adrenal Glands; Age Factors; Animals; Animals, Newborn; Embryonic and Fetal Development; Enzyme Activation; Female; Hyperthyroidism; Hypothyroidism; Insulin; Pregnancy; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine; Tyrosine; Tyrosine 3-Monooxygenase

Prenatal plus neonatal administration of methimazole (MMI), a procedure provoking marked hypothyroidism in rats, increased by about 100% the thymic content of oxytocin and severely (by approximately 80%) decreased the thymus weight, compared to euthyroid counterparts. Adult-onset, propylthiouracyl (PTU)-induced hypothyroidism, while provoking thymic involution, or thyroxine (T4) hyperthyroidism, did not affect oxytocin concentrations. Thymic involution and increases in thymus oxytoxin could also be obtained with repeated administration of the potent glucocorticoid dexamethasone. However, since corticosterone, unless subchronically injected at largely supraphysiological doses, was previously shown to have no influence on thymic parameters of young adult rats, a major involvement of the neonatal adrenal axis in oxytocin alterations could be excluded. It is suggested that the ontogenesis of thymic oxytocin production is under thyroid control.

Topics: Aging; Animals; Animals, Newborn; Dexamethasone; Female; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Organ Size; Oxytocin; Propylthiouracil; Rats; Rats, Inbred Strains; Thymus Gland; Thyroxine

The effect of altered thyroidal status on levels of immunoreactive (ir)- atrial natriuretic peptide (ANP) in serum and the four cardiac chambers, and of tissue ANP mRNA, was determined in groups of rats given vehicle, thyroxine (T4), propylthiouracil (PTU) or T4 plus PTU for 3 weeks. Serum levels of ir-ANP were approximately 3-fold higher in T4-treated animals compared with control; levels in PTU or PTU/T4 groups were not different from control. Right ventricular ANP mRNA was below detection; in other chamber, levels rose with T4, alone or plus PTU, and fell after PTU compared with control. Atrial ir-ANP levels were unchanged by T4, but increased (left atrium, LA) or decreased (right atrium, RA) after PTU alone. After PTU/T4, some indices (e.g. tissue weight) remained at control levels, others (e.g. ANP mRNA levels) were equivalent to levels in the T4-alone group, and others (e.g. LA ir-ANP) were equivalent to those seen with PTU alone. We conclude that the role of thyroid hormones on ANP synthesis may be similar between chambers but their effects on release appear to differ widely. The extent to which this represents secondary rather than direct effects, or possible T3-versus T4-specific events, awaits elucidation.

Topics: Animals; Atrial Natriuretic Factor; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Male; Myocardium; Nucleic Acid Hybridization; Propylthiouracil; Rats; Rats, Inbred Strains; RNA, Messenger; Thyroid Hormones; Thyroxine; Triiodothyronine

Thyroid hormone (T3) has been shown to regulate the level of its receptor in a number of tissues and cell lines. Recently, proteins encoded by the protooncogene c-erbA have been identified as T3 receptors. In the rat, four c-erbA gene products have been isolated, three of which, r-erbA alpha-1, r-erbA beta-1, and r-erbA beta-2, encode biologically active T3 receptors; the fourth, r-erbA alpha-2, may play an inhibitory role in T3 action. The present work examines the molecular nature of T3 receptor autoregulation using probes specific for each c-erbA mRNA. Rats were rendered hypothyroid with propylthiouracil and then treated with either saline or T3. Northern blot analyses reveal marked tissue-specific and differential regulation of the multiple c-erbA mRNAs by T3. In the pituitary the levels of r-erbA beta-1 mRNA increase, whereas the levels of the pituitary-specific r-erbA beta-2 mRNA decrease with T3 treatment. In heart, kidney, liver, and brain the levels of r-erbA beta-1 are unaffected by thyroidal status. The levels of both r-erbA alpha mRNAs decrease with T3 treatment in all tissues examined except for the brain, where there is no change. In addition, we find that changes in the mRNAs encoding specific subpopulations of T3 receptors do not always parallel changes in total nuclear T3 binding. Differential regulation of the specific c-erbA mRNA species could have important consequences for T3 action.

Topics: Animals; Gene Expression Regulation; Hyperthyroidism; Male; Organ Specificity; Propylthiouracil; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogenes; Rats; Rats, Inbred Strains; Receptors, Thyroid Hormone; Reference Values; RNA, Messenger; Triiodothyronine

1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the incubated soleus muscle. 3. Hypothyroidism decreased the concentrations of glutamine in the gastrocnemius muscle and plasma but was without effect on that in soleus muscle. Hypothyroidism also decreased markedly the rate of glutamine release from the incubated soleus muscle. 4. Thyroid status was found to have marked effects on the rate of glutamine release by skeletal muscle per se, and may be important in the control of this process in both physiological and pathological conditions.

Topics: Alanine; Animals; Glutamine; Hyperthyroidism; Hypothyroidism; Male; Muscles; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; Triiodothyronine

We have shown previously that the rat pancreas contains nuclear T3 receptors which exhibit a characteristic maturation pattern during development. To investigate whether these receptors are subjected to autologous regulation by thyroid hormones, the effect of T4 on the binding capacity (Bmax), dissociation constant (Kd), and receptor occupancy were followed in intact rat pups at various ages. Hyperthyroidism (by daily injection of T4 0.1 micrograms/g body wt to intact pups starting 4 days before death at 5, 10, 15, and 20 days of age) increased while hypothyroidism (by propylthiouracil feeding) decreased the total T3 binding capacity during preweaning ages (mean maximal binding capacities as estimated by Scatchard analysis, at 30 C for 14-20 days old eu-, hyper-, and hypothyroid pups: 186, 229, and 129 fmol/mg non-histone protein (NHP). The thyroid conditions also affected the percentage of T3 receptor occupancy but not the affinity of binding (as measured by Kd). Concomitantly, these conditions also caused corresponding changes in pancreatic weights, DNA and protein contents, and the concentrations of amylase, trypsinogen, and lipase. The postnatal developmental retardation induced by 6-n-propyl-2-thiouracil treatment was reversed by T4 replacement. The results suggest that rat pancreatic T3 nuclear receptors during postnatal ages are modulated by T4, and such modulation apparently in turn affects the development of the exocrine enzymes.

Topics: Animals; Animals, Newborn; Cell Nucleus; DNA; Exocrine Glands; Hyperthyroidism; Hypothyroidism; Pancreas; Propylthiouracil; Proteins; Rats; Receptors, Thyroid Hormone; Reference Values; Thyroid Gland; Thyroxine; Weaning

Red blood cell (RBC) zinc (Zn) concentration was measured by atomic absorption spectrophotometry in 28 healthy volunteers, in 46 patients with hyperthyroidism, and in 6 patients with hypothyroidism. The mean (+/- SD) RBC Zn concentration in euthyroid controls was 11.4 +/- 1.5 mg/L RBC, and the normal range defined as the mean +/- 2 SD was 8.5 to 14.3 mg/L RBC. The mean RBC Zn in patients with hyperthyroidism was decreased to 6.4 +/- 1.6 mg/L RBC, and 43 (93%) had low values. The mean RBC Zn in patients with hypothyroidism was not different from that in the controls. There was a significant negative correlation between the concentrations of RBC Zn and those of both plasma thyroxine (T4; r = -0.73) and plasma 3,5,3'-triiodothyronine (T3; r = -0.70). After the treatment of 17 hyperthyroid patients with antithyroid drugs, both mean plasma T4 and T3 levels became normal within 4 weeks, but the normalization of RBC Zn lagged about 2 months behind them. The RBC Zn levels significantly correlated with both the plasma T4 and T3 levels obtained 0, 4, 8, and 12 weeks prior to the RBC sampling, and the highest correlation was observed between the RBC Zn levels and plasma T4 and T3 levels measured 8 weeks previously. These data suggest that RBC Zn concentration in hyperthyroid patients reflects a patient's mean thyroid hormone level over the preceding several months as glycosylated hemoglobin level does in diabetic patients.

Topics: Adult; Erythrocytes; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Testosterone; Thyroid Hormones; Thyrotropin; Time Factors; Zinc

In pregnancy hyperthyroidism occurs with a prevalence of 0.04-0.2%. It occurs even less frequently de novo in previously undiagnosed patients. Within a short period of time we treated 3 patients, who also developed signs of pre-eclampsia. Specific principles of the management during pregnancy are explained.

Topics: Adult; Cesarean Section; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Lithium; Male; Methimazole; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Propylthiouracil; Thyroid Function Tests

Extrathyroidal production of 3,3',5-triiodothyronine from the thyroid secretory product, thyroxine, is catalyzed by tissue-specific iodothyronine 5'-deiodinases. Type I 5'-deiodinase (5'D-I) produces greater than 75% of the T3 found in the circulation and in thyroid hormone-responsive tissues and is most abundant in rat liver and kidney. In this study, we used the bromoacetyl derivatives of T4 (N-bromoacetyl-[125I]L-thyroxine, BrAcT4) and T3 (N-bromoacetyl-[125I]3,3',5-triiodothyronine, BrAcT3) as alkylating affinity labels to identify 5'D-I-related protein(s). BrAcT4 and BrAcT3 rapidly and irreversibly inactivated 5'D-I activity in liver and kidney microsomes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of affinity labeled 5'D-I preparations showed that approximately 80% of the affinity label was incorporated into a protein with a Mr of 27,000 (p27). 5'D-I substrates and inhibitors specifically blocked affinity labeling of p27 with a rank order of potency (BrAcT4 greater than BrAcT3 greater than 3,5,3'-triiodothyronine (rT3) approximately flavone EMD 21388 greater than iodoacetate greater than N-acetyl-T4 (NAcT4) greater than N-acetyl-T3 (NAcT3] identical to that determined for inhibition of 5'-deiodination. Hyper- and hypothyroidism-induced increases and decreases in 5'D-I activity, respectively, were matched by comparable changes in the quantity of affinity labeled p27. BrAcT3 was a less effective affinity label for p27 and minor labeling of a new band with 53 kDa was observed. Molecular sieve chromatography of detergent-solubilized 5'D-I showed coincident peaks of p27 and 5'-deiodinating activity with an apparent Mr approximately 51,000. Two-dimensional gel electrophoresis showed that p27 was a single polypeptide with a pI of 6.1. Approximately 2-5 pmol of p27 were present per mg of liver microsomal protein, equal to previous estimates for 5'D-I content. Our results suggest that p27 represents the substrate binding subunit of type I 5'-deiodinase, the enzyme catalyzing the key reaction in the activation of T4 to the thyromimetically active T3.

Topics: Affinity Labels; Animals; Binding Sites; Binding, Competitive; Chromatography, Gel; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Isoenzymes; Kidney Cortex; Kinetics; Macromolecular Substances; Male; Microsomes; Microsomes, Liver; Molecular Weight; Propylthiouracil; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Reference Values; Thyroxine

Propylthiouracil (PTU) is the most common antithyroid medication utilized in children for the treatment of hyperthyroidism. An adverse effect of PTU reported infrequently is hepatic injury. The child described here is the fifth reported case of severe hepatic injury in the pediatric age group and documents that clinical or biochemical evidence of hepatic injury requires immediate discontinuation of PTU.

Topics: Chemical and Drug Induced Liver Injury; Child; Exophthalmos; Female; Hepatic Encephalopathy; Humans; Hyperthyroidism; Propylthiouracil

The influence of altered thyroid state is investigated on plasma apolipoprotein-A-I (apo-A-I), apo-B, and apo-E levels and on apo-A-I, apo-A-II, apo-B, apo-E, hepatic triglyceride lipase (HTGL), and low density lipoprotein (LDL) receptor mRNA levels in rat liver and intestine. Plasma total cholesterol and triglycerides are unchanged in hyperthyroid rats. Liver apo-A-I mRNA levels increase 3-fold, whereas intestinal apo-A-I mRNA levels remain constant. Plasma apo-A-I levels almost double after L-T4. Liver apo-B and apo-E and intestinal apo-B mRNA levels are not influenced by L-T4, but plasma apo-B and apo-E decrease significantly. In the liver, apo-A-II mRNA levels decrease, whereas LDL receptor mRNA levels increase more than 50%. HTGL mRNA is not influenced by L-T4. N-Propyl-thiouracil-induced hypothyroidism does not influence plasma triglycerides, but plasma cholesterol levels nearly double. Liver and intestinal apo-A-I mRNA levels and plasma apo-A-I concentrations remain constant after propylthiouracil treatment. Accompanying the increase in plasma apo-B, liver and intestinal apo-B mRNA concentrations rise by approximately 100% and 40%, respectively. Plasma apo-E increases nearly 2-fold, but liver, apo-A-II mRNA rises, whereas HTGL and LDL receptor mRNA levels decrease 20% and nearly 50%, respectively. In conclusion, thyroid hormones regulate rat apo-A-I and apo-A-II gene expression in opposite directions. Furthermore, the LDL receptor is regulated at the mRNA level, whereas HTGL gene expression is relatively resistant to alterations in thyroid status.

Topics: Animals; Apolipoproteins; Gene Expression Regulation; Hyperthyroidism; Hypothyroidism; Intestinal Mucosa; Lipase; Lipids; Liver; Male; Nucleic Acid Hybridization; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, LDL; RNA, Messenger; Thyroxine

Side effects of antithyroid treatment were retrospectively analysed in 1256 patients with hyperthyroidism. Overall rate of side effects was 14.3%. Skin reactions were the most frequent ones (5.6%), followed by arthropathies (1.6%). The incidence of agranulocytosis was 0.14%. Median duration of all side effects was 1.5 months. In half the cases the side effects were controllable so that treatment was continued, although at a changed dosage. The rate of cross-reaction between carbimazole and thiamazole, on the one hand, and propylthiouracil, on the other, was 13.8% and 15.2%, respectively. The side effects became apparent after a mean of one month's treatment, almost always (in 97.1%) within the first year of treatment. There was a significant dose dependence for an initial thiamazole dose of over 20 mg (relative side effect risk of 2.3), and for an initial dose of over 30 mg for carbimazole (relative side effect risk of 1.6). Although most side effects were not dangerous, in normal instances the lowest possible dosage should be administered to control hyperthyroid metabolism. Long-term treatment with low doses seem to be without problems.

Topics: Adult; Antithyroid Agents; Carbimazole; Dose-Response Relationship, Drug; Drug Evaluation; Drug Interactions; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Time Factors

Amiodarone is a benzofuranic derivative widely used in cardiologic practice because of its excellent antiarrhythmic properties. Due to its high iodine content, it interferes with thyroid physiology and can cause either hyper or hypothyroidism. Amiodarone-induced hyperthyroidism should be considered as a serious complication since it develops in cardiac patients, the clinical diagnosis can be difficult and because conventional methods of therapy are said to be often ineffective. We analyze the outcome of 10 pts, chronically treated with Amiodarone (16-60 mo, mean 37.6 mo) who develop hyperthyroidism during the antiarrhythmic therapy. All patients had multinodular goiter. Overt clinical picture for thyrotoxicosis was seen in 7 of them and lab tests showed: rT3 = 101.1 +/- 14.9 ng/dl; T3 = 220.2 +/- 25 ng/dl; T4 = 15.6 +/- 1.9 micrograms/dl, TSH = 0.8 +/- 0.2 microU/ml and TRH response 0.0 microU/ml. Thyroid microsomal antibodies were negative in 3 pts studied. After Amiodarone was discontinued, patients were followed-up monthly. In 2, normalization of clinical and laboratory indexes were obtained at 40-60 d and no other medication was given. In the remaining, due to the intensity of clinical manifestations, PTU treatment was started (300 mg/d) After 4 mo, euthyroidism was achieved in 6 and it persisted after discontinuation of PTU has patient failed to respond to PTU, 131I was administered with excellent results. Patients have been followed-up up to 3 years after therapy without observing thyrotoxic relapses nor deterioration of their cardiological condition.2+ conventional therapies (PTU or 131I) have been, very effective.

Topics: Adult; Aged; Amiodarone; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Thyroid Hormones

Topics: Amiodarone; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Tachycardia; Thyroid Function Tests

We present evidence based on equilibrium and non-equilibrium binding studies, as well as on immunological techniques, that of the two rat specific thyroid-hormone-binding proteins, i.e., thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA), TBG but not TBPA is regulated by the thyroid hormones (TH). Hypothyroidism, induced from the day of birth by daily treatment with propylthiouracil (PTU-rats), leads to dramatic and sustained increases of the TH-binding abilities of the sera measured at equilibrium, whereas hyperthyroidism, induced by treatment with thyroxine (T4-rats), leads to the decrease of these abilities. Polyacrylamide gel electrophoresis and isoelectrofocalisation of radioiodinated T4-labelled sera, together with immunoassay of TBPA, demonstrate that both effects are due to TBG, the levels of which rise in PTU-rats and decline in T4-rats, while TBPA levels do not respond to either depletion or excess of the thyroid hormones. TBG rather than TBPA appears as the key thyroid-hormone-binding protein of the rat, inasmuch as it alone expresses a regulatory function of the thyroid hormones at protein synthesis level.

Topics: Aging; Animals; Hyperthyroidism; Hypothyroidism; Kinetics; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

The authors studied 389 Graves' hyperthyroid patients receiving either high propylthiouracil (PTU) or methimazole (MMI) daily doses or low doses to evaluate whether adverse effects were related to the thionamide drugs or its daily dose regimen. Group 1 patients (n = 286) received high PTU (728 +/- 216 mg/day, n = 92) or MMI (60 +/- 19 mg/day, n = 94) doses, and group 2 patients (n = 103) were treated with low PTU (255 +/- 85 mg/day, n = 39) or MMI (23 +/- 10 mg/day, n = 64) doses. Major adverse effects were observed in 11 (2.8%) patients. Of these, four (1.0%) had agranulocytosis, two (0.5%) were granulocytopenic and five (1.3%) had hepatotoxicity. Agranulocytosis occurred in two patients from each group, 0.7% and 1.9%, respectively from group 1 and group 2. There was no significant difference between the groups or the types of thionamide. There also was no correlation with the patients' age. All of the patients were hyperthyroid, and its onset occurred in the first to third month of treatment. Full recovery was achieved in all cases after drug withdrawal. Four of 5 patients with hepatotoxicity were treated with high PTU doses, and one patient received low MMI doses (p less than .05). All patients were euthyroid. Arthralgias, skin rash and gastric intolerance, the minor adverse effects of thionamides studied, were observed in 52 (13.4%) of the patients. Although no significant differences were found, most of the patients experiencing side effects were from group 1 an received MMI therapy. These adverse effects did not demand drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Agranulocytosis; Chemical and Drug Induced Liver Injury; Child; Dose-Response Relationship, Drug; Drug Eruptions; Graves Disease; Humans; Hyperthyroidism; Joints; Methimazole; Middle Aged; Pain; Propylthiouracil; Stomach Diseases

N-bromoacetyl-3,3',5-tri[3'-125I]iodo-L-thyronine was used to label intact heart mitochondria from eu, hypo- and hyperthyroid rats in order to identify proteins involved in T3-regulated mitochondrial processes. The results show strong labeling, competed for by T3 and other analogues, of two proteins with a molecular mass of 48,000 and 49,200 Da. No labeling is seen of the adenine nucleotide translocase, a likely target, neither at 0 degree C, at room temperature, nor after preincubation with the substrates or specific inhibitors. No difference in labeling intensity or distribution is seen in mitochondria from eu-, hypo- or hyperthyroid rats, and the abundance of the adenine nucleotide translocase is unchanged, but five other proteins show differential abundance.

Topics: Affinity Labels; Animals; Hyperthyroidism; Hypothyroidism; Liver; Male; Mitochondria, Heart; Mitochondrial ADP, ATP Translocases; Nucleotidyltransferases; Propylthiouracil; Proteins; Rats; Rats, Inbred Lew; Reference Values; Thyroid Gland; Thyroxine; Triiodothyronine

Thyroid hormone effects on pituitary ACTH have not been well established. Adult male Sprague-Dawley rats were rendered hypo- and hyperthyroid while undergoing treatment with 6-Propylthiouracil (PTU) and L-Thyroxine (T4). At the time of decapitation, plasma values for T4 (micrograms/100 ml) were 3.9 +/- 0.4 in the control, 17.3 +/- 2.2 in the T4 and less than 2 in the PTU treated group; plasma T3 and TSH confirmed hyper- and hypothyroidism in the T4 and PTU treated groups respectively. Plasma immunoassayable ACTH and corticosterone were significantly increased in hyperthyroid and decreased in the PTU treated animals. Pituitaries were removed and incubated in DMEM. After 3 h incubation, ACTH content and secretion to the medium were significantly lower in the PTU group. As expected, pituitary TSH content and secretion were decreased in the T4 treated animals. These data indicate that thyroid hormones influence pituitary-adrenal function by increasing ACTH secretion and consequently corticosterone production.

Topics: Adrenocorticotropic Hormone; Animals; Corticosterone; Culture Techniques; Hyperthyroidism; Hypothyroidism; Male; Pituitary Gland; Propylthiouracil; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyroid Hormones; Thyrotropin; Thyroxine

Topics: Adolescent; Adult; Carbimazole; Creatine Kinase; Female; Humans; Hyperthyroidism; Myositis; Propylthiouracil

1. Rats were made hypothyroid by giving them a low-iodine diet with propylthiouracil for 4 weeks, or were made hyperthyroid by injection with tri-iodothyronine (T3) over a 3-day period. 2. Brown adipocytes were isolated from the interscapular depots of these animals or from their euthyroid controls, followed by isolation of mitochondria from the cells. 3. Relative to cell DNA content, hypothyroidism decreased the maximum binding (Bmax.) of [3H]GDP to mitochondria by 50%. T3 treatment increased binding by 37%. 4. These findings, which are discussed in relation to previously observed changes in brown adipose tissue after alteration of thyroid status, suggest that mitochondrial uncoupling for thermogenesis is less or more effective in hypothyroidism or hyperthyroidism respectively.

Topics: Adipose Tissue, Brown; Animals; DNA; Guanine Nucleotides; Guanosine Diphosphate; Hyperthyroidism; Hypothyroidism; Male; Mitochondria; Propylthiouracil; Rats; Rats, Inbred Strains; Triiodothyronine

We have examined in isolated liver mitochondria the effect of cold exposure on DNA, RNA and protein synthesis in normal, hypothyroid and mildly hyperthyroid rats. In normal rats DNA polymerase activity increased from the first day of cold exposure remaining high up to the fifteenth day. RNA polymerase and protein synthesis were stimulated from the fifth day of cold exposure, maintaining a high level up to the fifteenth day. These activities were related to serum triiodothyronine (T3) levels. Indeed propylthiouracil (PTU) administration to cold-exposed rats drastically depressed the above activities, whereas T3 administration to PTU-treated cold-exposed rats restored them to about the values prevalent in normal cold-exposed rats. The translation products analyzed by gel electrophoresis showed that different effects may be exerted by T3 depending on whether its circulating levels are physiologically or pharmacologically modified. These findings suggest that T3 may be involved in the regulation of the acclimation process by acting, presumably with a permissive role, on those activities which determine a modification of the mitochondrial morphometric features and an increase in mitochondria number and turnover.

Topics: Animals; Cold Temperature; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerases; DNA, Mitochondrial; Hyperthyroidism; Hypothyroidism; Male; Mitochondria, Liver; Propylthiouracil; Protein Biosynthesis; Rats; Rats, Inbred Strains; RNA; RNA, Mitochondrial; Triiodothyronine

In order to assess the value of thyroid function testing during amiodarone therapy, we reviewed all available tests in 128 patients treated with this drug. Nine patients (7.0%) developed biochemical hyperthyroidism with elevation of both free thyroxine index (FT4I) and free triiodothyronine index (FT3I) and marked suppression of serum thyroid stimulating hormone (TSH) after 1-46 months of therapy; six of these nine patients had clear clinical evidence of thyroid overactivity. Where serial tests were available before development of hyperthyroidism, this complication developed suddenly, despite previously stable normal indices of thyroid function, and could not be predicted by currently-available biochemical tests such as T4, T3, sensitive TSH, thyroglobulin or sex hormone binding globulin (SHBG) assays. Clinical features such as unexplained weight loss, proximal myopathy, exacerbation of arrhythmia, or heat intolerance appear to be the key to prompt diagnosis of this complication. Hyperthyroxinemia without T3 excess was found in 32.8% of patients without progression to true hyperthyroidism. Serum TSH remained detectable by sensitive assay in 17 out of 18 patients with amiodarone-induced euthyroid hyperthyroxinemia and was significantly higher than in patients with equivalent hyperthyroxinemia due to thyroxine therapy. Serial levels of SHBG were higher in patients with true hyperthyroidism than in those with euthyroid hyperthyroxinemia. The effect of combined treatment with propylthiouracil (800 mg/day) and potassium perchlorate (800 mg/day) was evaluated in five of the six clinically hyperthyroid patients. Biochemical euthyroidism was achieved after 7-19 weeks, a response slower than previously reported, indicating that this drug combination does not result uniformly in prompt resolution of amiodarone-induced hyperthyroidism.

Topics: Adolescent; Adult; Aged; Amiodarone; Child; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Predictive Value of Tests; Propylthiouracil; Sex Hormone-Binding Globulin; Thyroglobulin; Thyroid Function Tests; Thyrotropin; Thyroxine

Topics: Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodine; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil

Topics: Adult; Amiodarone; Female; Glucocorticoids; Humans; Hyperthyroidism; Hypothyroidism; Male; Perchlorates; Plasmapheresis; Potassium; Potassium Compounds; Propylthiouracil; Thyroid Hormones; Thyroidectomy; Thyroxine

Previous findings have shown that thyroid hormone markedly increases the speed of diastolic relaxation in the heart. This thyroid hormone-dependent change is also accompanied by an increased Ca2+ pumping ability in the sarcoplasmic reticulum. In an effort to determine the underlying cause of improved Ca2+ transport, mRNA levels of the slow Ca2+-ATPase of the sarcoplasmic reticulum were quantified on Northern blots. In hypothyroid rat hearts, the steady state level of Ca2+-ATPase mRNA was only 36% of control levels, whereas hyperthyroid rat heart mRNA levels were 136% of control. Ca2+-ATPase mRNA responded rapidly to T3, as the mRNA level was significantly increased by 2 h and normalized by 5 h after T3 injection into hypothyroid rats. The well established effect of thyroid hormone on improved myocardial contractility and increased speed of diastolic relaxation may in part relate to specific alterations in the level of the mRNA coding for Ca2+-ATPase, resulting in increased pump units.

Topics: Animals; Calcium-Transporting ATPases; Cloning, Molecular; DNA; Genes; Heart; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Myocardium; Propylthiouracil; Rats; Rats, Inbred Strains; RNA, Messenger; Sarcoplasmic Reticulum; Thyroxine; Transcription, Genetic; Triiodothyronine

The effect of thyroid hormone on atrial natriuretic factor (ANF) production was investigated in hypothyroid, euthyroid, and hyperthyroid rats by measuring levels of ANF mRNA and ANF in myocardium. ANF mRNA was quantitated by dot blot hybridization, and ANF by specific RIA. Relative ANF mRNA concentrations (ANF mRNA to 18S RNA) were determined for right atria, left atria, and ventricular apices. The total chamber content of ANF mRNA was estimated (concentration X total chamber RNA) and used as a measure of each tissue's synthetic capacity. For both atrial tissues, ANF mRNA contents were significantly higher in hyperthyroidism. In right atria, mean ANF mRNA contents in hypothyroidism and hyperthyroidism were 41% and 176%, respectively, of that in euthyroidism (P less than 0.05, by analysis of variance). Left atrial ANF mRNA contents in hypothyroidism and hyperthyroidism were 94% and 272%, respectively, of the euthyroid value (P less than 0.05). In contrast, atrial ANF mRNA concentrations did not differ significantly between thyroid states. In ventricle, ANF mRNA content and concentration were both correlated with serum T4 concentration. Ventricular ANF mRNA contents in hypothyroidism and hyperthyroidism were 31% and 178%, respectively, of that in euthyroidism (P less than 0.02). The concentration of ventricular ANF mRNA was also significantly increased in hyperthyroidism (P less than 0.05). Tissue content of ANF increased in the hyperthyroid right atria and decreased in the hyperthyroid left atria and ventricles. These observations suggest that increased ANF production by both atria and, to a lesser extent, by the ventricles contributes to the higher circulating ANF levels reported in hyperthyroidism. Furthermore, hyperthyroidism is associated with a specific increase in ventricular ANF mRNA expression as has been observed in other conditions causing ventricular hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Heart Atria; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Male; Myocardium; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger; Thyroid Gland; Thyroxine; Transcription, Genetic

Urinary urgency and frequency and even enuresis may be manifestations of augmented adrenergic activity in hyperthyroidism, as are sweating, tremor, and tachycardia. Because patients rarely volunteer problems with urgency, frequency, and enuresis, it is worthwhile for the physician to inquire about such symptoms in patients with moderate to severe hyperthyroidism. Symptoms generally cease after treatment of the hyperthyroidism.

Topics: Adolescent; Adult; Enuresis; Female; Humans; Hyperthyroidism; Male; Propranolol; Propylthiouracil

The oral and intravenous disposition of the anti-thyroid drug propylthiouracil (PTU) was determined in six clinically healthy cats and four cats with naturally occurring hyperthyroidism. Compared with the normal cats, the mean plasma elimination half-life of PTU was significantly (P less than 0.001) shorter in the hyperthyroid cats (77.5 +/- 5.8 minutes compared with 125.5 +/- 3.7 minutes) and the total body clearance of PTU was significantly (P less than 0.05) more rapid in the cats with hyperthyroidism (5.1 +/- 0.8 ml kg-1 min-1 compared with 2.7 +/- 0.2 ml kg-1 min-1). Following oral administration, both the bioavailability (59.7 +/- 4.9 per cent compared with 73.3 +/- 3.7 per cent) and peak plasma concentrations (14.5 +/- 1.6 micrograms ml-1 compared with 18.9 +/- 0.9 micrograms ml-1) of PTU were significantly (P less than 0.05) lower in the hyperthyroid cats than in the control cats. No difference was noted, however, between the apparent volume of distribution for PTU in the two groups of cats. Overall, results of this study indicate that the oral bioavailability of PTU is decreased and PTU disposition is accelerated in cats with hyperthyroidism.

Topics: Animals; Cat Diseases; Cats; Female; Hyperthyroidism; Male; Propylthiouracil

Plasma and urinary levels of thiobarbituric acid reactive substances (TBAR) were determined in 24 hyperthyroid patients, 19 hypothyroid subjects, 35 controls, and 17 hyperthyroid patients before and after propylthiouracil (PTU) treatment (400 mg/day for 2-3 months), as indexes of lipid peroxidation. These measurements were carried out together with t-butyl hydroperoxide (t-BHP)-induced oxygen uptake and visible chemiluminescence in erythrocytes as functional tests related to the antioxigenic capacity of cells. Hyperthyroid patients exhibited increased levels of plasma and urinary TBAR compared to controls. Erythrocyte suspensions from hyperthyroid patients showed, compared to controls, higher rates of oxygen consumption with shorter induction periods upon addition of t-BHP, together with 142% and 75% increases in basal and t-BHP-induced chemiluminescence, respectively. Levels of TBAR in untreated hyperthyroid patients in plasma (16.2 +/- 1.3 pmol/mg of protein) and urine (15.9 +/- 1.5 nmol/mg of creatinine) were decreased after PTU treatment (Plasma, 9.5 +/- 0.7, p less than 10(-4); urine, 7.8 +/- 0.9, P less than 10(-5) to values not significantly different from those of the control group (plasma, 10.3 +/- 0.6; urine, 7.9 +/- 0.7). Compared to control, elevated rates of oxygen uptake induced by t-BHP, basal and t-BHP-induced chemiluminescence in erythrocyte suspensions from untreated hyperthyroid patients were reverted to normal by PTU, while decreased induction period (T0) values were enhanced. Determination of these lipid peroxidative parameters in hypothyroid patients revealed no significant changes over control values, excepted t-BHP-induced chemiluminescence in erythrocytes that was diminished. These data indicate that hyperthyroidism is associated with a pro-oxidant condition characterized by an enhancement in circulating and urinary lipid peroxidative indexes, which is suppressed by PTU treatment. It is suggested that this condition might reflect an oxidative stress at cellular level in tissues which are target for thyroid hormone action with a calorigenic response.

Topics: Adult; Erythrocytes; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Lipid Peroxidation; Male; Oxygen Consumption; Propylthiouracil; Reference Values

The authors report a case of chronic bulbar muscular dysfunction in a thyrotoxic man, with complete remission of the symptoms after the use of propranolol, with and without concomitant use of propylthiouracil. Some aspects of this unique complication of hyperthyroidism are discussed.

Topics: Adult; Cricoid Cartilage; Deglutition Disorders; Humans; Hyperthyroidism; Laryngeal Cartilages; Male; Muscles; Neuromuscular Diseases; Propranolol; Propylthiouracil; Voice Disorders

Topics: Adolescent; Adult; Child; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Male; Propylthiouracil; Thyroid Gland; Thyroid Hormones; Thyrotoxicosis

An additional disorder in the spectrum of thyroid related muscle disease is presented. Hypothyroid and hyperthyroid disease are both associated with a variety of muscle abnormalities, from myalgias to myopathy. Polymyositis, however, has never been reported immediately after treatment for active hyperthyroidism. A patient is presented with typical hyperthyroidism, who developed a severe proximal muscle weakness and a raised creatine phosphokinase after treatment for hyperthyroidism with propylthiouracil (100 mg orally, three times a day). Electromyography, muscle biopsy, and the course of the patient's illness were consistent with polymyositis. Whether this represents a cause-effect association or a chance occurrence is unknown. Physician awareness of the occurrence of a variety of muscle disorders including polymyositis in thyroid disease is emphasised. A brief discussion of thyroid myopathy, thionamide drug reactions, and polymyositis is included.

Topics: Adult; Female; Humans; Hyperthyroidism; Muscles; Myositis; Propylthiouracil

This study was designed to determine if peroxidation of biomembrane lipid and the protective system can be modified by the change in oxidative metabolism induced by thyroid dysfunction. The free radical scavengers (i.e. cuprozinc cytosolic and mangano mitochondrial superoxide dismutases, glutathione peroxidase, and catalase), mitochondrial oxidative marker enzymes (cytochrome c oxidase and fumarase), and lipid peroxide were measured in liver, heart, soleus (slow oxidative), and extensor digitorum longus (fast glycolytic) muscles. Rats were rendered hyper- or hypothyroid for 4 weeks and then killed. Superoxide dismutases were detected by specific RIAs: catalase by polarography, and lipid peroxide by fluorimetry. Hypothyroid rats failed to grow, while hyperthyroid rats had hypertrophied hearts but no growth failure. An increase in lipid peroxide was observed in the soleus and heart muscles of hyperthyroid rats. This was accompanied by an increase in mitochondrial superoxide dismutase and oxidative markers. No such change was observed in either fast glycolytic muscle or liver. Glutathione peroxidase decreased in all tissues of hyperthyroid rats, and there was a parallel decrease in catalase in most tissues. On the other hand, hypothyroidism induced a reduction in oxidative markers and mitochondrial superoxide dismutase in heart and skeletal muscles, but only a marginal change in lipid peroxidation. The cytosolic superoxide dismutase did not change in relation to either oxidative metabolism or lipid peroxidation. These results suggest that the enhanced oxidative metabolism and decreased glutathione peroxidase in hyperthyroidism result in an increase in lipid peroxidation and, in slow oxidative and heart muscle, possible organ damage. No adverse reaction mediated by active oxygen species was found in hypothyroid rat tissues.

Topics: Animals; Catalase; Electron Transport Complex IV; Free Radicals; Fumarate Hydratase; Glutathione Peroxidase; Heart; Hyperthyroidism; Hypothyroidism; Lipid Peroxides; Male; Muscles; Propylthiouracil; Rats; Rats, Inbred Strains; Superoxide Dismutase; Thyroid Diseases; Thyroxine; Triiodothyronine

Topics: Amiodarone; Humans; Hyperthyroidism; Male; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil

We measured plasma atrial natriuretic peptide (ANP) levels in 17 patients with newly diagnosed thyrotoxicosis. ANP was elevated compared to a group of healthy controls and fell to normal after treatment. Plasma cyclic guanosine monophosphate was also raised in untreated patients. Elevated circulating levels of ANP may play a part in the haemodynamic changes of hyperthyroidism.

Topics: Adult; Atrial Natriuretic Factor; Carbimazole; Cyclic GMP; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Thyrotoxicosis

The concentrations of glycogen phosphorylase protein were determined by rocket immunoelectrophoresis in liver extracts from rats that had artificially induced altered hormonal patterns. These levels were compared with measurements of total phosphorylase activity. Minipump-induced chronic hyperglucagonemia and streptozotocin-induced diabetes resulted in 47% and 67% decreases, respectively, in total phosphorylase activity along with corresponding 52% and 68% drop, respectively, in phosphorylase protein levels. Insulin replacement in diabetic rats returned both parameters to control values. Minipump-induced hyperinsulinemia or injection of glucagon antiserum, T3, or propylthiouracil had no effect. The results of this study indicate that conditions which lead to an elevation of the glucagon to insulin molar ratio to values higher than 1.0 cause a significant decrease in the liver phosphorylase protein level.

Topics: Animals; Diabetes Mellitus, Experimental; Glucagon; Hyperthyroidism; Hypothyroidism; Immune Sera; Insulin; Liver; Male; Phosphorylases; Propylthiouracil; Rats; Rats, Inbred Strains; Triiodothyronine

A patient who presented with bilateral frozen shoulders and unrecognized hyperthyroidism is described. Both frozen shoulder and the related shoulder-hand syndrome may occur in this setting. These poorly understood rheumatic conditions often are complications of stroke, spinal cord injury, or diabetes. Dysfunction of the autonomic nervous system is thought to be of pathogenic importance. It is postulated that the close resemblance of hyperthyroidism to activation of the sympathetic nervous system may underlie its association with frozen shoulder and shoulder-hand syndrome.

Topics: Diagnosis, Differential; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Rheumatic Diseases; Shoulder Joint; Thyroid Function Tests

We use an antithyroid drug for the treatment of hyperthyroidism due to Graves' disease in children and adolescents for as long as the patients are willing to comply and/or tolerate the drug. In more than 60 patients treated since 1961, the remission rate was 25% in the first 2 yr. This report looks at these same patients again, followed for an additional 5 yr. Survival analysis methods applied to the follow-up data on 63 children confirm our original statistical findings and suggest a continuing remission rate of 25% every 2.1 +/- 0.4 (+/- SE) yr regardless of the duration of previous therapy. The median time to remission was 4.3 +/- 1.5 yr, and 75% of patients are predicted to be in remission in 10.9 +/- 2.3 yr. Of 36 patients who went into remission, defined by their being euthyroid for 1 yr after cessation of therapy, 1 relapsed, and 2 developed spontaneous hypothyroidism; the remainder are euthyroid 1-11.7 yr after therapy was discontinued. Of 14 who switched from medical therapy, 2 of 7 treated surgically and 4 of 7 treated with 131I are hypothyroid. Only 1 patient had a significant adverse reaction to both methimazole and propylthiouracil. While medical therapy may have some direct effect on the autoimmune response in hyperthyroidism, its role in affecting the time to ultimate remission is unknown. These data, however, describe the course of children so treated and allow us to present therapeutic options initially or during treatment based on statistically derived probabilities of outcome.

Topics: Child; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Propylthiouracil; Statistics as Topic; Time Factors

We treated 69 hyperthyroid children with propylthiouracil, of whom 53 remained under surveillance. Of these children, 34 (64%) had an initial remission, but relapses were frequent (47%). At this writing, 24 patients (45%) were in remission, with a mean duration of remission of 55 months (range, ten to 132 months). We found that the triiodothyronine level took significantly longer than the thyroxine (T4) level to return to normal. Thus, based on the T4 level alone, treatment may have been stopped prematurely in some patients, causing the relapse rate to be falsely high. The response to therapy did not depend on the size of the goiter nor on the initial levels of T4 or triiodothyronine. Six patients had adverse reactions, which were serious in two patients.

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Male; Propylthiouracil

Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy. Its pathogenesis has been related to the presence of circulating immune complexes. The lesions may be purpuric or bullous hemorrhagic, possibly evolving into necrotic ulcerations. Usually, lesions develop on the extremities and earlobe. The vasculitis has been related to the duration of the treatment and disappears with the withdrawal of the drug, although a fatal case has been reported. Corticosteroid therapy is often prescribed, but its efficacy has not been demonstrated. We describe a patient in whom treatment with propylthiouracil for a year was associated with vasculitic lesions on the lower extremities and earlobe. Discontinuation of the drug was correlated with disappearance of the lesions.

Topics: Adult; Drug Hypersensitivity; Ear, External; Extremities; Female; Humans; Hyperthyroidism; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Abortion, Spontaneous; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Thyroxine; Triiodothyronine

Total L-thyroxine and triiodo-L-thyronine serum concentrations have been measured in 70-day-old male rats under normal conditions (controls) and in rats subjected to several experimental alterations of the thyroid function: hyperthyroidism, hypothyroidism and substitutive treatments. Since some problems appear when standard curves are performed with hormone serum, as consequence of differences in the affinity and inhibitory effects between heterologous proteins at the antigen-antibody reaction, RIA in this work has been carried out with standard curves performed with rat serum maintaining similar protein concentrations in standard and problems. This modification avoids errors by the use of extraction methods and shows a high degree of similarity between standard and problems.

Topics: Animals; Blood Proteins; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Radioimmunoassay; Rats; Thyroidectomy; Thyroxine; Triiodothyronine

Topics: Adolescent; Chorea; Euthyroid Sick Syndromes; Female; Humans; Hyperthyroidism; Propylthiouracil

We describe a case of a 29-year-old man with hyperthyroidism associated with autoimmune hemolytic anemia and periodic paralysis. Euthyroidism, which was achieved by propylthiouracil, brought inhibition of hemolysis and amelioration of anemia in spite of continuously positive direct and indirect Coombs' tests. Neither adrenocortical steroid nor blood transfusion was administered. Since indirect monospecific Coombs' test was negative against anti-human complements serum, the membrane of red blood cells may be less fragile. This is one reason why hemolysis was inhibited by anti-hyperthyroid therapy only. This may indicate that the hyperdynamic circulatory state secondary to hyperthyroidism plays an important role in the destruction of red blood cells which were coated by anti-red blood cell antibody.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Coombs Test; Hemolysis; Humans; Hyperthyroidism; Male; Paralysis; Periodicity; Propylthiouracil

We present a fatal case of acute submassive hepatic necrosis occurring in a 42-yr-old black woman treated for hyperthyroidism with propylthiouracil for 1 yr. Alcohol and drug abuse were ruled out and all serological tests for hepatitis A and B, cytomegalovirus, and Epstein-Barr virus infection were negative. At autopsy the liver was shrunken and presented a yellow granular appearance. Microscopy disclosed submassive necrosis with bile stasis and severe chronic inflammation, as well as mild bile duct proliferation. Although non-A, non-B hepatitis cannot be ruled out (there was no transfusion of blood or its products), this is considered to be the third fatal case and ninth instance of propylthiouracil-induced hepatic necrosis.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Liver; Necrosis; Propylthiouracil

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adrenal Cortex Hormones; Amiodarone; Antithyroid Agents; Humans; Hyperthyroidism; Ipodate; Lithium; Methimazole; Propranolol; Propylthiouracil; Thyroxine; Triiodothyronine

These studies in a mother and child describe the effects of multiple antibodies directed against the TSH receptor that influenced thyroid function in the fetus and infant. Blood was taken periodically for 6 months from a child (C3) whose mother (M) was known to have in her serum immunoglobulin G (IgG) that contained thyroid-stimulating antibody (TSAb), an inhibitor of TSAb and TSH binding and action, and an enhancer of TSH binding to its receptor, the last activity presumed to enhance both TSH and TSAb action. We correctly predicted that C3 and an older sibling, C2, would have delayed onset of hyperthyroidism (approximately 45 days of age) due to interaction of these antibodies. In addition, in both C2 and C3, fetal hyperthyroidism in the second trimester was postulated, and therefore, M was given propylthiouracil from then until term (C2) or 8 months (C3), with associated return of the fetal heart rate to normal in the one fetus (C3) in whom this was monitored. IgG was purified from C3's serum samples and tested for TSAb activity using human thyroid cells in monolayer culture and its ability to alter binding of [125I]TSH to human thyroid cell membranes. In the TSAb assays, samples obtained from birth to 4 months of age produced a negative dose response, and those obtained from 4-6 months showed a positive dose response. The effect on the binding of [125I]TSH was enhancement with all IgG obtained for 6 months, except that for the first 52 days a high concentration was inhibitory. The combined clinical and assay data are compatible with the following interpretations. M's IgG contained TSAb and both an inhibitor and an enhancer of that activity, the total effects varying at different times. In the second trimester, the net effect of transplacentally transferred IgG was to induce hyperthyroidism. At birth and perhaps during the third trimester, the inhibitor of TSAb prevented hyperthyroidism; from about 45 days of life, the enhancing effect facilitated TSAb action to produce hyperthyroidism until maternal IgG was completely cleared from the infant's circulation at about 7 months of age.

Topics: Antibody Affinity; Cells, Cultured; Cyclic AMP; Female; Fetal Diseases; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin

Thyroid function and serum TSI levels in two siblings with neonatal thyrotoxicosis are described. The first infant was treated with exchange transfusion and potassium iodide. The second infant was treated with intrauterine propylthiouracil followed by potassium iodide. In contrast to the first infant, the second infant had no clinical sign of neonatal thyrotoxicosis. He also had lower TSI levels with a biological half-life of 5 days. Only one of three assays showed some TSI activity in breast milk.

Topics: Adult; Antibodies; Exchange Transfusion, Whole Blood; Female; Follow-Up Studies; Half-Life; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Infant; Infant, Newborn; Male; Potassium Iodide; Pregnancy; Propylthiouracil; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroid Function Tests; Thyroid Gland; Time Factors

To characterize the nuclear receptor believed to mediate the thyroid hormones' actions on the heart, binding of L-[125I]T3 to extracts of myocardial cell nuclei from normal, propylthiouracil, and T4-treated rats has been investigated. Analysis of in vitro iodothyronine binding to this solubilized nuclear preparation revealed multiple saturable, specific binding sites for T3. High affinity binding for T3 (Kd = 4.2 +/- 1.0 X 10(-10) mol/L), and lower affinity (Kd approximately 10(-8) mol/L) binding activity appeared to be independent (Hill plot slope = 1). The mean maximal binding capacity of the high affinity binding site for T3 in euthyroid rats (84 +/- 8 fmol/mg DNA) was increased by approximately 50% in hypothyroidism (120 +/- 6 fmol/mg DNA) and unchanged in hyperthyroidism (88 +/- 25 fmol/mg DNA). The molecular weight of this T3 binding site is estimated to be 50,000-55,000 daltons. The properties of this solubilized binding activity from rat myocardial nuclei are consistent with its putative role as the biologic thyroid hormone receptor. The increase in binding capacity with hypothyroidism suggest regulation by thyroid hormone of its nuclear receptor in myocardium.

Topics: Animals; Binding, Competitive; Cell Nucleus; Chromatography, Gel; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Myocardium; Propylthiouracil; Radioligand Assay; Rats; Receptors, Cell Surface; Receptors, Thyroid Hormone; Solubility; Temperature; Thyroxine

Topics: Diarrhea; Female; Humans; Hyperthyroidism; Intestinal Mucosa; Iodine Radioisotopes; Middle Aged; Propylthiouracil; Thyrotropin-Releasing Hormone; Triiodothyronine

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

Topics: Animals; Growth Hormone; Growth Hormone-Releasing Hormone; Hyperthyroidism; Hypothyroidism; Male; Pituitary Gland; Propylthiouracil; Rats; Thyroid Hormones; Thyroxine

We investigated the effect of propylthiouracil (PTU)-induced hypothyroidism and T4-induced hyperthyroidism on the fetal and neonatal rabbit brain insulin receptors (number and affinity) using plasma membranes. PTU administration to the pregnant mothers resulted in low serum-free T4 and normal total T3 concentrations, while T4 therapy to the mothers resulted in high serum-free T4 and high total T3 concentrations in the fetus and neonate. PTU-induced hypothyroidism did not affect the fetal brain insulin receptors, cholesterol content (brain homogenate) or protein content. On the other hand, brain insulin receptor number and total brain cholesterol content decreased in the neonate. T4 therapy at 100 micrograms/kg reversed the serum T4 to the control value and normalized the neonatal brain insulin receptor number and cholesterol content while a higher dose of T4 (200 micrograms/kg) increased the neonatal brain insulin receptor number, cholesterol and protein content. We conclude that altered thyroidal states modulate the brain insulin receptor (number and affinity) in neonatal, but not fetal brain plasma membranes.

Topics: Animals; Blood Glucose; Brain; Cholesterol; Female; Hyperthyroidism; Hypothyroidism; Insulin; Pregnancy; Propylthiouracil; Rabbits; Receptor, Insulin; Thyroxine; Triiodothyronine

Three-dimensional images of blood vessels in thyroid glands from normal, low iodine diet-treated, thyroid-stimulating hormone (TSH)-treated and propylthiouracil (PTU)-treated rats were investigated by use of the corrosion-cast method. The vascular casts made by the injection of methacrylate resin were observed with the scanning electron microscope. In normal animals, each follicle is surrounded by a clearly defined basket-like capillary network, which is generally independent of adjacent networks, though a few anastomoses or common capillaries are sometimes seen. In low iodine diet-treated or TSH-treated animals, the capillaries in the basket-like network become markedly dilated and fuse with one another. Though the vascular casts of PTU-treated animals are similar to those of low iodine diet-treated or TSH-treated ones in some aspects, most basket-like networks become distorted and irregular in shape, and the capillaries are heterogeneously dilated and show many buds, branches and anastomoses. We consider that these peculiar changes in the thyroid of the PTU-treated animals are due not only to the elevation of serum TSH but also to other unknown factors. It is clear that the distribution and morphology of the thyroid capillaries are extremely affected and changed by functional states of the gland.

Topics: Animals; Capillaries; Hyperthyroidism; Hypothyroidism; Male; Microscopy, Electron, Scanning; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Gland; Thyrotropin

Previous studies have characterized the pharmacology of propylthiouracil (PTU) in normal and hyperthyroid subjects, but there is little information available regarding PTU pharmacokinetics in pregnant hyperthyroid women. We investigated the serum PTU response to an oral dose of PTU in six hyperthyroid pregnant women both ante- and postpartum. The serum PTU profile during the third trimester of pregnancy was qualitatively similar to that in nonpregnant subjects, but serum PTU concentrations were consistently lower in the late third trimester compared with postpartum values. Cord serum PTU concentrations were consistently higher than simultaneously obtained maternal serum PTU concentrations, suggesting slower PTU clearance in the fetus. There was a significant inverse correlation (r = -0.92; P = 0.026) between the maternal serum PTU area under the curve in the third trimester and the cord serum free T4 index.

Topics: Adult; Female; Fetal Blood; Humans; Hyperthyroidism; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Propylthiouracil; Reference Values; Thyroxine

Topics: Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

The clinical management of the hyperthyroid patient is controversial, because there is no perfect treatment. Factors that influence the choice of therapy include the patient's age, sex, and type of hyperthyroidism, as well as patient and physician preference.

Topics: Adenoma; Adolescent; Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Child; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Male; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms; Thyroxine; Triiodothyronine

Topics: Animals; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Carbimazole; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Immunosuppressive Agents; Methimazole; Propylthiouracil; Thiourea; Thyroid Hormones

Nine patients with hyperthyroidism due to Graves' disease did not respond to therapy with very large doses (800 to 2000 mg/d) of propylthiouracil. In eight patients, studies showed propylthiouracil was absorbed and metabolized normally. Five patients had no detectable propylthiouracil in their serum 2 to 3 hours after supposedly taking their medication at home, and three patients had markedly abnormal results of perchlorate discharge tests after receiving propylthiouracil under supervision. After evaluation, noncompliance was thought to be the reason for treatment failure in six of the nine patients; one patient was possibly resistant. In two patients, data were insufficient, although intermittent noncompliance could not be ruled out. Among patients who respond poorly to propylthiouracil therapy, noncompliance is the most likely reason. In such patients, methimazole should be substituted for continued massive doses of propylthiouracil.

Topics: Adolescent; Adult; Drug Resistance; Female; Graves Disease; Humans; Hyperthyroidism; Iodides; Male; Middle Aged; Patient Compliance; Perchlorates; Pregnancy; Propylthiouracil; Sodium Compounds; Thyroxine

Iopanoic acid (1 g/d) was used together with propylthiouracil (1200 mg/d) in the treatment of a patient with very severe hyperthyroidism and associated cardiac failure. Although serum total T3 decreased by 75% within 48 h and reached normal after 72 h, free T3 levels did not fall to normal. Total and free T4 remained markedly elevated and features of hyperthyroidism persisted. Estimations of theoretical in vivo occupancy of nuclear thyroid hormone receptors, based on serum free T4 and free T3, suggest that the marked decrease in total T3 would not result in a corresponding decrease in thyroid hormone action. Hence, estimates of potential benefit from oral cholecystographic contrast agents, based only on measurements of total T3, may be unduly optimistic. When temporary agranulocytosis developed in this patient, the prior use of iopanoic acid, by markedly reducing thyroidal iodine uptake, restricted the therapeutic options. Caution should, therefore, be exercised in the use of iodine-containing contrast media as adjunctive antithyroid agents.

Topics: Cell Nucleus; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iopanoic Acid; Middle Aged; Propylthiouracil; Receptors, Cell Surface; Receptors, Thyroid Hormone; Thyroid Gland; Thyroxine; Triiodothyronine

The effect of thyroid status on the postnatal development of the two molecular forms of Na+,K+-ATPase, distinguished kinetically on the basis of their ouabain sensitivity, was examined in rat brain. Hypothyroidism induced by PTU from day 1 postnatally significantly reduced the Na+,K+-ATPase activity in cerebellum (22-30 days) but not forebrain, whereas hyperthyroidism (T4 treatment from day 1) had no effect. The hypothyroidism-induced reduction in cerebellum was reflected by a 20-45% reduction in the activity of the alpha(+) form of Na+,K+-ATPase (high ouabain affinity) against control brains compared to a 60-70% reduction in the activity of the alpha form (low ouabain affinity). These results show that neonatally induced hypothyroidism leads to a selectively greater impairment of the ontogenesis of the activity of cerebellar alpha form of Na+,K+-ATPase. This may possibly reflect a retarded development of a selective cerebellar cell population containing predominantly the alpha form of the enzyme.

Topics: Adenosine Triphosphatases; Animals; Brain; Ca(2+) Mg(2+)-ATPase; Cerebellum; Chemical Phenomena; Chemistry; Diencephalon; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Sodium-Potassium-Exchanging ATPase; Telencephalon; Thyroxine

The binding of 1 alpha,25-dihydroxy (26,27-methyl-[3H]) cholecalciferol ([3H]1,25-(OH)2D3) to its receptor in cytosol of the anterior pituitary cells was examined in hyperthyroid- and hypothyroid rats, as well as in normal rats. The binding capacity increased by 41% in L-Thyroxine-treated hyperthyroid rats and decreased by 49% in propylthiouracil-ingested hypothyroid rats as compared with normal control rats, whereas the affinity of the receptor for [3H]-1,25(OH)2D3 showed no difference among these 3 animal groups. These findings indicate that the number of 1,25(OH)2D3 receptors in the pituitary may be regulated by thyroid hormone, and further suggest that 1,25-(OH)2D3 may play some role in regulating functions of the anterior pituitary.

Topics: Animals; Calcitriol; Centrifugation, Density Gradient; Cytosol; Hyperthyroidism; Hypothyroidism; Male; Pituitary Gland, Anterior; Propylthiouracil; Rats; Receptors, Calcitriol; Receptors, Steroid; Thyrotropin; Thyroxine

The sympathomimetic stimulation of choroid plexus transport and secretion in rat seems to be mediated by beta-adrenergic receptors. In the present report the effect of induced changes in thyroid function on transport mechanisms in the rat choroid plexus was studied. Following induction of hyperthyroidism (treatment with T3 for 10 days) the tissue/medium ratio (T/M) for choline uptake in choroid plexus in vitro decreased significantly by 68%. The Na+-K+-ATPase activity showed a statistically significant increase of about 16%. Also following cervical sympathectomy, T3 caused a reduction of the T/M for choline, to the same level as in the non-sympathectomized animals, while the effect of T3 on the Na+-K+-ATPase activity was changed into a 22% decrease. Hypothyroidism (administration of PTU in the drinking water) had little or no effect on the uptake and accumulation of choline in the choroid plexus. The Na+-K+-ATPase activity was reduced by 40%, in contrast to the stimulating effect of T3. There is, hence, reason to believe that the transport of choline in the choroid plexus is only partly regulated by adrenergic mechanisms acting via Na+-K+-ATPase. The major effect of T3 on the choline uptake may be exerted by a mechanism different from the ATPase activity and not involving adrenergic receptors.

Topics: Animals; Choline; Choroid Plexus; Female; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Proteins; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase; Sympathectomy; Thyroxine; Triiodothyronine

Topics: Animals; Capillaries; Diffusion; Electron Transport Complex IV; Female; Hyperthyroidism; Hypothyroidism; Muscles; Oxidation-Reduction; Oxygen Consumption; Propylthiouracil; Rats; Rats, Inbred Strains

Topics: Adult; Female; Humans; Hyperthyroidism; Propylthiouracil; Stress, Psychological

Topics: Abdomen; Anorexia; Body Weight; Dexamethasone; Diagnosis, Differential; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Hyperthyroidism; Middle Aged; Pain; Potassium Iodide; Propranolol; Propylthiouracil; Vomiting

Topics: Costs and Cost Analysis; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil

The enzymatic activities of two "key" enzymes of the glycolytic pathway, pyruvate kinase and lactic dehydrogenase, were studied in seven areas of the brain in male adult rats in states of pharmacologically induced hyper and hypothyroidism. The brain areas were: anterior cortex, adenohypophysis, hypothalamus, amygdaline nucleus, septum, hippocampus and cerebellum. In T3 treated animals, pyruvate kinase activity showed significant increase in all the areas studied while lactic dehydrogenase activity decreased. In propyl-thiouracil treated animals these enzyme activities showed no significant variations from those in animals of the control group.

Topics: Animals; Brain; Glycolysis; Hyperthyroidism; Hypothyroidism; L-Lactate Dehydrogenase; Male; Propylthiouracil; Pyruvate Kinase; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5'-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 microgram/g body weight (BW]. Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5'-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 microM T4 and 100 mM dithiothreitol at 37 degrees C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P less than 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P less than 0.01) compared with control rats. Serum TSH concentrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Female; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Kinetics; Peroxidases; Pituitary Gland; Pregnancy; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine

Hyporesponsiveness of GH to insulin-induced hypoglycemia has previously been reported in hyperthyroid patients. In order to clarify the GH secretion in thyrotoxic patients, sleep-related increases in the serum GH concentration were investigated. Eight thyrotoxic females ranging in age from 7 to 15 were treated with PTU. Blood samples for measurement of GH were drawn every 15 minutes during the first few hours of sleep before and during the treatment lasting about three months. The mean maximum serum GH level before the treatment was 10.0 +/- 5.5 ng/ml (mean +/- SD); this rose to 23.2 +/- 14.6 ng/ml (P less than 0.02) during the treatment. The maximum value of more than 10 ng/ml was detected in only 3 out of the 8 patients before treatment. On the other hand, serum GH levels during PTU administration rose to above 10 ng/ml in all patients except one. It was revealed that sleep-related elevations of GH occurred early in sleep and in close association with a slow-wave EEG pattern. The results show that sleep-related GH release is low in the hyperthyroid state, but becomes significantly elevated during PTU administration. However, even in the hyperthyroid state, the sleep-related secretion of GH is closely correlated with the slow-wave sleep stage as in the euthyroid condition.

Topics: Adolescent; Child; Female; Growth Hormone; Humans; Hyperthyroidism; Propylthiouracil; Sleep; Sleep Stages; Thyroid Hormones

Glucose-6-phosphate dehydrogenase activity increases following denervation of rat skeletal muscle. The specificity of this effect to muscle fibre type was studied. Basal activity of the dehydrogenase was higher in soleus, a muscle composed predominantly of type I fibres, than in extensor digitorum longus, a muscle composed predominantly of type IIa and b fibres. The enzymatic activity of the soleus was also greater than that of the red (RQ) and white (WQ) portions of quadriceps muscle (predominantly type IIa and type IIb fibres, respectively). Following denervation, glucose-6-phosphate dehydrogenase increased in extensor digitorum longus and RQ, but not in WQ or the soleus. Following chronic treatment of rats with 3,3',5-triiodothyronine, which converts type I muscle fibres to type II, the dehydrogenase activity increased in both denervated soleus and extensor digitorum longus. It is concluded that the effect of denervation on glucose-6-phosphate dehydrogenase activity is selective for type IIa (fast oxidative-glycolytic) muscle fibres.

Topics: Animals; Glucosephosphate Dehydrogenase; Hyperthyroidism; Hypothyroidism; Male; Muscle Denervation; Muscles; Propylthiouracil; Rats; Triiodothyronine

Cardiovascular alterations in hypo- and hyperthyroidism have been ascribed to changes of noradrenergic neurotransmission. In the present study the influence of thyroid hormones on adrenoceptors in the rat heart was further characterized. The effect of artificial hypothyroidism (induced by feeding 6-propyl-2-thiouracil, PTU) and hyperthyroidism (induced by daily injections of triiodothyronine, T3) on myocardial adrenoceptor binding, catecholamines, some physiological responses, and their interdependence was examined. The density of myocardial beta-adrenergic binding sites (3H-dihydroalprenolol, 3H-DHA) was reduced after PTU (by 38%) and enhanced after T3 treatment (by up to 82%). The increase was dose- and time-dependent and reversible within 4 days. No changes of the affinity of 3H-DHA to its binding sites were observed. Only L-T3 and L-T4 proved to be active, D-T3 and reverse T3 had no effect. The rise in beta-adrenoceptor density caused by T3 was prevented by concomitant administration of cycloheximide, indicating its dependence on protein synthesis. The density of myocardial alpha 1-adrenergic binding sites (3H-prazosin) was significantly reduced in the PTU group (by up to 28%) and even more distinctly by T3 treatment (by up to 50%). KD values remained unaltered. The noradrenaline content and turnover of rat hearts was significantly reduced by T3-induced hyperthyroidism. PTU treatment had no influence on content and turnover of noradrenaline. Plasma noradrenaline as well as adrenaline levels in freely moving rats were increased by PTU treatment 9- and 5-fold, respectively. In T3-injected animals no significant changes were measured. The density of adrenoceptors is known to be inversely correlated with catecholamine levels in several organs. Neither alpha- nor beta-adrenoceptor changes in the myocardium of dysthyroid rats could be attributed to such a homologous regulation, since they still occurred after chemical sympathectomy with 6-hydroxydopamine and adrenalectomy.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Cycloheximide; Decerebrate State; Dihydroalprenolol; Dose-Response Relationship, Drug; Electric Stimulation; Heart Rate; Hyperthyroidism; Hypothyroidism; Male; Myocardium; Norepinephrine; Organ Size; Prazosin; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Time Factors; Triiodothyronine

T4 (0.26 microM) was incubated in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA with homogenates (3-5 mg protein) of various rat tissues and up to 400 mM dithiothreitol (DTT) for 1 h at 37 C; the rT3 generated was measured by RIA of ethanol extracts of the incubation mixture. Among the various tissues of the male rat, homogenates of skin and cerebral cortex were very active in the conversion of T4 to rT3; other tissues demonstrated little or no T4 5-monodeiodinating activity (MA). The tissue content of rT3 was also greatest in these two tissues. The MA in skin increased linearly with incubation period (up to 4 h) and with increasing concentration of protein (up to 5 mg), substrate (up to 10 microM) and DTT (up to 400 mM); its optimal pH was 7.4, and optimal temperature was 37 C. Its Km and maximum velocity approximated 0.29 microM and 9.6 pmol/h X mg protein, respectively, in the presence of 400 mM DTT. There was no appreciable difference in T4 to rT3 MA of skin from different parts of the body. The MA was most abundant in microsomes and least in cytosol. The MA was unaffected by propylthiouracil (up to 25 microM), methimazole (up to 100 microM), sodium salicylate (up to 80 microM), or 8-anilino-1-naphthalene sulfonic acid (up to 75 microM). Ipodate (up to 80 microM) weakly inhibited the MA. T3 and 3,5-diiodothyronine inhibited dermal T4 to rT3 MA in a dose-dependent manner; T3 was 3-12 times more potent than 3,5-diiodothyronine on a molar basis in different experiments. Treatment of euthyroid rats with 3,5-dimethyl-3'isopropylthyronine (45 micrograms/day, ip) for 3 or 5 days significantly increased dermal T4 to rT3 MA. Similar treatment of rats with T4 (100 micrograms/day, ip) or T3 (20 or 80 micrograms/day, ip) did not change with MA appreciably. Hypothyroidism markedly inhibited the MA, and fasting inhibited it modestly. Pregnancy was associated with marked reduction in the MA of skin in the mother [0.30 +/- 0.11 (+/- SE) vs. 7.2 +/- 2.2 ng/h X mg protein; P less than 0.02] and fetus (0.67 +/- 0.075; P less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Dithiothreitol; Fasting; Female; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; Male; Microsomes; Pregnancy; Propylthiouracil; Rats; Skin; Temperature; Thyroxine; Time Factors; Tissue Distribution; Triiodothyronine, Reverse

A 12-year-old girl with hyperthyroidism who had started treatment with propylthiouracil (PTU) 100 mg tid developed hepatitis. The drug was stopped, and the clinical and laboratory findings of hepatitis disappeared within a week. She was not receiving other drugs that could cause hepatic damage, and investigations for various viral agents were negative. This is the ninth report of PTU-induced hepatitis. The clinical picture is similar to that of viral hepatitis. Recovery usually occurs after withdrawal of the drug, but there have been two fatal cases of PTU-induced hepatitis.

Topics: Chemical and Drug Induced Liver Injury; Child; Female; Humans; Hyperthyroidism; Propylthiouracil

The effect of thyroid status on histamine H1 receptors in adult and developing rat brain was investigated using the (3H) mepyramine binding assay. Hypothyroidism induced by treatment with 6-n-propyl-2-thiouracil resulted in a 31% decrease in the density and total content of adult rat brain (3H) mepyramine binding sites and a significant retardation of the developmental increase in H1 receptor binding in neonates. At 30 days of age, when euthyroid rats reached binding levels of the adult, hypothyroid animals presented reductions of 22 and 39% in (3H) mepyramine bound per unit weight and per brain respectively. In contrast, hyperthyroidism induced by treatment with L-thyroxine did not alter H1 receptor numbers in the adult rat brain but accelerated the developmental increase in (3H) mepyramine bound per unit weight that reached normal adult levels by 21 days of age. The results suggest that thyroid dysfunction during early life and adulthood may cause derangements of the histaminergic system in the brain.

Topics: Age Factors; Animals; Brain Chemistry; Female; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Pyrilamine; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H1; Thyroxine; Triprolidine

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Adult; Antithyroid Agents; Arthritis, Rheumatoid; Complement System Proteins; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thyroxine; Triiodothyronine

The structural similarities of the heavy chains (HC) of myosin isolated from atria and ventricles of hyper-, hypo-, and euthyroid rabbits were compared by immunological analysis, by one- and two-dimensional peptide mapping, and by electrophoresis under nondenaturing conditions. Monoclonal and polyclonal antibodies, which are specific for HC alpha of ventricular myosin, cross-reacted equally with the HCs of euthyroid atrial myosin. Our immunological analysis identified multiple epitopes common to euthyroid atrial HC and ventricular HC alpha. One- and two-dimensional gel electrophoretic analysis of peptides produced by partial proteolytic digestion of each type of HC reveal no differences between euthyroid atrial HCs and ventricular HC alpha, whereas marked differences are apparent between atrial HC and ventricular HC beta. Nondenaturing gel electrophoresis separates ventricular myosin from hyper- and hypothyroid rabbits into two forms, V1 and V3, respectively. In euthyroid atria, two isomyosins, A1 and A2, were resolved; with the slower moving A2 isomyosin having the same mobility as that of the V1 isomyosin. After cross-hybridization of light chains of ventricular myosin with euthyroid atrial HCs, only a single band having a mobility identical with that of the V1 isomyosin was seen. Furthermore, atrial myosin HCs isolated from hyper- and hypothyroid rabbits were indistinguishable from euthyroid atrial HC and from ventricular HC alpha by these procedures. We conclude that ventricular HC alpha and atrial HC are indistinguishable proteins, and that the type of HC expressed in the atria is unaffected by the thyroid state of the rabbit.

Topics: Animals; Antibodies, Monoclonal; Epitopes; Heart; Heart Atria; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Myocardium; Myosins; Organ Specificity; Propylthiouracil; Rabbits; Radioimmunoassay; Thyroid Gland; Thyroxine

Iodine-induced hyperthyroidism has been frequently described when iodine is introduced into an iodine-deficient area. However, it may also occur in patients with and without previous thyroid disease residing in iodine-sufficient areas. Five patients with iodine-induced hyperthyroidism seen in a 12-month period are described. All were exposed to iodine in the form of commonly used drugs (Betadine, Iodo-Niacin, amiodarone, and radiographic contrast dyes). The cause of iodine-induced hyperthyroidism is unclear, but it is probably more common in patients with goiters containing previously existing areas of autonomous function or iodine-poor thyroglobulin. Iodine-induced hyperthyroidism usually abates after iodine withdrawal in patients with multinodular goiters or normal thyroid glands. The hyperthyroidism is usually treated with beta-blockers and antithyroid thionamide drugs, although reinstitution of iodine to block thyroid hormone release or corticosteroids occasionally may be necessary. Iodine-containing drugs should be given with caution to patients with underlying thyroid disease.

Topics: Adult; Amiodarone; Chlorobutanol; Coloring Agents; Coronary Artery Bypass; Drug Combinations; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Male; Middle Aged; Niacinamide; Postoperative Complications; Povidone-Iodine; Propylthiouracil; Radiographic Image Enhancement; Sodium Iodide; Thyroid Hormones

Variations in renin- angiotensin-aldosterone system (RAAS) in experimentally induced hyperthyroidism were studied. The changes observed in the RAAS in these conditions, evaluated through the plasma renin activity (PRA), are parallel to serum aldosterone concentration (AC). An increase in PRA and AC is produced following the administration of triiodothyronine, possibly through elevated adrenergic activity: beta-blocker, propranolol, returned the PRA and AC to normal. The active hormone is seen to be triiodothyronine, confirmed by using the antithyroid preparation, propylthiouracil, to inhibit the conversion of thyroxine. Propylthiouracil administration to hyperthyroid animals lowers the PRA and AC.

Topics: Aldosterone; Animals; Hyperthyroidism; Male; Natriuresis; Potassium; Propranolol; Propylthiouracil; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System; Sodium; Thyroxine; Triiodothyronine

High concentrations of thyrotrophin-releasing hormone (TRH) in the rat pancreas were detected during the first few days of life decreasing thereafter while pancreatic TRH-degrading activity (TRH-DA) absent at birth appeared on day 14 and increased to reach adult values by day 21. This period of life is also remarkable by the low level of circulating thyroid hormones. Since TRH-degrading activity may be thyroid hormone dependent it was of interest to study the effects of thyroid status fluctuations both on TRH-DA and TRH content during the neonatal period. In this study, hypo- and hyperthyroidism were induced by 6-n-propyl-2-thiouracil (PTU) and triiodothyronine (T3) respectively. Pancreatic TRH-DA and TRH concentrations were measured at different ages from birth until day 29, in treated animals and results compared to control age-matched rats. In hypothyroid rats, pancreatic TRH concentrations remained significantly higher after day 16 while TRH-DA was lower during the whole period studied. Following T3 treatment, pancreatic TRH concentrations decreased significantly from day 3 onwards. However, no significant changes were found for TRH-DA except a two-fold increase on day 28. These results suggest that two different mechanisms may account for thyroid hormones action: 1) a direct effect on pancreatic TRH 2) an inductive saturable effect on TRH-DA. Furthermore a fine tuner modulatory role of TRH-DA on TRH concentrations cannot be excluded.

Topics: Age Factors; Animals; Female; Hyperthyroidism; Hypothyroidism; Pancreas; Pregnancy; Propylthiouracil; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyrotropin-Releasing Hormone; Triiodothyronine

The findings and course in a 55-year-old Black man with thyrotoxic periodic paralysis are described. This disorder appears to have a strong predilection for Orientals (approximately 90% of reported cases) with occasional reports in Caucasians and only one previous description in a Black. HLA phenotyping of the reported patient demonstrated neither of the two genetic markers previously noted among Chinese with thyrotoxic periodic paralysis, indicating that these haplotypes do not serve as markers for the disorder in Blacks.

Topics: HLA Antigens; Humans; Hyperthyroidism; Male; Middle Aged; Paralyses, Familial Periodic; Phenotype; Potassium; Propylthiouracil

Propylthiouracil-induced hepatitis is an uncommon entity. Two further cases are reported herein, and the clinical and laboratory features of the other six cases in the English literature are reviewed. The initial appearance of the disease is similar to that of viral hepatitis, characterized by nausea, vomiting, and jaundice. The biochemical pattern of injury is predominantly hepatocellular, with marked elevation of transaminase valves and less striking elevation of alkaline phosphatase values. Recovery is usually complete after withdrawal of the drug, but there have been at least two fatalities, including the first patient (to our knowledge) whose case is reported herein. Despite its rarity, the disease should be suspected in any patient receiving propylthiouracil in whom clinical or laboratory evidence of hepatocellular injury develops.

Topics: Adult; Antibodies, Antinuclear; Chemical and Drug Induced Liver Injury; Child; Diagnosis, Differential; Female; Graves Disease; Hepatitis B Surface Antigens; Hepatitis, Viral, Human; Humans; Hyperthyroidism; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Serologic Tests

Nine of 105 cats with hyperthyroidism treated with propylthiouracil developed a serious immune-mediated drug reaction during treatment. Adverse clinical signs, which developed after 19 to 37 days (mean, 24.8 days) of propylthiouracil administration, included lethargy, weakness, anorexia, and bleeding diathesis. Physical examination revealed pale mucous membranes, and petechial hemorrhages of the skin and oral cavity. Results of hematologic testing revealed severe anemia and thrombocytopenia. The direct antiglobulin (Coombs') test was positive in all 7 cats evaluated, whereas the serum antinuclear antibody titer was greater than or equal to 1:10 in 5 of the 8 cats tested. In 4 of the cats, treatment included appropriate supportive therapy and cessation of propylthiouracil; in these cats, anemia and thrombocytopenia resolved and Coombs' and antinuclear antibody tests became negative within 2 weeks.

Topics: Anemia, Hemolytic; Animals; Antibodies, Antinuclear; Autoimmune Diseases; Cat Diseases; Cats; Female; Hyperthyroidism; Male; Propylthiouracil; Thrombocytopenia

A patient presenting with hyperthyroidism had a rapidly enlarging thyroid mass that histopathologically was a diffuse histiocytic lymphoma arising in a gland with Hashimoto's thyroiditis. The concurrent development of both hyperthyroidism and lymphoma may have resulted from similar immunologic abnormalities. Appreciation of the relationship between thyroid lymphoma and Hashimoto's thyroiditis, and their presentation with either hypothyroidism or hyperthyroidism should lead to an earlier diagnosis of lymphoma and improved survival.

Topics: Body Weight; Female; Humans; Hyperthyroidism; Lymphoma; Middle Aged; Propranolol; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Thyroiditis

We describe a patient with TSH-induced hyperthyroidism successfully treated with bromocriptine. A 25-yr-old woman was found to have hyperthyroidism due to excessive TSH secretion; no pituitary tumor was found. Her serum T4 level ranged between 21.9 and 25.9 micrograms/dl and that of T3 between 283 and 314 ng/dl. Serum TSH was between 5 and 9 microU/ml with an exaggerated response to TRH. Basal metabolic rate was +26 to +38%. Serum PRL was also elevated (79 ng/ml). Administration of bromocriptine for 4 months decreased serum TSH and PRL levels to normal with a concomitant fall in levels of serum T3 and T4. Regression of the clinical manifestations of hyperthyroidism occurred during bromocriptine drug therapy. These results suggest that reduction in hypothalamic dopaminergic tone may have contributed to the inappropriately increased TSH secretion in the patient.

Topics: Adult; Bromocriptine; Female; Humans; Hyperthyroidism; Propylthiouracil; Thyrotropin; Triiodothyronine

Clusters of luminal dense bodies, limited by a triple-layered membrane, were found in all follicle lumina in thyroid glands of mice. After thyroxine treatment the number of luminal dense bodies increased, especially in the periphery of the lumen, where the intraluminal bodies often displayed a striking resemblance to microvilli. In hyperplastic goiters, obtained by feeding mice with propylthiouracil, luminal dense bodies were replaced by intraluminal vesicles. During goiter involution the vesicles were gradually replaced by luminal dense bodies; the presence of intermediate forms suggests that vesicles and dense bodies are basically the same formations. Luminal dense bodies were observed in colloid droplets indicating their removal by endocytosis. As demonstrated by electron-microscopic cytochemistry, luminal dense bodies contain a membrane-bound peroxidase, and electron-microscopic autoradiography after administration of 125I indicate that they possess an iodinating capacity. Our observations on mouse thyroid glands suggest that the luminal dense bodies, which appear as vesicles in hyperplastic glands, are formed by shedding of the apical plasma membrane of the follicle cell. The shedding process might be of importance for the turnover of plasma-membrane material.

Topics: Animals; Autoradiography; Cell Membrane; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Male; Mice; Mice, Inbred Strains; Microscopy, Electron; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine

Eleven pregnant women were treated for hyperthyroidism with carbimazole (CZ) and one with propylthiouracil (PTU). Based upon a previous study it was decided that lactation should be permitted if the dose required after delivery did not exceed 15 mg of CZ or 150 mg of PTU. In the patients studied here the daily dose of CZ varied from 5 to 15 mg and that of PTU was 125 mg. TSH was measured in cord blood and in the blood of the newborn infants usually after 2 and 3 weeks of lactation. Serum T4 was measured serially in the infants' blood from day 4 up to 21 day of age, at least. In all instances the TSH concentration in cord blood remained below 45 mU/l the level used in screening for neonatal hypothyroidism. Serum TSH and T4 were all within the appropriate reference limits during the 3 weeks of study with only one exception. In the infant whose mother was treated with PTU the serum T4 measured 5 d after birth was slightly below the lower limit but later returned to normal. Since serum TSH and T4 did not deviate from the reference range in newborn infants during lactation, we conclude that breast-feeding can be permitted if the daily dose of CZ does not exceed 15 mg (or 150 mg of PTU) and if facilities are available for measuring neonatal serum TSH and T4.

Topics: Carbimazole; Female; Fetal Blood; Humans; Hyperthyroidism; Infant, Newborn; Lactation; Pregnancy; Propylthiouracil; Thyrotropin; Thyroxine

The proportion of total, helper and suppressor T lymphocytes among mononuclear cell preparations from blood and spleen of rats made hypo- and hyperthyroid was measured using three monoclonal antibodies specifically directed against total, helper and suppressor T cells. Compared to normal rats, hypothyroid (thyroidectomized or treated with 6-propyl-2-thiouracil (PTU) rats had a decreased proportion of suppressor T cells in the spleen, which produced an increase in the helper/suppressor T cells ratio. The opposite alterations (increased suppressor T cells and decreased ratio) was found in the blood of the same animals. Triiodothyronine (T3) added to PTU in the drinking water prevented these alterations. Animals treated with high doses of T3 for 17 days did not develop any alteration either in the proportions or in the ratio of helper/suppressor T cells. Our results suggest that hypothyroidism but not hyperthyroidism alters the normal balance between helper and suppressor T cells in rats.

Topics: Animals; Antibodies, Monoclonal; Body Weight; Hyperthyroidism; Hypothyroidism; Leukocyte Count; Male; Organ Size; Propylthiouracil; Rats; Rats, Inbred Strains; Spleen; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Thyroidectomy; Triiodothyronine

After 2 weeks of goitrogen treatment [propylthiouracil (PTU), 0.02% in drinking water], the thyroids of rats increased to 280% of control wet weight, 270% of dry weight, and 250% of control DNA content. Two phases of growth were apparent, an initial hypertrophy phase lasting 3 days (increase in cell size and gland weight with no detectable increase in DNA) and a hyperplastic phase (increase in DNA with histological evidence of cell proliferation) starting at 3-4 days and continuing through 14 days. The cyclic AMP-dependent protein kinase activity ratio (-cyclic AMP/+cyclic AMP) showed a biphasic pattern during the 2-week thyroid growth period, with maxima at day 1 (132% of control) and day 6 (148% of control). Ornithine decarboxylase (EC 4.1.1.17), the initial enzyme in polyamine biosynthesis, showed a similar biphasic pattern with a 6- to 7-fold elevation in activity at 2-3 days and a 4-fold elevation at 6 days. S-Adenosyl-L-methionine decarboxylase (EC 4.1.1.50), the enzyme which catalyzes spermidine synthesis, was elevated 4-fold at 9 days of treatment. The thyroid total supernatant protein kinase activity (+cyclic AMP) increased to 160% of control by 4 days, returning to control by 14 days of PTU treatment. The thyroid had 10% Type I activity and 90% Type II cyclic AMP-dependent protein kinase activity. The specific activity of both Types I and II remained unchanged for the first 2 days of PTU treatment. Both types increased to 150% of control by 4 days. Type I remained elevated throughout the remainder of the 14 days, in contrast to Type II, which decreased conspicuously to control levels by 6 days. A single injection of thyroid-stimulating hormone (TSH, 1.0 unit/100 g of body weight, i.p.) resulted in a 20-fold increase in thyroid ornithine decarboxylase activity by 4 hr. The same dose of TSH produced only a 3-fold induction of ODC in rats hypophysectomized 2 weeks previously. The thyroid specific activity of Types I and II protein kinase was only 55% and 57% of control, respectively, in these unresponsive rats. Thyroids from rats chronically stimulated for 14 days showed an increase in ornithine decarboxylase following TSH administration similar to that of control rats. Changes in the activation as well as specific activity of Types I and II protein kinase during hypertrophy and hyperplasia underlie the complexity of a cyclic AMP-mediated response.

Topics: Adenosylmethionine Decarboxylase; Animals; Carboxy-Lyases; Cyclic AMP; Hyperplasia; Hyperthyroidism; Hypertrophy; Kinetics; Male; Ornithine Decarboxylase; Polyamines; Propylthiouracil; Protein Kinases; Rats; Rats, Inbred Strains; Thyroid Gland

Plasma cyclic AMP levels were studied in ten subjects with hyperthyroidism before and after propylthiouracilic treatment. In untreated hyperthyroid subjects the plasma cyclic AMP levels were significantly elevated but were normalized when plasma iodothyronine levels declined in the normal range.

Topics: Adolescent; Adult; Cyclic AMP; Female; Humans; Hyperthyroidism; Propylthiouracil

A 25 year old with vitiligo por 6 years now. For one year has being presenting hyperthyroidism, myasthenia gravis and periodic paralysis. The normalization of the thyroid function was followed by a significant improvement of the myasthenic syndrome that did not interfere with the paralytical attacks.

Topics: Adult; Humans; Hyperthyroidism; Male; Myasthenia Gravis; Propylthiouracil; Quadriplegia; Vitiligo

The control of weaning was studied in rat pups aged 17-24 days. The influence of two hormones, thyroxine (T4) and corticosterone, and the effect of declining intestinal lactase activity were evaluated. Hypothyroidism was induced by administration of n-propylthiouracil and hyperthyroidism was induced by injection of T4. Hypothyroid pups failed to begin nibbling chow while littermates injected with T4 weaned normally. Two abnormalities resulting from hypothyroidism, hypothermia and stunted incisors, were not responsible for the lack of weaning in hypothyroid pups. Hyperthyroidism did not cause precocious weaning. Glucocorticoid levels were manipulated by both adrenalectomy (ADX) and administration of corticosterone. ADX pups exhibited a delayed pattern of weaning while both ADX pups injected with corticosterone and sham-operated pups weaned normally. Corticosterone injected before its normal developmental surge did not cause precocious weaning. Lactase activity, measured throughout these experiments, did not consistently reflect the degree of weaning progression. We conclude that 1) the hormones, T4 and corticosterone, are necessary for the onset of weaning, but neither is a sufficient stimulus to initiate weaning, and 2) low lactase activity does not initiate weaning.

Topics: Adrenalectomy; Aging; Aldosterone; Animals; beta-Galactosidase; Corticosterone; Female; Hyperthyroidism; Hypothyroidism; Jejunum; Pregnancy; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine; Weaning

Serum protein binding of propylthiouracil (PTU) was measured by ultrafiltration in healthy and hyperthyroid patients. The serum protein binding in 12 euthyroid subjects was 76.2 +/- 1.2% (mean +/- s.d.), not significantly different from the values in 10 hyperthyroid patients: 76.6 +/- 1.3% Binding was unaffected by incubation time and temperatures between 25 and 37 degrees C, but increased from 76.5 to 79.1% when pH changed from 7.4 to 7.9. PTU is predominantly bound to albumin with two classes of binding groups with different number of binding sites and affinity. Displacement experiments showed interaction with acetylsalicylic acid, warfarin and phenylbutazone, but not with antipyrine and nortriptyline or other basic drugs.

Topics: Adult; Blood Proteins; Humans; Hydrogen-Ion Concentration; Hyperthyroidism; Male; Propylthiouracil; Protein Binding

The serum levels of propylthiouracil (PTU) were determined by radioimmunoassay in 10 normal subjects and in 11 patients with Graves' disease after a single 100 or 200 mg oral dose of PTU. The serum half-life of PTU in the normal subjects and in hyperthyroid patients with uneventful clinical course was 75 +/- 19 min (mean +/- SD, n = 6) and 73 +/- 13 min (n = 7), respectively. Maximum serum PTU concentrations were usually attained within 1 h after a single 200 mg oral dose and at 1 h were 5.3 +/- 1.4 micrograms/ml (3.1 +/- 0.82 X 10(-5) M) in normal subjects (n = 6) and 4.8 +/- 2.4 micrograms/ml (2.8 +/- 1.4 X 10(-5) M) in hyperthyroid patients (n = 7). These between-group differences were not significant. Serum PTU concentrations were low in a pregnant hyperthyroid patient with a weak response to PTU treatment. In another patient, who appeared resistant to PTU therapy, the serum PTU level increased as expected at testing, and it was later confirmed that, during treatment, he had not taken the drug as prescribed. In a patient who developed agranulocytosis due to methimazole and subsequently fever due to PTU, the half-life of PTU was prolonged to about 130 min. These findings suggest that monitoring the serum PTU levels in patients with Graves' disease can be of clinical value in patients who do not respond to treatment. Furthermore, it may provide some clues as to the mechanism by which toxic reaction develops.

Topics: Administration, Oral; Adult; Aged; Female; Graves Disease; Humans; Hyperthyroidism; Kinetics; Male; Middle Aged; Pregnancy; Pregnancy Complications; Propylthiouracil; Radioimmunoassay; Thyroid Hormones

Observations in a patient with recurrent hyperthyroidism, each time associated with neutropenia which resolved after therapy, prompted a chart review of other patients referred for radioactive iodine therapy. Of 99 untreated patients, 18 had neutrophil counts of less than 2,000/cu mm. After therapy with either thionamides or 131I, 41 of 53 (77%) evaluable patients had an increase in neutrophil count. Eleven of these evaluable patients had neutropenia before therapy; after therapy, all 11 had an increase in their neutrophil counts into the normal range, with a mean increase of 170%. In one patient, studies on the mechanism of neutropenia indicate that bone marrow production and reserve remain normal and that circulating neutrophils are normally marginated. A decreased neutrophil circulation time may be the cause of neutropenia associated with hyperthyroidism.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Leukocyte Count; Male; Middle Aged; Neutropenia; Neutrophils; Propylthiouracil; Retrospective Studies

Topics: Adult; Arthritis; Female; Humans; Hyperthyroidism; Leukopenia; Propylthiouracil; Skin; Vasculitis, Leukocytoclastic, Cutaneous

Thirty-three children with hyperthyroidism, an uncommon condition in childhood, were treated at the Hôpital Ste-Justine in Montreal during the period 1961 to 1974. Of these, 31 underwent medical treatment initially. Fifteen were cured by medical treatment only; the other 18 had to undergo subtotal thyroidectomy. When these two groups were compared the advantage of surgery in the treatment of this disease was clear. There were no major complications postoperatively. Two children became hypothyroid. The mean follow-up was 5 years and 6 months.

Topics: Adolescent; Adult; Child; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Thyroidectomy

A 45-year-old woman with thyrotoxicosis developed agranulocytosis after treatment with propylthiouracil. When the thyrotoxicosis recurred, accompanied by a severe psychotic reaction, administration of antithyroid medication was recommenced. The patient was given methimazole instead of propylthiouracil but, 10 weeks later, agranulocytosis again occurred. This is, to the best of our knowledge, the first report of a case in which agranulocytosis followed treatment with both propylthiouracil and methimazole in the same patient.

Topics: Agranulocytosis; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil; Recurrence

A woman with hypothyroidism and Graves ophthalmopathy was treated with propylthiouracil during her second pregnancy. This was employed because her first pregnancy resulted in an infant with severe intrauterine growth retardation and neonatal thyrotoxicosis. The antithyroid drug used during the second pregnancy crossed the placenta and treated the infant in utero. The infant was delivered by elective cesarean section at 36 weeks and was a live-born male with appropriate height and weight without evidence of thyrotoxicosis. The therapeutic benefit of propylthiouracil during this second pregnancy seems likely, based on the development of neonatal thyrotoxicosis after 4 days of life and on the presence of high thyroid-stimulating immunoglobulin levels in the mother and the infant.

Topics: Adult; Female; Fetal Diseases; Fetal Growth Retardation; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Alpha-Globulins; Female; Humans; Hyperthyroidism; Iodides; Pregnancy; Propylthiouracil; Puerperal Disorders; Thyroxine; Thyroxine-Binding Proteins

Appropriate dosage of levothyroxine for the treatment of hypothyroidism is assessed by determining the serum thyroxine (T4) concentration in secondary and tertiary types. In primary hypothyroidism, the optimal thyroid replacement is that which induces a normal thyroid-stimulating hormone level and a normal TSH response to administration of thyrotropin-releasing hormone. Hypothyroidism often occurs in the management of hyperthyroidism. Serial serum TSH measurements help in the early detection of hypothyroidism, whereas serum triiodothyronine (T3) aids in prompt recognition of recurrence of hyperthyroidism.

Topics: Antithyroid Agents; Drug Evaluation; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Perchlorates; Propylthiouracil; Sodium Compounds

The effects of thyroid status on the activity of hepatic cAMP phosphodiesterase (PDE) were studied in the rat. Male rats were rendered hyperthyroid by treatment with T3 or hypothyroid by treatment with propylthiouracil. The hepatic particulate low Km PDE was solubilized, and its activity was measured at concentrations of 0.12-1.3 microM cAMP. The Km decreased in hypothyroidism and tended to increase in hyperthyroidism with respect to individual controls. The maximal velocity (Vmax) was unaffected by changes in thyroid status. The increases in Km correlated with increasing plasma T3, whereas the Vmax did not. Concentrations of cAMP increased in the livers from hyperthyroid rats and decreased in those from hypothyroid, in comparison with euthyroid rat livers. The effects of thyroid status on various aspects of hepatic lipid metabolism reported from this laboratory may, in part, have resulted from alterations in hepatic cAMP concentrations. These alterations, may have resulted secondarily from changes in the activity of hepatic PDE by changes in the Km for cAMP with little change in the Vmax.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Cyclic AMP; Hyperthyroidism; Hypothyroidism; Kinetics; Liver; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Triiodothyronine

Topics: Anemia; Arrhythmias, Cardiac; Female; Goiter; Humans; Hypercalcemia; Hyperthyroidism; Iodine Radioisotopes; Middle Aged; Propranolol; Propylthiouracil; Thyroxine

Patients with both exophthalmos and hyperthyroidism were treated with different modes of therapy for their hyperthyroidism. Propylthiouracil followed by surgery, propylthiouracil followed by radioactive iodine, propylthiouracil alone, and radioactive iodine alone were used. Some of the patients became hypothyroid and were made euthyroid with levothyroxine sodium. Based on the mode of therapy and whether or not hypothyroidism occurred, each patient was assigned to one of seven groups and followed up for 18 months or longer. Careful exophthalmometry was performed at six-week intervals in all patients. Though progression of exophthalmos was noted in all groups, the group that received propylthiouracil demonstrated the greatest progression of exophthalmos. In the group receiving sodium iodide l 131 therapy and in the group treated surgically, the rate of progression of exophthalmos was lessened with the development of hypothyroidism. Since these hypothyroid patients were made euthyroid with supplemental levothyroxine, it appeared that loss of thyroid tissue, rather than the hypothyroidism per se, was responsible for the decrease in progression of the exophthalmos. The continued progression of exophthalmos in the propylthiouracil-treated group may be related to effects of propylthiouracil on the immune system.

Topics: Exophthalmos; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroidectomy; Thyroxine; Time Factors

The duration of the hyperthyroidism associated with lymphocytic thyroiditis (LT) with spontaneously resolving hyperthyroidism (SRH) was serially monitored in groups of patients who were not given any treatment (control subjects) or treated with propylthiouracil and/or propranolol hydrochloride and prednisone. The length of time for the thyroxine tests from diagnosis to the normal range was 57 +/- 17, 45 +/- 13, and 15 +/- 7 days (mean +/- SD) indicating a dramatic response to prednisone therapy but none to propylthiouracil and/or propranolol therapy. Five patients were found who had seven episodes of SRH while receiving thyroid hormone suppression therapy after having verified chronic LT (two patients) and LT-SRH (three patients). This indicates that thyroid suppression with thyroid hormone may be ineffective in preventing this disease. Two patients were treated by subtotal thyroidectomy because of recurrent or prolonged episodes of SRH. From this experience, the therapeutic alternatives available to the clinician are reviewed.

Topics: Humans; Hyperthyroidism; Prednisone; Propranolol; Propylthiouracil; Remission, Spontaneous; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

The interaction of thyroid status and oleic acid infusion rate on the thermal behavior of the very low density lipoprotein (VLDL) secreted by isolated perfused rat liver was examined. The livers were infused at 37 degrees C with oleate at rates of 0, 83, 166, or 332 mumoles/hr for 4 hours and VLDL was isolated from the perfusate at 12 degrees C. The lipid composition of the VLDL secreted by the perfused liver from hyperthyroid animals was dramatically different from controls at all infusion rates of oleate. Significant changes in the ratio of [phospholipid + cholesterol]/[triglyceride] and in fatty composition of secreted triglycerides occurred. Differential scanning calorimetry of the intact VLDL and extracted triglycerides secreted by euthyroid rats suggested the existence of four thermotropic endothermic transitions centered at -20.5, -14.0, -3.0, and 9.0 degrees C. Both the total enthalpies and the temperatures at which the phase alterations occurred in the triglyceride fraction from VLDL secreted by livers from euthyroid rats were highly dependent on the rate of infusion of oleate. Pretreatment of the rats with triiodothyronine and infusion of 332 mumoles oleate/hr abolished in the intact VLDL the temperature transitions centered at -20.8 and at 10.5 degrees C and decreased the total enthalpy from 8.13 to 38.5 cal/gm. Livers from rats pretreated with propylthiouracil and infused with oleate at 332 mumoles/hr secreted VLDL in which only one transition centered at -5.0 degrees C remained. The total enthalpy was unaffected. At all rates of infusion of oleate, the phase behavior of the intact VLDL or triglycerides extracted from the VLDL was altered by prior treatment of the rats with triiodothyronine or propylthiouracil. The thyroid state of the rat profoundly affected the thermal properties of the VLDL secreted by the perfused liver infused with the unsaturated fatty acid oleate.

Topics: Animals; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry; Hyperthyroidism; Hypothyroidism; Lipoproteins, VLDL; Liver; Male; Oleic Acid; Oleic Acids; Perfusion; Propylthiouracil; Rats; Rats, Inbred Strains; Thermodynamics; Thyroid Gland; Thyroxine; Triglycerides; Triiodothyronine

Two patients are described who depended on potentiation of tricyclic antidepressant effectiveness by thyroid superfunction for remission of an episode of unipolar depression. In one case, the excess thyroid hormone was the product of hyperthyroidism; whenever the hyperthyroidism was treated, the remission induced by imipramine was negated. In the other case, triiodothyronine was exogenously administered. These case studies suggested that some patients may require larger doses than 25 microgram of triiodothyronine per day for effective antidepressant potentiation. Some endocrinological similarities between hyperthyroidism and depressive illness are discussed.

Topics: Adult; Depressive Disorder; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Imipramine; Middle Aged; Propylthiouracil; Triiodothyronine

To determine whether hyperthyroidism or hypothyroidism affected the structure of the very low density lipoprotein (VLDL) secreted by the perfused rat liver, rats were pretreated with 0.9% NaCl, T3, or propylthiouracil. The livers were perfused with 0-332 mumol bovine serum albumin-oleate/h for 4 h. The structure of the secreted VLDL was determined by compositional analysis and the use of the fluorescence probe molecules diphenylhexatriene, trans-parinaric acid, and cis-parinaric acid. Compositional analysis indicated that the VLDL secreted by livers from rats pretreated with T3 had lower unsaturated to saturated fatty acid ratios than did controls, regardless of the amount of oleate infused. Fluorescence polarization of diphenylhexatriene indicated that the interior core lipids of VLDL secreted by livers from T3-treated rats were more rigid than those secreted by livers of euthyroid animals. Arrhenius plots of polarization and corrected fluorescence of diphenylhexatriene and trans-parinaric acid, but not cis-parinaric acid, revealed that characteristic temperatures were shifted 8 to 10 C higher in VLDL secreted by livers from rats pretreated with T3. Treatment of rats for 7 days with propylthiouracil under these mild conditions did not alter the structure or composition of the VLDL secreted by the perfused liver. In summary, the lipid changes in the VLDL secreted by perfused rat livers from hyperthyroid animals were consistent with these VLDL being more rigid particles than those secreted by livers from euthyroid rats, independent of the infusion rate of the FFA.

Topics: Animals; Chemical Phenomena; Chemistry; Fatty Acids; Fluorescence; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Lipids; Lipoproteins, VLDL; Liver; Male; Oleic Acid; Oleic Acids; Perfusion; Propylthiouracil; Rats; Rats, Inbred Strains; Temperature; Triiodothyronine

Topics: Acetaminophen; Animals; Glutathione; Hyperthyroidism; Hypothyroidism; Liver; Liver Glycogen; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Transaminases; Triiodothyronine

The role of thyroxine (T4) in the ontogeny of serum corticosteroid-binding globulin (CBG) and corticosterone has been studied in the rat. Daily injection of T4 (0.1 micrograms/g body wt) resulted in the precocious appearance of both CBG and corticosterone. A dose-response study revealed an increase in both CBG and corticosterone at thyroxine doses greater than 0.02 micrograms/g body wt. In propylthiouracil-induced hypothyroid pups, the developmental rise of both CBG and corticosterone was suppressed. To determine whether T4 elevation of CBG was mediated by corticosterone, serum CBG was measured in corticosterone-injected pups (10 micrograms/g body wt). No increase in CBG was detected on days 8 and 10. A slight increase, only one-eighth that elicited by T4, occurred on day 12. There was also no synergistic effect between T4 and corticosterone. We conclude that the postnatal increase in serum T4 concentrations cues the developmental rise of both CBG and corticosterone in the rat.

Topics: Aging; Animals; Corticosterone; Female; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Rats; Thyroxine; Transcortin

A 57-year-old woman with hyperthyroidism had a loud to-and-fro bruit which persisted when the patient was inadvertently rendered hypothyroid with antithyroid drugs. Symptoms suggestive of transient cerebral ischemia prompted an angiographic study which demonstrated both normal cerebral circulation and an enormous increase in the size of thyroid vasculature. The possibility that the enhanced blood supply to the thyroid had compromised cerebral circulation (thyroid steal syndrome) was considered. The angiographic presentation of hyperthyroidism is reviewed, and the lack of specificity of thyroid bruits as a marker of hyperthyroidism in patients on antithyroid drugs is stressed.

Topics: Carotid Arteries; Cerebrovascular Circulation; Female; Humans; Hyperthyroidism; Ischemic Attack, Transient; Middle Aged; Propranolol; Propylthiouracil; Radiography; Syndrome; Thyroid Gland

Lipid and lipoprotein concentrations were studied in 12 hypothyroid and 11 hyperthyroid female subjects, both before and after therapy, and in 27 age matched female controls. Recognized clinical and laboratory criteria established the diagnosis. Lipoproteins, including the sub-fractions of the high density lipoproteins (HDL), were isolated by preparative ultracentrifugation, and the cholesterol (c) and protein (p) contents of each were determined. Total cholesterol, and in particular HDL-c, were elevated in the hypothyroid patients. The low density lipoprotein (LDL) -c/HDL-c ratio was 1.9 in this group, compared to 2.2 in the control group and 1.35 in the hyperthyroid patients. The HDL-2/HDL-3 ratio in the hypothyroid group was 3.75, as compared to 1.75 in the controls and 4.2 in the hyperthyroid group. Plasma triglycerides were moderately elevated in the hypothyroid patients and were significantly reduced in the hyperthyroid group. Total cholesterol was significantly lower in the hyperthyroid group as compared to the control group. Very low density (VLDL) cholesterol and protein were significantly increased and LDL and HDL cholesterol were reduced in the hyperthyroid patients. On rendering the patients euthyroid, most of these changes were reversed. Thyroid function profoundly affects lipoprotein concentration and composition. The change in the plasma HDL concentrations of the hypothyroid group questions the relationship of this group to arteriosclerosis. Therapy partially corrects the abnormalities, but complete correction may be related to duration of therapy.

Topics: Adolescent; Adult; Aged; Cholesterol; Cholesterol, HDL; Female; Humans; Hyperthyroidism; Hypothyroidism; Lipoproteins, HDL; Lipoproteins, HDL2; Lipoproteins, HDL3; Middle Aged; Propylthiouracil; Thyroxine; Triglycerides

Topics: Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Propylthiouracil; Thyroidectomy

The case is reported of a patient with "refractory" type anemia and acute thyrotoxicosis. There was no evidence of iron or vitamin deficiency, a fact which suggested that the anemia was probably secondary to the acute thyrotoxicosis since correction of the anemia occurred following successful antithyroid therapy with Lugol's solution (aqueous iodine solution) and propylthiouracil without specific hematological treatment. This unusual association of "refractory" type anemia and acute thyrotoxicosis is discussed in the light of data from experimental animal models and the very small number of other cases reported in the literature.

Topics: Aged; Anemia, Aplastic; Erythrocytes; Female; Humans; Hyperthyroidism; Iodides; Iron; Propylthiouracil

Topics: Delta Rhythm; Diagnosis, Differential; Electroencephalography; Evoked Potentials; Female; Humans; Hyperthyroidism; Middle Aged; Neurocognitive Disorders; Propylthiouracil; Thyroid Hormones

Topics: Carbimazole; Female; Humans; Hyperthyroidism; Male; Propylthiouracil; Prospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

Propylthiouracil (PTU) disposition was investigated in hyperthyroid women during pregnancy and post partum. The plasma half-life after the first dose averaged 0.66 h and became greater than 1 h with chronic drug therapy. The apparent volume of distribution after the first dose averaged 0.26 liter/kg, similar to nonpregnant hyperthyroid patients. There was a tendency to increased apparent volume of distribution with chronic drug ingestion. Plasma clearance of PTU showed no change related to disease or to pregnancy. Our data suggest that pregnancy does not have a major effect on the pharmacokinetic disposition of PTU in the hyperthyroid mother. Observation of a prolonged plasma half-life for PTU in 1 patient post partum deserves further investigation to determine if this change is associated with clinically significant therapeutic or toxic effects.

Topics: Adult; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Postpartum Period; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroxine; Triiodothyronine

The basal levels of angiotensin I and kinetic parameters of renin-angiotensin system were studied under control, hyper- and hypothyroidism conditions. The serum levels of triiodothyronine (T3) and thyroxine (T4) and plasma angiotensin II have been measured radioimmunoassay. Hyperthyroidism was induced by 5.5 micrograms/200 g of T3 or 100 micrograms/200 g of T4 administration for 12 days, and hypothyroidism by propylthiouracil (PTU) administration of 1 mg/200 g for 12 days. Basal levels of angiotensin I and plasma renin activity (PRA) increased after T3 injection, were not altered by T4 and decreased after PTU administration. T3 and T4 induced an increase in plasma renin concentration (PRC), while PTU induced a decrease in PRC. Plasma renin substrate (PRS) decreased in hyperthyroid rats and was unchanged by experimentally induced hypothyroidism. A good correlation between T3 serum levels and PRA was found, but there was no such correlation between T4 serum levels and PRA.

Topics: Angiotensin I; Angiotensins; Animals; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Thyroxine; Triiodothyronine

A case of bleeding during operation due to propylthiouracil-induced thrombocytopenia is reported. A 55 year old male who had been treated with propylthiouracil for two months before operation underwent otherwise uneventful cervical laminectomy. Perioperatively he was transfused seven units of whole blood, two units of packed red cells, six units of platelets and two units of fresh frozen plasma for the estimated blood loss of 5500 ml. The patient underwent thyroidectomy without incident 45 days after withdrawal from propylthiouracil. The value of the preoperative coagulation studies of the patient treated with propylthiouracil is discussed.

Topics: Hemorrhage; Humans; Hyperthyroidism; Intraoperative Complications; Male; Middle Aged; Propylthiouracil; Thrombocytopenia

The aim of this study was to examine the temporal and dose characteristics of the corticosteroid-binding globulin (CBG) response to T4 and to determine whether this response is due to stimulation of hepatic biosynthesis of CBG. When n-propylthiouracil (PTU)-induced hypothyroid pups were given a single injection of T4 (0.1 microgram/g BW) on postnatal day 5, 6, or 7, only pups treated on day 7 showed a significant increase in CBG. In a T4 dose-response study conducted with 5- and 8-day-old pups, older pups exhibited maximum CBG concentrations (Rmax) which were 2.5-fold higher than those of younger pups. The D1/2 (dose required to elicit half the maximum response) values were similar at both ages. The effect of T4 withdrawal on serum CBG was also studied in PTU-treated pups. T4 injection on postnatal days 5-19 resulted in a progressive rise in CBG. In pups treated with T4 on days 5-9 and then withdrawn from treatment through day 20, serum CBG showed no further increase but was maintained at an elevated level. Using a liver slice system to assess CBG production in vitro, livers from 14-day-old hyperthyroid pups produced 4.77 ng corticosterone bound/g liver, while livers from euthyroid pups produced no CBG. We conclude: 1) the response of CBG to T4 is a function of the age of the animal; between days 5 and 8 this is due to increased Rmax without any change in sensitivity to T4 (D1/2); 2) T4 is required not only to initiate but also to sustain the developmental increase in CBG; and 3) T4 elicits an increase in circulating CBG by stimulating its synthesis.

Topics: Aging; Animals; Animals, Newborn; Dose-Response Relationship, Drug; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Liver; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine; Transcortin

Nine healthy female controls and 10 hyperthyroid female patients were studied. The intravenous administration of 200 mg cimetidine, an H2-receptor antagonist, was followed by a significant and marked rise in serum prolactin levels in all control subjects. There was no significant difference in serum PRL response to cimetidine injection between the euthyroid controls and hyperthyroid patients. But max delta PRL, the change from basal to peak values, is significantly lower in the hyperthyroid patients than in the controls. There was a significant negative correlation between max delta PRL and serum T4 or T3 levels in hyperthyroid patients before and after treatment with MMI or PTU. It appears from our data that cimetidine induced PRL release was blunted in hyperthyroid patients.

Topics: Adult; Cimetidine; Female; Guanidines; Humans; Hyperthyroidism; Kinetics; Methimazole; Prolactin; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Aged; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Insulin Antibodies; Methimazole; Propylthiouracil

Topics: Female; Fetus; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotropin; Triiodothyronine; Triiodothyronine, Reverse

Topics: Antithyroid Agents; Carbimazole; Female; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Methimazole; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Thyroid Diseases; Thyroid Gland

The authors describe the case of a 49-year-old woman who developed a goiter, mild symptoms of hyperthyroidism, and grossly elevated thyroid function tests after 2 years of treatment with lithium carbonate. Thyroid microsomal autoantibodies were also present. She was retreated with propylthiouracil and improved, but within 3 months she developed agranulocytosis. Propylthiouracil was discontinued, and the patient was treated with antibiotics and recovered. She was then given 131I to control her hyperthyroidism. The case is an example of the rare association of hyperthyroidism with lithium, which usually suppresses thyroid function, and demonstrates that lithium carbonate cannot prevent agranulocytosis caused by propylthiouracil.

Topics: Agranulocytosis; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Lithium; Lithium Carbonate; Middle Aged; Propylthiouracil; Thyroid Hormones

Topics: Adult; Aspirin; Blood Sedimentation; Diagnosis, Differential; Female; Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Function Tests; Thyroiditis; Thyroiditis, Autoimmune; Thyroxine

Topics: Adult; Aged; Antibodies, Antinuclear; Antibody Specificity; Female; Granulocytes; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil

Topics: Adolescent; Anesthesia, General; Child; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Male; Malignant Hyperthermia; Propylthiouracil

Topics: Adult; Choriocarcinoma; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodides; Middle Aged; Pregnancy; Propranolol; Propylthiouracil; Uterine Neoplasms

Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Lithium; Propranolol; Propylthiouracil; Thyroidectomy

Serum 3,3',5'-triiodothyronine (rT3), 3,5,3'-triiodothyronine (T3), thyroxine (T4) and propylthiouracil (PTU) were measured before and at short intervals for 8 hours after oral administration of 200 mg PTU to six patients with untreated thyrotoxicosis. The study was repeated on the 4th day of treatment with 200 mg PTU every 8 hours. Six other patients with untreated thyrotoxicosis were studied after a single administration of 800 mg PTU. The results indicated that PTU inhibition of T4 deiodination to T3, evaluated by the fall in serum T3, was of the same duration as the PTU inhibition of rT3 deiodination, evaluated by the increase in serum rT3. After 200 mg PTU inhibition was maximal for only a few hours, and there was no cumulative effect of PTU during the first four days of treatment, when 200 mg PTU was given every 8 hours. After 800 mg PTU the full effect was maintained for the 9 hour period studied, after which serum T3 had fallen to 65 +/- 2% of the pretreatment level (mean +/- SE). Thus, to obtain a permanent full effect of PTU on iodothyronine deiodination during the treatment of thyrotoxicosis it is necessary to use large doses or frequent administration.

Topics: Adult; Female; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Antibody Formation; Body Weight; Chickens; Concanavalin A; Hyperthyroidism; Immunity; Male; Organ Size; Propylthiouracil; Spleen; Thymus Gland; Thyroid Gland; Thyroxine

Urinary 3-methylhistidine (3MH) excretion has been studied in 20 thyrotoxic patients before, during and after treatment. 3MH excretion was high on diagnosis and fell significantly, when the patients had been rendered euthyroid, to levels measured in a control group. There was a significant linear correlation between 3MH excretion and free thyroxine index. The calculated muscle protein breakdown and 3MH/creatinine molar ratio also fell significantly after treatment of thyrotoxicosis.

Topics: Adult; Aged; Carbimazole; Creatinine; Female; Histidine; Humans; Hyperthyroidism; Kinetics; Male; Methylhistidines; Middle Aged; Muscle Proteins; Muscles; Propylthiouracil; Thyroxine

Topics: Administration, Oral; Animals; Cat Diseases; Cats; Chemical and Drug Induced Liver Injury; Hyperthyroidism; Liver Diseases; Propylthiouracil; Thyroxine; Triiodothyronine

1 Correlation between the kinetics of propylthiouracil and its antithyroid effect was studied in 17 hyperthyroid patients. The serum concentration of propylthiouracil 1 h after an oral dose of 400 mg of hyperthyroid patients. The serum concentration of propylthiouracil 1 h after an oral dose of 400 mg of the drug was used as kinetic parameter as this concentration from the previous study was found to correlate significantly (r = 0.84, P less than 0.01) with the area under the serum concentration-time curve. 2 After 3 weeks of treatment with 200 mg propylthiouracil three times daily the serum concentration of propylthiouracil was correlated to the decrease in various thyroid parameters such as total and free indexes of serum thyroxine, triiodothyronine and reverse triiodothyronine. 3 Significant correlations were found between the serum concentration of propylthiouracil and all the measured thyroid variables except reverse triiodothyronine. The highest degree of correlation was obtained between serum propylthiouracil and the percentage decrease in total and free indexes of triiodothyronine (r = 0.63 and 0.70, respectively, P less than 0.01). 4 It is suggested that a serum concentration of propylthiouracil above 4 to 5 micrograms/ml 1 h after an oral dose of 400 mg of the drug will secure a sufficient and rapid antithyroid effect during continuous therapy.

Topics: Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Thyroid Hormones

The results of medical and surgical therapy were determined in 107 hyperthyroid children. After surgery, 85% of patients were rendered free of hyperthyroidism; however, 62% became hypothyroid. After medical treatment, 30% of patients were euthyroid and 2% became hypothyroid. The relapse rate, however, was higher after medical (22%) than after surgical (9%) therapy. Serious drug-related complications (arthritis-, hepatitis-, and collagen disease-like syndromes) occurred in 14% of patients. Complications occurred in 9% of surgically treated patients, but recurrent laryngeal nerve injury or permanent hypoparathyroidism did not occur. In medically treated patients, both a goiter size less than three times normal prior to treatment and a reduction in goiter size to less than two times normal at the completion of therapy correlated with a successful outcome.

Topics: Adolescent; Arthritis; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Collagen Diseases; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Postoperative Complications; Propylthiouracil; Thyroidectomy

Topics: Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Carbimazole; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Thyroid Gland; Thyroidectomy

Multiple serum samples were obtained from six hypothyroid and six hyperthyroid females, 11--17 years of age, over the course of their corrective treatment with L-thyroxine (LT4) and propylthiouracil (PTU), respectively. Sera were assayed for total N-acetyl-beta-hexosaminidase (HEX), the A (heat-labile) and B (heat-stable) isozymes, and total T4. HEX activity (total HEX A) in sera from hypothyroid (< 4 micrograms/dl T4) patients (total HEX: 518 +/- 66 nmol/60 min/ml, mean +/- S.D.; HEX A: 325 +/- 55; n = 5) was significantly lower than that of the euthyroid control group (total HEX: 638 +/- 77 (p < 0.005); HEX A: 420 +/- 76 ( p < 0.01); n = 23); no difference in HEX B levels was noted. Serum samples from patients successfully treated for hypothyroidism via oral administration of LT4 (n = 12) displayed levels of total HEX (722 +/- 113) and HEX A (491 +/- 91) significantly higher than those of the control group (p < 0.01 in both cases); again, no change in levels of HEX B was observed. HEX activity in sera from hyperthyroid (> 13 micrograms/dl T4) individuals (total HEX: 839 +/- 96; HEX A: 540 +/- 74; HEX B: 299 +/- 52; n =20) was significantly higher than that of the control group (p < 0.005 in all cases). The depression of hormone activity to the euthyroid range by PTU was accompanied ay a decrease in enzyme activity to control levels (total HEX: 632 +/- 92; HEX A: 400 +/- 55; HEX B: 232 +/- 52; n = 16). Non-parametric analysis of the data shows highly significance differences between pre- and post-treatment enzyme levels (alpha < 0.001) in both hyper- and hypothyroid groups. Alteration of thyroid status, and specifically T4 level is, therefore, indicated to be a contributing factor in the regulation of serum HEX activity in humans, as evidenced by individual responsiveness to oral administration of this hormone, or inhibitors of its peripheral metabolism.

Topics: Adolescent; beta-N-Acetylhexosaminidases; Child; Female; Hexosaminidase A; Hexosaminidase B; Hexosaminidases; Humans; Hyperthyroidism; Hypothyroidism; Isoenzymes; Propylthiouracil; Thyroxine

Topics: Animals; Diiodothyronines; Dithiothreitol; Edetic Acid; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Kinetics; Liver; Male; NADP; Peroxidases; Propylthiouracil; Rats; Starvation; Thyroidectomy; Thyronines; Triiodothyronine; Triiodothyronine, Reverse

Two cases of propylthiouracil-induced liver damage have been observed. The first case is of an acute type of damage, proven by rechallenge; the second presents a clinical and histologic picture resembling chronic active hepatitis, with spontaneous remission.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Graves Disease; Humans; Hyperthyroidism; Liver; Liver Cirrhosis; Middle Aged; Propylthiouracil

Topics: Adult; Female; Humans; Hyperthyroidism; Propylthiouracil; Pseudotumor Cerebri

Topics: Humans; Hyperthyroidism; Iodine; Lithium; Mercaptopurine; Methimazole; Postoperative Care; Preoperative Care; Propranolol; Propylthiouracil; Thyroidectomy

Topics: Adolescent; Adult; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy

We studied the noradrenaline content, and monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) activities in brown adipose tissue (BAT) of normal, hypothyroid, and hyperthyroid developing rat. In the newborn, thyroid hormones are necessary for the increase in noradrenaline content which occurs between 0 and 5 days. Hypothyroidism increases both MAO and COMT activities. Hyperthyroidism decreases MAO activity but not noradrenaline content or COMT activity. In the full-term fetus, hypothyroidism decreases noradrenaline content as in the newborn, and also decreases MAO and COMT activities. It is suggested that thyroid hormones could modulate BAT nonshivering thermogenesis by regulating the level of noradrenaline, the direct mediator of heat production.

Topics: Adipose Tissue, Brown; Aging; Animals; Animals, Newborn; Catechol O-Methyltransferase; Female; Hyperthyroidism; Hypothyroidism; Male; Monoamine Oxidase; Norepinephrine; Pregnancy; Propylthiouracil; Rats; Thyroxine

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Prognosis; Propylthiouracil; Retrospective Studies; Sex Factors; Time Factors; Triiodothyronine

40 hyperthyroid children were followed for 0.2--12 (mean 4.5) years. The treatment was antithyroid drugs in 20, subtotal thyroidectomy after a drug trial in 18 and primary thyroidectomy in 2 patients. 4 patients who relapsed (3 after surgery and 1 after a drug trial) were given radioiodide. 11 of the surgically treated glands were nodular. At the follow-up study 24 patients were euthyroid, 7 were on thyroxine therapy and in 5 others hypothyroidism was discovered. 2 subjects were still on antithyroid drugs and 2 relapsed. In 5 euthyroid patients the TRH test revealed a low thyroid reserve. In 28 of 34 subjects examined circulating antibodies to thyroid microsomes were present in high titres. Evidently, regular follow-up is needed because of the high risk of hypothyroidism.

Topics: Adolescent; Antibodies; Carbimazole; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Hyperthyroidism; Iodides; Male; Propylthiouracil; Radioisotopes; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine

Topics: Adult; Bone and Bones; Calcium; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Muscles; Potassium; Propranolol; Propylthiouracil; Reference Values

In order to compare the acute effects of three methods of treatment in hyperthyroid patients with diffuse goitre, values of thyroxine (T4), triiodothyronine (T3) in serum, T3-resin uptake (T3-U), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were employed as thyroid function parameters. In iodide (I-) group given iodine (3 or 6 mg/day) as iodinated lecithine once daily, the parameters were reduced acutely within one week after the start of treatment, reaching a plateau during the next week. In contrast to the changes in I- group, the thyroid function was decreased gradually and consistently for two weeks in the propylthiouracil (PTU 300 mg/day) group. In PT1+I- (300 mg/PTU plus 3 or 6 mg/iodide/day) group, the parameters were reduced acutely and progressively for two weeks. These results indicate that PTU+I- therapy is much more effective than PTU or I- alone in early phase treatment of hyperthyroidism. Another new finding was that the thyroid function increased again during the later addition of PTU (300 mg/day) in the patients treated with I- (3 or 6 mg/day) for one or two weeks. The well-known escape phenomenon from iodide inhibition took place counteracted the effect of PTU. Since blocking of thyroidal secretion by I- is only transient while synthesis of T3 and T4 continues, leading to greater amount of hormone stored in the gland, the treatment of hyperthyroidism with I- alone is a risky procedure.

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodides; Male; Middle Aged; Phosphatidylcholines; Propylthiouracil; Thyroid Function Tests; Thyroxine; Triiodothyronine

rT3 metabolism in patients treated for thyrotoxicosis with prophylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT3 and measurements of the increase in serum rT3 and serum 3,3'-diiodothyronine. The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3,3'-T2 which was similar whether PTU or MMI was given. However, after stopping rT3 infusion there was a more rapid fall serum 3,3'-T2 during MMI treatment, compatible with an inhibitory effect of PTU on 3,3'-T2 degradation.

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyronines; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Body Weight; Cholesterol; Fasting; Female; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Species Specificity; Thyroid Gland; Thyroxine; Triglycerides

Topics: Animals; Female; Hyperthyroidism; Hypothyroidism; Kinetics; Prolactin; Propylthiouracil; Rats; Thyroid Gland; Thyroxine

In order to assess the effects of perinatal hypothyroidism or hyperthyroidism on the development of an integrated behavioral response, we tested hypothyroid, hyperthyroid, and control pups, as well as pups receiving thyroxine replacement therapy, for the development of the home orientation response. Hypothyroidism was induced in the pups by feeding the pregnant or lactating female a diet of .2% propylthiouracil from Day 15 of gestation to Day 22 postpartum. Pups receiving replacement therapy and pups made hyperthyroid were injected daily with thyroxine, starting at birth. The ability of the pups to initiate and maintain locomotion toward the nest was assessed between Days 4 and 22. Hyperthyroid, control, and replacement therapy pups behaved very similarly on the task, showing a peak in the percentage of pups homing between Days 12 and 16. Hypothyroid pups showed a delay in the peak percentage until Day 20, although the percentage of pups was similar to that found in other treatments. An integrated behavioral response can be delayed by hypothyroidism and still emerge apparently intact at a later age.

Topics: Animals; Female; Hyperthyroidism; Hypothyroidism; Motor Activity; Orientation; Pregnancy; Propylthiouracil; Rats; Social Environment; Thyroxine

Recent evidence indicates that the paraventricular nucleus of the hypothalamus (PVN) contains both neurons that produce thyrotropic releasing hormone (TRH) and neurons that are destroyed or disconnected by the knife cuts that produce hypothalamic hyperphagia and obesity. This, and other evidence, suggested linkage between thyroid regulation and appetite control. As predicted, hyperthyroidism potentiated and hypothyroidism tempered the weight gains of knife cut rats. However, these effects were due entirely to increased and decreased, respectively, linear growth, not to differences in the degree of obesity. Enhanced linear growth and elevated growth hormone levels are a minor component of the enhanced weight gain of hypothalamically knife cut rats. Most of the weight gain is due to fat deposition. Only the enhanced linear growth and growth hormone aspect appear to possibly be mediated via the thyroid. In addition, obesifying knife cuts did not reduce goiterogenesis in PTU treated rats, as would be expected if the elaboration of TRH were blocked by obesifying knife cuts. Thus, neither TRH nor thyroxine is involved in the etiology of hypothalamic obesity.

Topics: Animals; Body Weight; Brain; Hyperthyroidism; Hypothalamus; Hypothyroidism; Male; Obesity; Paraventricular Hypothalamic Nucleus; Propylthiouracil; Rats

We measured behavioral dysfunction in hyperthyroid patients to determine if improvement occurred with therapy. The Sickness Impact Profile (SIP), an interview designed to measure sickness-related behavior, was administered to 14 hyperthyroid patients on initial diagnosis and at intervals during treatment. All patients received medical therapy (propranolol hydrochloride, propylthiouracil, and/or radioactive iodine) and showed both biochemical improvement as measured by adjusted serum thyroxine (T4) levels and functional improvement as measured by the SIP score. Patients were less productive during the day and required naps and rest. Although they were irritable, critical, and demanding in their family and social interactions, they were not less affecionate, isolated, or less interested in others. Altered sleep and rest patterns may have been responsible for disrupting normal daily activities. Treating the underlying metabolic disorder resulted in a relatively prompt resolution of the patients' dysfunctional behavior.

Topics: Adolescent; Adult; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Social Behavior Disorders; Thyroxine

Thyroid hormones play an important role in growth and development. Therefore, we investigated the effects of neonatal hypo- and hyperthyroidism on pituitary GH content in the rat. In control rats, pituitary GH content increased from 4.16 +/- 0.34 at 2 days to 43.7 +/- 4.2 microgram/gland (mean +/- SE) at 15 days of age, with a t 1/2 of increment of 3.48 +/- 0.40 days. Between 18-60 days of age, pituitary GH content increased from 56.9 +/- 4.0 to 300 +/- 28 microgram/gland, with a t 1/2 of 18.2 +/- 1.5 days. The administration of T3 had no significant effect on the pituitary GH content of these animals. In neonatal hypothyroid rats, pituitary GH content was significantly lower than that of controls at 2 days of age (P < 0.01) and decreased from 8 days on, with a t 1/2 of 3.71 +/- 0.25 days. However, 24 h after the administration of T3 (100 microgram/100 g BW), pituitary GH content was significantly increased in these animals. Similarly, the administration of T3 (0.4 microgram/100 g BW) to 14-day-old hypothyroid rats restored the pituitary GH content to 70-80% of normal after 5 days of therapy. Conversely, hyperthyroidism induced in 14-day-old normal or hypothyroid rats resulted in a significant decrease in their pituitary GH contents after 5 days of treatment. Therefore, the present results indicate that during the neonatal period, thyroid hormones play a primary role in the control of GH accumulation in the pituitary. Furthermore, the lack of increase in pituitary GH content after the administration of T3 during development might suggest that the rate of formation of GH is already maximum during this period of life in the rat, or, alternatively, that the pituitary nuclear T3 receptors are near full saturation during development. Finally, a generally similar effect of T3 on pituitary GH response was observed in the neonatal rat as well as in the adult animal.

Topics: Aging; Animals; Animals, Newborn; Growth Hormone; Hyperthyroidism; Hypothyroidism; Pituitary Gland; Propylthiouracil; Rats; Triiodothyronine

The major drawback to treatment of hyperthyroidism with antithyroid compounds is the reported low rate of remission. Eighty patients have been given long-term (at least one year; average, 4.4 years; range, one to 14 years) continuous treatment with a remission rate of 76% and an average follow-up of 7.8 years (one to 21 years). The prognostic test of suppressed uptake by the thyroid of less than 20% was about 75% accurate in predicting continuing remission when treatment was stopped. Of those in remission, 14 (23%) were treated for one year, 35 (57%) for one to five years, and 12 (20%) for more than five years. Mild reactions occurred in five (6%), hypothyroidism in two (3%). An antithyroid drug is safe and effective therapy for hyperthyroidism.

Topics: Adult; Aged; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Sex Factors; Time Factors

Topics: Acromegaly; Female; Growth Hormone; Humans; Hyperthyroidism; Menopause; Methimazole; Middle Aged; Prednisolone; Prolactin; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Plasma cyclic AMP and cyclic GMP levels were studied in a group of normal subjects and 10 subjects with hyperthyroidism. In the control group, mean plasma cyclic AMP levels were 15.3 +/- 1.3 nmol/l (SEM), and plasma cyclic GMP levels were 9.4 +/- 0.58 nmol/l (SEM). In untreated hyperthyroid subjects, both plasma cyclic AMP and cyclic GMP levels were significantly elevated above normal with mean values of 35.0 +/- 2.4 nmol/l (SEM) (P less than 0.001) and 14.7 +/- 0.2 nmol/l (SEM), (P less than 0.001), respectively. Six of the hyperthyroid subjects were re-studied when they became euthyroid; plasma cyclic nucleotide concentrations all fell within the normal range. To evaluate the relative contribution of triiodothyronine and thyroxine to elevated plasma cyclic nucleotide levels, two hyperthyroid subjects were treated with propylthiouracil and iodide. Plasma cyclic nucleotide levels were normalized when plasma triiodothyronine levels declined to normal range, at the time when plasma thyroxine levels were still elevated. These preliminary data suggest that increased triiodothyronine production is responsible for the increased cyclic nucleotide levels in hyperthyroidism.

Topics: Adult; Aged; Cyclic AMP; Cyclic GMP; Humans; Hyperthyroidism; Male; Middle Aged; Potassium Iodide; Propylthiouracil; Thyroxine; Triiodothyronine

A girl aged 4 years with goiter and accelerated physical and skeletal growth was found to be hyperthyroid on the basis of elevated serum thyroid hormone level, nevertheless both the basal TSH and TSH responsiveness to TRH were maintained within the normal range. Serum TSH was suppressed by exogenous T3 and dexamethasone administration, but not significantly changed after propylthiouracil (PTU) treatment. The diurnal rhythmicity of anterior pituitary hormones was preserved with the high nocturnal peak of TSH and prolactin. Clinically, neither thyrotoxic signs nor evidences of pituitary tumor were observed. Her accelerated growth and elevated thyroid hormone level appeared to be induced by inappropriate secretion of TSH. In view of the literature, this is the first case of the syndrome of inappropriate secretion of TSH excluding the neoplastic origin in Japan.

Topics: Adrenocorticotropic Hormone; Child, Preschool; Dexamethasone; Female; Growth Hormone; Humans; Hyperthyroidism; Luteinizing Hormone; Prolactin; Propylthiouracil; Syndrome; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

A case of fetal thyrotoxicosis in utero in a boy with familial predisposition to thyrotoxicosis is reported. At 26 weeks of gestation fetal hyperkinesia and fetal tachycardia developed. This was preceded by a significant pathologic increase in long-acting thyroid stimulator (LATS) in the mother. The fetal hyperkinesia and tachycardia were considered to be signs of fetal thyrotoxicosis, possibly induced by placentally transferred LATS. The fetal thyrotoxicosis responded well to propylthiouracil given to the mother. After birth the boy developed slight signs of neonatal thyrotoxicosis although his serum thyroxine values increased analogous to those of his elder sister, who had presented classical neonatal thyrotoxicosis.

Topics: Female; Fetal Diseases; Humans; Hyperkinesis; Hyperthyroidism; Infant, Newborn; Long-Acting Thyroid Stimulator; Male; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Tachycardia; Thyroxine

Topics: Adult; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Thyroidectomy

Topics: Animals; Chromium; Chromium Radioisotopes; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Thyroidectomy; Thyroxine; Time Factors

Thyroid disease is often accompanied by changes in the concentrations of serum lipids and lipoproteins. To evaluate the hepatic contribution to the serum abnormalities in thyroid disease, we examined fatty acid metabolism in perfused livers from pair-fed rats made hypothyroid with propylthiouracil (PTU) or made hyperthyroid by treatment with triiodothyronine (T(3)). The animals treated with T(3) became hyperphagic, depending on dose of drug and duration of hyperthyroidism. It was necessary, therefore, for appropriate controls, that food intake of T(3)-treated rats be restricted to quantities consumed by euthyroid rats. Animals treated with PTU for 2 wk became hypophagic, and therefore, food consumption of controls was restricted to that eaten by rats receiving PTU. Dependent on dose of T(3) and duration of treatment, the output of triglyceride and glucose was diminished, whereas output of ketone bodies was increased by livers from hyperthyroid animals. In contrast, livers from PTU-treated animals secreted increased amounts of triglyceride and glucose, whereas ketogenesis was diminished. The best models for study proved to be animals treated with either 10 mug T(3)/100 g body wt per d or 1 mg PTU/100 g body wt per d for 7 d. Under these conditions, all animals consumed the same quantity of food as did the euthyroid rats, but continued to display the metabolic alterations outlined above. The effects of PTU on hepatic metabolism were readily reversible by simultaneous administration of T(3). It is clear from these data that the thyroid status of the rat regulates hepatic triglyceride formation and secretion, and ketogenesis.

Topics: Animals; Dose-Response Relationship, Drug; Eating; Fatty Acids, Nonesterified; Glucose; Hyperthyroidism; Hypothyroidism; Ketone Bodies; Lipid Metabolism; Liver; Male; Propylthiouracil; Rats; Time Factors; Triglycerides; Triiodothyronine

Serum thyroxine levels peak earlier and are significantly higher in audiogenic seizure-susceptible DBA/2J mice than in seizure-resistant C57BL/6J mice during early postnatal life. The seizure susceptibility of DBA/2J mice is suppressed by administration of an antithyroid drug or by radiothyroidectomy, while the seizure susceptibility of C57BL/6J mice is enhanced by treatment with excess thyroxine.

Topics: Acoustic Stimulation; Animals; Hyperthyroidism; Hypothyroidism; Mice; Mice, Inbred Strains; Propylthiouracil; Seizures; Thyroxine

The management of hyperthyroidism and hypothyroidism in pregnancy is discussed and illustrated with appropriate cases. The dangers of the usage of high doses of antithyroid drugs and of propranolol are described.

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Hypothyroidism; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Thyroid Diseases

Topics: Child; Female; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Hormones; Thyroidectomy

The treatment of benign forms of thyroid disease is reviewed. Endemic goiter is a public health problem preventable by the addition of iodine to the food or water supply. Endemic and familial goiters are treated with replacement doses of I-thyroxine, as are sporadic colloid goiters and goiters resulting from chronic thyroiditis. Hyperfunctioning autionomous nodules without thyrotoxicosis and cystic nodules require no specific therapy. Prophylaxis against diffuse or nodular goiter after radiation to the head or neck for therapeutic purposes with thyroxine replacement therapy is debatable. All forms of hypothyroidism, including incipient types, require replacement thyroxine therapy, but this should be undertaken cautiously in older patients and in those with evidence of ischemic myocardial disease. Myxedema coma requires vigorous treatment and detailed supervision because of dismal mortality rates. Iodine 131 is the treatment of choice in diffuse toxic goiter, but alternative forms.

Topics: Adolescent; Adult; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Radiation Dosage; Thyroid Diseases; Thyroxine

Topics: Adult; Agranulocytosis; Female; Humans; Hyperthyroidism; Hypocalcemia; Propylthiouracil

A case of thyrotoxic periodic paralysis based on clinical grounds, laboratory data and therapeutic response as well is reported. The authors comment on the differential diagnosis with the most frequent types of periodic paralysis. The importance of a correct diagnosis and treatment as early as possible is stressed as to prevent further development of permanent paralysis due to irreversible degenerative myofibril changes as stated in literature.

Topics: Adult; Carbohydrate Metabolism; Diagnosis, Differential; Humans; Hyperthyroidism; Male; Membrane Potentials; Microscopy, Electron; Myofibrils; Paralyses, Familial Periodic; Paralysis; Propylthiouracil

Topics: Adult; Athetosis; Chorea; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Potassium Iodide; Propranolol; Propylthiouracil

A 10-year-old girl initially presented with clinical features and thyroid function tests consistent with hyperthyroidism. She was treated with propylthiouracil, 100 mg, three times a day. She developed jaundice and hepatitis following treatment with propylthiouracil for 40 days. Clinical features of hepatitis improved after the discontinuation of propylthiouracil and she became euthyroid. At this time, an immunofluorescent technique revealed antibodies consistent with autoimmune thyroiditis. From this report, it appears that hepatitis is one of the infrequent complications of treatment with propylthiouracil and transient hyperthyroidism may be associated with autoimmune thyroiditis.

Topics: Chemical and Drug Induced Liver Injury; Child; Female; Humans; Hyperthyroidism; Jaundice; Propylthiouracil

Topics: Chemical and Drug Induced Liver Injury; Child; Female; Humans; Hyperthyroidism; Propylthiouracil

33 cases of hyperthyroidism have been treated at "L'Hôpital Sainte-Justine" of Montréal, during the period 1961-1974. Nearly all patients were submitted to medical treatment. 15 were cured with medical treatment only, and 18 had to be submitted to a subtotal thyroidectomy. These two groups are compared and show the clear advantage of surgery in the treatment of this disease. There was no major post-operative complication. Two patients became definitively hypothyroid. The mean follow-up is five years and six months.

Topics: Adolescent; Carbimazole; Child; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Propylthiouracil

Topics: Adolescent; Child; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Iodine Radioisotopes; Male; Propylthiouracil; Thyroid Hormones; Thyroid Neoplasms; Thyroiditis, Autoimmune

Topics: Female; Fetal Diseases; Humans; Hyperthyroidism; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Female; Hyperthyroidism; Hypothyroidism; Liver; Mammary Neoplasms, Experimental; Prolactin; Propylthiouracil; Rats; Thyroid Gland; Thyroxine

The regulation of adrenergic receptors in rat heart was measured in rats made hyperthyroid by injection with thyroxine and made hypothyroid by addition of propylthiouracil to the drinking water. Hyperthyroid rats display cardiac hypertrophy and a decrease in epididymal fat pad weight. The maximal beta-receptor level of ventricular membranes, as determined by (-)-[3H]dihydroalprenolol binding, was increased 60% by thyroxine treatment and decreased about 30% by propylthiouracil treatment. The affinity of the beta receptor was unchanged after thyroxine or propylthiouracil treatment. The maximal activity of the isoproterenol-stimulated adenylate cyclase (EC 4.6.1.1) varied with thyroid state in a manner parallel to the increase in beta-adrenergic binding sites. Thyroxine treatment also increases by 2-fold the beta receptors in isolated rat fat cells. Propylthiouracil treatment lowered the level of alpha receptors in heart by 30% as measured by [3H]dihydroergocryptine binding, but increased the affinity about 2.5-fold. The highest level of alpha receptors was seen in control hearts. These studies indicate that thyroxine may control the turnover of beta-adrenergic receptors in heart and fat cells and regulate physiological responses in these tissues via a hormone-hormone interplay system. Thyroxine treatment reduced the activity of the membrane-bound Mg2+-ATPase (EC 3.6.1.3) and 5'-mononucleotidase (EC 3.1.3.5) but appears to increase the activity of the (Na+ + K+)ATPase (EC 3.6.1.4).

Topics: Adenosine Triphosphatases; Adenylyl Cyclases; Adipose Tissue; Alprenolol; Animals; Cell Membrane; Dihydroergotoxine; Heart; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Receptors, Adrenergic; Sympathomimetics; Thyroxine

Adipocytes isolated from normal, hypothyroid, and hyperthyroid rats were characterized with respect to their lipolytic activity (assessed by glycerol release) and beta-adrenergic receptors (assessed by binding of (--) [3H]alprenolol). Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals. Adipocytes from hypothyroid rats were unresponsive to epinephrine in a concentration range of 0.1-10 micron, with moderate responses at higher concentrations; injection of T3 in hypothyroid rats restored lipolytic responsiveness of the adipocytes to normal levels. Quabain (1 mM) inhibited lipolytic responses to epinephrine by 40--45% in normal and hyperthyroid rats; the lipolytic increment due to the hyperthyroid state was uninfluenced by ouabain. The lipolytic refractoriness to epinephrine of hypothyroid adipocytes was restored to normal levels by theophylline (1 mM) or EGTA (1 mM); the theophylline and EGTA effects were not additive, suggesting that they stimulated lipolysis via a common mechanism. Epinephrine-induced lipolysis in all groups was progressively inhibited by increasing concentrations of Ca2+ in the medium. The Ca ionophore, A23187, showed a concentration-dependent inhibitory action. Theophylline (1mM) almost completely overcame the inhibitory action of the ionophore; in the presence of lower concentrations of theophylline, the inhibitory effect of the ionophore was least in hypothyroid and greatest in hyperthyroid fat cells. The findings suggest that the differences in the lipolytic response to epinephrine observed in hyperthyroid, euthyroid, and hypothyroid adipocytes are not due to alterations in the number or affinity of beta-adrenergic receptors nor to a membrane mechanism that might show differential ouabain sensitivity, but may be related to altered cellular Ca2+ concentrations which may indirectly alter cellular phosphodiesterase activity.

Topics: Adipose Tissue; Alprenolol; Animals; Calcimycin; Calcium; Epinephrine; Hyperthyroidism; Hypothyroidism; Kinetics; Lipid Mobilization; Male; Propylthiouracil; Rats; Receptors, Adrenergic, beta; Thyroid Gland; Triiodothyronine

A radioreceptor assay for human thyroid stimulators has been employed in various groups of patients. The ability of Ig to displace the labeled TSH from the receptors is referred to as "TSH displacement activity (TDA)." In active Graves' disease, TDA was above normal in 76% of the cases, and in the remaining patients, it was above the 76th percentile, suggesting that thyroid-stimulating Ig (TSIg) may have been present in all cases, but not always demonstrable by this method. Significant TDA was not found in normal persons or in toxic or nontoxic nodular goiters. It was also negative in some patients with "euthyroid ophthalmic Graves' disease." In patients with Graves' disease controlled with antithyroid drugs, positive TDA accurately predicted the recurrence of hyperthyroidism in eight of nine cases from whom the drugs were withdrawn. Thus, TSIg appears to be a prerequisite of the hyperthyroidism of Graves' disease. Moreover, the remission of hyperthyroidism was due to the disappearance of TSIg (immunological remission) in most cases in this small series. Serum TDA may provide a means of detecting immunological remission. The exophthalmos of Graves' disease does not require thyroid-stimulating Ig.

Topics: Binding, Competitive; Chromatography, Gel; Graves Disease; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins; Propylthiouracil; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroid Gland; Thyrotropin

Blood samples for determination of serum total and free reverse triiodothyronine (rT3), triiodothyronine (T3) and thyroxine (T4) were obtained daily in 6 previously untreated thyrotoxic patients during periods of propylthiourazil (PTU) (600 mg per day) or methimazol (MMI) (45 mg per day) administration. PTU induced about 60 per cent increase in both total and free serum rT3. This was accompanied by a rapid decrease in serum T3 and a more gradual decline in serum T4. MMI administration to untreated patients was followed by a gradual parallel decrease in rT3, T3 and T4. Turn from PTU to MMI produced a rapid decrease in serum rT3 and increase in serum T3 in all 6 patients. The relative variations in the free and total concentrations of iodothyronines were practically identical. The increase in serum rT3 after PTU is most likely explained either by enhanced deiodination of T4 to rT3 or by an inhibitory effect of PTU on rT3 degradation.

Topics: Adult; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Myocardial Contraction; Propylthiouracil; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adrenal Glands; Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Sympatholytics; Thyroid Crisis; Thyroxine; Triiodothyronine

The rate of ethanol metabolism was studied in 3 hyperthyroidism patients without therapy and in 2 after 1 week of treatment with propylthiouracil and reserpine. The rate of ethanol metabolism (mg/kg/h +/- SEM) was 386 +/- 57 in the 3 hyperthyroid patients, 184.5 +/- 2.5 in the 2 treated patients and 159 +/- 15 in 12 euthyroid non-alcoholic subjects. The results suggest that hyperthyroidism markedly increases ethanol metabolism.

Topics: Adult; Ethanol; Female; Humans; Hyperthyroidism; Propylthiouracil; Reserpine

Topics: Age Factors; Animals; Cerebellar Cortex; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Thyroxine

Topics: Adult; Anemia, Hemolytic; Humans; Hyperthyroidism; Male; Microcirculation; Propylthiouracil

Topics: Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil

Topics: Animals; Bile; Hyperthyroidism; Hypothyroidism; Lactates; Liver; Male; Oleic Acids; Propylthiouracil; Pyruvates; Rats; Thyroxine

Topics: Aging; Animals; Animals, Newborn; Brain; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Rats; Serotonin; Synaptosomes; Thyroid Gland; Triiodothyronine

Absolute activity measurement of I-123 by coincidence counting was used to study the early thyroidal iodide uptake in 20 hyperthyroid children. Patients were pretreated either with methimazole or propylthiouracil before injection of Na123I. The usual method of analysis of the early uptake was modified to account for a rapidly equilibrating compartment, to give thyroidal iodide trapping rate constant (K1) and absolute iodide uptake (AIU). The suppressibility of the early uptake by triiodothyronine (T3) was evaluated in some patients. The upper limit of normal for K1 was 0.03 min-1 and for AIU was 0.04 microgram/min. In the hyperthyroid subjects, K1 and AIU were in the hyperthyroid range before and after T3 suppression. For patients with suppressible uptake, remission from hyperthyroidism was maintained for 6 mo to 2 1/2 yr. Only two patients with nonsuppressible uptake achieved remission from hyperthyroidism, perhaps because of coexistence of thyroiditis.

Topics: Adolescent; Child; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Triiodothyronine

Topics: Adult; Carbimazole; Child; Congresses as Topic; Female; Germany, West; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Prednisone; Pregnancy; Prognosis; Propylthiouracil

Treatment of rats with propylthiouracil for the first 30 days of postnatal life drastically retards the ontogenesis of D-amino acid oxidase in the brain stem and cerebellum. There is a marked terminal deficit of D-AAO in both the brain stem (--64%) and cerebellum (--67%) at 94 days (adults) despite the near euthyroid status at this age. If initiated early enough, thyroxine replacement therapy reverses the effects of PTU on the development of D-AAO. Hyperthyroidism significantly accelerates the development of D-AAO in both brain stem and cerebellum. Nonetheless, animals treated with thyroxine the first month of life display a net deficit of cerebellar D-AAO content in adulthood. The results are discussed in terms of the localization of D-AAO in cell types especially sensitive to thyroid hormone: (1) a cell type which is among the last to derive from the external germinal zone in the developing cerebellum, and which in the adult is located adjacent to the Purkinje cell soma; and (2) mossy fiber neurons and cerebellar glomeruli.

Topics: Animals; Animals, Newborn; Brain Stem; Cerebellum; D-Amino-Acid Oxidase; Female; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Thyroxine

Topics: Antithyroid Agents; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Thyroid Function Tests

Congestive heart failure in neonatal thyrotoxicosis is attributed to sympathetic overstimulation of the myocardium with resulting high-output cardiac failure. An additional case of neonatal thyrotoxicosis with congestive heart failure is discussed; three possible causes (thyrotoxicosis, maternal propranolol therapy, and ventricular septal defect) were present. Along with the usual procedures, the echocardiogram is of value in separating these factors. In addition, we discuss the potential dangers to the newborn of a mother receiving long-term propranolol hydrochloride therapy during pregnancy.

Topics: Digitalis Glycosides; Echocardiography; Female; Graves Disease; Heart Failure; Heart Septal Defects, Ventricular; Humans; Hyperthyroidism; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil

Triiodothyronine (T3) toxicity has been well documented in adults, but only isolated cases have been reported in children. Two girls presented with firm goitres and overt hyperthyroidism. In each patient, total serum thyroxine (T4) values by competitive protein binding were normal, however total T3 values by radioimmunoassay were elevated. One patient had Graves' disease, the second patient had Hashimoto's disease which has been only infrequently associated with T3 toxicity in adults. Both patients responded to therapy with propylthiouracil. The mechanisms by which T3 is preferentially secreted in thyrotoxic states in man are poorly understood, but iodine deficiency and poor iodination of thyroglobulin may be important factors.

Topics: Child; Female; Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Function Tests; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

Topics: Adrenal Cortex Hormones; Child; Female; Graves Disease; Humans; Hyperthyroidism; Pregnancy; Prognosis; Propylthiouracil; Recurrence; Thyroxine; Triiodothyronine

The evolution of monoamine oxidase (MAO) activity towards tryptamine has been studied from birth to 20 days post-natal in the brain and heart of male rats. Hyperthyroidism was induced by thyroxine injections and hypothyroidism by PTU administration. The results are expressed per unit of fresh weight and per unit of protein weight. Cardiac MAO is higher in the hyperthyroid animals than in controls as soon as 5 days following birth; the difference between the 2 groups increases until 20 days. The deficiency in thyroid hormones, on the other hand, was followed by a slight decrease in the cardiac enzyme, this decrease reflecting the general deficit in protein synthesis. Brain MAO is not affected by hyperthyroidism, but a clear deficit follows PTU administration. This deficit is significant beginning at 10 days and the difference between the 2 groups increases up to 20 days. The effects of PTU-induced hypothyroidism can be corrected by thyroxine injections. Except for the decrease in the level of cardiac enzyme in hypothyroid animals, all the effects on MAO activity are independent of the total protein content of both organs.

Topics: Animals; Brain; Heart; Hyperthyroidism; Hypothyroidism; Male; Monoamine Oxidase; Myocardium; Propylthiouracil; Rats; Thyroxine

Hyperthyroidism is generally considered to be ameliorated during pregnancy, and there appears to be a high incidence of postpartum exacerbation. These phenomena have to our knowledge not been related to neonatal thyrotoxicosis, a transient hyperthyroidism seen only in newborns of previous or current hyperthyroid mothers. The first of two siblings of a previously thyrotoxic mother had marked symptoms of neonatal thyrotoxicosis and high levels of thyroid hormones. The mother had not received antithyroid treatment during her first pregnancy. During her next pregnancy she was treated with propylthiouracil from the second trimester. This infant had only minimal thyrotoxic signs but almost as high levels of thyroid hormones during the neonatal period as the elder. The mother had no signs of postpartum exacerbation but her thyroid hormones were significantly elevated in the postpartum period analogous to the infants. Neither the mother nor the infants presented any increase in thyroid-stimulation hormone and long-acting thyroid stimulator during the hyperthyroid periods. The possibility is discussed, that postpartum exacerbation of hyperthyroidism and neonatal thyrotoxicosis may be related. They could be the result of a changed balance between a thyroid stimulator and an inhibitor after birth.

Topics: Female; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Puerperal Disorders; Thyroxine; Triiodothyronine

Hyperthyroidism during pregnancy may be dangerous to the infant. The major risks are prematurity and neonatal thyrotoxicosis. The latter may be due to placental transfer of thyroid stimulating immunoglobulins from mother to fetus. Of two siblings of a previously thyrotoxic mother the first had marked symptoms of neonatal thyrotoxicosis after a pregnancy where no antithyroid treatment was given. The second child had only minimal thyrotoxic symptoms but almost as high levels of thyroid hormones as the first. During the second pregnancy propylthiouracil was given to the mother from 26 weeks' gestation, because of increased fetal movements and fetal tachycardia. Fetal movements and fetal heart rate were considered to be most valuable indicators of thyroid function in the fetus. Intense control is necessary from the beginning of the second trimester.

Topics: Adult; Female; Fetal Diseases; Fetal Heart; Heart Rate; Humans; Hyperthyroidism; Infant, Newborn; Long-Acting Thyroid Stimulator; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Adolescent; Child; Female; Humans; Hyperthyroidism; Male; Propylthiouracil

It is well known that the metabolic clearance rate (MCR) of a hormone is influenced highly by the level of its specific binding protein. It was interesting, therefore, to study the metabolism of estradiol-17beta (E2) in an animal model such as the rabbit where there is a lack for a highly specific binding protein for the steroid. The kinetics of the hormone was studied in relation to the thyroid state, namely in rabbits receiving thyroxin or propylthiouracil. In the absence of any significant decrease of the level of the rabbit androgen binding protein (R-ABP), the accelerated MCRE2 and the elevated conversion ratio of estradiol to estrone (CR E2 leads to E1) observed in hyperthyroid rabbits were attributed to the important role of metabolizing enzymes in the liver and/or extrahepatic tissues. In hypothyroid rabbits, while the CR E2 leads to E1 decreased significantly the MCRE2 was not altered.

Topics: Animals; Dihydrotestosterone; Estradiol; Estrone; Hyperthyroidism; Male; Metabolic Clearance Rate; Propylthiouracil; Rabbits; Receptors, Androgen; Thyroid Gland; Thyroxine

Topics: Adolescent; Adult; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Sulfamethizole; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Antibody Specificity; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Isomerism; Methimazole; Myocardial Infarction; Pregnancy; Propylthiouracil; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Aged; Child; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodides; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroxine; Triiodothyronine

A patient with malignant lymphoma developed goiter and thyrotoxicosis during the course of her disease. A thyroid biopsy revealed involvement of the thyroid gland with a malignant lymphoma. This was associated with the high levels of circulating thyroglobulin and thyroid hormones. The patient was treated with propylthiouracil, local radiotherapy, and nitrogen mustard and prednisone. The patient became euthyroid with the disappearance of goiter. Circulating levels of thyroglobulin and thyroid hormones returned to the normal range.

Topics: Adult; Female; Goiter; Humans; Hyperthyroidism; Lymphoma, Non-Hodgkin; Propylthiouracil; Thyroglobulin; Thyroid Function Tests; Thyroid Neoplasms; Thyrotropin; Thyroxine

Heat production has been measured in erythrocytes of 17 hyperthyroid patients both before treatment and when the patients had become clinically euthyroid. The decrease in heat effect during treatment was significant. The initial mean value was significantly higher than the corresponding value for normal subjects. A good correlation was found between heat effect values and the clinical condition. Measurement of heat production in erythrocytes can provide useful information about the peripheral effect of thyroid hormones.

Topics: Buffers; Calorimetry; Carbimazole; Erythrocytes; Glucose; Hot Temperature; Humans; Hyperthyroidism; Iodine Radioisotopes; Propranolol; Propylthiouracil; Thyroid Function Tests; Thyroidectomy; Thyroxine; Triiodothyronine

Responsiveness to synthetic thyrotropin-releasing hormone (TRH), thyroid suppressibility by triiodothyronine (T3) and the outcome of hyperthyroidism following prolonged therapy with thionamides were studied in a group of 35 patients with toxic diffuse goiter. TRH and T3 suppression tests were performed 10 days to 24 months (mean 4 months) after withdrawal of antithyroid drugs. Nineteen patients were euthyroid and had a normal thyrotropin (TSH) response to TRH, while 4 were recovering from mild hypothyroidism due to overtreatment and had an exaggerated response. No response was observed in 12 patients with recurrent hyperthyroidism. Positive T3 suppression tests were found only in 10 of the 30 cases examined. Peak and net 2 h secretion responses of TSH to TRH exhibited a significant inverse correlation with the levels of serum thyroxine and serum triiodothyronine, but were unrelated to the degree of thyroid suppressibility. Relapse or recurrence of thyrotoxicosis occurred in at least 9 of the 23 patients having no evidence of hyperthyroidism at the time of TRH test. Each of them was found to be responsive to TRH, while the T3 suppression test was negative in 8 and had to be discontinued in one because of thyrotoxic symptoms. The present data indicate that during the early period after completion of a prolonged course of antithyroid drug therapy responsiveness to TRH in toxic diffuse goiter is: a) correlated with circulating thyroid hormones, b) unrelated to the degree of thyroid suppressibility by T3 and c) of little value in predicting the long-term results of treatment.

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Radioimmunoassay; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Time Factors; Triiodothyronine

The inactivation of synthetic [3H]thyrotrophin-releasing hormone (TRH) by plasma was studied in rats treated with propylthiouracil (PTU) alone or with PTU and thyroxine. 48 h after the onset of treatment with thyroxine, the capacity of rat plasma to inactivate [3H]TRH was significantly increased. The percentage of deamidation of TRH to TRH-free acid was increased 2-fold after 4 days of administration of thyroid hormone. The inactivation of TRH by plasma from hypothyroid patients was compared to that obtained from hyperthyroid patients. Extraction of human plasma incubated with [3H]TRH, followed by thin-layer electrophoresis, showed that transformation of [3H[TRH into TRH-free acid was 44% higher in plasma from hyperthyroid than from hypothyroid patients (P less than 0-05). These data suggest that the inactivation process of TRH by blood proteins could be an important factor in the regulation of the hypothalamo-hypophyseal-thyroid axis in rat and man.

Topics: Animals; Blood Proteins; Electrophoresis, Cellulose Acetate; Humans; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Thyrotropin-Releasing Hormone; Thyroxine

In young Rats made hypothyroid from birth, the activity of monoamine oxidase at 20 days is smaller than controls in brain, heart and kidney. In Rats made hyperthyroid by injections of thyroxine, the activity is lower in brain kidney and liver and is 3.8 times higher in the heart.

Topics: Animals; Animals, Newborn; Brain; Female; Hyperthyroidism; Hypothyroidism; Kidney; Liver; Male; Monoamine Oxidase; Myocardium; Pregnancy; Propylthiouracil; Proteins; Rats; Thyroid Hormones; Thyroxine

The influence of thyroid function on the kinetics of glucose-induced insulin secretion from the isolated perfused rat pancreas has been studied. L-Thyroxine (L-T4) administration did not modify the immediate insulin secretory response of the perfused pancreas to glucose. L-Triiodothyronine (L-T3) treatment as well as propylthiouracil (PTU) treatment decreased the immediate insulin secretory response of the pancreas slightly. Only thyroidectomy (Tx) reduced the immediate secretory response of the pancreas significantly. L-T4 and L-T3 treatment inhibited the late phase of glucose-induced insulin secretion from the isolated perfused rat pancreas, whereas TX and PTU treatment resulted in increased insulin secretion. D-Thyroxine (D-T4) did not affect glucose-induced insulin release from the pancreas. Concomitantly, several parameters indicative of thyroid function were determined in these animals. When changes in body weight, rectal temperature, plasma glucose, plasma cholesterol, and plasma butanol-extractable iodine (BEI) in these rats were compared with the insulin secretory responses, it was evident that experimental hyperthyroidism results in decreased insulin release, whereas experimental hypothyroidism induces increased insulin secretion from the pancreas. The transitions from hypothyroid to euthyroid to hyperthyroid states are accompanied by a steady decrease in glucose-induced insulin release from the rat pancreas. Inhibition of glucose-induced insulin secretion from the pancreas is therefore a specific effect of thyroid hormones.

Topics: Animals; Hyperthyroidism; Hypothyroidism; Insulin; Insulin Secretion; Male; Pancreas; Perfusion; Propylthiouracil; Rats; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Thyroxine; Triiodothyronine

The radioimmunoassay for T3 is now widely available and is a useful diagnostic tool for hyperthyroidism, especially in T3-thyrotoxicosis. It is an essential tool in the management of hyperthyroidism that persists after treatment with normal T4 serum levels or, in euthyroid cases, with low T4 serum levels. In these conditions, it reflects the metabolic state more accurately than serum levels of T4. A promising new test is the response of radioimmunoassayable TSH to protirelin (TRH) administration. An absent response indicates pituitary suppression and thyroid autonomy as seen in frank hyperthyroidism or euthyroid Graves disease, treated or untreated. It is safer and quicker than the conventional T3 suppression test of thyroid radioactive iodine uptake and may replace it at least partly in the future.

Topics: Adult; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Thyroid Function Tests; Thyroidectomy

Little attention has been given the existence of male infertility in hyperthyroidism and the mechanisms adversely affecting spermatogenesis therein. The chance presentation of three young thyrotoxic men within a short period of time allowed us to document the common findings in all three of reversibly impaired semen quality. The unexpected finding of elevated testosterone and gonadotropin levels in each case, with return of these values to normal on attaining euthyroidism, and the finding of maturation arrest in one patient prior to treatment of his thyrotoxicosis, allow some considerations of the altered physiology and spermatogenic defect and suggest a need for further attention to this disorder.

Topics: Adult; Follicle Stimulating Hormone; Graves Disease; Humans; Hyperthyroidism; Infertility, Male; Luteinizing Hormone; Male; Oligospermia; Propylthiouracil; Testosterone

In fifteen hyperthyroid patients treated for 5 or more consecutive years with propylthiouracil four or more yearly prognostic 'suppression' tests (Cassidy & VanderLaan, 1960) were done. In nine of the fifteen patients there was a progressive diminution over a period of 3-6 years in the values of these suppressed uptakes to 20% or below. Eight of these nine patients have remained euthyroid off therapy for 1-8 years (average 3-1 years). None have become hypothyroid. The data suggest a gradual continuing change in thyroid function over the course of years in some hyperthyroid patients on antithyroid therapy. This may be a long-term effect of the drug and may have prognostic significance.

Topics: Adult; Female; Humans; Hyperthyroidism; Iodine; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Time Factors

The follicular architecture of the thyroid gland of the rat following experimentally induced states of hypo- and hyperactivity was investigated by scanning electron microscopy and the findings correlated with both light and transmission electron-microscopic observations. By scanning electron microscopy, the microvilli on the apical surfaces of the follicular cells showed the most striking changes; following hypophysectomy, the cells were flattened and the microvilli had decreased in both size and number, whereas following propylthiouracil (PTU) administration the epithelial cells were enlarged, and marked hyperplasia and hypertrophy of the microvilli was present. Of particular interest is that the changes observed following PTU appeared to be identical in short- and long-term PTU-treated rats. Similarly, the heterogeneity of the follicular cells observed within the follicles was maintained under the various experimental conditions. Although the functional significance of these observations is not quite clear, it appears justifiable to assume that a reduction of luminal surface area of the follicular epithelial cell may hinder, whereas an increase may facilitate transport process across the apical cell membrane.

Topics: Animals; Cell Membrane; Epithelial Cells; Epithelium; Hyperthyroidism; Hypophysectomy; Hypothyroidism; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Propylthiouracil; Rats; Thyroid Gland; Time Factors

In order to compare the acute effects of three kinds of antithyroid agents of iodide (I-), propylthiouracil (PTU) and PTU combined with iodide (PTU+I-) on thyroid function in hyperthyroid patients with diffuse goiter, serum concentrations of thyroxine (T4), triiodothyronine (T3), T3-resin sponge uptake (T3-RU) and free thyroxine index (FT4I) were employed as thyroid function parameters. In the group given iodine (1 mg/day) as iodinated-lecithine, the initial values of T4, T3, T3-RU and FT4I were 20.9 +/- 1.6 microng/100 ml (T4), greater than 740 ng/100 ml (T3), 49.5 +/- 2.3% (T3-RU) and 14.7 +/- 1.8 (FT4I). At the end of one week of therapy, they decreased clearly to 15.6 +/- 2.2 microng/100 ml, 457 +/- 87 ng/100 ml, 42.2 +/- 4.0% and 9.7 +/- 2.4. The so-called "escape phenomenon" from iodide inhibition was observed in serum T4, T3-RU and FT4I values at the end of two weeks of iodide therapy, while serum T3 continued to decrease but the value of T3 was far outside of the normal range. In the PTU group (300 mg/day), thyroid function parameters were 22.5 +/- 0.8 microng/100 ml (T4), greater than 592 ng/100 ml (T3), 54.9 +/- 1.0% (T3-RU) and 18.7 +/- 1.0 (FT4I) before treatment. They decreased continually week by week. At the end of four-week treatment with PTU, the value of each thyroid function parameter was 11.1 +/- 1.9 microng/100 ml, 229 +/- 56 ng/100 ml, 36.6 +/- 4.4% and 5.7 +/- 1.7. In the group of hyperthyroidism simultaneously given both PTU and iodide (300 mg/PTU and 1 mg/iodine), these thyroid function parameters decreased as well as in the group treated with PTU alone for more than two weeks. More rapid or significant decrease of T4, T3, T3-RU and ft4i in PTU+I- group than in PTU group was observed in the present study. These results suggested strongly that iodide alone was not an adequate therapy for hyperthyroidism as well known and they were also compatible with the idea that the concomitant administration of PTU and iodide was more effective in the early phase of therapy of hyperthyroidism than PTU alone.

Topics: Adolescent; Adult; Child; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodides; Male; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroxine; Triiodothyronine

Hyperthyroidism is a clinically dramatic but usually benign syndrome that is most commonly associated with the clinical triad known as Graves' disease. Although the diagnosis and treatment usually are straightforward and clinically rewarding, there are occasional patients in whom considerable clinical and laboratory expertise are required before the problem is identified and solved. Although among the most common endocrine disorders, the etiology of the hyperfunction of the thyroid gland in Graves' disease remains unknown and the mechanism by which thyroid hormones produce their effect is equally obscure. However, if the rate of progress in the past decade is typical, both these questions may well be answered before another 10 years have elapsed.

Topics: Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Thyroid Neoplasms; Thyroxine; Triiodothyronine

The effect of thyroid status on plasma and tissue levels of labeled nonextractable iodine (NEI) derived from the metabolism of radioiodothyronines was examined in the rat. Concentrations of radioiodoprotein were substantially elevated in plasma, kidney, and liver in thyroidectomized animals 72 h postinjection of [125I]triiodothytonine ([125I]T3). Similarly, total rat concentrations of radioactive NEI were increased (52%) 72 h after injection of [125I]T3. NE125I concentrations from [125I]T3 in plasma, kidney, and liver were diminished progressively in thyroidectomized animals maintained on increasing doses of thyroxine replacement, demonstrating that iodoprotein levels were inversely related to thyroid state. The plasma disappearance rate of radioiodoprotein from [125I]T3 was markedly slowed in hypothyroid animals and accelerated in intact controls rendered hyperthyroid with daily injections of T4, 8 mug/100 g BW. Propylthiouracil (PTU) treatment of thyroidectomized rats maintained on T4, 2 mug/100 g BW per day resulted in increased NE125I from [125E]T3 in plasma, kidney, and liver. The results of the foregoing investigations suggest that thyroid hormone regulates levels of iodothyronine-derived iodoproteins by influencing the rate of degradation of iodoproteins. Moreover, the observed elevation of iodoprotein levels in T4-maintained thyroidectomized animals after PTU administration appears consistent with the modification of thyroid status due to the peripheral antithyroxine effect of PTU.

Topics: Animals; Body Weight; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Iodoproteins; Kidney; Liver; Male; Propylthiouracil; Rats; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Thyroxine; Triiodothyronine

The rate of disappearance of antipyrine from the plasma is a useful indicator for the in vivo capacity of mixed function oxidation. The half-life of antipyrine was measured before and after treatment in three hypothyroid and three hyperthyroid children, aged three months to 14 years, in order to examine the effect on drug metabolism of thyroid disorders in children. The half-life of antipyrine decreased in all three hypothyroid subjects and increased in all three hyperthyroid subjects after treatment. The mean half-life decreased from 34.5 h to 8.6 h after treatment of the hypothyroid subjects and increased from 6.1 to 10.1 h after treatment of the hyperthyroid subjects. The mean metabolic clearance rate of antipyrine increased from 11.7 to 25 ml/h in the hyothyroid patients while in the hyperthyroid children there was a decrease from 43 to 25 ml/h. The apparent volume of distribution did not change significantly in the treatment, thus changes in the half-life of antipyrine were most likely attributable to alterations in the metabolic clearance rate of antipyrine.

Topics: Adolescent; Antipyrine; Child; Child, Preschool; Half-Life; Humans; Hyperthyroidism; Hypothyroidism; Infant; Methimazole; Propylthiouracil; Thyroidectomy; Thyrotropin; Thyroxine; Time Factors

Fulminant hepatic failure developed in a 24-year-old black woman who had been treated with propylthiouracil and propranolol for hyperthyroidism. Clinical and biochemical recovery followed discontinuation of drug therapy. Liver biopsy disclosed submassive hepatic necrosis. During the acute phase of the disease, lymphocyte transformation studies revealed sensitization of the patient's lymphocytes to propylthiouracil but not to propranolol. Sensitization remained demonstrable 2 months after cessation of the former drug. Lymphocytes obtained from a hyperthyroid patient treated with propylthiouracil without complications failed to show evidence of sensitization. These observations indicate that submassive hepatic necrosis may result from treatment with propylthiouracil and are consistent with the notion that sensitization mechanisms may be responsible for the hepatic injury induced by this drug.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Liver; Lymphocyte Activation; Lymphocytes; Necrosis; Propylthiouracil

Twenty-one women were studied who had received propylthiouracil or methimazole during 26 pregnancies. Four of the infants had a goiter at birth, and 3 of these had neonatal thyrotoxicosis. In 2 children neonatal thyrotoxicosis was not evident at birth because of maternal antithyroid therapy. Five children had congenital defects. Two mothers were responsible for 4 of the children with abnormalities, and both mothers had been treated with thiourea drugs for long periods, ranging from 7 to 11 years. The majority of children who are exposed to these drugs in utero appear to have no subsequent ill effects. However, prolonged therapy with these agents may be undesirable.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Female; Fetal Blood; Fetal Death; Goiter; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Long-Acting Thyroid Stimulator; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Scalp; Thyroid Function Tests; Thyroxine

From 1959 to 1970, 272 operations for thyrotoxicosis were performed. Most of the patients received anti-thyroid drugs and thyroid hormones preoperatively. The patients were continuously followed up. The primary results with low morbidity and no mortality as well as the long term results with a low rate of recurrence and a relatively high incidence of thyroid substitution are discussed. A safe and effective programme for surgical treatment of thyrotoxicosis is described. Anti-thyroid drugs and thyroid hormones should be administered as the method of choice in preparing these patients for surgery.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Child; Female; Goiter; Humans; Hyperthyroidism; Hypocalcemia; Hypothyroidism; Laryngoscopy; Length of Stay; Male; Methimazole; Middle Aged; Paralysis; Postoperative Complications; Preoperative Care; Propylthiouracil; Recurrent Laryngeal Nerve; Thyroxine; Triiodothyronine

The effect of chronic treatment with tyroxine (T4) or propylthiouracile (PTU) on the turnover of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) has been studied in various areas of the rat brain (brain stem, hypothalamus, striatum and "rest of the brain"). The turnover of NE and DA was determined by the decay in endogenous levels after inhibition of tyrosine hydroxylase by alpha-methylparatyrosine and the turnover of 5-HT was evaluated by the initial accumulation of endogenous 5-HT after inhibition of monoamine oxydase by pargyline. T4 treatment accelerated the release of DA from the striatum but had no significant effects on NA release in the various cerebral areas : nevertheless the NE endogenous level was significantly reduced in the brain stem. PTU treatment delayed the release of DA and NA only from the "rest of the brain". Concerning 5-HT, the only significant variation was observed in the hypothalamus of PTU-treated rats and implied increased turnover. The possible relations between the changes in cerebral monoamines turnover and the behavioural alterations which are observed in thyroid disfunction are discussed.

Topics: Animals; Brain; Brain Stem; Corpus Striatum; Dopamine; Hyperthyroidism; Hypothalamus; Hypothyroidism; Male; Methyltyrosines; Norepinephrine; Propylthiouracil; Rats; Serotonin; Thyroxine; Tyrosine 3-Monooxygenase

In nine patients with thyrotoxicosis (three patients with ophthalmopathy, one patient with T3 thyrotoxicosis) we followed plasma levels of triiodothyronine (T3) and thyroxine (T4) and the TRH induced TSH release before and under treatment with propythiouracil (PTU), carbimazole or methimazol. The patients were observed for 2-8 months and did not receive any thyroid hormones during this time. Before treatment the TSH responses to TRH were absent in all patients. After commencement of antithyroid drug therapy the T3 and T4 plasma values decreased to normal (T3) or subnormal levels (T4) within 1-5 weeks and the patients became euthyroid, but at that time the TRH test was still negative in all patients. Moreover, there was a lag between 2 weeks and 4 months in five of the patients before the TRH test became positive. The duration of this lag could not be correlated with any data of the history or the clinical signs. Several possible explanations for this observation are discussed. Our results suggest that the TRH-test is not suited for the control of the therapeutic effect of antithyroid drug therapy.

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

In an attempt to study pituitary-thyroid feedback control in thyrotoxic patients, TRH tests were performed in 10 thyrotoxic patients who were treated for varying intervals with propylthiouracil. Plasma TSH was undetectable before and after administration of 500 mug TRH in 7 patients (euthyroid or hypothyroid) after therapy for 1 to 4 months. Also, plasma TSH was undetectable before and after TRH in 3 patients who had been euthyroid for at least 6 months. To explore this abnormality, rats were made thyrotoxic by administering large doses of thyroxine or desiccated thyroid for 3 to 28 days. Discontinuation of thyroid hormone administration was followed by a significant but temporary fall of plasma thyroxine and triiodothyronine concentration below control levels. Duration of the low plasma thyroxine and triiodothyronine concentration was longer with the prolonged administration of thyroid hormone. Despite low plasma thyroxine and triiodothyronine concentrations, plasma TSH was below normal before and after administration of TRH. This unresponsiveness of the pituitary to TRH may be comparable to that found in thyrotoxic patients receiving antithyroid drugs for a certain period. Since this pituitary unresponsiveness to TRH in rats is due to a depletion of pituitary TSH content, it is suggested that depletion of pituitary TSH in thyrotoxic patients during antithyroid therapy is the cause of pituitary unresponsiveness to TRH.

Topics: Adult; Animals; Female; Humans; Hyperthyroidism; Intracellular Fluid; Male; Middle Aged; Pituitary Gland; Propylthiouracil; Rats; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Time Factors; Triiodothyronine

Rats made thyrotoxic with large doses of thyroxine (T4) during the neonatal period (neo-T4) show many abnormalities as adults. These usually include impaired body, pituitary and thyroid growth, diminished pituitary and serum TSH concentrations, a diminished serum T4 and a diminished response to PTU challenge and to thyrotropin-releasing hormone (TRH) stimulation. Experiments are presented which show that these rats are hypersensitive to feedback regulation by T4 in a manner similar to that seen after bilateral anterior hypothalamic lesions. They show a subnormal response to PTU challenge and an excessive suppression of serum TSH and goiter growth after T4. Pituitary TSH was less depleted in neo-T4 rats when a small dose of T4 was given daily with PTU and pituitary TSH was more sensitive to suppression by a larger dose of T4 in the neo-T4 group. There was an impaired rebound increase in pituitary TSH following a single inhibitory dose of T4 injected into the adult hypothyroid rat. Although the hypothalamic TRH content is increased in the neo-T4 rat, the circulating concentration of TRH was found to be significantly decreased, supporting the theory that the defects observed in the neo-T4 rat may be the consequence of an impaired hypothalamic secretion of TRH.

Topics: Animals; Depression, Chemical; Female; Hyperthyroidism; Hypothalamus; Male; Pituitary Gland; Propylthiouracil; Rats; Stimulation, Chemical; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine

An approach to the management of patients with thyroid storm is described. The treatment regimen, which is directed against the abnormalities as they are presently understood, incorporates: (a) Propranolol to inhibit the catecholamine-mediated peripheral effects of the circulating thyronines; (b) Propylthiouracil to inhibit thyroid hormone synthesis and to inhibit peripheral conversion of thyroxine to triiodothyronine (T3), the predominant source of T3 production; (c) Iodine to block the glandular release of thyroid hormones; (d) Dexamethasone along with general supportive therapy. The regimen has been used for a 13 year old schoolgirl with thyroid storm, and the induced rapid fall in serum T3 levels is illustrated. It has also been used in patients with florid thyrotoxicosis undergoing emergency surgery and has resulted in marked clinical improvement associated with rapid decreases in serum T3 levels. It is a simple and efficient regimen, rendering cumbersome forms of therapy such as plasmapheresis and peritoneal dialysis unnecessary.

Topics: Adolescent; Dexamethasone; Female; Humans; Hyperthyroidism; Iodides; Propranolol; Propylthiouracil; Triiodothyronine

Topics: Agranulocytosis; Anemia, Hemolytic; Child; Female; Humans; Hyperthyroidism; Propylthiouracil

In normal, nonmedicated volunteers and in patients with thyroid disorders the plasma half-lives of antipyrine, propylthiouracil, and methimazole were determined after single oral doses. The plasma half-liver plus or minus S.D. of antipyrine, propylthiouracil, and methimazole were 11.9 plus or minus 1.4 hr, 6.7 plus or minus 1.0 hr, and 9.3 plus or minus 1.4 hr, respectively, in normal volunteers, but were shortened to 7.7 plus or minus 1.2 hr, 4.3 plus or minus 0.7 hr, and 6.9 plus or minus 0.6 hr, respectively, in hyperthyroid patients. In hypothyroid patients the plasma half-lives of these drugs were prolonged to 26.4 plus or minus 4.0 hr, 24.7 plus or minus 34.5 hr, and 13.6 plus or minus 4.8 hr, respectively. Return to the euthyroid state restored plasma half-lives to or toward normal. Alterations in plasma drug half-lives during thyroid dysfunction appear to result mainly from accelerated hepatic microsomal drug metabolism in hyperthyroidism and retarded drug biotransformation during hypothyroidism.

Topics: Adult; Aged; Antipyrine; Biotransformation; Female; Half-Life; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Methimazole; Middle Aged; Propylthiouracil; Spectrophotometry; Thyroid Diseases; Thyroid Function Tests

The influence of thyroid hormone on serotonin was studied in different regions of the rat brain. Surgical thyroidectomy of adult male rats led to significant increases in the level of serotonin in the hypothalamus but had no effect on this biogenic amine in the brain stem and basal ganglia. Experimental cretinism, induced by daily propylthiouracil treatment starting at birth, caused increased serotonin levels in all brain regions studied. In contrast. neonatal hyperthyroidism, produced by daily administration of L-triiodothyronine from birth, had no effect on the ontogenic patterns of serotonin. The turnover of serotonin, estimated by determining the rate of increase of the amine following administration of the monoamine oxidase inhibitor, pargyline, was decreased in the brains of 30-day-old cretinous rats when compared to their control littermates. The data suggest that thyroid hormone may exert an important regulatory influence on serotonin metabolism in the developing brain.

Topics: Animals; Animals, Newborn; Basal Ganglia; Brain; Brain Stem; Congenital Hypothyroidism; Hyperthyroidism; Hypothalamus; Hypothyroidism; Male; Pargyline; Propylthiouracil; Rats; Serotonin; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Time Factors; Triiodothyronine

Topics: Adolescent; Adult; Child; Female; Guanethidine; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Phenobarbital; Propranolol; Propylthiouracil; Reserpine; Thyroidectomy

This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.

Topics: Chemical and Drug Induced Liver Injury; Chronic Disease; Humans; Hyperthyroidism; Male; Microscopy, Electron; Middle Aged; Propylthiouracil

Serum levels of propylthiouracil were measured in 8 normal persons and in 7 patients with hyperthyroidism after a single, 300 mg, oral dose of 6-n-propyl-2-thiouracil (PTU). The patients with hyperthyroidism were restudied after 3, 6, and 9 weeks of individualized treatment with PTU. The serum half-life of the drug in normal subjects was 1.65 h. In patients with hyperthyroidism the serum half-life was similar, and it did not change significantly as the euthyroid state was achieved.

Topics: Half-Life; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Gland; Thyroxine; Time Factors

Topics: Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil

Topics: Administration, Oral; Arterial Occlusive Diseases; Cerebral Arteries; Female; Heparin; Humans; Hyperthyroidism; Hypoprothrombinemias; Injections, Intravenous; Middle Aged; Propylthiouracil; Prothrombin Time; Sodium; Thyroid Crisis; Warfarin

Three patients with hemiagenesis of the typhoid gland are described. One was clinically euthyroid, whereas the other two were more unusual in that one had coincident Graves' disease with thyrotoxicosis, and one had primary myxodema. In all three cases diagnosis of hemiagenesis was established by the administration of thyroid-stimulating hormone (TSH). The literature on hemiagenetic thyroid glands with and without associated thyroid disease is reviewed. Although the anomaly is uncommon, awareness and recogniton of its existence may clarify an otherwise puzzling clinical thyroid evaluation, and thus possible avert an unnecessary surgical procedure.

Topics: Adult; Congenital Abnormalities; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Myxedema; Propylthiouracil; Radionuclide Imaging; Thyroid Gland; Thyrotropin; Thyroxine

A euthyroid woman with ophthalmic Graves disease developed endogenous hyperthyroidism coincident with T3 suppression test. There is a putative role of liothyronine administration in precipitating or activating hyperthyroidism. Aberrancies in T3 suppression testing in graves disease occur.

Topics: Bendroflumethiazide; Female; Graves Disease; Humans; Hyperthyroidism; Middle Aged; Prednisone; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Triiodothyronine

Serum T3 level in various thyroid diseases was determined in unextracted serum with the Dainabot kit for T3 RIA. The serum T3 level in 33 normal subjects was 0.8-1.6 ng/ml. It was 5.7 +/- 3.5 ng/ml (mean +/- S.D.) in 36 hyperthyroid patients, and undetectable to 0.8 ng/ml in 21 hypothyroid patients. Generally the serum T4 and serum T3 decreased in parallel after radioiodine therapy for hyperthyroidism. However, in some cases the serum T3 level remained high in spite of normalized serum T4 after radioiodine therapy. This state indicated "T3-toxicosis", and hyperthyroidism was apt to recur. When thyroid function was observed for 2 years following radioiodine treatment, the ratio of serum T3 (T3 level before treatment/T3 level after treatment) decreased more significantly as compared with the ratio of serum T4 in euthyroid cases. Serum T3 provides a more sensitive index of thyroid function than serum T4 in euthyroid states after radioiodine or anti-thyroid drug therapy. The present data indicate that the serum T3 level and the T4/T3 ratio are valuable aids in the estimation of prognosis of hyperthyroid patients after various treatments.

Topics: Adult; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Middle Aged; Propylthiouracil; Thyroxine; Triiodothyronine

Over a 7-yr period from January 1967 to January 1974, 141 patients underwent thyroid surgery for various pathology at the Bexar County Hospital - University of Texas Medical School at San Antonio. Of these, 113 patients underwent subtotal thyroidectomy for benign diseases, including 28 of thyrotoxic patients who underwent subtotal thyroidectomy as definitive treatment. In this group of patients special interest and emphasis was placed in the preoperative and intraoperative management of the difficult and complicated hyperthyroid patient. Preoperative treatment was accomplished by the utilization of multiple drug combinations - including antithyroid drugs, adrenergic blocking agents, and iodine - which resulted in significant decrease in preparation time for surgery. Furthermore, this short intensive preoperative management of complicated hyperthyroid patients allowed satisfactory correction of their problems with little or no morbidity which otherwise would have been extremely difficult if not impossible to resolve. At operation, 28 patients were diagnosed to have malignant disease; 23 underwent total thyroidectomy and the other 5 had subtotal thyroidectomy. In addition to total or subtotal thyroidectomy, 23 patients had either classical or modified radical neck dissection including 9 patients who had bilateral neck dissection. The various surgical techniques utilized, the rationale for rapid preoperative preparation of complicated hyperthyroid patients, morbidity, and long-term follow-up are discussed.

Topics: Adolescent; Adult; Aged; Child; Dexamethasone; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Neck Dissection; Potassium Iodide; Propylthiouracil; Reserpine; Thyroid Diseases; Thyroid Neoplasms; Thyroidectomy

Topics: Administration, Oral; Adult; Aged; Female; Half-Life; Humans; Hyperthyroidism; Injections, Intravenous; Kinetics; Male; Middle Aged; Models, Biological; Propylthiouracil

Topics: Antithyroid Agents; Female; Fetal Death; Gestational Age; Humans; Hyperthyroidism; Infant, Newborn; Infant, Premature; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy

In 66 untreated patients with hyperthyroidism, serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were measured by immunoassay. The mean T(3) level was 478+/-28 ng/100 ml (all values mean+/-SEM) and the T(4) was 20.6+/-0.6 mug/100 ml. The serum T(4)/T(3) ratio by weight was 48+/-2 as opposed to a value of 71+/-3 in euthyroid adults. There was a significant inverse correlation of the T(4)/T(3) ratios with serum T(3) (r=0.77; P<0.01) but not with serum T(4)(r=0.21). These results suggested that relative overproduction of T(3) is consistently present in patients with hyperthyroidism. To examine the acute effects of various antithyroid agents on serum T(3) and T(4) concentrations, iodide, propylthiouracil (PTU), and methylmercaptoimidazole (MMI) were given alone to mine patients, and serial T(3) and T(4) measurements were made. There was an acute decrease in serum T(3) over the first 5 days in the three iodide and three PTU-treated patients which was greater than that seen in the MMI group. This suggested that PTU and MMI had different effects on T(3) production. To compare the effects of PTU and MMI under conditions in which thyroidal hormone release was minimized, these drugs were given in combination with iodide. The mean daily dosage of PTU was 827 (n=11) and of MMI was 88 (n=8). In the PTU+iodide group, the initial serum T(3) concentration was 586+/-61 ng/100 ml and decreased significantly to 326+/-41 on day 1 and to 248+/-21 on days 2 and 3, respectively, and did not change further on days 4 and 5. In the MMI + iodide group, basal serum T(3) was 645+/-90 ng/100 ml and decreased to 568+/-81, 452+/-73, and 344+/-51 on days 1, 2, and 3, respectively, and did not change thereafter. While the initial T(3) concentrations in serum were not different in the PTU and MMI groups, the T(3) concentrations in the PTU patients were significantly lower on days 1 and 2 and during the apparent plateau period on days 3-5. Serum T(4) concentrations decreased gradually in both groups, from 23.9+/-2.0 mug/100 ml, initially, to 17.5+/-1.6 on day 5 in the PTU group and from 22.0+/-2.6 to 14.6+/-2.0 in the MMI-treated patients. The T(4) values were not significantly different at any time. These changes resulted in increases in the serum T(4)/T(3) ratios in both groups, but these ratios were substantially higher in the patients treated with PTU + iodide. The initial serum T(4)/T(3) ratio was 43+/-3 and increased to 74+/-7 and 88+/-7 on days 1 and 2 in the PTU grou

Topics: Antithyroid Agents; Dose-Response Relationship, Drug; Humans; Hyperthyroidism; Iodine; Methimazole; Propylthiouracil; Thyroid Gland; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Antithyroid Agents; Drug Therapy, Combination; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Triiodothyronine

Topics: Abortion, Spontaneous; Antithyroid Agents; Basal Metabolism; Female; Humans; Hyperthyroidism; Infant, Newborn; Iodine Radioisotopes; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Congenital Hypothyroidism; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Male; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Twins

Topics: Adult; Electrocardiography; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroid Function Tests; Wolff-Parkinson-White Syndrome

Topics: Adolescent; Adult; Aged; Bicarbonates; Carbimazole; Diphosphoglyceric Acids; Erythrocytes; Female; Hemoglobins; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroxine; Triiodothyronine

Topics: Animals; Antithyroid Agents; Child; Goiter; Graves Disease; Humans; Hyperthyroidism; Methimazole; Phenylthiourea; Propylthiouracil; Rats; Sulfaguanidine; Thioglycosides; Thyroid Gland; Vegetables

Topics: Adolescent; Agglutination Tests; Antibodies; Biopsy; Child; Child, Preschool; Complement Fixation Tests; Female; Follow-Up Studies; Humans; Hyperthyroidism; Infant; Iodine; Male; Propylthiouracil; Recurrence; Remission, Spontaneous; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Dopamine beta-Hydroxylase; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroxine

Topics: Aging; Animals; Animals, Newborn; Cerebellum; Fasting; Hyperthyroidism; Hypothyroidism; Leucine; Nerve Tissue Proteins; Propylthiouracil; Rats; Thyroxine; Time Factors; Tritium

Topics: Female; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Intelligence Tests; Iodine; Maternal-Fetal Exchange; Methimazole; Patient Care Team; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Carotid Arteries; Electrocardiography; Heart; Humans; Hyperthyroidism; Iodine Radioisotopes; Phonocardiography; Propylthiouracil; Pulse; Radioimmunoassay; Triiodothyronine

Topics: Animals; Biological Transport; Carbon Radioisotopes; Cholesterol; Chromatography, Thin Layer; Feces; Hyperthyroidism; Hypothyroidism; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Propylthiouracil; Rats; Thyroid Gland; Thyroxine; Time Factors; Triglycerides

Topics: Age Factors; Animals; Animals, Newborn; Cerebellar Cortex; Cerebellum; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Purkinje Cells; Rats; Rats, Inbred Strains; Thyroxine

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Long-Term Care; Male; Middle Aged; Prognosis; Propylthiouracil; Radiotherapy Dosage; Thyroid Function Tests; Triiodothyronine

Topics: Adenoma; Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodides; Methimazole; Propylthiouracil; Sulfur Isotopes; Thyroid Gland; Thyroid Neoplasms

Topics: Adolescent; Adult; Antithyroid Agents; Erythrocytes; Female; Follow-Up Studies; Glucosephosphate Dehydrogenase; Humans; Hyperthyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests

Topics: Adolescent; Diagnosis, Differential; Female; Graves Disease; Growth Hormone; Humans; Hyperthyroidism; Propylthiouracil; Radioimmunoassay; Serum Globulins; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Age Determination by Skeleton; Age Factors; Body Height; Bone Development; Child; Child Development; Child, Preschool; Evaluation Studies as Topic; Female; Follow-Up Studies; Growth Disorders; Humans; Hyperthyroidism; Infant; Male; Propylthiouracil

The relative roles of triiodothyronine (T(3)) and thyroxine (T(4)) in modulating pituitary responsiveness to thyrotropin-releasing hormone (TRH) have been assessed. (a) 10 hyperthyroid patients with elevated serum T(2) and T(4) levels showed no pituitary response to TRH. After 2 wk of propylthiouracil therapy T(4) levels had fallen to normal in only five patients while T(2) levels were normal in all. Pituitary responsiveness to TRH returned in all patients with normal or high T(4) concentrations. (b) Patients with isolated elevations of serum T(3) (T(3) toxicosis) failed to respond to TRH. TRH responsiveness was restored when T(3) levels fell to normal after propylthiouracil therapy. (c) When pituitary responsiveness to TRH was tested 60 min after a single oral dose of 50 mug of T(3), which increased serum T(3) levels to slightly above the normal range, no rise in thyrotropin (TSH) was seen in six subjects. These findings indicate that T(3) elevations alone can rapidly inhibit pituitary responsiveness to TRH.

Topics: Administration, Oral; Adult; Female; Graves Disease; Humans; Hyperthyroidism; Injections, Intravenous; Male; Middle Aged; Pituitary Gland; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Adolescent; Humans; Hyperthyroidism; Male; Metacarpus; Osteoarthropathy, Secondary Hypertrophic; Propylthiouracil; Thyroid Hormones; Thyroidectomy

Topics: Adolescent; Female; Goiter; Hemorrhage; Humans; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Iodine; Methylthiouracil; Postoperative Care; Postoperative Complications; Potassium Iodide; Preoperative Care; Propylthiouracil; Thyroid Diseases; Thyroidectomy; Thyroiditis; Time Factors; Vocal Cord Paralysis

Topics: Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones

Topics: Adolescent; Child; Female; Graves Disease; Humans; Hyperthyroidism; Hypocalcemia; Laryngeal Edema; Male; Methimazole; Methods; Postoperative Complications; Potassium Iodide; Propranolol; Propylthiouracil; Thyroid Hormones; Thyroidectomy

Topics: Abortion, Spontaneous; Adolescent; Adult; Cesarean Section; Cholesterol; Female; Fetal Death; Gestational Age; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Iodine; Iodine Radioisotopes; Maternal Mortality; Methimazole; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Triiodothyronine

Topics: Adult; Arrhythmias, Cardiac; Electrocardiography; Heart Block; Heart Conduction System; Humans; Hypercalcemia; Hyperthyroidism; Male; Propylthiouracil

Topics: Animals; Animals, Newborn; Body Weight; Cell Division; Cerebellum; DNA; Fetus; Hyperthyroidism; Hypothyroidism; Nerve Tissue Proteins; Nutrition Disorders; Organ Size; Propylthiouracil; Rats; RNA; Spectrophotometry, Ultraviolet; Thyroxine

Topics: Age Factors; Animals; Centrifugation, Density Gradient; Cerebellum; Hyperthyroidism; Hypothyroidism; Microscopy, Electron; Nerve Tissue Proteins; Nutrition Disorders; Propylthiouracil; Rats; Synaptosomes; Thyroxine

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Long-Acting Thyroid Stimulator; Methimazole; Neoplasms; Propylthiouracil; Thyroidectomy

Topics: Albumins; Animals; Antibody Specificity; Binding Sites; Globulins; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Iodine Isotopes; Methimazole; Methods; Propylthiouracil; Rabbits; Radioimmunoassay; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins

Topics: Adult; Aged; Antithyroid Agents; Chemical Phenomena; Chemistry; Female; Humans; Hyperthyroidism; Imidazoles; Male; Methylthiouracil; Perchlorates; Propylthiouracil; Sympatholytics; Thiouracil; Thyroid Hormones; Thyronines

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Child; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Male; Middle Aged; Organ Size; Postoperative Complications; Preoperative Care; Propylthiouracil; Thyroid Gland; Thyroidectomy; Voice

Topics: Antithyroid Agents; Follow-Up Studies; Humans; Hyperthyroidism; Iodine Isotopes; Methimazole; Propylthiouracil; Radioimmunoassay; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Female; Half-Life; Humans; Hyperthyroidism; Male; Methimazole; Methods; Perchlorates; Potassium; Propylthiouracil

Topics: Adenosine Triphosphatases; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenalectomy; Ammonia; Animals; Calcium; Chromatography, Ion Exchange; Growth Hormone; Heart; Hyperthyroidism; Hypophysectomy; Hypothyroidism; Magnesium; Male; Muscle Proteins; Myocardium; Myosins; Pituitary Hormones; Potassium; Propylthiouracil; Rats; Sodium; Sulfhydryl Compounds; Thyroid Hormones; Thyroxine

Topics: Adrenal Gland Diseases; Adult; Asthma; Black People; Bronchodilator Agents; Female; Humans; Hyperthyroidism; Iodine Isotopes; Male; Middle Aged; Positive-Pressure Respiration; Propylthiouracil; Skin Tests; White People

Topics: Age Factors; Animals; Cell Fractionation; Cerebellar Cortex; Hyperthyroidism; Hypothyroidism; Membranes; Nerve Endings; Nerve Tissue Proteins; Propylthiouracil; Rats; Synapses; Synaptic Vesicles; Synaptosomes; Thyroid Hormones; Thyroxine

Topics: Animals; Binding Sites; Cattle; Chromosome Aberrations; Chromosome Disorders; Dogs; Female; Graves Disease; Guinea Pigs; Haplorhini; Humans; Hyperthyroidism; Iodine Isotopes; Male; Methods; Pregnancy; Propylthiouracil; Protein Binding; Rabbits; Radioimmunoassay; Rats; Serum Albumin; Serum Globulins; Sheep; Thyronines; Thyroxine; Triiodothyronine

Topics: Administration, Oral; Colorimetry; Humans; Hyperthyroidism; Indicators and Reagents; Methods; Propylthiouracil; Quinones; Spectrophotometry

Topics: Humans; Hyperthyroidism; Iodine Isotopes; Methimazole; Propylthiouracil; Radioimmunoassay; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Amino Acids; Animals; Animals, Newborn; Brain; Cerebellum; Cerebral Cortex; Diencephalon; Hyperthyroidism; Hypothyroidism; Leucine; Liver; Microsomes; Mitochondria; Nerve Tissue Proteins; Propylthiouracil; Rats; Subcellular Fractions; Synaptic Vesicles; Thyroidectomy; Thyroxine; Tritium

The number of synapses in the molecular layer of the rat cerebellum is reduced by early hypo-and hyperthyroidism within 30 days. Hypothyroidism retards synaptogenesis after 10 days, while hyperthyroidism accelerates synaptogenesis initially, but by 21 days the number of synapses is reduced. The sensitivity of developing synapses to thyroid hormone may permit analysis of the events triggering synaptogenesis.

Topics: Age Factors; Animals; Animals, Newborn; Cerebellum; Female; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Synapses; Thyroid Hormones; Thyroxine

Topics: Animals; Bile; Bile Acids and Salts; Cholelithiasis; Cricetinae; Diet; Female; Hyperthyroidism; Liver; Male; Propylthiouracil; Thyroid Gland; Thyroxine

Topics: Acetaldehyde; Acetates; Animals; Caproates; Carbon Dioxide; Carbon Isotopes; Citric Acid Cycle; Ethanol; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Lactates; Liver; Male; Oxidoreductases; Perfusion; Propylthiouracil; Pyrazoles; Pyruvates; Rats; Triiodothyronine

Topics: Female; Heart Diseases; Heart Failure; Humans; Hyperthyroidism; Infant; Infant, Newborn; Long-Acting Thyroid Stimulator; Pregnancy; Propylthiouracil

Topics: Adipose Tissue; Animals; Carboxy-Lyases; Coenzyme A; Glycerol; Hyperthyroidism; Hypothyroidism; Lipid Metabolism; Lipids; Methods; Oxidoreductases; Propylthiouracil; Pyruvate Kinase; Pyruvates; Rats; Triglycerides; Triiodothyronine

Topics: Analysis of Variance; Animals; Animals, Newborn; Autoradiography; Body Weight; Cell Differentiation; Cerebellar Cortex; Hyperthyroidism; Hypothyroidism; Organ Size; Propylthiouracil; Rats; Sodium Chloride; Thymidine; Thyroid Hormones; Thyroxine; Tritium

Topics: Animals; Animals, Newborn; Cell Differentiation; Cerebellar Cortex; Dendrites; Hyperthyroidism; Hypothyroidism; Microscopy, Electron; Phosphotungstic Acid; Propylthiouracil; Purkinje Cells; Rats; Sodium Chloride; Synapses; Thyroid Hormones; Thyroxine

Topics: Adolescent; Adult; California; Humans; Hyperthyroidism; Male; Mexico; Paralysis; Philippines; Propylthiouracil

Topics: Esterases; Fasting; Female; Glycerides; Goiter; Graves Disease; Heparin; Humans; Hyperthyroidism; Insulin; Iodine Isotopes; Lipase; Lipoprotein Lipase; Male; Methimazole; Propranolol; Propylthiouracil; Triglycerides

Topics: Eye Manifestations; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Male; Methimazole; Neurotic Disorders; Pregnancy; Pregnancy Complications; Propylthiouracil; Psychotic Disorders; Skin Manifestations; Thyroidectomy; Triiodothyronine

Topics: Adolescent; Adult; Aged; Brain; Electroencephalography; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests; Time Factors

Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Methimazole; Methylthiouracil; Propylthiouracil; Radioimmunoassay; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Aged; Carbimazole; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Iodine Isotopes; Male; Middle Aged; Nigeria; Propylthiouracil; Thyroid Gland; Thyroidectomy

Topics: Adolescent; Audiometry; Child; Cochlea; Deafness; Female; Goiter; Humans; Hyperthyroidism; Labyrinth Diseases; Lupus Erythematosus, Systemic; Propylthiouracil; Tinnitus

Topics: Child; Chromatography; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Protein Binding; Radioimmunoassay; Recurrence; Thyroxine; Triiodothyronine

Topics: Female; Humans; Hyperthyroidism; Infant, Newborn; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Male; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Radiography; Thyroid Function Tests; Thyroidectomy

Topics: Birth Weight; Body Weight; Digitalis Glycosides; Exophthalmos; Female; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Propylthiouracil; Tachycardia; Thyroid Function Tests

Topics: Adolescent; Antithyroid Agents; Atrial Fibrillation; Digitalis Glycosides; Diuretics; Electrocardiography; Heart Auscultation; Heart Failure; Humans; Hyperthyroidism; Male; Mitral Valve Insufficiency; Propylthiouracil; Quinidine; Reserpine; Streptococcal Infections

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Carbimazole; Chemical Phenomena; Chemistry; Humans; Hyperthyroidism; Hypothyroidism; Imidazoles; Iodine Isotopes; Methimazole; Methylthiouracil; Myocardial Infarction; Perchlorates; Potassium; Potassium Iodide; Propranolol; Propylthiouracil; Psychotic Disorders; Thiourea; Thyroxine; Time Factors

Topics: Adult; Age Factors; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Iodine Isotopes; Middle Aged; Perchlorates; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Age Factors; Cardiomegaly; Child; Electrocardiography; Female; Heart Auscultation; Heart Failure; Humans; Hyperthyroidism; Prednisone; Propylthiouracil; Recurrence; Remission, Spontaneous; Tachycardia

Topics: Cardiomegaly; Hepatomegaly; Humans; Hyperthyroidism; Infant; Iodine; Long-Acting Thyroid Stimulator; Male; Propylthiouracil; Splenomegaly; Thyroid Function Tests

Topics: Adenocarcinoma; Aged; Autoradiography; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Ion Exchange Resins; Neoplasm Metastasis; Propylthiouracil; Radionuclide Imaging; Thyroid Neoplasms; Triiodothyronine

Topics: Adolescent; Athetosis; Chorea; Female; Humans; Hyperthyroidism; Neurologic Manifestations; Propylthiouracil

Topics: Acetaldehyde; Alcohol Drinking; Animals; Ethanol; Hyperthyroidism; Hypothyroidism; Male; Oxygen Consumption; Propylthiouracil; Rats; Triiodothyronine

Topics: Adolescent; Adult; Bone Development; Child; Child, Preschool; Craniosynostoses; Female; Fingers; Graves Disease; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intellectual Disability; Long-Acting Thyroid Stimulator; Male; Pedigree; Propylthiouracil

Topics: Adult; Aged; Alkaline Phosphatase; Calcium; Female; Humans; Hydroxyproline; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Serum Albumin

Topics: Child, Preschool; Female; Humans; Hyperthyroidism; Hypothyroidism; Menstruation; Propylthiouracil; Puberty, Precocious

Topics: Adenosine Triphosphate; Animals; Coenzyme A; Ethanol; Fructose; Hyperthyroidism; Hypothyroidism; Ketone Bodies; Lactates; Liver; Male; Oxidation-Reduction; Propylthiouracil; Pyruvates; Rats; Triiodothyronine

Topics: Child; Cineangiography; Female; Heart Ventricles; Humans; Hyperthyroidism; Hypoxia; Male; Mitral Valve Insufficiency; Papillary Muscles; Phonocardiography; Propylthiouracil

Topics: Humans; Hyperthyroidism; Iodine; Iodine Isotopes; Methimazole; Propylthiouracil

Topics: Adolescent; Antibodies, Antinuclear; Biopsy; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Hyperthyroidism; Kidney Glomerulus; Prednisone; Propylthiouracil; Purpura; Skin

Topics: Body Weight; Diarrhea; Female; Humans; Hyperthyroidism; Infant; Propylthiouracil; Thyroid Function Tests

Topics: Adult; Aged; Basal Metabolism; Ethchlorvynol; Female; Goiter; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Serum Globulins; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Adolescent; Agranulocytosis; Alkaline Phosphatase; Bone Resorption; Calcium; Drug Eruptions; Female; Humans; Hypercalcemia; Hyperthyroidism; Iodine Isotopes; Phosphorus; Propylthiouracil; Serum Albumin; Thyroid Hormones; Thyroidectomy; Thyrotropin; Vitamin D

Topics: Acetoacetates; Animals; Citric Acid Cycle; Coenzyme A; Depression, Chemical; Ethanol; Fasting; Hydroxybutyrates; Hyperthyroidism; Hypothyroidism; Ketone Bodies; Liver; Male; Metabolism; Mitochondria, Liver; NAD; Oxidation-Reduction; Oxygen Consumption; Propylthiouracil; Rats; Sorbitol; Stimulation, Chemical; Thyroid Diseases; Time Factors; Triiodothyronine

Topics: Adolescent; Agranulocytosis; Child; Child, Preschool; Drug Hypersensitivity; Female; Fever; Humans; Hyperthyroidism; Kidney Glomerulus; Leukocyte Count; Leukopenia; Lupus Erythematosus, Systemic; Male; Propylthiouracil; Urticaria

Topics: Animals; Body Weight; Chickens; Hyperthyroidism; Hypothyroidism; Male; Organ Size; Phosphates; Phosphorus Isotopes; Pituitary Gland; Propylthiouracil; Secretory Rate; Stimulation, Chemical; Testis; Thyrotropin; Thyroxine

Topics: Adult; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Thiocyanates

Topics: Animals; Ear, Middle; Hyperthyroidism; Hypothyroidism; Mucous Membrane; Propylthiouracil; Rats

Topics: Adolescent; Adult; Aged; Goiter; Humans; Hyperthyroidism; Immunoglobulin G; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Triiodothyronine

Topics: Animals; Erythrocytes; Glucosephosphate Dehydrogenase; Glycolysis; Hexokinase; Hyperthyroidism; Male; Propylthiouracil; Rats; Transferases; Triiodothyronine

Topics: Adult; Calcitonin; Calcium; Female; Humans; Hypercalcemia; Hyperthyroidism; Injections, Intravenous; Male; Middle Aged; Myxedema; Propylthiouracil; Thyroidectomy; Time Factors

Topics: Animals; Female; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Propylthiouracil; Radiation Injuries, Experimental; Rats; Thyroid Gland; Thyroxine

Topics: Animals; Body Weight; Ethanol; Hyperthyroidism; Hypothyroidism; Liver; Male; Organ Size; Oxidation-Reduction; Oxygen Consumption; Propylthiouracil; Rats; Sorbitol; Thyroid Diseases; Triiodothyronine

Topics: Alcohol Drinking; Alcohol Oxidoreductases; Animals; Body Weight; Depression, Chemical; Diet; Ethanol; Hyperthyroidism; Hypothyroidism; Liver; Male; Organ Size; Oxygen Consumption; Propylthiouracil; Proteins; Rats; Sorbitol; Stimulation, Chemical; Triiodothyronine

Topics: Adult; Chorea; Female; Humans; Hyperthyroidism; Phenobarbital; Prednisone; Propranolol; Propylthiouracil; Sympathetic Nervous System

Topics: Adult; Eye Manifestations; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Propylthiouracil; Skin Manifestations; Thyroid Diseases

Topics: Adolescent; Aged; Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodine Isotopes; Propylthiouracil; Thyroidectomy

Differences in the metabolic fate of antithyroid drugs influence the optimal frequency of administration and their therapeutic efficacy. (35)S propylthiouracil differed from the (35)S imidazoles (carbimazole and methimazole) in the more rapid absorption and excretion and the shorter biological half-life in the plasma of the former. Renal function may have a more important influence on the biological half-life of the drugs than thyroid status. Further work is required to determine the optimal frequency of administration for each compound.

Topics: Antithyroid Agents; Carbimazole; Chromatography, Thin Layer; Female; Humans; Hyperthyroidism; Imidazoles; Kidney Failure, Chronic; Methimazole; Propylthiouracil; Sulfur Isotopes

Topics: Adult; Basal Metabolism; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Myxedema; Propylthiouracil; Thyroid Function Tests; Thyroxine-Binding Proteins

Topics: Adult; Antithyroid Agents; Electromyography; Humans; Hyperthyroidism; Hypokalemia; Male; Methimazole; Paralysis; Periodicity; Propylthiouracil; Reserpine; Thyroid Function Tests

Topics: Adult; Aged; Antibodies; Chronic Disease; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Myxedema; Propranolol; Propylthiouracil; Pulse; Thiocyanates; Thyroid Diseases; Thyroid Function Tests; Thyroiditis; Time Factors; Triiodothyronine

Topics: Animal Feed; Animals; Cervix Uteri; Contraceptives, Oral; Diet, Reducing; Estrogens; Female; Hemangioendothelioma; Hyperthyroidism; Injections, Subcutaneous; Lymphoma, Large B-Cell, Diffuse; Mestranol; Mice; Norethynodrel; Propylthiouracil; Uterine Cervical Neoplasms

Topics: Acetaldehyde; Animals; Ethanol; Fasting; Hyperthyroidism; Hypothyroidism; Lactates; Liver; Male; Oxidation-Reduction; Propylthiouracil; Pyruvates; Rats; Thyroid Gland; Triiodothyronine

Topics: Age Factors; Female; Humans; Hyperthyroidism; Infant; Propylthiouracil; Prothrombin; Prothrombin Time

Topics: Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Long-Acting Thyroid Stimulator; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Animal Nutritional Physiological Phenomena; Animals; Diet; Feedback; Growth; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Thiamine Deficiency; Thyroid Gland; Thyroxine; Time Factors

Topics: Adolescent; Anesthesia, General; Carbimazole; Female; Follow-Up Studies; Goiter; Halothane; Horner Syndrome; Humans; Hyperthyroidism; Hypoparathyroidism; Laryngeal Edema; Male; Nitrous Oxide; Oxygen; Postoperative Complications; Preoperative Care; Propylthiouracil; Thyroidectomy; Thyroxine; Tracheotomy

Topics: Adolescent; Adult; Aged; Anemia; Erythrocyte Aging; Female; Humans; Hyperthyroidism; Iron; Male; Middle Aged; Phenobarbital; Propylthiouracil; Reserpine

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant; Laryngeal Edema; Male; Postoperative Complications; Propylthiouracil; Thyroidectomy; Vocal Cord Paralysis

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anesthesia, Spinal; Anti-Bacterial Agents; Child; Cortisone; Female; Guanethidine; Humans; Hyperthyroidism; Iodides; Liver; Lung; Male; Methimazole; Middle Aged; Myocardium; Propylthiouracil; Reserpine; Sex Factors; Sodium; Thyroid Crisis; Thyroid Gland

Topics: Adult; Familial Mediterranean Fever; Humans; Hyperthyroidism; Male; Paralysis; Propylthiouracil

Topics: Animals; Body Weight; Female; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Propylthiouracil; Radiation Injuries, Experimental; Rats; Thyroid Gland; Thyroxine; Time Factors

Topics: Acacia; Anemia; Animals; Erythrocytes; Erythropoiesis; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Rats; Resins, Plant; Thyroxine

Topics: Blood Proteins; Cholesterol; Chromatography, Gel; Contraceptives, Oral; Dextrans; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Isotopes; Ion Exchange Resins; Mass Screening; Methods; Pregnancy; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Triiodothyronine

Topics: Adult; Aged; Analysis of Variance; Antithyroid Agents; Calcitonin; Calcium; Female; Graves Disease; Humans; Hyperthyroidism; Hypocalcemia; Middle Aged; Phosphates; Propylthiouracil; Thyroid Gland; Thyroidectomy; Thyroiditis

Topics: Antithyroid Agents; Female; Goiter; Humans; Hyperthyroidism; Iodine Isotopes; Pregnancy; Propylthiouracil; Thyroidectomy; Thyroxine

Topics: Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Long-Acting Thyroid Stimulator; Propylthiouracil; Thyroid Function Tests; Triiodothyronine

Topics: Antithyroid Agents; Creatine Kinase; Fructose; Glucose; Glycogen; Humans; Hyperthyroidism; In Vitro Techniques; Ischemia; Lactates; Male; Middle Aged; Muscle Cramp; Muscles; Propylthiouracil

Topics: Adolescent; Adult; Aged; Basal Metabolism; Drug Synergism; Female; Humans; Hyperthyroidism; Male; Methods; Middle Aged; Perchlorates; Potassium; Propylthiouracil; Thyroid Function Tests; Time Factors

Topics: Acidosis; Adult; Coma; Cortisone; Diabetic Ketoacidosis; Glucose Tolerance Test; Humans; Hyperglycemia; Hyperthyroidism; Male; Propylthiouracil; Starvation

Topics: Child, Preschool; Female; Goiter; Growth; Humans; Hyperthyroidism; Infant; Intelligence; Intelligence Tests; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Psychological Tests; Thyroid Function Tests

Topics: Ammonia; Animals; Antithyroid Agents; Aspartic Acid; Dactinomycin; Depression, Chemical; Diet; Ethionine; Glutaminase; Glutamine; Hyperthyroidism; Hypothyroidism; Kidney; Ligases; Liver; Male; Ornithine; Phosphotransferases; Propylthiouracil; Puromycin; Rats; Stimulation, Chemical; Thyroid Hormones; Transaminases; Transferases; Urea

Topics: Adolescent; Cerebrospinal Fluid; Exophthalmos; Female; Fluoresceins; Fluoroscopy; Fundus Oculi; Humans; Hyperthyroidism; Ophthalmoscopy; Papilledema; Phenobarbital; Photography; Pressure; Propylthiouracil

Topics: Female; Humans; Hyperthyroidism; Middle Aged; Myxedema; Propylthiouracil

Topics: Blood Pressure; Humans; Hyperthyroidism; Iodine Isotopes; Propylthiouracil

Topics: Aged; Blood Pressure Determination; Cardiac Output; Catecholamines; Guanethidine; Humans; Hyperthyroidism; Hypothyroidism; Male; Mandelic Acids; Physical Exertion; Propylthiouracil; Pulse; Sympathetic Nervous System; Thyroid Function Tests

Topics: Animals; Bile; Carbon Isotopes; Glucosyltransferases; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Iodine Isotopes; Liver; Norepinephrine; Normetanephrine; Oxygen Consumption; Perfusion; Propylthiouracil; Rats; Thyroxine; Transferases

Topics: Anemia, Aplastic; Blood Cell Count; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; DNA; Female; Hematocrit; Hemoglobinometry; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; RNA

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Iodine Isotopes; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy

Topics: Absorption; Animals; Biological Assay; Chromatography; Chromatography, Gel; Electrophoresis; Guinea Pigs; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Iodine Radioisotopes; Propylthiouracil; Rabbits; Rats; Thyrotropin; Ultraviolet Rays

Topics: Animals; Ascorbic Acid; Glucuronates; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Isotopes; Kidney Function Tests; Male; Methanol; Models, Biological; Propylthiouracil; Rats; Stimulation, Chemical; Thyroid Gland; Thyroxine; Uracil Nucleotides

Topics: Adolescent; Adult; Antithyroid Agents; Blood Cell Count; Diagnosis, Differential; Diagnostic Errors; Female; Goiter; Heart Auscultation; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methylthiouracil; Myxedema; Nervous System Diseases; Neurotic Disorders; Propylthiouracil; Radioisotope Dilution Technique; Thiazoles; Thiouracil; Thiourea; Thyrotropin

Topics: Animals; Humans; Hyperthyroidism; Hypothyroidism; Propylthiouracil; Rats; Sleep; Thyroxine

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Hormones

Topics: Adolescent; Adult; Alopecia; Antithyroid Agents; Fatigue; Female; Goiter; Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Menstruation Disturbances; Middle Aged; Obesity; Propylthiouracil; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Child; Female; Humans; Hyperthyroidism; Male; Perchlorates; Propylthiouracil

Topics: Amphetamine; Animals; Body Temperature; Brain Chemistry; Hyperthyroidism; Hypothyroidism; Liver; Male; Propylthiouracil; Rats; Thyroidectomy

Topics: Amidohydrolases; Ammonia; Animals; Glutamate Dehydrogenase; Glutamates; Glutaminase; Hyperthyroidism; Hypothyroidism; Kidney; Liver; Propylthiouracil; Rats

Topics: Adolescent; Adult; Basal Metabolism; Cholesterol; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Male; Potassium Iodide; Propylthiouracil; Thyroid Function Tests; Thyroxine

Topics: Adrenal Glands; Angiography; Animals; Constipation; Diarrhea; Gastrointestinal Motility; Hyperthyroidism; Hypothyroidism; Male; Oxygen Consumption; Parathyroid Glands; Propylthiouracil; Radiometry; Rats; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine; Vagotomy; Vagus Nerve

Topics: Child, Preschool; Female; Humans; Hyperthyroidism; Propylthiouracil

Topics: Female; Humans; Hyperthyroidism; Iodine Isotopes; Middle Aged; Propylthiouracil; Pruritus

Topics: Animals; Brain; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Liver; Mice; Pentobarbital; Propylthiouracil; Rats; Sleep; Thiopental; Thyroidectomy; Thyroxine

Topics: Calcium; Feces; Humans; Hyperthyroidism; Hypothyroidism; Magnesium; Phosphates; Propylthiouracil; Triiodothyronine

Topics: Adult; Body Weight; Cortisone; Humans; Hypercalcemia; Hyperparathyroidism; Hyperthyroidism; Iodine Isotopes; Male; Propylthiouracil; Thyroidectomy; Thyroxine

Topics: Adolescent; Adult; Aged; Antibodies; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Isotopes; Male; Middle Aged; Myxedema; Postoperative Complications; Propylthiouracil; Solutions

Topics: Adult; Humans; Hyperthyroidism; Male; Mediastinal Diseases; Myasthenia Gravis; Prednisone; Propylthiouracil; Sarcoidosis

Topics: Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Joint Diseases; Male; Movement Disorders; Muscular Diseases; Propylthiouracil; Thyroidectomy

Topics: Child; Congenital Hypothyroidism; Diagnosis; Humans; Hyperthyroidism; Infant; Infant, Newborn; Propylthiouracil; Thyroid Function Tests; Thyroiditis; Thyroiditis, Autoimmune; Thyrotoxicosis; Thyroxine; Triiodothyronine

Topics: Adolescent; Antithyroid Agents; Child; Drug Therapy; Humans; Hyperthyroidism; Iodine Isotopes; Neoplasms; Neoplasms, Radiation-Induced; Perchlorates; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Toxicology

Topics: Antithyroid Agents; Drug Therapy; Humans; Hyperthyroidism; Iodine Isotopes; Pharmacology; Prognosis; Propylthiouracil; Thyroid Function Tests

Topics: Blood; Drug Therapy; Erythrocytes; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Magnesium; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Drug Therapy; Humans; Hyperthyroidism; Propylthiouracil

Topics: Adolescent; Child; Drug Therapy; Enuresis; Humans; Hyperthyroidism; Nocturnal Enuresis; Propylthiouracil

Topics: Chromosomes; Down Syndrome; Drug Therapy; Humans; Hyperthyroidism; Propylthiouracil; Trisomy

Topics: Adrenal Glands; Aldosterone; Atrophy; Growth Hormone; Heart Rate; Human Growth Hormone; Hyperthyroidism; Liver; Myxedema; Pharmacology; Potassium; Propylthiouracil; Rats; Research; Respiration; Sodium; Spleen; Thyroxine; Urine

Topics: Adolescent; Calcium; Calcium, Dietary; Child; Drug Therapy; Humans; Hyperthyroidism; Hypoparathyroidism; Infant; Postoperative Complications; Propylthiouracil; Thyroid Hormones; Thyroidectomy; Thyrotoxicosis; Vitamin D; Vocal Cord Paralysis

Topics: Adult; Female; Humans; Hyperthyroidism; Muscular Diseases; Porphyrias; Propylthiouracil

Topics: Adult; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyroid Hormones; Thyroidectomy

Topics: Animals; Epinephrine; Hyperthyroidism; Hypothyroidism; Liver; Metabolism; Mice; Pentobarbital; Pharmacology; Propylthiouracil; Research; Sleep; Thyroid Hormones

Topics: Adolescent; Antithyroid Agents; Black People; Drug Hypersensitivity; Humans; Hyperthyroidism; Lupus Erythematosus, Systemic; Prednisolone; Propylthiouracil; Radiography, Thoracic; Thyroid Function Tests; Toxicology

Topics: Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Iodine; Propylthiouracil

Topics: Aging; Alanine; Amino Acids; Aminobutyrates; Animals; Aorta; Carbon Isotopes; Diabetes Mellitus, Experimental; Geriatrics; Glycine; Hyperthyroidism; Hypothyroidism; Insulin; Leucine; Propylthiouracil; Proteins; Rats; Research; Thyronines

Topics: Adrenocorticotropic Hormone; Antithyroid Agents; Goiter; Graves Disease; Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Prednisone; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Thyroiditis; Thyroiditis, Autoimmune

Topics: Adenoma; Goiter; Hyperthyroidism; Pathology; Propylthiouracil; Rats; Research; Thyroid Neoplasms; Thyrotropin; Toxicology

Topics: Blood Chemical Analysis; Chromatography; Geriatrics; Goiter; Hyperthyroidism; Iodine Isotopes; Monoiodotyrosine; Myxedema; Neoplasms; Propylthiouracil; Thiourea; Thyronines; Thyroxine; Tyrosine

Topics: Adolescent; Antithyroid Agents; Child; Female; Goiter; Graves Disease; Guanethidine; Heart Diseases; Humans; Hyperthyroidism; Infant; Iodides; Iodine Isotopes; Myxedema; Ophthalmology; Perchlorates; Pituitary Gland; Potassium; Pregnancy; Pregnancy Complications; Propylthiouracil; Radiotherapy; Reserpine; Thyroid Function Tests; Thyroidectomy; Thyrotoxicosis; Toxicology

Topics: Adrenocorticotropic Hormone; Digoxin; Female; Genetics, Medical; Goiter; Graves Disease; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Propylthiouracil; Thymus Gland; Thyroid Gland; Thyrotoxicosis

Topics: Adrenal Cortex Hormones; Blood Transfusion; Goiter; Hyperthyroidism; Hypoprothrombinemias; Iodine Isotopes; Propylthiouracil; Prothrombin Time; Reserpine; Toxicology; Vitamin K

Topics: Adolescent; Amino Acids; Anions; Antithyroid Agents; Diiodotyrosine; Drug Therapy; Electrophoresis, Paper; Humans; Hyperthyroidism; Iodine; Propylthiouracil; Thyroid Gland; Thyrotoxicosis; Thyroxine; Triiodothyronine

Topics: Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Perchlorates; Potassium; Propylthiouracil; Thyrotropin

Topics: Biological Transport; Blood Protein Electrophoresis; Blood Proteins; Chemical Phenomena; Chemistry; Humans; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Iodine Isotopes; Myxedema; Pharmacology; Pregnancy; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Adenoma; Adenoma, Chromophobe; Child; Diagnostic Imaging; Drug Therapy; Hyperthyroidism; Intracranial Pressure; Pathology; Pituitary Neoplasms; Propylthiouracil; Radiography; Surgical Procedures, Operative; Visual Fields

Topics: Desipramine; Hyperthyroidism; Imipramine; Mice; Propylthiouracil; Research; Toxicology

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adolescent; Child; Humans; Hyperthyroidism; Iodine Isotopes; Propylthiouracil; Thiourea

Topics: Humans; Hyperthyroidism; Hypopituitarism; Propylthiouracil

Topics: Autoimmune Diseases; Drug Hypersensitivity; Humans; Hypersensitivity; Hyperthyroidism; Leukopenia; Propylthiouracil

Topics: Barbiturates; Humans; Hypercalcemia; Hyperthyroidism; Propylthiouracil

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine Isotopes; Methylthiouracil; Propylthiouracil

Topics: Hyperthyroidism; Iodine Isotopes; Propylthiouracil; Reserpine; Surgical Procedures, Operative; Thyrotoxicosis

Topics: Adolescent; Agranulocytosis; Basal Metabolism; Black People; Humans; Hyperthyroidism; Imidazoles; Iodine Isotopes; Propylthiouracil; Thyroid Function Tests; Thyroidectomy; Thyrotoxicosis; Toxicology

Topics: Carbohydrate Metabolism; Carbon Dioxide; Carbon Isotopes; Glucose; Hyperthyroidism; Manometry; Pharmacology; Propylthiouracil; Thyroid Gland; Thyroiditis

Topics: Aged; Antithyroid Agents; Basal Metabolism; Carbimazole; Cholesterol; Humans; Hyperthyroidism; Methylthiouracil; Propylthiouracil; Toxicology

Topics: Administration, Rectal; Humans; Hyperthyroidism; Propylthiouracil; Thyrotoxicosis

Topics: Amyl Nitrite; Angina Pectoris; Anticoagulants; Arteriovenous Fistula; Cholesterol; Erythrityl Tetranitrate; Hernia, Diaphragmatic; Humans; Hyperthyroidism; Hypotension; Magnesium; Nitroglycerin; Procainamide; Propylthiouracil; Stellate Ganglion; Stomach Ulcer; Sympathectomy; Syphilis; Syphilis, Cardiovascular; Tachycardia; Tachycardia, Paroxysmal

Topics: Child; Electrocardiography; Epinephrine; Ergotamine; Humans; Hyperthyroidism; Pharmacology; Phonocardiography; Propylthiouracil; Wolff-Parkinson-White Syndrome

Topics: Antithyroid Agents; Exophthalmos; Humans; Hyperthyroidism; Iodides; Iodine; Iodine Isotopes; Methylthiouracil; Perchlorates; Propylthiouracil; Radioisotopes; Radionuclide Imaging; Thyroid Neoplasms; Toxicology

Topics: Combined Modality Therapy; Hyperthyroidism; Manipulation, Osteopathic; Perchlorates; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Humans; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Radioisotopes; Propylthiouracil; Radioisotopes; Thiouracil; Thyroxine

Topics: Agranulocytosis; Heart Failure; Hyperthyroidism; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Child; Disease; Diseases in Twins; Female; Goiter; Humans; Hyperthyroidism; Infant; Pregnancy; Propylthiouracil; Thiouracil; Twins

Topics: Blood Transfusion; Cortisone; Hemostatics; Hyperthyroidism; Hypoprothrombinemias; Propylthiouracil; Prothrombin; Thiouracil; Vitamin K

Topics: Hyperthyroidism; Iodine; Iodine Radioisotopes; Propylthiouracil; Radioisotopes; Thiouracil; Thyroid Gland; Viscera

Topics: Humans; Hyperthyroidism; Iodine; Kinetics; Propylthiouracil; Thiouracil; Thyroid Gland; Viscera

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Crisis

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Humans; Hyperthyroidism; Iodides; Kinetics; Physics; Propylthiouracil; Thiouracil; Thyroid Gland; Viscera

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Hyperthyroidism; Propylthiouracil; Smell; Taste; Thiouracil

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Humans; Hyperthyroidism; Preoperative Care; Propylthiouracil; Thiouracil; Thyroidectomy

Topics: Goiter; Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Patient Selection; Propylthiouracil; Thiouracil

Topics: Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Language; Propylthiouracil; Thiouracil; Thyroid Gland; Viscera

Topics: Agranulocytosis; Chemical and Drug Induced Liver Injury; Death; Humans; Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Humans; Hyperthyroidism; Long-Term Care; Propylthiouracil; Thiouracil

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Bone Marrow; Eosinophils; Hyperthyroidism; Methylthiouracil; Propylthiouracil; Thiouracil

Topics: Edema; Graves Disease; Hyperthyroidism; Myxedema; Propylthiouracil; Thiouracil

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thiouracil

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Methimazole; Propylthiouracil; Sodium Iodide

Topics: Humans; Hyperthyroidism; Iodine; Propylthiouracil; Radioisotopes; Thiouracil; Thyroidectomy

Topics: Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Diabetes Complications; Diabetes Mellitus; Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Confusion; Databases, Genetic; Female; Humans; Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Humans; Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroidectomy; Thyrotoxicosis

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Cardiomyopathies; Heart; Hyperthyroidism; Methylthiouracil; Propylthiouracil; Thiouracil; Thiourea; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiourea; Thyroid Gland; Thyrotoxicosis

Topics: Biomedical Research; Hyperthyroidism; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Adolescent; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperthyroidism; Leukocyte Count; Leukocyte Disorders; Leukocytes; Leukopenia; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiourea

Topics: Gastrointestinal Hemorrhage; Gastrointestinal Tract; Hemorrhage; Hyperthyroidism; Propylthiouracil

Topics: Endocrine System Diseases; Hyperthyroidism; Musculoskeletal Diseases; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Hyperthyroidism; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Disease Management; Endocrine System Diseases; Hyperthyroidism; Musculoskeletal Diseases; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiourea

Topics: Hyperthyroidism; Propylthiouracil; Thiourea; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Humans; Hyperthyroidism; Propylthiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thyroid Gland; Thyrotoxicosis

Topics: Humans; Hyperthyroidism; Iodine; Parathyroid Glands; Propylthiouracil; Thyroid Gland; Thyrotoxicosis

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Humans; Hyperthyroidism; Propylthiouracil

Topics: Goiter; Graves Disease; Humans; Hyperthyroidism; Paralyses, Familial Periodic; Propylthiouracil

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Humans; Hyperthyroidism; Propylthiouracil; Thyroid Gland; Thyrotoxicosis

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Goiter; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Barbital; Barbiturates; Hyperthyroidism; Propylthiouracil; Thiopental; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Propylthiouracil; Thiouracil; Thyroid Gland