propylthiouracil and Graves-Disease

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 diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb.. Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis.. The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug.. The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

Topics: Antithyroid Agents; Carbimazole; Causality; COVID-19; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Hormones; Thyrotropin; Ultrasonography

Propylthiouracil (PTU)-induced otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is an extremely rare adverse event associated with anti-thyroid drugs and is not well recognized. A 42-year-old woman with Graves' disease undergoing PTU therapy for 8 years visited our hospital because of earache and congested feeling in her left ear. Blood tests, a computed tomography scan and pure tone audiometry revealed otitis media and moderate mixed hearing impairment. Antibiotics, ear drops with antibiotics and painkillers were administered. However, her earache and hearing loss gradually got worse and symptoms of facial nerve palsy appeared. At several weeks after initiation of the treatment, a high serum level of myeloperoxidase (MPO)-ANCA, 75.6 U/mL, was revealed. After excluding other causes, she was diagnosed with OMAAV. PTU was suspected as the cause of her OMAAV and was immediately discontinued, and prednisolone was started. Hearing impairment in her left ear gradually got better and showed substantial improvement. Facial nerve palsy disappeared. Although PTU-induced OMAAV is an extremely rare disease, it is important to recognize the disease, as delayed treatment can lead to irreversible hearing loss, hypertrophic pachymeningitis, and subarachnoid hemorrhage. When patients taking anti-thyroid drugs, especially PTU, are diagnosed with refractory otitis media or hearing loss, it is possible that OMAAV might be the cause and thus serum ANCA levels should be evaluated.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Female; Graves Disease; Humans; Otitis Media; Propylthiouracil

Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and meta-analysis was undertaken to clarify the numerous aspects of long-term treatment with ATD.. Medline and the Cochrane Library for trials published between 1950 and May 2016 were systematically searched. Studies containing data for long-term (>24 months) ATD treatment were included. Summary estimates of pooled prevalence, odds ratio, and weighted mean difference were calculated with a random effects model.. Of 587 related articles found, six fulfilled the inclusion criteria. Long-term ATD treatment induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that was higher in adults than in non-adults (61% vs. 53%). The rate of complications was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual remission rate for each year of treatment was 16% [CI 10-27%], which was higher in adults than non-adults (19% vs. 14%). However, it should be noted that this is not a true linear correlation, but a positive relationship can be suggested between time and remission rate. Meta-regression revealed that smoking had a significant lowering effect on remission rate.. Long-term ATD treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for Graves' disease.

Topics: Antithyroid Agents; Drug Administration Schedule; Graves Disease; Humans; Methimazole; Propylthiouracil; Remission Induction; Time Factors; Treatment Outcome

Graves' hyperthyroidism is associated with significant morbidity and mortality risk. The thionamides, methimazole, its pro-drug derivative carbimazole, and propylthiouracil, remain a cornerstone of management. Yet despite decades of use, optimal strategies for maximising treatment response and curtailing adverse effect risk remains uncertain.. We reviewed the current literature on the evidence based medical management of Graves' disease. Specifically, we evaluated current approaches to the use of thionamides, adjunctive therapies, and potential novel agents for controlling Graves' hyperthyroidism.. Primary medical therapy is successful in less than 50% of cases and so careful selection of patients for medical treatment based on a combination of pathological and pragmatic considerations is essential. Carbimazole or methimazole is the treatment of choice in the non-pregnant population driven by its more favourable pharmacokinetic and adverse effect profile over propylthiouracil. In pregnancy the choice of treatment is less straightforward and an approach that minimises undue fetal exposure to all thionamides should be adopted. Additional data is needed on the value of adjunctive therapies including potassium perchlorate, iodides, glucocorticoids, lithium, and cholestyramine. Novel agents directed against pathogenetic targets including TSH receptor blocking monoclonal antibodies and small molecule antagonists may hold promise for the future.

Topics: Antibodies, Monoclonal; Antithyroid Agents; Combined Modality Therapy; Graves Disease; Humans; Methimazole; Prodrugs; Propylthiouracil

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

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

Hyperthyroidism is not a rare entity in pregnancy and 85% of these cases attributed to Graves' disease (GD). There is no therapeutic modality for GD considered as totally safe in pregnancy. Fetal and neonatal risks of maternal hyperthyroid disease are related to the hyperthyroidism itself and/or to the medical treatment of the disease. There are no data supporting an association between congenital anomalies in the fetus and propylthiouracil (PTU). Hepatotoxicity, cytopenias--especially agranulocytosis and quite rarely, angioedema, may be seen as side effects of PTU. In this case report, we examine an instance of Graves' hyperthyroidism diagnosed during pregnancy. In this case, a serious side effect during anti-thyroid drug usage was encountered, eventually resulting in surgery in the second trimester. This intervention was assisted by the use of plasmapheresis to obtain rapid normalization of serum thyroid hormone levels.

Topics: Angioedema; Antithyroid Agents; Female; Graves Disease; Humans; Plasmapheresis; Pregnancy; Pregnancy Complications; Preoperative Care; Propylthiouracil; Thyroidectomy; Young Adult

Antithyroid drugs (ATDs) have been widely and effectively used for the treatment of pediatric and adult thyrotoxicosis for more than a half century. Since the very beginning of ATD use, reports of hepatic dysfunction related to propylthiouracil (PTU) therapy have been published. We describe a case of a 12-year-old girl, who, after 4 weeks of therapy for Graves disease (GD) with PTU (300 mg/day at 100 mg given three times a day), developed fatigue, fever, diarrhea, nausea, and vomiting. The initial diagnosis was "viral gastrointestinal infection". Few days after the initiation of her symptoms, the patient developed jaundice, hepatic tenderness, and dark urine. She was admitted to the hospital where, after an extensive investigation, it was found that serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were elevated (2312 and 1435 IU/L, respectively), alkaline phosphatase (ALP) was 171 IU/L and total bilirubin was 12.7 mg/dL, whereas direct bilirubin was 7.6 mg/dL and prothrombin time was 23.2 s (normal ratio, < 14.5 s). Serology for hepatitis A and B was negative. The diagnosis of PTU-induced hepatitis was established. PTU was discontinued, and a treatment with prednisone (50 mg/day) and vitamin K was initiated. Four weeks after admission, her hepatic tests returned to normal. We searched the English literature and we present details of all cases with PTU-related hepatic toxicity in children and adolescents published so far. Also, we provide information regarding the mechanisms and treatment of this appalling clinical entity. Finally, after recent recommendations from American Thyroid Association (ATA) and European Thyroid Association (ETA), PTU should be administered only in the first trimester of pregnancy and in cases of drug allergy to methimazole.

Topics: Antithyroid Agents; Child; Female; Graves Disease; Hepatitis; Humans; Liver Function Tests; Propylthiouracil; Review Literature as Topic; Vitamin K

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

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

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

This minireview gives a clinical overview of the efficacy and of the side effects of the thyrostatic drug propylthiouracil, which is in use for the treatment of Graves' disease for more than 5 decades. It is the aim of this minireview to give convincing evidence of the value of propythiouracil in the treatment of thyrotoxic patients with Graves' disease: The modalities of treatment are given. The advantages in comparison to methimazole are mentioned: Especially for thyrotoxic nursing mothers it represents the only thyrostatic drug approved by the American Academy of Pediatrics. Patients who experience side effects with methimazole usually can be switched successfully to propylthiouracil and vice versa. Its use for the treatment of thyrotoxicosis in pregnant women is recommended by many centres because of the comparatively little placental transfer of the drug, although the effect for the newborn does not seem to differ from that of methimazole. The minireview should remind the medical community of the value of propylthiouracil as a very valuable thyrostatic drug representing a good alternative to methimazole. It should attract interest in the drug, in spite of the fact that after 5 decades in the market there is probably only little financial profit left in selling it.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Male; Pregnancy; Propylthiouracil

Graves' disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. Caused by immunologic stimulation of the thyroid-stimulating hormone receptor, lasting remission occurs in only a minority of pediatric patients with GD, including children treated with antithyroid drugs (ATDs) for many years. Thus the majority of pediatric patients with GD will need thyroidectomy or treatment with radioactive iodine (RAI; (131)I).. When ATDs are used in children, only methimazole should be used. Propylthiouracil is associated with an unacceptable risk of severe liver injury in children and should never be used as first-line therapy. If remission (defined as normal thyroid function off ATDs) is not achieved after 1 or 2 years of ATD therapy, (131)I or surgery may be considered, with the choice influenced by the age of the individual. When (131)I is used, administered doses should be >150 μCi/g of thyroid tissue. When surgery is performed, near total or total thyroidectomy is recommended.. Choosing a treatment approach for childhood GD is often a difficult and highly personal decision. Discussion of the advantages and risks of each therapeutic option is essential to help the patient and family select a treatment option.

Topics: Antithyroid Agents; Child; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Propylthiouracil

Topics: Adolescent; Adrenergic beta-Antagonists; Antithyroid Agents; Chorea; Diagnosis, Differential; Drug Therapy, Combination; Female; Graves Disease; Humans; Magnetic Resonance Imaging; Propranolol; Propylthiouracil; Tomography, Emission-Computed, Single-Photon

Antithyroid drugs sometimes cause severe complications. Propylthiouracil (PTU) can be associated to ANCA positive vasculitis, most often related to myeloperoxidase subtype (ANCA-MPO). Our objective is to describe a female patient with Graves' disease, who developed PTU induced-autoimmune disease, with cutaneous, pulmonary, and renal lesions, associated with ANCA. Histopathological examination revealed diffuse pulmonary hemorrhage, and focal segmental glomerulosclerosis at the kidney biopsy. She was treated with systemic corticosteroid therapy and cyclophosphamide, with clinical improvement. This case highlights the need for greater awareness of this relatively rare adverse effect of propylthiouracil.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmune Diseases; Female; Graves Disease; Humans; Immunologic Factors; Peroxidase; Propylthiouracil; Vasculitis

To evaluate the evidence supporting the use of propylthiouracil (PTU) versus methimazole for the treatment of Graves' disease during pregnancy.. An English-language literature search was conducted using MEDLINE (1966-March 2007). Identified articles were then reviewed for additional sources. Search terms included hyperthyroidism, Graves' disease, pregnancy, propylthiouracil, and methimazole.. All clinical trials and case reports that were published in English and reported either subjective or objective outcomes were reviewed.. Rationale supporting the use of PTU over methimazole in treatment of Graves' disease during pregnancy is limited. Theories suggesting that PTU has less placental transfer to the fetus than methimazole are not supported by current literature. Studies demonstrating a causal relationship between methimazole use during pregnancy and congenital anomalies and/or fetal hypothyroidism do not exist.. The selection of PTU versus methimazole for the treatment of Graves' disease during pregnancy should not be based solely on the following assumptions: that PTU crosses the placenta less than methimazole, that PTU leads to less fetal hypothyroidism, or that exposure to methimazole during pregnancy leads to decreased intellectual function in children. However, due to a possible association between the use of methimazole during pregnancy and fetal anomalies such as aplasia cutis, esophageal atresia, and choanal atresia, methimazole may be a less desirable first-line treatment for Graves' disease in pregnancy than PTU. Therefore, in the absence of a compelling indication for the use of methimazole, PTU should still be considered as the first-line agent in the treatment of Graves' disease during pregnancy. Methimazole should be considered a viable second choice if the patient is intolerant to PTU, has an allergic reaction to PTU, or fails to become euthyroid while receiving PTU.

Topics: Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Thionamides, selective inhibitors of thyroid peroxidase-mediated iodination by tyrosine residues in thyroglobulin, have been effectively used in the treatment of hyperthyroidism. The choices for initial treatment of patients with Graves' disease differ in various countries, and many physicians around the world prefer to administer thionamide drugs as the first choice of treatment for patients with hyperthyroidism. Although some thyroidologists more often consider radioiodine to be the treatment of choice because of its safety and ease of administration, thionamides remain the mainstay of treatment in thyrotoxic children and adolescents and in hyperthyroid women during pregnancy, postpartum period and lactation. A recent study with continuous thionamide treatment for patients with Graves' disease shows its efficacy, safety and cost-benefit properties. Further studies of the effectiveness of continuous thionamide therapy in patients with thyrotoxicosis need to be designed and implemented to determine indications for such therapy in children, adolescents and adults with diffuse toxic goiter, in particular, in those who have had recurrence of hyperthyroidism after discontinuation of one complete course of treatment.

Topics: Adolescent; Adult; Age Factors; Antithyroid Agents; Child; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Diagnosis, Differential; Goiter, Nodular; Graves Disease; Humans; Prognosis; Propranolol; Propylthiouracil; Thyrotoxicosis; Triiodothyronine

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

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

Because of the low frequency of childhood Graves' disease, detailed evidence-based clinical studies have not been reported. Practical clinical work has been performed on the basis of adult clinical references. Therapeutic management includes antithyroid drugs, surgical thyroidectomy and radiologic therapy. Recently in the U.S.A. radiotherapy has become the recommended course of action, even for childhood Graves' disease, whereas in Japan, antithyroid drug therapy is the primary course of action for childhood Graves' disease. In some cases, thyroidectomy is performed following drug therapy. Methimazole (MMI) and propylthiouracil (PTU) have been used, however, MMI is the preferred drug treatment. Compared to PTU, MMI is administered once a day and the frequency of side effects is lower than that of PTU. Evaluation of the TSH receptor antibody value before administration of antithyroid drugs is very useful in estimating the duration of the treatment. No appropriate index has been established guiding when to quit antithyroid drug therapy.

Topics: Antithyroid Agents; Autoantibodies; Biomarkers; Child; Combined Modality Therapy; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Propylthiouracil; Radiotherapy; Thyroidectomy

Antineutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis, including vasculitis induced by drugs such as the thionamides. The affected organ systems in thionamide-induced vasculitis have been primarily renal, musculoskeletal, and dermatologic. We describe the first case of thionamide-induced central nervous system vasculitis presenting as confusion, with complete resolution after discontinuation of propylthiouracil. We review the literature and summarize 42 additional cases of thionamide-induced ANCA-positive vasculitis since 1992. Propylthiouracil was responsible in 93% of cases and the predominant ANCA pattern on immunofluorescent staining was perinuclear (p-ANCA). Clinical improvement occurred after drug discontinuation in 93%, steroid therapy was used in some cases. The mean duration of treatment with thionamides was 35 months prior to presentation. Long-term medical treatment with thionamides for hyperthyroidism may increase the risk of this severe side effect.

Topics: Central Nervous System Diseases; Confusion; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Vasculitis

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

Topics: Adult; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Syndrome

Preoperative thyrotoxicosis is a potentially life-threatening condition that requires medical intervention before surgery. Most patients are undergoing thyroidectomy for persistent thyrotoxicosis, usually Graves' disease, either having contraindications to or failing medical therapy. Fewer patients are undergoing nonthyroidal surgery that is likely urgent or emergent. The choice of treatment depends on the time available for preoperative preparation, the severity of the thyrotoxicosis, and the impact of any current or previous therapies. Generally treatment is directed at a combination of targets in the thyroid hormone synthetic, secretory, and peripheral pathway with concurrent treatment to correct any decompensation of normal homeostatic mechanisms. Thionamides are the preferred initial treatment unless contraindicated, but do require several weeks to render a patient euthyroid. beta-Blockers should always be used unless absolutely contraindicated because they improve thyrotoxic symptoms especially of the cardiovascular system. Other agents including iodine and steroids can be used if rapid preparation is required or more severe thyrotoxicosis is present. The goal of therapy is to render the patient as close as possible to clinical and biochemical euthyroidism before surgery. Overall, the morbidity and mortality of adequately prepared patients is low.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Graves Disease; Humans; Iodine; Iopanoic Acid; Perioperative Care; Propranolol; Propylthiouracil; Thyroid Crisis; Thyrotoxicosis

We experienced a coincidental case of two types of glomerulopathy associated with Graves' disease. A 64-year-old man, who had been treated with propylthiouracil(PTU) for Graves' disease for 15 years, was admitted to our hospital for macroscopic hematuria and rapidly progressive deterioration of renal function. Although his thyroid function had been within the normal range during treatment, the level of thyrotropin receptor antibody(TRAb) gradually increased from a year before admission. Serological tests revealed that he was positive for myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA). The renal biopsy specimen showed necrotizing and crescentic glomerulonephritis(GN) superimposed on membranous nephropathy(MN). This is a rare case of MN complicated with ANCA associated crescentic GN in a Graves' disease patient. Association of these two renal alterations was not clearly defined. MN involved with Graves' disease also has been rarely reported. Some reports demonstrated deposition of thyroglobulin and other thyroid related antigens in the glomeruli. In the present case, long-term impairment of Graves' disease and elevation of TRAb might have been responsible for the formation and deposition of thyroid-associated immune complex in the glomeruli. As for crescentic GN, PTU might have induced ANCA-associated GN independently of MN. This case is instructive for considering the relation between Graves' disease and renal injury.

Topics: Administration, Oral; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Glomerulonephritis; Glomerulonephritis, Membranous; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil

First cause of hyperthyroidism among women of childbearing age, Graves' disease raises the risk of maternal and fetal complications, including eclampsia, cardiac failure, abortion, prematurity, fetal death, all of which can be avoided if maternal hyperthyroidism is closely controlled. The risk of transplacental hyperthyroidism has been shown to correlate to the titre of anti-TSH receptor antibodies and has to be evaluated not only in women treated for Graves' disease during pregnancy, but also in women who have previously received radio iodine treatment or undergone surgery for Graves' disease: TSH-receptor antibodies may indeed remain at a high level several years after initial treatment. Both methimazole and propylthiouracil are equally effective to restore maternal euthyroidism. Accumulation of case-reports relating congenital malformations (mostly aplasia cutis, but in some cases, severe malformations) among the offspring of methimazole-treated women suggests the possibility of a teratogenic effect of methimazole. Despite the fact that the link between severe congenital defects and methimazole exposure during pregnancy is not formally established, propylthiouracil should be preferred to methimazole for the treatment of young hyperthyroid women.

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

A 50-year-old woman was admitted because of severe exophthalmos associated with Graves disease. She underwent methimazole (MMI) and methylprednisolone pulse therapy against exophthalmos. She noticed photophobia and blurred vision 3 weeks after the start of pulse therapy and she was diagnosed as having uveitis. Methylprednisolone pulse therapy was performed again for both exophthalmos and uveitis, followed by daily administration of 20 mg of prednisolone and instillation of betamethasone for 2 weeks and the uveitis was improved. Western blot analysis confirmed that human T lymphotropic virus type 1 (HTLV-1) antibody was present in her serum. Propylthiouracil was substituted for MMI and HTLV-1-associated uveitis (HAU) has not recurred. Six months after the beginning of administration of PTU, anti-neutrophil cytoplasmic antibody-related vasculitis developed in the patient. We review 43 cases of HAU with Graves disease, including the present case, in the literature. Only 2 of 27 cases (except unknown cases) (7.4%) had Graves ophthalmopathy. To the best of our knowledge, there has been no investigation of HAU and Graves ophthalmopathy.

Topics: Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; HTLV-I Infections; Humans; Magnetic Resonance Imaging; Methimazole; Methylprednisolone; Middle Aged; Prednisolone; Propylthiouracil; Severity of Illness Index; Thyroid Hormones; Time Factors; Treatment Outcome; Uveitis; Vasculitis

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

Topics: Antithyroid Agents; Congenital Hypothyroidism; Female; Goiter; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Female; Graves Disease; Humans; Hypothyroidism; Immunosuppressive Agents; Male; Methimazole; Mutation; Propylthiouracil; Receptors, Thyrotropin; Syndrome; Thyroid Gland; Thyroid Hormones

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 21-year-old woman was diagnosed as having Graves' disease in April, 1995. Thiamazole was administered; about a month later the patient had a skin rash and propylthiouracil (PTU) was given instead. Two months after commencing PTU, she rapidly developed jaundice, accompanied by severe liver damage. The drug-induced lymphocyte stimulating test was positive for PTU and she was diagnosed as having severe hepatitis induced by PTU. After pulse therapy with 500 mg of methylprednisolone was given for 3 days, liver function test results were gradually improved, and became normalized 1 1/2 months after admission. The pathology findings of the liver biopsy sample taken before administration of corticosteroid showed necrosis of hepatocytes predominantly around the central veins (i.e., zone 3 necrosis), and moderate to severe infiltration of lymphocytes and neutrophils in portal areas and lobules. Severe hepatic damage due to PTU is rare; 25 cases have been reported so far in the English-language literature. When we use PTU for patients with hyperthyroidism, we should keep in mind that severe liver damage induced by PTU can be fatal, and we should therefore diagnose it earlier by liver biopsy and lymphocyte stimulating test.

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Female; Graves Disease; Humans; Propylthiouracil

The use of propylthiouracil (PTU) in patients with Graves' disease has been associated with multiple complications including rash, leukocytoclastic vasculitis, pulmonary hemorrhage, glomerulonephritis, and the presence of perinuclear antineutrophilic cytoplasmic antibodies (pANCA).. To report the association of Wegener's granulomatosis (WG) with the use of PTU in a patient with Graves' disease and to review the spectrum of systemic vasculitis seen in patients with Graves' disease taking PTU.. Retrospective review of data collected in a patient with WG. In addition, a Medline search (1980 to present) for PTU-associated vasculitis was conducted.. We report WG in a patient treated with PTU who fulfilled the criteria of the American College of Rheumatology for this disease. Furthermore, his serum was positive for cytosolic antineutrophil cytoplasmic antibodies (cANCA) and anti-proteinase-3 (PR3) antibodies by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA), respectively. WG is associated with high morbidity and mortality and usually requires extensive therapy with prednisone and cyclophosphamide. Our patient, however, did not need specific therapy except discontinuation of PTU to make a full recovery. In previous reports, PTU has been associated with different forms of vasculitis, but this is a the first description of classic WG in a patient treated with PTU.. PTU is capable of causing WG in susceptible patients with Graves' disease. Our patient did not require specific therapy for vasculitis and improved after discontinuation of PTU.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Granulomatosis with Polyangiitis; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil

We treated a 13-year-old girl who developed myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related crescentic glomerulonephritis (GN) during propylthiouracil (PTU) treatment for Graves' disease. MPO-ANCA-related crescentic GN during PTU therapy has been described previously in only one recent report of 2 children. We report this case here and describe 15 (13 adult cases) more patients with MPO-ANCA-related GN associated with PTU found in a literature review. The mean age at onset was 41.3 years, and the length of PTU administration ranged from 2 weeks to 6 years (mean 3.5 years). Clinical signs and symptoms were hematuria (100%), proteinuria (100%), arthralgia (7 of 16 cases; 43.8%), fever (4 cases; 20.0%), purpura (2 cases; 12.5%), skin ulcer (1 case; 6.3%) and dyspnea (1 case; 6.3%). These patients were treated with steroid (15 cases; 93.8%), cyclophosphamide (8 cases; 50.0%), steroid pulse therapy (4 cases; 25.0%), or plasma exchange (1 case; 6.3%), or were not treated (1 case; 6.3%). Most patients revealed crescentic GN (15 cases; 93.8%) on renal biopsy, while one exhibited mesangial proliferative GN (6.3%). For 2 of the 16 patients (12.5%) irreversible renal dysfunction persisted and hemodialysis was started. Patients with Graves' disease treated with PTU should be observed carefully by urinalysis and monitoring of the serum creatinine level.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Graves Disease; Humans; Peroxidase; Propylthiouracil

A 68-year-old man who developed MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) treatment is reported. In 1986, he was diagnosed as having interstitial pneumonitis. Although he tested positive for antinuclear antibody and rheumatoid factor, he had no symptoms and was followed up without therapy. Five years later, the diagnosis of Graves's disease was made after complaints of body weight loss, diplopia and exophthalmos. Tests showed positivity for anti-thyroid stimulating hormone (TSH) receptor antibody, antithyroidperoxidase antibody and antithyroglobulin antibody. He was treated with PTU and prednisolone for four years. In November 1995, hematuria and proteinuria developed, and renal function deteriorated rapidly. A renal biopsy revealed crescentic glomerulonephritis and the serum titer of MPO-ANCA was markedly elevated. He was treated with a high dose of prednisolone and cyclophosphamide. Although the serum creatinine level gradually decreased, irreversible renal dysfunction persisted. In this patient, the presence of various autoantibodies had been recognized for several years before MPO-ANCA-associated glomerulonephritis developed. Polyclonal B-cell activation and PTU treatment may have played a role in the pathogenesis of MPO-ANCA-associated glomerulonephritis.

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Glomerulonephritis; Graves Disease; Humans; Lung Diseases, Interstitial; Male; Peroxidase; Propylthiouracil

Propylthiouracil (PTU), used to treat Graves' disease, occasionally induces a lupus-like syndrome. A 39-year-old woman developed clinical manifestations of systemic lupus erythematosus with rash, serositis, myocarditis, and acute renal insufficiency, associated with serologies for lupus, after 3 wk of exposure to the drug. Renal biopsy revealed diffuse proliferative lupus nephritis. This article reviews the side effects of PTU and the literature on PTU-induced nephrotoxicity. Possible mechanisms and management of drug-induced lupus nephritis are also reviewed. To facilitate early and specific intervention, clinicians should be aware of the propensity of PTU to cause lupus-like syndromes with renal involvement.

Topics: Adult; Antigen-Antibody Complex; Antithyroid Agents; Female; Fluorescent Antibody Technique, Direct; Graves Disease; Humans; Kidney; Lupus Nephritis; Propylthiouracil

We described a case of pulmonary hemorrhage associated with myeloperoxidase-antineurophil cytoplasmic antibodies (MPO-ANCA) without renal involvement during propylthiouracil (PTU) treatment. A 36-years old female was admitted to our hospital because of progressive dyspnea with hemosputum after flu-like symptom and episcleritis. She had been receiving PTU for three years to Graves' disease. On admission her chest Xp showed bilateral massive infiltrative shadow and bronchofiberscopy demonstrated pulmonary hemorrhage. MPO-ANCA and anti-thyroperoxidase antibodies were positive, but she had normal urinalysis and normal renal function. After withdraw of PTU, pulmonary hemorrhage disappeared. But 15 days later pulmonary hemorrhage recurred associated with high MPO-ANCA titer. Corticosteroid bolus therapy and oral cyclophasphamide administration improved pulmonary hemorrhage, and MPO-ANCA titer also decreased. It is suggested that MPO-ANCA and PTU might be closely related to the pathogenesis of pulmonary hemorrhage in this case.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arteritis; Female; Graves Disease; Hemorrhage; Humans; Lung Diseases; Peroxidase; Propylthiouracil

We report the rare case of a 43-year-old African-American man with thyrotoxic periodic paralysis associated with hypokalemia and hypophosphatemia. Both serum potassium and serum phosphate levels returned to normal after supplementation with only potassium. We consider the unusual condition of hyperthyroid-related hypokalemia and hypophosphatemia to have contributed to the acute paralysis in this patient.

Topics: Acute Disease; Adult; Antithyroid Agents; Graves Disease; Humans; Hypokalemia; Hypophosphatemia; Infusions, Intravenous; Male; Paralysis; Periodicity; Potassium Chloride; Propylthiouracil; Thyrotoxicosis

Pregnancy is characterised by a physiological increase in bound thyroxine but normal values of free hormone. Human chorionic gonadotrophin (hCG may stimulate the thyroid to produce hyperemesis gravidarum (with mild to moderate hyperthyroidism) or result in high thyroid hormone levels associated with gestational trophoblastic disease. Hyperthyroidism occurring during pregnancy is usually due to Graves' disease and must be treated to prevent congenital anomalies, low birth weight and premature labour. Thionamide drugs should be used with a preference for propylthiouracil (PTU) and continued in low doses up to labour. Breast feeding is possible in patients on low dose PTU. In the management of hypothyroidism during pregnancy thyroxine dose may require to be increased but excess dosage should be avoided because of its unwanted effects on foetal cerebral maturation. Neonatal hyperthyroidism due to transplacental passage of thyroid stimulating antibodies (TsAb) should be checked for in pregnant patients with autoimmune thyroid disease. As antithyroid drugs cross the placenta they may be used as therapy in this condition. Prevention of neonatal goitre is vital. Postpartum development of hyperthyroidism may be due to an exacerbation of pre-existing Graves' disease, development of new Graves' hyperthyroidism or postpartum thyroiditis with transient hyperthyroidism. Differentiation by measurement of TsAb and thyroidal iodine uptake is important because of therapeutic considerations.

Topics: Antithyroid Agents; Embryonic and Fetal Development; Female; Graves Disease; Humans; Hyperthyroxinemia; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Iodine; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyroiditis, Autoimmune

Propylthiouracil is a drug used commonly to treat hyperthyroidism. Among its side effects, hepatotoxicity is one of the rarest but one of the most serious. This complication may be due to an immune mechanism. However, particular risk factors associated with the development of hepatotoxicity are not known, and its occurrence is unpredictable. I report a case of acute hepatitis developing during propylthiouracil therapy for Graves' disease and review the literature related to this problem.

Topics: Acute Disease; Adult; Chemical and Drug Induced Liver Injury; Female; Graves Disease; Humans; Propylthiouracil; Risk Factors

Topics: Adrenergic beta-Antagonists; Carbimazole; Female; Graves Disease; Humans; Iodine; Iodine Radioisotopes; Lithium; Lithium Carbonate; Male; Methimazole; Pregnancy; Propylthiouracil

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

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

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

Evaluation of a child with goiter includes historical review, physical examination, and measurement of serum concentrations of PBI, T4 and T3RU, TSH, and titers of antithyroglobulin and antithyroid microsomal antibodies. If there are no indications for more intensive evaluation such as history of cervical irradiation, a palpable abnormality of the thyroid gland or unusual laboratory findings (e.g., a significant PBI-thyroxine iodine discrepancy in the absence of a positive antithyroid antibody titer), a trial of TSH-suppressive therapy with thyroxine is undertake, even if the cause of thyromegaly has not been identified. If thyroid size diminishes in the ensuing six to 12 months, treatment is maintained for approximately two years and then discontinued. If the goiter recurs, or if there is impaired thyroid function, treatment is resumed. Periodically, antithyroid antibody titers and indices of thyroid function are determined. If the goiter does not diminish after a reasonable trial of suppressive therapy with adequate amounts of thyroxine (i.e., those quantities which will inhibit TRH-induced secretion of TSH), subtotal thyroidectomy is recommended to be certain that an underlying neoplasm has not been overlooked. A biopsy of the thyroid is not performed routinely in such children prior to operative therapy. Almost invariably, examination of the surgical specimen reveals CLT. Postoperatively, suppressive doses of thyroxine are maintained indefinitely. Inasmuch as thyroxine suppression of TSH secretion is essential in the management of patients with thyroid neoplasms, a limited medical trial, as described, does not place the patient at undue risk.

Topics: Adolescent; Child; Graves Disease; Humans; Iodine Radioisotopes; Neoplasms, Radiation-Induced; Propylthiouracil; Thioamides; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy; Thyroiditis, Autoimmune; Thyroxine

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

Topics: Female; Graves Disease; Humans; Immunoglobulins; Infant, Newborn; Long-Acting Thyroid Stimulator; Propylthiouracil; Thyroid Gland

Topics: Eye Diseases; Graves Disease; Humans; Iodine Isotopes; Long-Acting Thyroid Stimulator; Methimazole; Propylthiouracil; Thyroid Function Tests; Thyroxine

Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD).. We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, would increase remission rates when administered with a short course of ATD.. This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A'Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3'-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine.. A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A'Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission.. Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

Topics: Adolescent; Antithyroid Agents; Child; Drug Therapy, Combination; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Immunologic Factors; Male; Propylthiouracil; Recurrence; Rituximab; Treatment Outcome; Young Adult

Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves' disease.. This study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves' hyperthyroidism.. This study was a single-blind, randomized clinical trial conducted on 36 patients with Graves' disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves' disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)].. By the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707-977) vs. 510 (402-630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1-42.7) vs. 28.2 (21.6-36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565-904) vs. 472 (367-590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group.. Antithyroid treatment in Graves' disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.

Topics: Adult; Antithyroid Agents; Atherosclerosis; Biomarkers; Female; Follow-Up Studies; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Middle Aged; Propylthiouracil; Pulse Wave Analysis; Single-Blind Method; Thyroid Hormones; Treatment Outcome; Vascular Cell Adhesion Molecule-1

Use of the antithyroid drugs (ATDs) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). We investigated side effects associated with the 1st and 2nd ATDs.. Four hundred forty-nine patients with untreated Graves' disease (GD) were randomly assigned to three groups according to ATD type and/or dosage: 15 mg/day MMI, 30 mg/day MMI and 300 mg/day PTU. The type, frequency and onset of side effects were assessed. We also studied the side effects associated with the 2nd ATD after cessation of the 1st ATD.. Cutaneous reactions, liver dysfunction and other side effects were examined every 2 weeks after starting ATD administration.. The overall frequency of side effects in patients taking 15 mg/day MMI was low. The frequencies of cutaneous reactions in patients taking 30 mg/day MMI and hepatotoxicity in those taking 300 mg/day PTU were high. Hepatotoxicity developed later than cutaneous reactions with PTU. Hepatotoxicity developed earlier in the 30 mg/day MMI group than in the other two groups. The frequency of side effects did not differ between the 2nd and 1st ATDs. Hepatotoxicity occurred at a higher frequency in patients who were switched from MMI to PTU because of hepatotoxicity of the former.. Attention to the onset times of side effects and cross-reactivity of ATDs can lead to safer treatment of GD.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Liver; Male; Methimazole; Middle Aged; Propylthiouracil; Skin; Young Adult

The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI).. Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n=64) and group P (PTU: n=69) and into four subgroups by initial dose: group M1 (<0.75 mg/kg of MMI, n=34), group M2 (> or = 0.75 mg/kg, n=30), group P1 (<7.5 mg/kg of PTU, n=24) and group P2 (> or = 7.5 mg/kg, n=45).. The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared.. Mean durations for normalization of T4 (+/- SD) were 1.7 +/- 1.0 months in group M and 2.3 +/- 2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1 +/- 3.3) was significantly longer than those in the other subgroups (M1: 1.9 +/- 1.2; M2: 1.4 +/- 0.7; P2; 1.7 +/- 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n=20) and PTU-treated group (50.0%, n=40).. PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

Topics: Adolescent; Antithyroid Agents; Child; Drug Eruptions; Female; Graves Disease; Humans; Liver; Male; Methimazole; Propylthiouracil; Retrospective Studies; Thyroxine; Time Factors; Treatment Outcome

Some precursor P wave changes on electrocardiogram (ECG) before the atrial fibrillation (AF) episodes occur in the hyperthyroidism. Our aim was to compare the effect of two antithyroid drugs (ATD) on P wave duration and dispersion (PWD) in patients with hyperthyroidism.. Fifty patients (13 men, 37 women; mean age 39.2+/-13.2 years) with newly diagnosed overt hyperthyroid patients with Graves' disease (GD) were enrolled in the prospective, randomized study. The maximum P wave duration (Pmax) and the minimum P wave duration (Pmin) were measured in all 12-lead surface ECGs. The patients were consecutively randomized to propylthiouracil (PTU) (n=24) and methimazole (MMZ) (n=26) groups. Electrocardiogram was repeated within euthyroid state after the 18-month ATD treatment. Student t-test, Mann-Whitney U and Pearson Chi-square tests were used for comparisons of the data between groups. The differences between pre- and post-treatment measurements within groups were evaluated by Wilcoxon Sign Rank test. The correlation of data was tested by using Spearman correlation analysis.. The maximum P wave duration (Pmax) was 90 (80-110) and 90 (90-110) msec, (p=0.586), and PWD was 35 (22.5-48.7) and 40 (30-40) msec, respectively (p=0.952) in PTU and MMZ groups. After euthyroidism was achieved, Pmax was 80 (80-90) and 87.5 (80-90) msec (p=0.676), and PWD was 27.5 (20-35) and 27.5 (20-30) msec in PTU and MMZ groups, respectively (p=0.540). After ATD treatment PWD decreased (p=0.009 and p<0.001, respectively) in both of PTU and MMZ groups. However effects of ATD on PWD change were similar (p=0.486).. P wave duration and PWD are found to be prolonged in hyperthyroid patients with GD. Both propylthiouracil and methimazole reduce the P wave duration and dispersion. Thus, we can conclude that improvements in atrial conduction properties are not associated with the type of ATD but with only achievement of euthyroidism.

Topics: Adult; Antithyroid Agents; Atrial Fibrillation; Electrocardiography; Female; Graves Disease; Heart Conduction System; Humans; Male; Methimazole; Propylthiouracil; Prospective Studies; Thyroid Hormones

Preoperative preparation of the patient with Graves' disease (GD) is crucial to avoid intraoperative or postoperative complications associated with anesthesia or surgery. We aimed to evaluate thyroid blood flow and microvessel density in patients with GD according to antithyroid drug (ATD) treatment, preoperatively.. Forty-three patients were divided into two groups according to the ATD type. Patients in group 1 (n = 25) were treated with methimazole, whereas patients in group 2 (n = 18) were treated with propylthiouracil, preoperatively. Blood flow through the thyroid arteries was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed immunohistochemically and via Western blot analysis using the level of CD-34expression in thyroid tissue.. There was a positive correlation between blood loss and thyroid volume (r(s) = 0.953, P = .0001) and blood flow (r(s) = 0.720, P = .0001) and CD-34 expression (r(s) = 0.331, P = .03) and MVD (r(s) = 0.442, P = .003). No correlation was observed between ATD type and thyroid vascularity. In patients with longer treatment duration before operation, thyroid vascularity was significantly lower relative to patients with shorter treatment durations. According to logistic regression analysis, longer treatment duration had a 142-fold decreased rate of intraoperative blood loss independent of ATD type.. Preoperative ATD treatment duration may predict intraoperative blood loss during thyroidectomy. Longer treatment duration might be useful in reducing intraoperative bleeding, allowing better visualization and preservation of the nerves and parathyroid glands.

Topics: Adolescent; Adult; Antithyroid Agents; Blood Flow Velocity; Blood Loss, Surgical; Female; Graves Disease; Humans; Male; Methimazole; Microcirculation; Middle Aged; Preoperative Care; Propylthiouracil; Reference Values; Thyroid Gland; Thyroidectomy; Ultrasonography, Doppler, Color

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

Hyperthyroidism is rare in early childhood and most commonly caused by Graves' disease. We report 14 children (4 boys, 10 girls) aged 3.4-7.5 yr. At diagnosis, all patients had weight loss, hyperkinetic activity, tachycardia, difficulty sleeping, and poor concentration and 11 presented with proptosis. Four patients developed long-term neuropsychological problems. There was a family history in 7 cases. All patients had goiters, clinically assessed to be large and diffuse in 21%, medium-sized in 43%, and small in 36%. At diagnosis, height was increased with median (range) height; 1.25 standard deviation score (SDS) (-0.2-5.24) and body mass index (BMI) was decreased; -0.48 SDS (-1.65-1.26). Height and BMI SDS values were statistically different (p<0.032) Bone age was advanced in 4 of 5 children, who had assessments. Total or free T4 levels were elevated and TSH was undetectable. Ninety percent of patients (12/14) had positive thyroid peroxidase autoantibodies, mean level 680 IU/ml (range 50-1347). Initial treatment was with antithyroid medication using carbimazole; median dose 0.75 mg/kg/day (no.=13) or propylthiouracyl 15 mg/kg/day (no.=1). T4 was added in 6 patients. Normalisation of serum T4 occurred at 4 months (1- 9) and TSH at 7 months (3-24) after start of therapy. Treatment was discontinued after a minimum of 2 yr in 11 patients, relapse occurring in 9. Median duration of total therapy was 58 months (18-132). During adolescence, 4 patients had curative therapy by surgery (no.=2) or radioiodine (no.=2). In conclusion, disturbance of growth, behavioral difficulties and infrequent spontaneous remission are key features of Graves' disease in early childhood.

Topics: Age of Onset; Antithyroid Agents; Attention Deficit Disorder with Hyperactivity; Carbimazole; Child; Child, Preschool; Exophthalmos; Female; Graves Disease; Growth Disorders; Humans; Hyperkinesis; Iodide Peroxidase; Male; Propylthiouracil; Recurrence; Retrospective Studies; Sleep Wake Disorders; Tachycardia; Thyrotropin; Thyroxine; Weight Loss

P-wave duration is defined as the time measured from the onset to the offset of the P-wave in surface electrocardiogram (ECG). Prolonged P wave duration and increased P wave dispersion (PWD) have been reported to carry an increased risk for atrial fibrillation.. Our aim was to evaluate the role of hyperthyroidism on P wave duration and dispersion, to investigate the effect of anti-thyroid therapy on P wave duration and dispersion.. A total of 44 consecutive subjects (22 patients with newly diagnosed overt hyperthyroidism and 22 randomly selected euthyroid healthy subjects) were enrolled in the study. Transthoracic echocardiography, 12 lead surface ECG and thyroid hormone levels were studied at the time of enrollment, in the first and third months of the 6-8 mg/kg/day propylthiouracil therapy. Patients were followed-up for 3 months.. Patient and control groups were consisted of age and sex matched subjects. Baseline left atrial diameter was similar between the patient and control groups (3.4+/-0.3 cm and 3.4+/-0.3 cm respectively, p=0.813). The maximum P-wave duration (P maximum) was 113.1+/-6.6 and 105.7+/-4.1 ms in patient and control groups (p=0.001). PWD was 31.5+/-9.5 and 25.2+/-5.9 ms in patient and control groups respectively (p=0.015). At the third month of propylthiouracil treatment P maximum and PWD were decreased in the patient group at statistically significant level and returned back in normal limits (p<0.001 and p=0.001).. P wave duration and PWD are found prolonged in hyperthyroid patients and propylthiouracil treatment decreased them effectively. This mechanism may establish how the anti-thyroid treatment may prevent the development of atrial fibrillation in hyperthyroid patients.

Topics: Adult; Antithyroid Agents; Atrial Fibrillation; Electrocardiography; Female; Follow-Up Studies; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Thyroid Hormones

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Iodides; Iodine; Male; Middle Aged; Propylthiouracil; Prospective Studies; Sodium Chloride, Dietary; Thyroid Hormones

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 study aims to evaluate the efficacy of combination therapy with propylthiouracil (PTU) and cholestyramine in the treatment of Graves' hyperthyroidism.. Thyroxine (T4) is metabolized mainly in the liver by conjugation to glucuronides and sulphates that enter the enterohepatic circulation. Thyrotoxic patients have an abnormal increase in thyroid hormone in their enterohepatic circulation. Previous studies on combination therapy with methimazole and cholestyramine for Graves' hyperthyroidism have shown it to be an effective adjunctive treatment. In this study, we examined the efficacy of combination therapy with PTU and cholestyramine in the treatment of Graves' hyperthyroidism.. Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups: group I (n = 15) received PTU 100 mg twice a day, propranolol 40 mg twice a day and cholestyramine 4 g twice a day for 4 weeks; group II (n = 15) received PTU 100 mg twice a day and propranolol 40 mg twice a day for 4 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), free thyroxine (FT4) and TRAb levels at baseline, and at the end of 2 and 4 weeks during the study period.. There was no significant difference in baseline thyroid function parameters. At the end of 2 and 4 weeks of the study period, serum TT3 and FT4 levels of group I were significantly lower than those of group II. No significant differences in the TRAb level were found between the two groups.. Cholestyramine contributed to a more rapid and complete decline in thyroid hormone levels in patients with Graves' hyperthyroidism. It was thus proved to be an effective and well-tolerated adjunctive therapy.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Autoantibodies; Cholestyramine Resin; Drug Administration Schedule; Drug Therapy, Combination; Female; Graves Disease; Humans; Ion Exchange Resins; Male; Middle Aged; Propranolol; Propylthiouracil; Receptors, Thyroid Hormone; Thyroid Function Tests; Thyroxine; Time Factors; Treatment Outcome; Triiodothyronine

The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism.. Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels.. Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period.. There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study.. During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.

Topics: Adolescent; Adult; Analysis of Variance; Antibodies, Monoclonal; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroxine; Triiodothyronine

In order to assess the effect of propylthiouracil (PTU) or methimazole (MMI) pretreatment on patient outcome after radioiodine therapy, we examined 100 patients with Graves' disease 3, 6, 9, and 12 months after administration of a 10-mCi standard single dose of 131I. They were assigned to one of three groups: no drug (ND) treatment (30 cases); MMI (45 cases); and PTU (25 cases). Antithyroid drugs (ATD) were withdrawn 15 days before radioiodine administration. The groups were similar concerning age, gender, ATD pretreatment duration, goiter size, and initial serum triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), antithyroid autoantibody levels, 24-hour radioiodine uptake and 131I dose administered per gram of thyroid tissue. ND and MMI groups presented a similar rate of cure of 73.3% and 77.8% respectively (p = NS). In contrast, the PTU group showed a rate of cure of only 32% (p < 0.05). Logistic regression analysis indicated that PTU administration (p = 0.003) and thyroid size (p = 0.02) were the variables related to radioiodine therapy failure. Our data demonstrate that the chance of 131I treatment failure is higher in individuals using PTU than in patients using MMI or not using any ATD before radioiodine (odds ratio [OR] 5.84; 95% confidence interval [CI] 1.82-18.76) suggesting that PTU should be avoided in the treatment of patients with Graves' disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Combined Modality Therapy; Contraindications; Dose-Response Relationship, Radiation; Female; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Prospective Studies; Thyroid Function Tests

Although many researchers have reported clinical and laboratory parameters for prediction of remission in Graves' disease during or after anti-thyroid drug therapy, there is no reliable one to assure the complete remission. We prospectively examined a practical therapy with minimum maintenance dose of anti-thyroid drugs for prediction of remission in Graves' disease. Fifty-seven patients with Graves' disease were treated with anti-thyroid drugs at the initial dose of 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU). Then, doses were gradually decreased, and finally discontinued when the patients were able to maintain euthyroid (normal FT4 and TSH) for at least 6 months with the minimum maintenance dose (MMI 5 mg every other day or PTU 50 mg every other day). After discontinuation of drugs, FT4, FT3, TSH and TSH-binding inhibitory immunoglobulin (TBII) were measured every one to two months for the first 6 months and every 3-4 months for the next 18 months to confirm continuous remission. After 2 years of drug cessation, 46 (81%) of 57 patients were in remission and the other 11 patients had relapsed into thyrotoxicosis. At the time of drug discontinuation, the serum concentration of FT4, FT3 and TSH, titers of anti-thyroglobulin antibodies and anti-thyroid microsomal antibodies, goiter size were not different between the remission and relapse groups. At the time of drug cessation, the activities of TBII and thyroid-stimulating antibodies (TSAb) overlapped between the two groups, although they were significantly lower in the remission group than in the relapse group (p<0.01). Forty percent (4/10) of TBII positive patients and 71% (23/32) of TSAb positive patients continued to be in remission. On the other hand, thyrotoxicosis relapsed in 5 (11%) of 47 TBII negative and 2 (8%) of 25 TSAb negative patients. These data indicate that minimum maintenance therapy to keep euthyroid (normal FT4 and TSH) for 6 months is a practical measure for 81% prediction of remission in Graves' disease. The measurement of TBII or TSAb gave little additional information for predicting remission.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Predictive Value of Tests; Propylthiouracil; Prospective Studies; Recurrence; Remission Induction

To ascertain whether the therapoutic effect of 131I is affected by the additional use of thyrostatic medication.. One hundred and eighty-seven patients with Graves' disease (GD) were randomly assigned to treatment with 131I alone or plus thyrostatic medication(PTU) 3 days after the beginning of 131I therapy. All patients were examined every month for six months after treatment.. The cure of hyperthyroidism occurred in 71 of 93 patients(76.3%) treated with 131I alone and in 76 of 94 patients(80.5%) treated with 131I plus thyrostatic medication(PTU). There were no significant differences in cure rate between the two groups.. The additional use of thyrostatic medication 3 days after the beginning of 131I therapy will not affect the efficacy of 131I in the treatment of GD.

Topics: Adult; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil

Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease.. Seventy-one patients with newly diagnosed Graves' disease were studied.. Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period.. There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group.. During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Chi-Square Distribution; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

In Graves' hyperthyroidism treated with antithyroid drugs (ATD), the overall relapse rate reaches 30-50% following ATD discontinuation. Conflicting results have previously been reported with regard to the usefulness of combining ATD with thyroxine (l-T4), and thereafter maintaining l-T4 treatment after ATD withdrawal. Also, clinicians are in search of useful parameters to predict the risk of a recurrence of hyperthyroidism after ATD treatment.. Eighty-two consecutive patients (70 women and 12 men; mean age 36 years) with a first episode of Graves' hyperthyroidism were investigated prospectively; they were treated with ATD for a total of 15 months, combined with l-T4 (for at least 12 months) after they had reached euthyroidism, with the aim of maintaining serum TSH below 2.5 mU/l during the combined therapy. Following ATD discontinuation, the patients were randomly assigned (double-blind placebo-controlled trial) to taking 100 microg/day l-T4 (vs placebo) for an additional year.. The following determinations were carried out at initial diagnosis: serum total T4 and tri-iodothyronine (T3), free T4 and T3, TSH, TSH-receptor antibodies (TSHR-Ab), thyroid scintigraphy and echography. During ATD treatment, serum free T4 and T3 and TSH concentrations were recorded after 1 (optional), 2, 4, 6, 9, 12 and 15 months, and echography at the end of ATD treatment. During the randomized trial, serum free T4 and T3 and TSH concentrations were checked every 3 months (or until a recurrence). TSHR-Ab titers were measured at initial diagnosis, after 6 months with ATD, and at the end of ATD treatment.. l-T4 administration, both during and after ATD treatment, did not improve the final outcome and recurrence rates were similar in placebo and l-T4-treated patients (30%). Two parameters were identified that might be useful to help predict recurrence risks after ATD: (i) positive TSHR-Ab (at the end of ATD treatment) was significantly associated with a greatly increased recurrence risk; and (ii) despite the relatively small number of patients who were smokers, regular cigarette smoking was shown, for the first time, to be significantly associated with an increased recurrence risk. Also, the deleterious effect of smoking was shown to manifest its impact independently of TSHR-Ab titers at the end of ATD treatment. Thus, compared with the overall 30% recurrence risk, non-smoking patients with a negative TSHR-Ab (at the end of ATD) had a lower (18%) recurrence risk; smoking patients with negative TSHR-Ab (at the end of ATD) had a 57% recurrence risk; non-smoking patients with positive TSHR-Ab (at the end of ATD) had a high (86%) recurrence risk; the recurrence risk was 100% in those few patients who both smoked and maintained a positive TSHR-Ab at the end of ATD treatment.. The present study confirmed that l-T4 administration during and after ATD withdrawal did not improve remission rate. Two factors, namely positive TSHR-Ab at the end of ATD treatment and regular smoking habits may represent clinically useful (albeit not absolute) predictors of the risk of recurrence in patients with Graves' hyperthyroidism treated with ATD. However, due to the relatively small number of smoking patients in the present cohort, this conclusion needs to be confirmed by a larger study.

Topics: Adult; Antithyroid Agents; Double-Blind Method; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Prospective Studies; Receptors, Thyrotropin; Recurrence; Risk Factors; Smoking; Thyroid Function Tests; Thyroid Hormones; Thyroxine

Oxygen free radicals (OFR) play a role in the pathogenesis of tissue damage in many pathological conditions via the peroxidation of membrane phospholipids. Experimental studies showed an elevated oxidative stress during hyperthyroidism, which is reduced by treatment. Therapy per se might decrease oxidative stress.. Fasting plasma levels of thiobarbituric acid reacting substances (TBARS), vitamin E and coenzyme Q10 were measured in 22 hyperthyroid patients, before treatment for their thyroid disease, after 13.9 [SD 9.2] weeks, when they achieved an euthyroid state on thyrostatic drugs, and again after 47.7 [21.0] weeks, off therapy. No patient presented additional risk factors for increased lipoperoxidation and/or increased OFR levels. Smokers were asked to abstain from smoking overnight.. All analytes were measured by HPLC.. In hyperthyroidism, plasma levels of TBARS were increased, whereas vitamin E and coenzyme Q10 were reduced. Average levels of TBARS and antioxidant agents returned to normal in euthyroid patients, without differences in relation to stop of thyrostatic therapy.. Our data confirm the presence of oxidative stress and decreased anti-oxidant metabolites in hyperthyroid patients, which are corrected in euthyroidism, without any influence of thyrostatic drugs per se. Nutritional support with antioxidant agents, which are defective during hyperthyroidism, is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Coenzymes; Female; Graves Disease; Humans; Lipid Peroxidation; Male; Methimazole; Middle Aged; Oxidative Stress; Propylthiouracil; Thiobarbituric Acid Reactive Substances; Thyroiditis, Autoimmune; Treatment Outcome; Ubiquinone; 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

To obtain a simple standard regimen, suitable for general practice, and based upon the addition of antithyroid drug plus thyroxine for attaining euthyroidism in patients with Graves' disease.. Prospective, randomized trial of patients with Graves' disease followed for 3 months after the initiation of therapy with an antithyroid drug and combined with the later addition of triiodothyronine to keep the patient euthyroid. The patients were randomized, according to birth date, between methimazole and propylthiouracil. Three dose schemes were tested for each antithyroid drug.. The study was performed at the thyroid outpatient units of two general hospitals, with the patients having been referred from primary care.. Ninety-four patients with Graves' disease who were suitable for treatment with antithyroid drugs.. The patients were allocated into six groups. Three groups received methimazole (10 mg every 6th, 8th or 12th h) and three received propylthiouracil (100 mg every 6th, 8th or 12th h). Twenty micrograms of triiodothyronine was added when the patients were euthyroid to avoid hypothyroidism.. The lowest serum free thyroxine level within 3 months of the initiation of the antithyroid treatment.. Fourteen per cent of the patients on methimazole 10 mg every 12th h and 29% on propylthiouracil 100 mg every 12th h did not achieve euthyroidism within the 3-month observation period. All but one patient on methimazole 10 mg every 8th h or propylthiouracil 100 mg every 8th h reduced the free serum thyroxine levels to the normal or hypothyroid range within the observation period. All of the patients on methimazole 10 mg every 6th h and 56% on propylthiouracil 100 mg every 6th h reduced the serum T4 values into the hypothyroid range within the period.. A standard regimen, based upon the addition of methimazole 10 mg every 8th or 6th h or propylthiouracil 100 mg every 8th or 6th h and followed by the addition of thyroxine or triiodothyronine when euthyroid to avoid hypothyroidism, seems to be suitable for attaining euthyroidism within 3 months in patients with Graves' disease. A dose scheme based on methimazole 10 mg every 12th h or propylthiouracil 100 mg every 12th h were found to be unsuitable due to an unacceptably high incidence of failure to attain euthyroidism or hypothyroidism within 3 months.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Prospective Studies; Thyroxine

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

Thyroid stimulating antibodies (TsAb) and thyrotropin releasing hormone (TRH) test were used as the indices for predicting relapse and remission in 58 patients. The variation of TsAb activities was observed before and after antithyroid drug (ATD) treatment. The findings showed that TsAb activities of untreated patients were significantly higher than those of patients treated by ATD, and TsAb activities were weak or negative after ATD treatment. When TsAb was positive or TRH test was abnormal at the time of cessation of ATD therapy, nearly 93% patients relapsed. Further analyses of relapsed patients indicated that there was no correlation between the two indicators, and the TsAb positive rate (84%) was significantly higher than the rate of abnormal TRH test (45%). The average ATD treatment duration in relapsed patients was shorter than that in remission patients. It is concluded that TsAb is more useful than TRH test when they are used for predicting the prognosis of Graves' disease. The duration of ATD treatment could affect relapse or remission. The immunosuppression effect of ATD was also identified.

Topics: Adult; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Recurrence; Thyrotropin; Thyrotropin-Releasing Hormone

We evaluated whether antithyroid drug treatment could be terminated more appropriately when both the serum basal thyrotrophin (TSH) level and TSH receptor antibody activity have become normal.. This was a prospective randomized study of patients with Graves' disease followed for a mean of 28 months after the withdrawal of antithyroid drug treatment.. A total of 174 patients with hyperthyroid Graves' disease were entered consecutively into this study, 11 of whom were subsequently excluded. One hundred and sixty-three patients were divided randomly into two groups having different criteria for the discontinuation of the antithyroid drug. Group 1 consisted of 79 patients whose antithyroid drug treatment was discontinued if both their serum TSH level and thyrotrophin binding inhibitor immunoglobulin (TBII) activity normalized. Group 2 consisted of 84 patients who were treated for 24 months irrespective of their serum TSH level and TBII activity. All patients were treated initially with 400 mg/day of propylthiouracil followed by decreasing doses that maintained a euthyroid state.. Serum basal TSH levels and TBII activities were measured using a radioimmunometric assay and a radioreceptor assay, respectively, every 2 months during the antithyroid drug treatment.. The remission rate of Group 1 (51.9%) was not significantly different from that (63.1%) of Group 2. The mean duration of treatment in Group 1 was 10.2 +/- 4.5 months (range 5-24, median 10). Median duration of treatment in Group 1 was 14 months shorter than in Group 2. In Group 1, the relapse rate was independent of the duration of the treatment. Further, the mean duration of treatment in the relapsed patients was not significantly different from that for patients who went into remission (9.9 +/- 3.8 vs 10.7 +/- 5.7 months; P greater than 0.1). In Group 2, the relapse rate was dependent on the time when both the serum TSH level and TBII activity were normalized (chi 2 = 27.0, d.f. = 4; P less than 0.001). When both the serum TSH level and TBII activity were normalized, the relapse rate of Group 2 was not significantly different from that of Group I for treatment periods of 6-12 months (25 vs 24.2%, P greater than 0.1), 12-18 months (33.3 vs 40%, P greater than 0.1), and 18-24 months (46.2 vs 50%, P greater than 0.1). However, the relapse rate of Group 2 was significantly lower than that of Group 1 when there was only a 6-month treatment period (5.6 vs 42.9%, P less than 0.05). Of the clinical and laboratory parameters measured, male sex, change of goitre size during treatment, and TSH levels and TBII values at the end of treatment, were of prognostic significance in predicting a relapse.. The present study suggests that antithyroid drugs treatment can be terminated more appropriately when both the serum TSH level and TBII activity are made normal, thus avoiding prolonged and unnecessary drug treatment.

Topics: Adult; Autoantibodies; Drug Administration Schedule; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Prognosis; Propylthiouracil; Prospective Studies; Random Allocation; Receptors, Thyrotropin; Recurrence; Thyroid Gland; Thyrotropin; Time Factors

We studied the efficacy of amiodarone (800, 600, 400 and 200 mg orally daily during weeks 1, 2, 3 and 4, respectively) plus propylthiouracil (PTU, 100 mg orally every 8 h) in comparison to PTU alone in the early treatment (28 days) of Graves' disease patients. Circulating T3 and T4 decreased earlier and more markedly in the amiodarone plus PTU-treated group. An initial rise of circulating rT3 above the base-line value followed by a gradual decline was observed in the former group while only a decline below the base-line values was observed in the latter group. The resting pulse rate decreased and body weight increased significantly in the amiodarone plus PTU-treated group. In the PTU-treated group, significant weight gain was observed later in the course of treatment while no significant reduction in pulse rate was observed. No major side-effects of amiodarone were observed during the course of treatment. This study suggested that the combination of amiodarone and PTU was more efficacious than PTU alone in reducing circulating T3, T4 and clinical hyperthyroidism early in the course of treatment of patients with Graves' disease. This regimen has an additional potential advantage because of the antiarrhythmic property of amiodarone, especially in situations when a beta-blocker is contraindicated.

Topics: Adult; Amiodarone; Drug Therapy, Combination; Female; Graves Disease; Hemodynamics; Humans; Middle Aged; Propylthiouracil; Thyroxine; Triiodothyronine; Weight Gain

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

This study represents an international double-blind collaborative study of abnormal immunoglobulin activity in untreated Graves' disease. Laboratories in two countries participated in a comparison of thyrotrophin binding inhibiting (TBII), thyroid stimulating (TSAb), and growth stimulating (TGI) immunoglobulins with clinical data, including ultrasonically measured thyroid size. The correlation between TGI and thyroid volume (n = 25, Rs = 0.54, P less than 0.05) and the fact that 9 of 10 patients with high range TGI values had large goitres establish the relationship between TGI and goitre, confirming that the in-vitro activity of these antibodies is related to an in-vivo action. In addition, both TBII and TSAb correlated with serum free T3 indices (TBII: n = 60, Rs = 0.46, P less than 0.001, and TSAb: n = 60, Rs = 0.64, P less than 0.001). Moreover, both TBII and TSAb correlated with thyroid volume (TBII: n = 60, Rs = 0.37, P less than 0.01, and TSAb: n = 60, Rs = 0.41, P less than 0.01) suggesting that these antibodies are also important in development of goitre in Graves' disease. Finally, some correlation between the antibodies was observed. TBII correlated with TSAb (n = 60, Rs = 0.47, P less than 0.001), and in the 16 patients with positive TGI results, this activity correlated with TBII (Rs = 0.54, P less than 0.05), but not with TSAb. Also some cases were found with corresponding high range TBII and TGI, while negative for TSAb, suggesting a close relationship between the in-vitro measurement of TSH binding and TGI.

Topics: Adult; Aged; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroid Gland; Triiodothyronine

From March 1980 to August 1982, 108 patients with Graves' disease participated in a prospective study at Yonsei University College of Medicine. Preoperatively, 22 patients were prepared with propranolol alone (group 1) and 86 with propranolol and propylthiouracil (PTU) (group 2). The duration of preparation averaged 11.5 days for group 1 and 10.8 days for group 2. Bilateral subtotal thyroidectomy was performed, leaving 4 to 6 grams at both upper poles. No significant difference was noted in the average weight of the removed gland or the amount of blood loss between both groups. During the operation, the pulse rate of group 1 was significantly faster than that of group 2 but evened out by the day of discharge. The incidence of high fever during and immediately after operation was 27.3 per cent in group 1 which is greater than the 17.4 per cent in group 2. In group 1, the incidence of postoperative transient hypocalcemia was 27.3 per cent, transient or prolonged hypothyroidism was 13.6 per cent and recurrence of thyrotoxicosis was 4.5 per cent. In group 2, the values were 22.1, 18.6 and 4.7 per cent, respectively. High fever developed in one patient from group 1 during operation and this patient died on the third day postoperatively. From the results of our study, it appears to be more beneficial to administer both propranolol and PTU as preoperative medication to patients with Graves' disease prior to undergoing operation.

Topics: Adult; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fever; Follow-Up Studies; Graves Disease; Humans; Hypocalcemia; Male; Postoperative Complications; Premedication; Preoperative Care; Propranolol; Propylthiouracil; Prospective Studies; Pulse; Random Allocation; Thyroidectomy; Time Factors

We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves' hyperthyroidism. The patients were randomly divided into 2 groups. In group A, 65 patients received either methimazole (MMI): 60 +/- 14.5 mg/day (mean +/- SD); range 40-100 mg/day, or propylthiouracil (PTU): 693 +/- 173 mg/day; range 500-1200 mg/day. These high doses were maintained throughout treatment with later addition of 50-75 micrograms T3 daily. Forty eight patients (group B) were treated with lower doses of MMI or PTU without thyroid hormone addition. The maintenance dose of MMI was 13.6 +/- 7 mg/day (range 5-25 mg/day) and that of PTU was 180 +/- 58 mg/day (range 100-300 mg/day). The treatment period was 15.1 +/- 4.2 (range 10-30) months for group A and 13.5 +/- 2.2 (range 12-20) months for group B. Remission occurred in 75.4% patients from group A and in 41.6% patients from group B (P less than 0.001). The mean follow-up was 42 +/- 14 months (17-81 months). The free T4 index (FT4I) in group A remained below the normal range during treatment. The mean FT4I, obtained during the course of treatment, of patients who went into remission from group A was significantly (P less than 0.001) lower than in relapsed patients (4.8 vs. 6.5). Moreover, there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI (r = -0.567; P less than 0.001), or PTU (r = -0.379; P less than 0.01). A fall in microsomal antibody (MCHA) titer occurred mainly in remission patients, and was more significant (P less than 0.05) in group A patients. In contrast, 11 (7 from group B) of the 16 patients with an increase of microsomal antibody levels relapsed. The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients (71%) than in group B (29%) at the end of therapy (P less than 0.01). No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment. Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen. These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens. Furthermore, a high dosage regimen could permit the restoration of the immune surveillance mechanisms and, thus, lasting remission of Graves' disease.

Topics: Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Autoantibodies; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

The relation between serum concentrations of thyroglobulin antibodies (TgAb), thyroid-stimulating antibodies (TSAb) and serum immunoglobulins during treatment of Graves' disease was studied in 36 consecutive patients treated randomly with 131-iodine (n = 16) or propylthiouracil (n = 20). The patients were investigated before treatment was started and on seven occasions within the following year. In the entire patient group 78% were positive for TSAb and 47% for TgAb. There was a significant correlation between TSAb and TgAb in 15 patients concomitantly positive. There were no significant changes in serum immunoglobulins during treatment in either group of patients. In the radioiodine-treated group of patients TgAb was reduced after 1 week, whereas TSAb showed insignificant variations. After 5-10 weeks both antibodies increased, for TgAb with a median peak level 3 time above the initial concentration. Of 16 patients treated with radioiodine five developed myxoedema and four of these were positive for TgAb. There was a relation between the development of myxoedema and the ratio between increases of TSAb and TgAb. Increase in TSAb was not related to serum thyroglobulin (Tg) measured in TgAb-negative patients. Propylthiouracil showed minor effects on the studied variables, but with lower mean values of Tg, TgAb and TSAb at the end of the observation period. The results indicate an immunological relation between TSAb and TgAb, although differences between their course exist in some situations.

Topics: Adult; Aged; Antibodies; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Middle Aged; Myxedema; Propylthiouracil; Serum Albumin; Thyroglobulin

In a prospective study the ocular manifestations of 105 thyrotoxic patients were carefully observed and registered during a 24-month antithyroid drug therapy. The treatment was supervised very closely and every effort was made to avoid iatrogenic hypothyroidism. None of the patients required any ocular surgery and in none did the ophthalmopathy become significantly worse. This favourable experience may indicate that a careful antithyroid regimen as outlined is not likely to be accompanied by worsening of the endocrine ophthalmopathy.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Clinical Trials as Topic; Drug Evaluation; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Prospective Studies

Forty-nine patients with Graves' disease were randomly divided into two groups. One group received propylthiouracil, 150 mg every eight hours, and the other group received propylthiouracil, 450 mg as a single daily dose. All patients' conditions were evaluated clinically anc chemically at two-week intervals. The response to the divided dosage schedule was prompt and predictable, and by ten weeks all but one patient had achieved remission. The group that received the single daily dose regimen responded less favorably, and at ten weeks ten patients had failed to achieve remission (P less than .001). However, when these patients' regimens were switched to the every-eight-hour schedule, all but one patient became euthyroid in an additional four weeks.

Topics: Drug Evaluation; Female; Graves Disease; Humans; Male; Methods; Propylthiouracil; Remission, Spontaneous; 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: Antithyroid Agents; Clinical Trials as Topic; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Perchlorates; Potassium; Propylthiouracil; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

The most common cause of hyperthyroidism is Graves' disease. Propylthiouracil (PTU) is one of the drugs used to treat this disease. Leukocytoclastic vasculitis is described among dermatologic adverse effects of PTU.. A 18-year-old woman, allergic to methimazole, developed a vasculitis associated to ANCAs with characteristics of leukocytoclastic vasculitis, associated to PTU treatment. She did not present systemic involvement. PTU treatment was suspended. Two months later, the skin lesions had almost completely resolved.. Leukocytoclastic vasculitis should be considered in the spectrum of complications caused by the consumption of propylthiouracil. The lesions can manifest over time, from a few weeks to years after taking the drug. When there is no systemic involvement, propylthiouracil suspension is sufficient to cure the disease.. La causa más frecuente de hipertiroidismo es la enfermedad de Graves. El propiltiouracilo es uno de los medicamentos más prescritos para esta enfermedad. Uno de los efectos adversos dermatológicos del propiltiouracilo es la vasculitis leucocitoclástica.. Paciente femenina de 18 años, alérgica al metamizol, con vasculitis asociada a ANCAs, con características de vasculitis leucocitoclástica provocada por el consumo de propiltiouracilo. No se observó afectación sistémica. Dos meses después de suspender el propiltiouracilo desaparecieron casi por completo las lesiones en la piel.. La vasculitis leucocitoclástica debe considerarse en el espectro de complicaciones provocadas por el consumo de propiltiouracilo. Las lesiones pueden manifestarse con el paso del tiempo, desde unas semanas hasta años después de consumir el fármaco. Cuando no existe afectación sistémica, la suspensión del propiltiouracilo es suficiente para detener la enfermedad.

Topics: Adolescent; Antithyroid Agents; Drug-Related Side Effects and Adverse Reactions; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Adult; Antithyroid Agents; Cheek; Female; Graves Disease; Humans; Propylthiouracil; Purpura; Vasculitis

Topics: Adult; Antithyroid Agents; Computed Tomography Angiography; Conservative Treatment; Echocardiography, Transesophageal; Electrocardiography; Female; Graves Disease; Heart Failure; Humans; Hypertension, Pulmonary; Image Processing, Computer-Assisted; Methimazole; Propylthiouracil; Scimitar Syndrome; Thyroid Function Tests; Treatment Outcome; Tricuspid Valve Insufficiency; Vena Cava, Inferior

A 30-year-old female patient with a past medical history of pernicious anaemia presented with pleuritic chest pain, palpitations, fatigue, coryzal symptoms and a high temperature. She was hypoxic and tachycardic and was extensively investigated as well as aggressively treated. A type 1 'gut feeling' assessment by the admitting medical registrar made the diagnosis possible as thyroid function tests were grossly deranged and pointed to Graves' disease causing heart failure, complicated by pneumonia. The patient was discharged on carbimazole, antibiotics and beta blockers. Due to a resultant thrombocytopaenia, she has now been swapped onto propylthiouracil and is under active follow up.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Heart Failure; Humans; Propylthiouracil; Thyrotoxicosis

Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Infant, Newborn; Methimazole; Pregnancy; Propylthiouracil; Thyrotropin

Graves' disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. There is some debate regarding the optimal treatment and predicting factors of remission or relapse in children and adolescents with GD. In this study, we report a retrospective study of 195 children and adolescents with GD treated at a single tertiary institution in Korea.. This study included children and adolescents with GD diagnosed before 19 years of age from January of 2000 to October of 2020. The diagnosis of GD was based on clinical features, high thyroxine (FT4), suppressed thyroid-stimulating hormone, and a positive titer of thyrotropin receptor antibodies. Remission was defined as maintenance of euthyroid status for more than six months after discontinuing antithyroid drug (ATD).. A total of 195 patients with GD were included in this study. The mean age at diagnosis was 12.9 ± 3.2 years, and 162 patients (83.1%) were female. Among all 195 patients, five underwent thyroidectomy and three underwent radioactive iodine therapy. The mean duration of follow-up and ATD treatment were 5.9 ± 3.8 years and 4.7 ± 3.4 years, respectively. The cumulative remission rates were 3.3%, 19.6%, 34.1%, 43.5%, and 50.6% within 1, 3, 5, 7, and 10 years of starting ATD, respectively. FT4 level at diagnosis (P = 0.001) was predicting factors for remission [HR, 0.717 (95% CI, 0.591 - 0.870), P = 0.001]. Methimazole (MMI)-related adverse events (AEs) occurred in 11.3% of patients, the most common of which were rash and hematologic abnormalities. Of a total of 26 AEs, 19 (73.1%) occurred within the first month of taking MMI.. In this study, the cumulative remission rate increased according to the ATD treatment duration. Long-term MMI treatment is a useful treatment option before definite treatment in children and adolescents with GD.

Topics: Adolescent; Antithyroid Agents; Child; Female; Goiter; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Remission Induction; Retrospective Studies; Treatment Outcome

Nephritis has been rarely associated with methimazole, primarily in the development of nephrotic syndrome. We describe a case of acute kidney injury without evidence of nephrotic syndrome following methimazole initiation.. We present the relevant history, laboratory data, and nuclear medicine data and review relevant documentation from the literature.. A 72-year-old male recently diagnosed with new-onset atrial fibrillation was found to have suppressed thyroid-stimulating hormone (TSH) levels; elevated free T. Acute kidney injury with or without the presence of nephrotic syndrome may occur during treatment with methimazole. Renal function should be closely monitored after the initiation of methimazole to prevent progressive renal dysfunction.

Topics: Acute Kidney Injury; Aged; Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Nephrotic Syndrome; Propylthiouracil

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Antithyroid Agents; Bilirubin; Chemical and Drug Induced Liver Injury; Child; Female; Graves Disease; Humans; Japan; Male; Methimazole; Middle Aged; Prevalence; Propylthiouracil; Retrospective Studies; Severity of Illness Index; Young Adult

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare in children and is characterised as necrotising vasculitis predominantly affecting small and medium-sized vessels. Propylthiouracil (PTU), an antithyroid drug, has been implicated in drug-induced AAV. In contrast, Kawasaki disease (KD) is a common systemic vasculitis, typically observed in children, which affects the medium-sized vessels, including the coronary arteries. An 11-year-old girl who developed AAV while receiving PTU therapy for Graves' disease is described. She was admitted to hospital following a 2-day history of fever, cervical adenopathy, cheilitis and papular rash, 3 weeks after an increase in the PTU dose. Despite discontinuation of PTU and the administration of intravenous antibiotic therapy, her clinical condition deteriorated and over the next 2 days she developed severe diarrhoea, conjunctival injection and swelling and redness of the right index finger. Additional findings included liver dysfunction, hydrops of the gallbladder, coagulopathy and urine abnormalities, suggesting glomerulonephritis. She met the diagnostic criteria for KD and received intravenous immunoglobulin (IVIG) combined with prednisolone, with rapid resolution of clinical and laboratory parameters. Peeling of the right index fingertip became evident on Day 12 of admission. Serial ultrasound cardiography demonstrated no evidence of cardiac involvement. A high titre of myeloperoxidase ANCA was detected in the patient's serum on admission, and the titre decreased during the convalescent stage. This case demonstrates that children with PTU-associated AAV may present with clinical features mimicking KD, and that IVIG along with corticosteroid therapy may be effective in treating patients with drug-induced severe systemic AAV.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Blood Chemical Analysis; Child; Diagnosis, Differential; Female; Graves Disease; Humans; Mucocutaneous Lymph Node Syndrome; Propylthiouracil

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Upper Extremity Deep Vein Thrombosis

Neutrophil extracellular traps (NETs) are immune defence systems that release extracellular chromatin and myeloid granules including myeloperoxidase (MPO) to kill pathogens. An experimental animal study recently demonstrated that disordered NETs induced by propylthiouracil (PTU) could contribute to the production of MPO anti-neutrophil cytoplasmic antibody (ANCA) and the development of ANCA-associated vasculitis (AAV). However, the role of dysregulated NETs in the pathogenesis of human AAV remains unclear.. We report a 19-year-old woman with Graves' disease on PTU presented fever, polyarthralgia, and lung hemorrhage with high titer of MPO-ANCA. This patient had a variety of atypical ANCAs and disordered NETs in vitro.. A diagnosis of PTU-induced AAV (PTU-AAV).. The PTU was discontinued and she was treated with immunosuppressants and plasmapheresis for reducing pathogenic autoantibodies.. Clinical manifestations including fever, polyarthralgia, and lung hemorrhage were on remission with a decrease of dysregulated NETs.. The clinical course of this PTU-AAV case indicated that dysregulated NETs would play a role in the development of ANCA and the pathogenesis of AAV.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Extracellular Traps; Female; Graves Disease; Humans; Immunosuppressive Agents; Propylthiouracil; Young Adult

Topics: Carbimazole; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Thyroidectomy; Vasculitis, Leukocytoclastic, Cutaneous

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism. Antithyroid drugs (ATDs) are available as therapy. Agranulocytosis is a rare but potentially fatal complication of this therapy. In this study, we report agranulocytosis induced by propylthiouracil (PTU) in a patient with GD and the difficulties of clinical management.. RNBA, male, 30 years old, with GD, treated with propylthiouracil (PTU). He progressed with pharyngotonsillitis. Then, PTU was suspended and antibiotic, filgrastim, propranolol, and prednisone were initiated. Due to the decompensation of hyperthyroidism, lithium carbonate, dexamethasone, and Lugol's solution were introduced. Total thyroidectomy (TT) was performed with satisfactory postoperative progression.. We describe here the case of a young male patient with GD. For the treatment of hyperthyroidism, thioamides are effective options. Agranulocytosis induced by ATDs is a rare complication defined as the occurrence of a granulocyte count <500/mm3 after the use of ATDs. PTU was suspended, and filgrastim and antibiotics were prescribed. Radioiodine (RAI) or surgery are therapeutic alternatives. Due to problems with ATD use, a total thyroidectomy was proposed. The preoperative preparation was performed with beta-blocker, glucocorticoid, lithium carbonate, and Lugol solution. Cholestyramine is also an option for controlling hyperthyroidism. TT was performed without postoperative complications.. Thionamide-induced agranulocytosis is a rare complication. With a contraindication to ATDs, RAI and surgery are definitive therapeutic options in GD. Beta-blockers, glucocorticoids, lithium carbonate, iodine, and cholestyramine may be an adjunctive therapy for hyperthyroidism.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Graves Disease; Humans; Male; Propylthiouracil; Rare Diseases; Thyroid Function Tests; Thyroidectomy

Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions.. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Topics: Adult; B-Lymphocytes; Cross-Sectional Studies; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; T-Lymphocytes; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

We herein report a case of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) induced by propylthiouracil (PTU). A 30-year-old Japanese woman with Graves' disease, who was treated with PTU, reported with otitis media with sensorineural hearing loss bilaterally and trigeminal neuralgia on the left side, as well as elevated serum levels of myeloperoxidase-ANCA. Prior treatment with antibiotics was ineffective even after tympanostomy. However, clinical remission was immediately achieved after initiating prednisolone together with PTU withdrawal. These findings suggest that PTU therapy induces localized otological involvement as the concept of OMAAV.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Asian People; Female; Graves Disease; Humans; Otitis Media; Prednisolone; Propylthiouracil; Treatment Outcome

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antinuclear; Antithyroid Agents; Female; Graves Disease; Humans; Myeloblastin; Peroxidase; Propylthiouracil; Skin; Skin Diseases

Liver transplantation (LT) for acute liver failure is an uncommon occurrence in the setting of pregnancy given the risk of fetal demise, and rarely is it undertaken with a viable fetus. Maternal hyperthyroidism increases fetal risk in the setting of LT, particularly in the setting of thyrotoxicosis. We report the first case of propylthiouracil-induced acute liver failure in a hyperthyroid patient in her second trimester resulting in LT. The multidisciplinary management led to a favorable outcome for the patient and the subsequent delivery of a healthy infant at 38-weeks' gestation.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Live Birth; Liver Failure, Acute; Liver Transplantation; Pregnancy; Pregnancy Complications; Propylthiouracil

Fetal goitrous hypothyroidism is mainly caused by maternal treatment of Graves' disease. Fetal goiter sometimes compresses the trachea and esophagus and may cause polyhydramnios, preterm labor, complications of labor and delivery, and neonatal respiratory disorder.. We report a case of fetal goitrous hypothyroidism in which the mother had Graves' disease, which was treated with propylthiouracil. Intra-amniotic levothyroxine (L-T4) administration was performed, and the fetal goiter decreased in size. A female infant was delivered without goiter and complications. Thyroid function was within the normal range.. Previous reports on fetal goitrous hypothyroidism that was treated with intra-amniotic L-T4 showed that patients who had intra-amniotic L-T4 administration were likely to have a good outcome compared with patients who did not have L-T4. Thyroid function of the mother and fetus should be carefully monitored and treated appropriately.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroxine; Treatment Outcome; Ultrasonography, Prenatal

This study sought to investigate the clinical characteristics and outcomes of propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in patients with Graves' disease.. Sixteen patients diagnosed with PTU-induced ANCA-associated vasculitis at the authors' hospital from January 2010 to June 2017 were analyzed retrospectively.. All 16 patients with PTU-induced ANCA-associated vasculitis were female. The mean age ± standard deviation of the patients was 39.4 ± 15.3 years (range 19-69 years), and the median time of onset was 36 months (range 1-193 months) post-PTU initiation. The median dose at the onset of PTU-induced ANCA-associated vasculitis was 150 mg/day (range 50-300 mg/day). All patients had a positive serum perinuclear staining pattern (p-ANCA) and antibodies directed against myeloperoxidase (anti-MPO). Six patients tested positive for both anti-MPO antibodies and antibodies directed against proteinase-3. Seven (43.8%) patients presented with involvement of a single organ. The kidney was the organ most commonly affected, as 12 (75%) patients were found to have disease involving this organ. PTU was stopped in all patients, corticosteroids were administered to two patients, and immunosuppressive agents and corticosteroids were administered to five patients. Three patients were lost to follow-up. However, the remaining patients achieved remission after a median follow-up period of 38 months (range 6-76 months). Patients who were positive for pANCA and displayed cytoplasmic staining showed negative findings at rates of approximately 53.8% (7/13) and 100% (6/6), respectively, following treatment.. PTU-induced ANCA-positive vasculitis occurs at varying times and after exposure to various doses of PTU. The condition has a milder course and has a better prognosis after PTU cessation.

Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; China; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Retrospective Studies; Young Adult

Relapsing polychondritis (RP) is a rare and heterogeneous disease complex of unknown origin which basically affects cartilaginous structures, 40% of which accompanied by rheumatic, hematologic, and endocrine disease. Among them, vasculitis is the most common accompanying type and usually presented with positive antineutrophilic cytoplasmic antibody (ANCA). The presence of ANCA could be primary or drug-induced like propylthiouracil (PTU). Central involvement of RP is very rare, and there is almost no report of cerebral vasculopathy manifested as moyamoya.. A 26-year-old woman complained about recurrent fever, auricular chondritis, ocular inflammation, and arthritis. She had an 8-year drug intake of PTU for Graves disease. Myeloperoxidase antineutrophilc cytoplasmic antibodies (MPO-ANCA) were found positive. Magnetic resonance angiography (MRA) detected multiple intracranial vasculopathy which we highly suspected it as moyamoya disease.. Relapsing polychondritis, Graves disease and suspected moyamoya disease were clinically diagnosed.. In case of possible PTU-induced vasculitis and the aggravation of vasculopathy, PTU was replaced by Iodine-131 (I) therapy. Induction treatment included oral prednisone 30 mg daily and oral cyclophosphamide 100 mg daily. Symptoms rapidly relieved before discharge. Inflammation markers were normal and MPO-ANCA decreased in 3 weeks after admission. Prednisone was gradually tapered to 7.5 mg daily and at month 10 azathioprine was continued for maintenance.. RP can overlap with Graves disease and moyamoya disease; comprehensive tests should be performed when admission. When relapsing polychondritis is accompanied with Graves disease, especially when ANCA is positive, PTU should be avoided.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Female; Graves Disease; Humans; Moyamoya Disease; Polychondritis, Relapsing; Propylthiouracil

Management of Graves' disease (GD) in Europe was published in 1987. Aim of this survey was to provide an update on clinical practice in Europe, and to compare it with a 2011 American survey.. Members of the European Thyroid Association (ETA) were asked to participate in a survey on management of GD, using the same questionnaire of a recent American survey.. A total of 147 ETA members participated. In addition to serum TSH and free T4 assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (85·6%) and thyroid ultrasound (70·6%) to confirm aetiology, while isotopic studies were selected by 37·7%. Antithyroid drug (ATD) therapy was the preferred first-line treatment (83·8%). Compared to the previous European survey, Europeans currently more frequently use TRAb measurement and thyroid ultrasound for diagnosis and evaluation, but first-line treatment remains ATDs in a similar percentage of respondents. Current clinical practice patterns differ from those in North America, where isotopic studies are more frequently used, and radioiodine (RAI) still is first-line treatment. When RAI treatment is selected in the presence of mild Graves' orbitopathy and/or associated risk factors for its occurrence/exacerbation, steroid prophylaxis is frequently used. The preferred ATD in pregnancy is propylthiouracil in the first trimester and methimazole in the second and third trimesters, similar to North America.. Significant changes in clinical practice patterns in Europe were noted compared to the previous European survey, as well as persisting differences in diagnosis and therapy between Europe and North America.

Topics: Antithyroid Agents; Autoantibodies; Europe; Female; Graves Disease; Humans; Methimazole; North America; Practice Patterns, Physicians'; Pregnancy; Pregnancy Complications; Propylthiouracil; Receptors, Thyrotropin; Surveys and Questionnaires; Thyrotropin; Thyroxine

A 23-year-old man, on treatment for Graves' disease, presented to the emergency department, with 2 separate episodes of loss of consciousness. During the first episode, the initial serum glucose was 19 mg/mL, and 44 mg/dL during the second episode. The patient was non-diabetic, and had elevated blood insulin, C peptide and insulin antibody levels. His abdominal radiographic findings were normal. He was diagnosed with Hirata disease, and put on propylthiouracil as a replacement for carbimazole. Hypoglycaemia was managed with dextrose infusions and frequent meals. The patient's condition improved and he had no further episodes of hypoglycaemia during the follow-up period.

Topics: Blood Glucose; Carbimazole; Disease Management; Glucose; Graves Disease; Humans; Hypoglycemia; Male; Propylthiouracil; Young Adult

Whether radioactive iodine treatment of Graves' disease (GD) during pregnancy will increase pregnancy loss and affect fetal development is still a matter of concern. From May 2005 to December 2015, 2,276 childbearing-age women with GD received iodine-131 treatment in our departments and were retrospectively enrolled in our study. When some of them were found to have been pregnant, their thyroid functions were measured every 4 weeks, in addition, thyroid-stimulating hormone (TSH) was measured 6 weeks after delivery. When necessary, levothyroxine or propylthiouracil (PTU) was given in order to control their TSH levels during pregnancy. Finally, 69 pregnant women (29 ± 3.5 years old) and 1346 women who were not pregnant during the follow-up period were enrolled into this study. They were all hyperthyroid before or during pregnancy. Among 69 pregnant women, the administrated amount of iodine-131 was 254.9 ± 99.9 MBq. Fifty patients became subclinically hypothyroid after treatment and were administrated levothyroxine (55 ± 25 μg/d). Seven patients were diagnosed with subclinical hyperthyroidism during pregnancy and they received PTU (25 ± 12.5 mg/d). Twelve patients with normal thyroid function were also clinically followed. Among 69 women, 63 had a single birth, 3 had dizygotic twins, 2 had two pregnancies and 1 had a single twin birth. Sixty five babies were born full-term, while 9 were premature (4 ± 1 weeks early) with birth weight 3.2 ± 0.5 kg. Six new born babies were considered to be low birth weight infants (< 2.5 kg) while 5 were high birth weight (> 4 kg), but the weights of all the infants were within the normal range. During the period of observation to December 2015, all the infants were found to grow and develop normally. Among 1346 women who were not pregnant were in the further follow-up. Our study found no detrimental effects of the iodine-131 treatment in the pregnant women or their offspring so far.

Topics: Abortion, Spontaneous; Adult; Female; Fetal Development; Graves Disease; Humans; Iodine Radioisotopes; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Propylthiouracil; Retrospective Studies; Sex Ratio; Thyrotropin; Thyroxine

Thionamides are associated with a high risk of recurrence following cessation. Thyrotropin receptor-stimulating antibody (TRAb) levels at diagnosis and/or after thionamides may be biomarkers of this risk. This study assesses the natural history of Graves' thyrotoxicosis following thionamide withdrawal and factors that predict recurrence, particularly TRAb levels at diagnosis and cessation.. An observational study was conducted of patients with a first presentation of Graves' disease, who were prescribed (and completed) a course of primary thionamide treatment (n = 266) in a university teaching hospital endocrine clinic. Recurrence rates over four years and factors predictive of recurrent thyrotoxicosis were assessed.. The relapse rate was 31% at one year and 70% at four years. Younger age (39 years [range 30-49 years] vs. 47 years [range 37-53 years]; p = 0.011), higher TRAb levels at diagnosis (8.8 IU/L [range 5.3-17.0 IU/L] vs. 5.7 IU/L [range 4.1-9.1 IU/L]; p = 0.003), and higher TRAb levels at cessation of therapy (1.2 IU/L [range 0-2.3 IU/L] vs. <0.9 IU/L [range 0-1.3 IU/L]; p = 0.003) were associated with a higher risk of relapse. By four years, cessation TRAb <0.9 IU/L was associated with a 58% risk of recurrence compared with 82% with TRAb >1.5 IU/L (p = 0.001). TRAb at diagnosis >12 IU/L was associated with an 84% risk of recurrence over four years compared with 57% with TRAbs <5 IU/L (p = 0.002).. High TRAb at diagnosis and/or positive TRAb at cessation of therapy suggest a high likelihood of relapse, mostly within the first two years. They stratify patients likely to need definitive therapy (radioiodine or surgery).

Topics: Adult; Age Factors; Antithyroid Agents; Autoantibodies; Carbimazole; Female; Graves Disease; Humans; Male; Middle Aged; Prognosis; Propylthiouracil; Receptors, Thyrotropin; Recurrence; Thyroxine; Triiodothyronine

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

Propylthiouracil is the most common drug used to treat hyperthyroidism. However, this drug could cause a severe disease, antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), which was usually misdiagnosed.. We reported a 60-year-old woman of propylthiouracil-induced AAV manifested as blood coagulation disorders. The patient was admitted because of hyperthyroidism and leukopenia. At the time of hospitalization, she suffered from dry cough, erythema and knee joints ache, and gradually became febrile. And then BP decreased and PLT was reduced with coagulation disorders. ANCA: c-ANCA positive (1:100), p-ANCA positive (1:320), MPO-IgG positive, PR3-IgG positive, GBM-IgG negative. Erythrocyte sedimentation rate and C-reactive protein increased markedly. Chest high-resolution computed tomography (HRCT) showed that scattered spots, patch and ground-glass opacity.. Finally, we made a terminal diagnosis of PTU-induced AAV possibly. After drug withdrawal and use of steroid, the patient recovered well and then accepted RAI therapy. As the patient was given imipenem-cilastatin before the reduction of PLT and coagulation disorders, we considered that the hematologic disorders might be caused by antibiotics or a clinical presentation of the vasculitis itself.. Drug-induced vasculitis is relatively good prognosis, but early diagnosis and timely withdrawal of associated drugs are the key to the treatment.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Blood Coagulation Disorders; Diagnosis, Differential; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Tomography, X-Ray Computed; Vasculitis

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting with renal failure, acute hepatic failure, and cerebral angiitis is a rare yet fatal disease. Early diagnosis and management may help in reducing mortality and morbidity. Plasmapheresis and induction with either cyclophosphamide or rituximab is indicated. Understanding the pathophysiology and complex management of this disease poses challenges to clinicians.. A 42-year-old woman presented with acute renal and hepatic failure. She had been on PTU for 11 months for Graves' disease. Initial urine microscopy showed red blood cell casts. Anti PR-3 antibodies were positive. Kidney biopsy revealed pauci-immune glomerulonephritis with crescent formation. Renal and hepatic failures were attributed to PTU-induced c-ANCA production as other serological workup was negative. Pulse steroids and plasmapheresis were initiated. Later she developed pneumonia. She was also given rituximab. After the first dose of rituximab, plasmapheresis was held for 3 days. The second dose of rituximab was given in 5 days owing to removal by plasmapheresis. She got 8 sessions of plasmapheresis. She also developed seizures and MRA of her head revealed cerebral infarct, with findings suggestive of cerebral angiitis. She did not recover and expired 20 days after presentation.. PTU can cause ANCAassociated vasculitis resulting in multiorgan failure. Plasmapheresis should be held for 3 days after rituximab infusion in order to allow maximum exposure. The second dose of rituximab may be given before the recommended 7-day interval in cases in which plasmapheresis is being performed to maximize therapeutic benefit.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Biopsy; Combined Modality Therapy; Disease Progression; Fatal Outcome; Female; Glomerulonephritis; Graves Disease; Humans; Immunosuppressive Agents; Liver Failure, Acute; Magnetic Resonance Angiography; Microscopy, Electron; Multiple Organ Failure; Plasmapheresis; Propylthiouracil; Pulse Therapy, Drug; Rituximab; Steroids; Time Factors; Treatment Failure; Vasculitis, Central Nervous System

Propylthiouracil (PTU)-associated vasculitis is a potentially life-threatening disease with a recent increase in the reported cases in the medical literature. This increase may suggest that some earlier cases have been unrecognized or assigned to an alternative nosology category. Although the skin can be the only organ affected by PTU-associated vasculitis, there are many reports with multiple-system involvement. Classically, the symptoms appear under a tetrad of fever, sore throat, arthralgia, and skin lesions. Cutaneous lesions in reported cases of PTU vasculitis have most commonly consisted of retiform acral, purpuric plaques, or nodules. We report a case of perinuclear antineutrophil cytoplasmic antibody-associated vasculitis developed during treatment with PTU for Grave's disease.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biopsy; Female; Graves Disease; Humans; Propylthiouracil; Vasculitis

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

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

Antineutrophil cytoplasmic antibodies (ANCAs) are the serologic hallmark of ANCA-associated primary small-vessel vasculitides (AAVs), but these antibodies have also been described in other autoimmune diseases such as inflammatory bowel diseases. Furthermore, different drugs are linked to the induction of ANCA, including propylthiouracil (PTU). However progression into clinical overt vasculitis is less common.. We describe the case of a young girl with Graves' disease presenting with fatigue, fever, episcleritis and arthritis. The unexpected double myeloperoxidase/proteinase 3-ANCA positivity triggered a multidisciplinary diagnostic work-up and resulted in the diagnosis of a clinically overt PTU-induced AAV. After PTU-withdrawal and treatment with high-dose corticosteroids, a favorable clinical and biochemical evolution was obtained.. The use of PTU in the management of hyperthyroidism is not considered first-line treatment in Europe and is even less commonly used in children. Nevertheless, pediatricians should be aware of the possibility of PTU-induced AAV, especially in the presence of multiple ANCA reactivities. Therefore, the use of this drug should be weighed carefully in children.

Topics: Adolescent; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Propylthiouracil

The side effects of propylthiouracil, including cytopenia and vasculitis, are well established.  We present an interesting case in which cytopenia and cutaneous vasculopathy occurred concomitantly in a critically ill patient.  The patient was initially treated for suspected infection until dermatologic and rheumatologic workup revealed ANCA-positivity and vasculopathy on histopathology, most consistent with an atypical presentation of ANCA-positive vasculitis.  Upon initiation of immunosuppressive therapy, the patient's condition rapidly improved emphasizing the importance of early recognition of this condition.

Topics: Adult; Anorexia; Anti-Inflammatory Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Blister; Eyelid Diseases; Fatigue; Female; Graves Disease; Hemorrhage; Humans; Immunosuppressive Agents; Methylprednisolone; Pancytopenia; Pharyngitis; Prednisone; Propylthiouracil; Respiratory Insufficiency

The management of Graves' disease (GD) in children is associated with a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults, and severe propylthiouracil-induced adverse events (AEs) are an issue. Definitive treatments are effective, but they often result in permanent hypothyroidism and the need for lifelong T4 supplementation.. The objective of this study was to investigate the outcome of ATD treatment, identify significant predictors of a remission, and evaluate the AEs of ATDs in a large pediatric population of GD patients.. We retrospectively assessed the reports of 1138 children up to 18 years of age who had been newly diagnosed with GD at our institution between 1982 and 2006. Their median age at diagnosis was 16 years (range: 3-18 years), and there were 995 females and 143 males. All patients were initially treated with an ATD. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing ATD treatment and the absence of any relapses during the follow-up period.. Of the 1138 patients, 723 continued on ATD treatment, 271 underwent surgery or radioactive iodine therapy, and 144 dropped out. Of the 723 patients who continued on ATD treatment, ATD treatment was subsequently ongoing in 84 and was discontinued in 639 (median duration of treatment: 3.8 years; range: 0.3-24.8 years). Of the 639 patients who discontinued ATD treatment, 334 (46.2%) achieved a remission, 247 (34.2%) experienced a relapse, and 58 (8.0%) dropped out. The cumulative remission rate increased with the duration of ATD treatment up until five years. No significant predictors of a remission were identified. The overall incidences of AEs associated with methimazole and propylthiouracil were 21.4% and 18.8% respectively. There were no fatal AEs in our population. While most AEs (91.6%) occurred within the first three months of ATD treatment, 2.7% developed more than two years after the start of ATD treatment. Seven of the eight late-onset AEs were induced by propylthiouracil.. Long-term ATD treatment is a useful treatment option for GD in children.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Female; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Recurrence; Remission Induction; Retrospective Studies; Treatment Outcome

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Graves Disease; Humans; Lupus Nephritis; Male; Middle Aged; Peroxidase; Propylthiouracil

Agranulocytosis is a serious adverse effect of antithyroid drugs (ATDs) and mainly develops within three months after the start of uninterrupted ATD treatment. Agranulocytosis can also develop for the first time after interruption and subsequent resumption of the same ATD treatment. However, little is known with regard to agranulocytosis that develops after resumption of the same ATD treatment.. We investigated the characteristics of patients who developed agranulocytosis during their second or later course of ATD treatment.. A total of 81 patients at our hospital were diagnosed with ATD-induced agranulocytosis. In 14 of the cases (methimazole (MMI), n=10; propylthiouracil (PTU), n=4), the agranulocytosis developed for the first time in the context of the second or later course of treatment with the same ATD; those patients were designated the "resumed group." The 35 patients (MMI, n=28; PTU, n=7) who developed agranulocytosis during their first uninterrupted course of ATD therapy were designated the "first group.". The median total duration of ATD treatment before the diagnosis of agranulocytosis was 559 days (range 86-1775 days), and the median interval between the final day of the previous course and the first day of the course in which agranulocytosis was diagnosed was 916.5 days (range 153-8110 days). There were no cases in which agranulocytosis developed when treatment with the same ATD was resumed after discontinuation for less than five months. The difference between the start of ATD treatment in the course in which agranulocytosis was diagnosed and the time interval at which agranulocytosis was diagnosed was similar when comparing the first group and the resumed group (39 (20-98) days in the first group vs. 32.5 (21-95) days in the resumed group; n.s.). There were no significant differences between the groups in terms of granulocyte count at the time agranulocytosis was diagnosed, mortality rate, or the interval between the diagnosis of agranulocytosis and recovery.. When ATD treatment is resumed, patient follow-up is essential in order to monitor for the development of agranulocytosis.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antithyroid Agents; Drug Monitoring; Electronic Health Records; Female; Granulocytes; Graves Disease; Hospitals, Urban; Humans; Japan; Leukopoiesis; Male; Methimazole; Middle Aged; Propylthiouracil; Time Factors; Young Adult

A 48-year-old woman was diagnosed and treated for Graves' disease (GD) in 1999 but she discontinued treatment at her own discretion. In 2011, she was admitted to a local hospital for management of thyrotoxic crisis. Treatment with propylthiouracil, iodide potassium (KI), and prednisolone (PSL) was started, which resulted in improvement of the general condition. PSL and KI were discontinued before she was transferred to our hospital. At the local hospital, fasting plasma glucose (FPG) was 212 mg/dL and hemoglobin A1c concentration was 11.2%; intensive insulin therapy had been instituted. Upon admission to our hospital, FPG level was 122 mg/dL, but insulin secretion was compromised, suggesting aggravation of thyroid function and deterioration of glycemic control. The FPG level increased to 173 mg/dL; continuous glucose monitoring (CGM) identified dawn phenomenon at approximately 0400 h. Resumption of KI resulted in improvement of FPG and disappearance of the dawn phenomenon, as assessed by CGM. These results indicate that in patients with compromised insulin secretion, hyperthyroidism can induce elevation of not only postprandial blood glucose, but also FPG level due to the dawn phenomenon and that the dawn phenomenon can be alleviated with improvement in thyroid function. To our knowledge, no studies have assessed glucose variability by CGM before and after treatment of Graves' disease. The observations made in this case shed light on the understanding of abnormal glucose metabolism associated with Graves' disease.

Topics: Antithyroid Agents; Blood Glucose; Delayed Diagnosis; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Therapy, Combination; Female; Glycated Hemoglobin; Graves Disease; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Secretion; Insulin-Secreting Cells; Insulin, Long-Acting; Middle Aged; Monitoring, Ambulatory; Potassium Iodide; Propylthiouracil; Thyroid Crisis; Thyroid Gland; Treatment Outcome

The aim of this study was to evaluate clinical manifestations, laboratory findings, and effects of antithyroid drugs in younger children with Graves' disease (GD).. A retrospective and collaborative study.. Nine facilities in Chiba prefecture, Japan.. We analyzed 132 children and adolescents with GD. The subjects were divided according to the median age into a group of young children (group I, 4.1-12.4 years, n=66) and an adolescent group (group II, 12.5-15.9 years, n=66).. Clinical manifestations, laboratory findings, incidence of adverse effects, and remission rates 5 years after initial therapy were assessed.. The mean height SD score of group I (1.0) was higher than that of group II (0.3, p<0.001). The mean BMI SD score of group I (-0.7) was lower than that of group II (-0.3, p<0.05). The most common presentations were goiter, sweating, and hyperactivity in group I, whereas the most common presentations were goiter, sweating, and easy fatigability in group II. Hyperactivity was more frequent in group I (56.7%) than in group II (37.9%, p<0.05). Liver dysfunction appeared more often in group I (14.3%) than in group II (1.9%, p<0.05). There was no difference in the appearance of adverse effects between the two groups. The remission rate was slightly lower in group I (23.1%) than in group II (31.3%), but was not significant.. Thyrotoxicosis had more influence on the growth and liver function in younger children.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Female; Graves Disease; Growth; Humans; Japan; Liver; Male; Methimazole; Propylthiouracil; Retrospective Studies; Thyrotoxicosis; Treatment Outcome

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

Thionamides have various side effects.. The effectiveness of potassium iodide (KI) was evaluated in hyperthyroid patients who experienced side effects to thionamides.. An observational study was conducted at an academic medical center.. Among 1388 patients with Graves' hyperthyroidism treated with thionamides, 204 (14.7%) exhibited side effects, and 44 were treated with KI and followed for 17.6 (median; range, 8.6-28.4) years.. The primary endpoint was the initial response to KI, and the secondary endpoint was the long-term prognosis.. The conditions of 29 (65.9%) of the 44 patients were well controlled with KI alone (10-400 mg/d) (A group), and 17 (38.6%) patients went into remission after 7.4 (1.9-23.0) years. The conditions of 15 (34.1%) patients were not controlled with KI alone (B group), even at a high dose (100-750 mg/d), but seven patients (15.9%) were controlled with a combination of KI and low-dose thionamides, resulting in remission after 7.2 (2.8-10.8) years. The initial parameters did not predict the response to KI or long-term prognosis. However, remission occurred in 70.8% of the patients treated with less than 200 mg of KI, compared with 35.0% of the patients who required 200 mg or more of KI (P < .05).. Among hyperthyroid patients with thionamide-associated side effects, KI therapy was effective in two-thirds of cases, and about 40% of the patients experienced remission after KI therapy alone. The chance of remission was small among the patients refractory to KI.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Potassium Iodide; Propylthiouracil; Remission Induction; Retreatment; Treatment Outcome; Young Adult

Pulmonary manifestations of hyperthyroidism not only include pulmonary hypertension and hydrostatic pulmonary oedema, but also treatment/drug-associated pulmonary diseases have to be considered as an exclusion diagnosis. A 27-year-old woman with hypoxaemic respiratory failure under an arterial-venous extra-corporeal membrane oxygenator (AV-ECMO) was admitted to the intensive care unit (ICU). The patient had progressive dyspnoea with haemoptysis, palpitations and failure to thrive. The patient had Graves' disease treated previously with propylthiouracil (PTU). Diffuse alveolar haemorrhage is a non-specific syndrome characterised by evidence of diffuse alveolar damage, exclusion of infectious aetiology and progressively bloodier bronchoalveolar lavage (and/or 20% hemosiderin laden macrophages on cytological examination). PTU associated perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) vasculitis appears to be more common in younger female patients presenting with leukocytoclastic vasculitis, myalgias and arthralgias. The latter compared to non-drug associated ANCA vasculitis which are more common in older males with visceral involvement. PTU-induced ANCA vasculitis prognosis appears to be better compared to primary ANCA syndromes.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Graves Disease; Hemoptysis; Humans; Hypoxia; Peroxidase; Propylthiouracil; Respiratory Insufficiency; Thyrotoxicosis

Tubulointerstitial nephritis and uveitis syndrome is a disorder characterized by a combination of acute tubulointerstitial nephritis and uveitis. Immunoglobulin A nephropathy is defined by the presence of immunoglobulin A deposits in glomerular mesangial areas. In this report, we describe a rare case of tubulointerstitial nephritis and uveitis syndrome complicated by immunoglobulin A nephropathy and Graves' disease, which was successfully treated with corticosteroids. To the best of our knowledge, this is the first time such a case has been documented since tubulointerstitial nephritis and uveitis syndrome was first described.. A 64-year-old Japanese woman presented with tubulointerstitial nephritis and uveitis syndrome accompanied by immunoglobulin A nephropathy and Graves' disease. She had renal dysfunction, proteinuria, and hematuria. Two weeks after her admission, she developed anterior chamber uveitis. She received corticosteroids, resulting in significant clinical improvement.. Tubulointerstitial nephritis and uveitis syndrome is a relatively uncommon cause of tubulointerstitial nephritis. Clinicians should recognize that tubulointerstitial nephritis and uveitis syndrome with immunoglobulin A nephropathy can occur in the presence of Graves' disease. Additionally, this report may provide important clues in terms of the management of a concomitant case of these diseases.

Topics: Antithyroid Agents; Biopsy; Female; Glomerulonephritis, IGA; Glucocorticoids; Graves Disease; Humans; Kidney; Methylprednisolone; Middle Aged; Nephritis, Interstitial; Prednisolone; Propylthiouracil; Syndrome; Treatment Outcome; Uveitis

The main clinical manifestations of autoimmune thyroid diseases are Graves' disease (GD) and Hashimoto's thyroiditis (HT). Graves' disease is the cause of most cases of hyperthyroidism in childhood. Indications for radical therapy (surgery or 131I treatment) in children are still a matter of discussion, as sustained (sometimes very long) remission of GD is possible, while the radical therapy almost always leads to hypothyroidism. Spontaneous evolution from GD with hyperthyroidism to HT with hypothyroidism may also be observed.. The aim of the study was to analyze the clinical course of 6 cases of hyperthyroid girls with GD in whom a normalization of previously increased autoantibodies against thyrotropin (TSH) receptor (anti-TSHR) was observed together with a significant increase in autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg), with concomitant hypo- or euthyroidism but no recurrence of hyperthyroidism.. Patients' age at diagnosis ranged from 5.0 to 16.5 years. Two (2) patients had Turner syndrome, another one (1), diabetic, was on insulin therapy.. In all the girls, antithyroid drugs were administered and euthyroid state was achieved during the first 2.0-3.5 months of the treatment. Mild side effects were observed in only one case. The therapy was continued up to 1.5-4.0 years. Relapses during the therapy were observed in 2 cases. Up to now, no relapses have been observed for 0.5-7.5 years since the therapy withdrawal in 5 patients (1 patient was lost to follow-up), 2 patients are currently treated with levothyroxine due to hypothyroidism.. It seems that the prolonged pharmacotherapy with antithyroid drugs, followed by observation after remission of hyperthyroidism, may be an appropriate therapeutic option at least in some children with GD as they can be cured without radical therapy and the potential risks of such treatment.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Child; Child, Preschool; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Male; Methimazole; Propylthiouracil; Receptors, Thyrotropin; Remission Induction; Thyrotropin

Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit.. We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU).. Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8).. Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

To assess immunologic remission in patients with Graves' disease following euthyroid condition at the end of treatment with maintenance dose of PTU.. This is an intervention study using one-group pre-post design. Subjects were 25 Graves' disease patients visiting Metabolic Endocrinology Clinic at Dr. M.Djamil hospital Padang and met the inclusion criteria. Patients were given PTU treatment for 12 months. Blood samples were taken at the beginning and at the end of treatment to determine immunological remission reflected by differences in IL-4serum levels.. After maintenance therapy, we found significant decrease of T3 levels (2.29±0.57 nmol/L vs. 1.87±0.34 nmol/L, p<0.05), significant decrease of T4 levels (118.15±25.99 nmol/L vs. 94.15±23.76 nmol/L, p<0.05), significant increase of TSH levels (0.379±0.548 vs. 0.859±0.990, p<0.05) and significant decreased levels of IL-4 (12.23±5.74 vs. 3.84±0.42, p<0.05). The IL-4 level, however, did not decrease to the normal levels.. PTU administration in maintenance dose can significantly reduce thyroid hormonal parameter levels down to euthyroid condition, but cannot reduce immunological parameter (IL4) to normal limit.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Interleukin-4; Male; Propylthiouracil; Thyroxine; Triiodothyronine

Thyrotoxicosis is a rare clinical syndrome resulting from an exacerbation of hyperthyroidism, with various etiology and triggering factors. Its approach may be accomplished by blocking the synthesis of hormones, their secretion and/or inhibition of their peripheral action, besides treating the triggering factors. However, in refractory cases, plasmapheresis appears as an important option for treatment. We report a patient with Graves' disease who was admitted with thyrotoxicosis and signs of severe hepatotoxicity induced by propylthiouracil. Plasmapheresis was indicated, with the aim of rapidly reducing thyroid hormones in the preparation for total thyroidectomy.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Liver; Male; Plasmapheresis; Preoperative Care; Propylthiouracil; Thyroidectomy; Thyrotoxicosis; Thyroxine; Treatment Outcome

Thyrotoxic periodic paralysis is rare in Caucasian populations, but affects approximately 2% of East Asians with thyrotoxicosis (13% of males, 0.17% of females). The presentation is characterized by abrupt-onset hypokalemia and profound proximal muscular weakness, and commonly occurs after carbohydrate loading or exercise.. To raise awareness of this condition through the description of a typical case of thyrotoxic periodic paralysis; to remind readers that, despite intravascular hypokalemia, total body potassium is normal and that correction must be done with caution; to highlight the differences in treatment compared to familial hypokalemic periodic paralysis.. We describe the presentation of a 36-year-old Filipino man with a background history of Graves disease. Over-administration of intravenous potassium was narrowly averted in this case.. It may be important to check thyroid function in patients presenting with acute paralysis, especially those of Asian origin. In patients with thyrotoxic periodic paralysis, administration of potassium, with cardiac monitoring and a total dose of <50 mmol, limits the dysrhythmia risk. Patients are likely to benefit from the prescription of non-selective beta-blockers until they become euthyroid. In contrast to familial periodic paralysis, regular oral potassium supplementation is ineffective in thyrotoxic periodic paralysis, and acetazolamide precipitates, rather than prevents, attacks.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Graves Disease; Humans; Hypokalemia; Male; Muscle Weakness; Potassium; Propranolol; Propylthiouracil; Thyrotoxicosis

Optimal treatment of Graves' disease (GD) remains controversial. The authors retrospectively reviewed the surgical cases of GD at a single academic tertiary center.. Demographic, clinical, and surgical data were analyzed for all patients with GD undergoing thyroidectomy over 25 years, in 3 periods: 1985 to 1993 (n = 32), 1994 to 2002 (n = 91), and 2003 to 2010 (n = 177).. There were 300 patients with GD (85.7% women; mean age, 39.3 years; median length of follow-up, 24.6 months). Overall, perioperative morbidity occurred in 36 patients (12.0%), and there was no mortality. Thyroidectomy-specific morbidity was very low, and the incidental malignancy rate was 10.3%.. Surgical treatment of GD has a very high safety profile, with low perioperative and thyroidectomy-specific morbidity, even in patients with overt hyperthyroidism. Incidental malignancy in patients with GD is not uncommon.

Topics: Ablation Techniques; Adult; Antithyroid Agents; Drainage; Female; Graves Disease; Humans; Incidental Findings; Iodine Radioisotopes; Length of Stay; Male; Massachusetts; Methimazole; Operative Time; Postoperative Complications; Preoperative Care; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy

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

Agranulocytosis is a rare but serious complication of antithyroid drug (ATD) therapy. Characteristics of agranulocytosis have been reported in only a small number of patients.. We studied 754 cases of ATD-induced agranulocytosis reported over 30 years. The age distribution and sex ratio were compared with those in 12 503 untreated Graves' patients at Kuma Hospital. The annual number of new Graves' patients in Japan was estimated from the Japan Medical Data Center Data Mart-Pharmacovigilance health insurance receipt database.. Agranulocytosis developed within 90 days after starting ATD therapy in most patients (84.5%). The methimazole dose given at onset was 25.2 ± 12.8 mg/d (mean ± SD). The mean age was 43.4 ± 15.2 years, and the male to female ratio was 1:6.3. When compared with patients at Kuma Hospital, patients with agranulocytosis were older (P < .001) and more females (P < .0001). Of 211 patients with more than 1 granulocyte measurement before onset, 131 (62%) showed normal counts (>1000/μL) within 2 weeks before onset, demonstrating real sudden onset of agranulocytosis. In contrast, some of the 20 patients with more than 4 measurements showed gradual decreases in granulocyte counts. Analysis of physician reports for 30 fatal cases revealed that some deaths might have been prevented. The number of new Graves' patients treated with ATD was estimated at about 35 000 per year, and the incidence rate of agranulocytosis was 0.1% to 0.15% in Japan.. This is the largest study of agranulocytosis. Agranulocytosis tends to occur abruptly within 3 months after initiation of ATD therapy, although it develops gradually in some patients. Providing every patient with sufficient information on agranulocytosis is critical.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Agranulocytosis; Anemia, Aplastic; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Hospitals, Urban; Humans; Incidence; Japan; Leukopoiesis; Male; Methimazole; Middle Aged; Pancytopenia; Pharmacovigilance; Propylthiouracil; Sex Distribution

Propylthiouracil (PTU) is commonly used to treat hyperthyroidism. However, it is also associated with a number of adverse events. In particular, pulmonary complications, although rare, can be serious. Therefore, early detection is paramount. We herein describe a first case of PTU-induced bronchiolitis obliterans organizing pneumonia (BOOP) pathologically confirmed on a surgical lung biopsy. The present case shows that early detection coupled with the immediate withdrawal of PTU can lead to a successful resolution of symptoms and radiographic abnormalities without the need for corticosteroids. Although rare, PTU-induced BOOP should be considered in the differential diagnosis of pulmonary opacity in patients receiving PTU therapy.

Topics: Antithyroid Agents; Biopsy; Cryptogenic Organizing Pneumonia; Diagnosis, Differential; Female; Graves Disease; Humans; Lung; Middle Aged; Propylthiouracil; Tomography, X-Ray Computed

Antithyroid medications are the preferred therapy for the treatment of Graves' disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole (MMI) due to potential teratogenic concerns with MMI. This study was to determine the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or vehicle control (water) from stages 2 to 45. Treated embryos were examined for gross morphological defects, ciliary function, and gene expression by in situ hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping defects and shortening along the anterior-posterior axis. PTU exposure during gastrulation (stage 8-12.5) was identified as the critical period of exposure leading to left-right (LR) patterning defects. Abnormal cilia polarization, abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and aberrant expression of both Coco and Pitx2c were associated with abnormal LR symmetry observed following PTU exposure. PTU is teratogenic during late blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary-driven flow and disrupts the normal genetic program involved in LR axis determination. These studies have important implications for women taking PTU during early pregnancy.

Topics: Animals; Antithyroid Agents; Body Patterning; Cilia; Digestive System Abnormalities; Female; Gene Expression Regulation, Developmental; Graves Disease; Heart Defects, Congenital; Humans; Methimazole; Models, Animal; Pregnancy; Pregnancy Complications; Propylthiouracil; Teratogens; Time Factors; Triiodothyronine; Xenopus

Propylthiouracil (PTU) is recommended as a first-line antithyroid drug (ATD) during first trimester organogenesis in pregnancy because recent evidence suggests that methimazole (MMI) may be associated with congenital anomalies. However, PTU more commonly causes myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which usually occurs during prolonged treatment, compared with MMI. We report a case of MPO-ANCA-associated vasculitis in a 35-year-old woman with Graves'disease. Although her thyroid function could be maintained euthyroid by MMI, her ATD was switched to PTU because she wished to become pregnant. The patient presented with flu-like symptoms 8 days after starting PTU and developed hemoptysis and dyspnea at 22 days. Her MPO-ANCA titer was 21 ELISA units (EUs) before PTU treatment but increased to 259 EUs at 22 days after PTU treatment. Her clinical condition improved with the discontinuation of PTU and with immunosuppressive therapy. This case indicated that MPO-ANCA vasculitis occurred within several weeks after the initiation of PTU and that this side effect could be caused by the change from MMI to PTU. Thus, our clinical observation suggests that patients treated with PTU should be carefully monitored for MPO-ANCA titers and variable manifestations of MPO-ANCA-associated vasculitis regardless of the period of administration.

Topics: Abnormalities, Drug-Induced; Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Antithyroid Agents; Graves Disease; Humans; Male; Propylthiouracil; Thyrotoxicosis

Maternal thyrotoxicosis, predominantly secondary to Graves' disease, affects 0.2% of all pregnancies. The Endocrine Society guidelines recommend the use of propylthiouracil as a first-line drug for thyrotoxicosis in pregnancy because of associations between carbimazole or methimazole and congenital anomalies. However, recent studies have highlighted the risk of severe liver injury with propylthiouracil. Here, we report another case with multiple congenital anomalies following in utero exposure to carbimazole and review the literature to consider the risks and benefits of available pharmacological treatments for thyrotoxicosis in pregnancy.

Topics: Antithyroid Agents; Carbimazole; Ectodermal Dysplasia; Face; Female; Graves Disease; Humans; Infant; Lacrimal Apparatus Diseases; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotoxicosis; Thyroxine

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: Adult; Agranulocytosis; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Propylthiouracil; Treatment Outcome

Although antithyroid drug (ATD)-induced hematopoietic damage is a significant concern, it has not been comprehensively investigated.. Our objective was to describe the clinical features of ATD-induced hematopoietic damage.. This was a retrospective cohort study in Tokyo, Japan.. Between January 1983 and December 2002, 50,385 patients at Ito Hospital were diagnosed with Graves' disease. We retrospectively reviewed their medical, pathological, and laboratory records between January 1983 and December 2010.. Incidence and clinical features of ATD-induced agranulocytosis and pancytopenia were evaluated.. Of 55 patients with documented hematopoietic damage, 50 had agranulocytosis and 5 had pancytopenia. All of them received ATD, either methimazole (n = 51) or propylthiouracil (n = 4). Median intervals between initiation of ATD therapy and the onset of agranulocytosis and pancytopenia were 69 d (range, 11-233 d) and 41 d (range, 32-97 d), respectively. Either anemia or thrombocytopenia was also documented in seven of the 50 patients with agranulocytosis. Agranulocytosis was the first manifestation of hematopoietic damage in four of the five patents with pancytopenia. Hematopoietic damage recovered with supportive measures including granulocyte colony-stimulating factor (n = 37), steroids (n = 10), and other supportive measures (n = 8) in 54 patients, whereas the remaining patient died of complications from infection. This study failed to identify the risk factors for ATD-induced hematopoietic damage.. This study showed that ATD cause hematopoietic changes, which are occasionally severe and potentially fatal. The pathogenesis of agranulocytosis and pancytopenia might overlap, and additional studies are warranted to clarify this and to establish an optimal treatment strategy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Antithyroid Agents; Child; Cohort Studies; Female; Graves Disease; Hematopoiesis; Humans; Japan; Male; Methimazole; Middle Aged; Pancytopenia; Propylthiouracil; Retrospective Studies; Tokyo; Young Adult

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients with Graves' disease (GD) is linked with the use of anti-thyroid drugs (ATDs). We report the co-occurrence of AAV and GD in a patient that was independent of ATD therapy. A 38-year-old white male presented with systemic symptoms, palpitations, tremors, purpuric skin lesions, and digital pain. Physical examination and biological tests confirmed GD. He quickly developed multiple digital gangrenes and testicular pain/mass. Skin and testicular biopsies showed granulomatous vasculitis of the small- and medium-sized vessels, while his serum contained anti-proteinase-3 antibody.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Azathioprine; Biomarkers; Drug Therapy, Combination; Glucocorticoids; Graves Disease; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Myeloblastin; Propylthiouracil; Remission Induction; Skin; Testis; Treatment Outcome

Several reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy.. We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women.. We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations.. The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation.. In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Case-Control Studies; Female; Graves Disease; Humans; Infant, Newborn; Live Birth; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Prevalence; Propylthiouracil; Young Adult

The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by xenobiotic substances such as dioxin. After activation, it binds to dioxin response elements of DNA, thereby inducing transcription of a variety of xenobiotic metabolizing enzymes. To investigate whether AhR-activating substances accumulate in patients with endocrine disorders, we tested serum samples for AhR-stimulating activity.. Serum AhR-stimulating activity was evaluated by exposing the HepG2 cells transiently transfected with an AhR-responsive reporter plasmid to serum samples. On the basis of preliminary findings that implicated methimazole (MMI), wild-type and AhR-null mice were treated with MMI, and their plasma AhR-stimulating activities and thyroxine levels were quantified.. In 28 randomly chosen patients, 7 out of 10 Graves' disease patients exhibited increased serum AhR-stimulating activity. The increased activity did not correlate with thyroid hormone status. However, we hypothesized that it might be caused by MMI. Subsequent analyses revealed that in 25 of 26 MMI-treated Graves' patients, serum samples collected after the MMI treatment had significantly higher AhR-stimulating activity compared to samples obtained when the same patients were not on MMI. By contrast, serum AhR-stimulating activity was unchanged in samples from the seven patients on propylthiouracil (PTU) compared to serum taken before the PTU treatment. In vitro experiments demonstrated that an MMI metabolite 3-methyl-2-thiohydantoin, but not MMI, activated AhR. MMI increased plasma AhR-stimulating activities and reduced plasma thyroxine concentrations, in both wild-type and AhR-deficient mice.. Graves' patients taking MMI have increased serum AhR-stimulating activity, which is unrelated to thyroid hormone status, but correlates with MMI treatment. The AhR activation is likely caused by 3-methyl-2-thiohydantoin. Further studies are required to determine the potency of 3-methyl-2-thiohydantoin as an AhR activator and the significance of the differences between MMI and PTU observed in this study.

Topics: Adult; Aged; Aged, 80 and over; Animals; Female; Graves Disease; Hep G2 Cells; Humans; Male; Methimazole; Mice; Middle Aged; Propylthiouracil; Receptors, Aryl Hydrocarbon; Thiohydantoins

Topics: Adolescent; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Drug Dosage Calculations; Graves Disease; Hormone Replacement Therapy; Humans; Infant; Infant, Newborn; Practice Guidelines as Topic; Propylthiouracil; Thyroid Hormones; United Kingdom

Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function.. The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies.. DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of (125)I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH.. We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.

Topics: Animals; Graves Disease; Iodides; Methimazole; Propylthiouracil; Rats; Real-Time Polymerase Chain Reaction; RNA, Messenger; Symporters; Thyroid Gland; Thyrotropin

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Emergency Service, Hospital; Female; Graves Disease; Humans; IgA Vasculitis; Middle Aged; Pain; Propylthiouracil; Skin

A 43-year-old female with antiphospholipid syndrome and Graves' disease developed a cutaneous leukocytoclastic vasculitis associated with antineutrophil cytoplasmic antibody (ANCA) against myeloperoxidase (MPO-ANCA) and proteinase-3 (PR3-ANCA), whilst treated with propylthiouracil (PTU). The skin lesions were progressively resolved after withdrawal of PTU and treatment with oral steroids. Patch testing with PTU at 1%, 5%, and 10% in petrolatum was positive at 48 h. Despite positive ANCA titers after 1 year of follow-up, the patient maintains complete clinical remission. PTU is a common antithyroid drug, which has been known to induce ANCA-positive vasculitis. Although most patients with this rare side effect have a good outcome, some fatal cases have been reported. Therefore, patients treated with PTU should be carefully followed and monitored, not only for their thyroid state but also for early detection of potential serious complications of this drug. Early diagnosis and prompt cessation of PTU therapy are essential to improve the outcome. Also key aspects of PTU-induced ANCA-positive vasculitis are reviewed.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Lethal Dose 50; Propylthiouracil; Skin Tests; Vasculitis, Leukocytoclastic, Cutaneous

Treatment of Graves' disease during pregnancy with antithyroid drugs (ATDs) poses a risk of inducing hypothyroidism and, thus, development of a goiter to the fetus.. We report two patients referred to our department after discovery of a fetal goiter by ultrasound examination in the second trimester of pregnancy. The women receiving 400 mg/day propylthiouracil and 10 mg/day thiamizole, respectively, had thyrotropin and total thyroxine values within the normal reference range but a lowered free thyroxine level. Fetal blood sampling by cordocentesis revealed severe fetal hypothyroidism as the cause of goiter development. Reduction of maternal ATD dose and injection of levothyroxine intra-amniotically quickly reduced the goiter size, and both babies were born euthyroid and without goiters.. Two pregnant women with Graves' disease were overtreated with ATDs inducing iatrogenic goiter in the fetuses. Successful treatment with intra-amniotic levothyroxine injections rendered the babies euthyroid and nongoitrous at birth.. Correct interpretation of thyroid function tests during pregnancy in general--and during ATD therapy of Graves' disease in particular--is difficult. Awareness of pregnancy-related changes in maternal thyroid status, and a close teamwork among endocrinologists, obstetricians, and experts in fetal medicine, is pivotal in ensuring normal growth and development of the unborn child of these patients.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Propylthiouracil; Thyrotropin; Thyroxine

According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves' disease, discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves' disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb) levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however, this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.

Topics: Adolescent; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Japan; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Remission Induction; Retrospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Treatment Outcome

A 46-year-old woman with Graves' disease was admitted for anemia and thrombocytopenia. She had previously been treated with methimazole but she self-discontinued the treatment 6 months prior to admission. She was diagnosed with Evans syndrome associated with Graves' disease and treated with propylthiouracil without corticosteroids, which normalized her thyroglobulin level. Surprisingly, while Evans syndrome is characterized by frequent relapses, this patient has been in remission of Evans syndrome for approximately 4 years. The remission of Evans syndrome associated with Graves' disease in the absence of immunosuppressive therapy suggests that these 2 diseases have a common pathogenetic mechanism.

Topics: Anemia, Hemolytic, Autoimmune; Female; Graves Disease; Humans; Propylthiouracil; Thrombocytopenia; Treatment Outcome

Aplasia cutis congenita (ACC) has been observed after fetal exposure to the antithyroid drug methimazole (MMI), but not reported after propylthiouracil (PTU), the current antithyroid drug of choice during pregnancy. This occurrence has implications for patient information and causal research.. We describe a surviving term co-twin to a mother with hyperthyroidism exposed to PTU from conception to 34 weeks of gestation presenting with ACC at birth.. The association between PTU exposure and ACC is clinically relevant and allows speculation on the etiology. A similar mechanism to the classical MMI-induced ACC is postulated, unless a vascular etiology suggested by a vanishing twin or maternal hyperthyroidism itself is causal. Coincidence of PTU exposure and ACC seems unlikely.. ACC in a newborn after PTU exposure during pregnancy hitherto observed only after MMI strongly encourages further reports of similar cases that may remain clinically underdiagnosed or unreported. Such confirmation could have significant implications for maternal treatment of hyperthyroidism, common in women of childbearing age.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Diseases in Twins; Ectodermal Dysplasia; Female; Gestational Age; Graves Disease; Humans; Infant, Newborn; Maternal Exposure; Pregnancy; Pregnancy Complications; Propylthiouracil

Patients with severe Graves' orbitopathy often have hyperthyroidism that is difficult to treat and a high proportion of patients experience relapse of hyperthyroidism after a course of antithyroid drug (ATD) therapy of fixed duration. The aim of the study was to evaluate the feasibility of prolonged low-dose ATD therapy for attaining stable euthyroidism in patients with severe Graves' orbitopathy and hyperthyroidism.. We performed retrospective analyses of data collected during observation of a cohort of patients (n = 108) treated for severe Graves' orbitopathy and for hyperthyroidism using partial block with low-dose thionamide + replacement with levothyroxine (L-T4) for >2 years. The study was performed at a university hospital referral center for patients with severe Graves' orbitopathy.. The median duration of thionamide therapy was 80 months (25-75 percentiles: 55-115 months); 101 patients received methimazole (median: 5 mg/day) without side effects during prolonged therapy, and 7 propylthiouracil (median: 200 mg/day); median L-T4 dose was 0.1 mg/day. Ninety percent of patients remained euthyroid throughout the period of therapy, and 65% of them had thyroid stimulating hormone (TSH) receptor antibodies in serum within the assay reference interval at the last observation. Only four (3.7%) developed episodes of hyperthyroidism during stable therapy, and 94% had serum TSH within 0.1-4.0 mU/L at the last observation. One patient developed reversible cutaneous vasculitis after 6 years of propylthiouracil therapy.. Prolonged partial block plus replacement therapy with low-dose ATD + L-T4 keeps the majority of patients with severe Graves' orbitopathy and hyperthyroidism stable and euthyroid.

Topics: Adult; Antithyroid Agents; Biomarkers; Denmark; Drug Administration Schedule; Feasibility Studies; Female; Graves Disease; Graves Ophthalmopathy; Hormone Replacement Therapy; Hospitals, University; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Retrospective Studies; Severity of Illness Index; Thyroxine; Time Factors; Treatment Outcome

Little information is available about changes in body weight and body mass index in children before, during, and after treatment for Graves' disease (GD).. Our objective was to examine changes in body weight after treatment for GD in children as related to clinical features.. The medical records of 43 pediatric patients with GD [35 girls and eight boys, aged 4.0-18.5 (mean 10.9) yr] were examined. Patients were included if clinical data were available for 1 yr before and after the diagnosis of GD.. Weight, height, body mass index (BMI) z-scores, and thyroid hormone levels were assessed.. Overall, patients presented with an average BMI z-score of -0.02 ± 1.05 that was not different from the normal population (P = 0.921) or their premorbid values (P = 0.07). However, in the subset of patients who were initially overweight or obese in the premorbid state, the BMI decreased significantly during the development of hyperthyroidism (P < 0.05). After initiation of treatment, patients gained significant amounts of weight over the first 6 months leading to elevated BMI z-scores (P < 0.0001), and elevations in BMI persisted in about 25% of the patients.. Excessive weight gain within 6 months of treatment is seen in children treated for GD, and the gain in weight can persist.

Topics: Adolescent; Aging; Antithyroid Agents; Body Mass Index; Body Weight; Child; Child, Preschool; Cohort Studies; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Sex Characteristics; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Weight Gain

Propylthiouracil (PTU) is an antithyroid drug which is known to cause drug-induced vasculitis. PTU is implicated in 80-90% of cases of anti-neutrophil cytoplasm circulating antibody (ANCA)-associated vasculitis caused by anti-thyroid drugs which induce ANCA production. Sweet's syndrome is characterized by fever, leucocytosis, neutrophilia and the sudden onset of painful skin lesions. The pathology of the disease is still unclear. Cytokine dysregulation including interleukin-6 and endogenous granulocyte colony-stimulating factor (G-CSF) are thought to play a role in the pathogenesis of Sweet's syndrome. PTU and G-CSF are known to cause Sweet's syndrome and other neutrophilic dermatosis. The presence of ANCA can have a diagnostic value in Sweet's syndrome. Systemic corticosteroids are the first-line therapy for both diseases. Here we report a female patient with Graves' disease who developed ANCA and Sweet's syndrome after using PTU and G-CSF.

Topics: Adult; Agranulocytosis; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Neutropenia; Propylthiouracil; Skin; Sweet Syndrome; Thyroid Gland

A 58-year-old woman was referred to our hospital because of liver dysfunction. Her serum levels of AST (619 IU/l) and ALT (603 IU/l) had increased. Histological findings in the liver biopsy were compatible to autoimmune hepatitis (AIH), and the diagnosis of AIH was confirmed by the diagnostic criteria. She was admitted to a nearby hospital 3 years ago, and diagnosed with Graves' disease. She received methimazole (MMI) at first, which was discontinued due to liver injury in one month, then propylthiouracil (PTU) was administered. One year later, transaminase increased and was decreased by stopping PTU administration. PTU was restarted after her transaminase decreased, but a recurrence of hepatotoxicity was observed, and she was referred to our hospital. Oral prednisolone decreased liver function immediately. In this case, PTU-induced liver injury was suspected as a possible trigger of AIH. While PTU remains a commonly used drug in the treatment of hyperthyroidism, severe liver injury is reported in some cases. If liver injury is observed in patients treated with PTU, rechallenge is not recommended in order to avoid severe hepatotoxicity.

Topics: Antithyroid Agents; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Middle Aged; Propylthiouracil

To describe a case of propylthiouracil-induced lupus, complicated with antiphospholipid syndrome and acute ischemic stroke.. Case report.. Academic medical center.. A 27-year-old man with a diagnosis of Graves disease developed multiple ischemic strokes 2 weeks after starting treatment with propylthiouracil. Thyrotoxicosis and abnormal hypercoagulable and rheumatological profiles were remarkable, with prolonged partial thromboplastin time, elevated anticardiolipin antibody level, and positive antinuclear antibody, lupus anticoagulant, Sjögren antibody, and anti-double-stranded DNA antibody test results, which were more than 8-fold greater than normal values. No clinical manifestations of systemic lupus erythematosus were present.. Discontinuation of propylthiouracil and treatment with radioactive iodine.. Hyperthyroidism resolved and anti-double-stranded DNA antibodies returned to normal levels. Eventually, antiphospholipid syndrome was diagnosed. He was treated with oral anticoagulation and remained asymptomatic for 1 year of follow-up.. In this young man with Graves hyperthyroidism, treatment with propylthiouracil was associated with transient autoimmune reactions suggestive of drug-induced lupus, antiphospholipid syndrome, and acute ischemic stroke.

Topics: Adult; Antiphospholipid Syndrome; Antithyroid Agents; Brain Ischemia; Follow-Up Studies; Graves Disease; Humans; Lupus Erythematosus, Systemic; Male; Propylthiouracil; Stroke

Propylthiouracil (PTU) is known to induce myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves disease (GD). Previously, we showed that serum MPO-ANCA were frequently seen in patients with GD treated with PTU. In this study, we analyzed 13 patients with positive MPO-ANCA examining a long-term clinical consequence of these patients as well as antibody titers during 5.6 +/- 3.0 years. PTU therapy was continued in 8 patients and discontinued in 5 patients. Antibody titers decreased in 7 of 8 patients who discontinued PTU therapy but remained positive in 5 patients 5 years after PTU withdrawal. The initial MPO-ANCA levels were significantly higher in those antibody titers remained positive for longer than 5 years (n=5) than in those titers turned to be negative within 5 years after PTU withdrawal (n=3) (203 +/- 256 EU and 22 +/- 2 EU, respectively, P=0.04), but there were no significant differences in age, gender, duration of PTU therapy or dosage of PTU. Among 5 patients who continued PTU therapy, 2 patients with initially low MPO-ANCA titers turned to having negative antibody. No patients had new symptoms or signs of vasculitis throughout the follow-up periods. The long-term follow-up study suggests that higher MPO-ANCA levels remain positive for years after PTU withdrawal but are rarely associated with vasculitis.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Statistics, Nonparametric

Multidrug resistance 1 gene is responsible for the resistance of a large variety of drugs in human cells. We tried to evaluate this in the present study in thyroid stimulant hormone receptor antibody positive subjects.. In study enrolled 23 female and 10 male subjects. Hyperthyroid subjects were treated with PTU and remission was assured between 6-12 months. Blood samples were collected before the start of this treatment. Permission for this study was taken from the patients and the local ethical committee.. Serum F-T3, F-T4 levels in Graves subjects were markedly high, whereas TSH levels were markedly low than normal range. We also found that with increased age of the Graves' subjects, MDR-1 gene expression decreased. There was also a direct correlation between blood MDR-1 gene expression and TSH-R Ab levels in patients with Graves's disease. We observed that the duration of being euthyroid was lengthened with the elevation of MDR-1 gene expression. There was a direct correlation between blood MDR-1 gene expression levels and ultrasonografic size of thyroid gland.. As a result, raised blood MDR-1 gene expression levels in patients with Graves-Basedow disease may be associated with the activity of the disease and the resistance to its treatment. The more blood MDR-1 expression increases the more the duration of being euthyroid increases.

Topics: Adult; Age Factors; ATP Binding Cassette Transporter, Subfamily B, Member 1; Drug Resistance; Female; Gene Expression; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Middle Aged; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Ultrasonography

ANCA is detected in several vasculitic diseases, including drug-induced systemic vasculitis: propylthiouracil (PTU), hydralazine, minocycline, penicillamine, allopurinol, procainamide, carbimazole, thiamazole, clozapine and phenytoin. All have been known to induce ANCA positive vasculitis in adult patients.. To study the clinical manifestation, renal pathology and outcome of patients with ANCA positive vasculitis associated with propylthiouracil treatment in Siriraj Hospital.. Retrospective study in 7patients with Graves' disease who were treated with propylthiouracil and developed ANCA-positive glomerulonephritis between 2000-2008.. Seven cases with Graves' disease who received propylthiouracil whose ages were 43 +/- 14 years. The duration of propylthiouracil treatment was 68.5 +/- 39 months and the doses were 50-150 mg per day. Six cases had P-ANCA and one case had C-ANCA in the serum. Proteinuria ranged from 0.49-2.9 gram per day. Mean serum creatinine was 2.05 mg/dl with creatinine clearance of 44 +/- 35 ml/min. The propylthiouracil was withdrawn in every patient and corticosteroid was administered. Renal remission was found until 1 year of follow-up.. ANCA positive glomerulonephritis associated with propylthiouracil is not uncommon. The average onset of glomerulonephritis is 2 years or more. The propylthiouracil dosage was not necessary high. Urinalysis and other glomerulonephritis symptoms should be screened for early diagnosis and appropriate treatment in patients treated with PTU.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Graves Disease; Humans; Kidney Diseases; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome

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: Adult; Antithyroid Agents; Cordocentesis; Female; Fetal Diseases; Goiter; Graves Disease; Hormone Replacement Therapy; Humans; Hypothyroidism; Injections, Intramuscular; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroxine; Ultrasonography

Drug-induced vasculitis is a known side effect of prolonged treatment with several drugs. It is characterized by inflammation and cellular infiltration of small vessels and presence of anti-neutrophil cytoplasmic antibodies (ANCA). Propylthiouracil and hydralazine (anti-thyroid and antihypertensive drugs) are the drugs most commonly associated with drug-induced vasculitis. Small vessels of the skin are most frequently affected, while affection of the vessels of the kidneys, central nervous system and lungs make the diagnosis life-threatening. When drug-induced vasculitis is suspected, quick and punctual diagnostic procedure should be carried out to exclude systemic manifestations. Treatment comprises of elimination of the causative drug, which is sufficient in most cases, but sometimes oral or parenteral glucocorticoids and even immunosuppressants are indicated. A case is presented of an 18-year-old male with a history of Graves disease treated with standard dose of propylthiouracil. Approximately 2.5 years after starting therapy he noticed formation of shallow skin ulcerations on both of his ear lobes and elbows. Detailed hospital work-up found high titers of perinuclear-staining anti-neutrophil cytoplasmic antibodies/myeloperoxidase (pANCA/MPO, 1:1024). Biopsy of the affected skin revealed leukocytoclastic vasculitis. Additional tests excluded systemic vasculitis. The patient was diagnosed with propylthiouracil-induced vasculitis, a form of drug-induced vasculitis. Propylthiouracil was discontinued and the skin lesions disappeared over time without the need of any specific therapy (such as glucocorticoids).

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Croatia; Graves Disease; Humans; Male; Propylthiouracil; Skin Diseases, Vascular

Thionamide-induced agranulocytosis in pregnancy is a rare event that poses unique therapeutic challenges.. A 37-year-old woman developed agranulocytosis while taking propylthiouracil in the third trimester. After she took broad-spectrum antibiotics and discontinued propylthiouracil, her neutrophil counts recovered. She was initially managed expectantly but later underwent an uncomplicated total thyroidectomy at 35 weeks of gestation because of patient choice coupled with worsening thyrotoxicosis.. In circumstances in which thionamides are contraindicated, management options of hyperthyroidism in pregnancy are limited. The proximity to term in the third trimester makes expectant management an attractive approach when maternal thyroid indices are stable, allowing for a choice of postpartum therapies without the worry of fetal implications. However, this strategy carries risks, and thyroidectomy in the third trimester can be a safe alternative.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Trimester, Third; Propylthiouracil; Thyroidectomy

Propylthiouracil (PTU) is the mainstay of antithyroid drug therapy. Previous studies reported antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis in patients treated for Graves' disease. ANCA has been associated with either PTU or to the disease itself. However, this issue has not been investigated in toxic multinodular goitre (TMNG). The aim of this study was to evaluate the frequency of ANCA positivity in both TMNG and Graves' disease patients treated with PTU, and to investigate the clinical importance of this issue.. We studied the presence of ANCA in 46 patients treated with PTU (30 Graves' disease, 16 TMNG). Two years after the discontinuation of PTU, ANCA was re-evaluated in 29 patients (18 Graves' disease, 11 TMNG).. By indirect immunofluorescence, 19 of the 46 patients (41.3%) on PTU treatment were ANCA positive [13 of the 30 patients in Graves disease (43.3%), six of the 16 patients in TMNG (37.5%)]. There was no statistically significant difference between Graves' disease and TMNG patients for ANCA positivity (p = 0.362). ANCA positivity was not related to gender, thyroid autoantibodies, alanine aminotransferase, aspartate aminotransferase, neutrophil count and PTU dose. Two years after withdrawal of PTU treatment, 10.3% of patients continued to have positive ANCA (p < 0.0001). Signs and symptoms of vasculitis could not be detected in any of the ANCA-positive patients.. Our study suggests that PTU but not Graves' disease itself is the most important factor for ANCA development. The frequency of ANCA positivity is 41.3% in our country which was not different in Graves' disease and TMNG patients. The dose of PTU and ethnic factors are not associated with ANCA positivity. After cessation of PTU, vasculitis did not develop during the 2 years of follow-up despite positive ANCA.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests; Young Adult

Development of antineutrophil cytoplasmic antibody (ANCA) during therapy with propylthiouracil (PTU) is not uncommon and PTU-induced ANCA-positive vasculitis is also reported. The aim of this study was to assess the presence and clinical significance of ANCA positivity in Graves' patients treated with PTU. Newly diagnosed Graves' disease patients (prospective group, n = 58) were evaluated before and during therapy with PTU to investigate the development of ANCA positivity. ANCA positivity is also investigated in previously diagnosed Graves' patients who had already been receiving PTU treatment (cross-sectional group, n = 51). Comparisons with Hashimoto thyroiditis (n = 55) and toxic nodular goitre (n = 20) patients, and healthy control subjects (n = 20) were carried out to define the possible influence of hyperthyroidism and/or thyroid autoimmunity on ANCA positivity. At baseline evaluation, ANCA was negative in all newly diagnosed Graves' patients. Only 28 of the 58 patients in prospective group completed 2 years of follow-up which occurred at 3-month intervals. ANCA positivity was detected 32.1% (n = 9) in a mean period of 11.7 +/- 6.1 months in prospective group. Only two (3.9%) patients in a cross-sectional group had ANCA positivity in a mean treatment period of 7.6 +/- 4.6 months. None of the patients with ANCA positivity developed symptoms and signs related to vasculitis. None of the patients with Hashimoto thyroiditis and toxic nodular goitre, and healthy control subjects had ANCA positivity. PTU therapy is associated with asymptomatic production of ANCA in a time-dependent manner, which mostly disappears after discontinuation of therapy. Hyperthyroidism or autoimmunity per se does not appear to have effect on development of ANCA positivity.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Cross-Sectional Studies; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Prospective Studies; Young Adult

Topics: Antithyroid Agents; Exanthema; Female; Fever; Graves Disease; Humans; Middle Aged; Oral Ulcer; Propylthiouracil; Vasculitis

Topics: Antithyroid Agents; Child; Drug Utilization; Graves Disease; Humans; Liver Failure; Propylthiouracil; United States; United States Food and Drug Administration

Propylthiouracil is one of the thionamides used in the treatment of Graves' disease. The drug has serious side effects and long-term treatment might be needed to achieve remission. We designed this study to evaluate the clinical and thyroid Doppler characteristics that might predict time to remission and treatment failure in propylthiouracil treated Graves' patients.. 26 patients, among 134 presenting to our university hospital outpatient clinic between Feb -July 2007 and with first time diagnosis of clinical thyroid dysfunction, were clinically and ultasonographically diagnosed with Graves' disease. Doppler parameters, serum thyrotropin, free thyroxine and free triiodothyronine were measured at the beginning of the study and thyroid studies were repeated every 4 weeks until remission. Propylthiouracil 300 mg/day was started for each patient at the time of diagnosis and doses were titrated according to repeat thyroid studies. Patients were treated and followed up for 18 months.. Treatment failure was associated with smoking (P = 0.001) and male gender (P= 0.037). Stepwise multiple regression analysis revealed that age, free thyroxine and superior thyroid artery flow rate were predictors of time to remission (P= 0.001, 0.002 and 0.003, respectively).. The time to remission in Graves patients treated with propylthiouracil can be predicted using age, serum free thyroxine and superior thyroid artery flow rate. This may help early consideration of alternative treatment for the patients requiring prolonged treatment for remission or for those who fail medical treatment. This would decrease unnecessary, long-term propylthiouracil exposure with its serious side effects.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Male; Propylthiouracil; Sex Factors; Smoking; Thyroxine; Treatment Failure

Topics: Adult; Agranulocytosis; Antibodies, Antineutrophil Cytoplasmic; Bone Marrow Diseases; Female; Graves Disease; Humans; Plasma Cells; Propylthiouracil; Vasculitis

Topics: Adult; Antithyroid Agents; Autoantibodies; Congenital Hypothyroidism; Female; Graves Disease; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Receptors, Thyrotropin; Thyroxine

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Glomerulonephritis; Graves Disease; Humans; Propylthiouracil; Takayasu Arteritis

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Societies, Medical; United States; United States Food and Drug Administration

Topics: Adult; Anti-Arrhythmia Agents; Antithyroid Agents; Anxiety; Arrhythmias, Cardiac; Dyspnea; Graves Disease; Humans; Hypokalemic Periodic Paralysis; Malaysia; Male; Methimazole; Muscle Weakness; Neurologic Examination; Potassium; Propranolol; Propylthiouracil; Sleep Initiation and Maintenance Disorders; Tremor; Weight Loss

A 35-year-old man with multiple bone fractures underwent an emergency operation. On arriving at the operating room, his heart rate was 160 beats x min(-1), and blood pressure was 100/50 mmHg. We anesthetized him with oxygen, sevoflurane, fentanyl and remifentanil. We suspected hypovolemia, and treated him with crystalloid and transfused red cells and fresh frozen plasma so that heart rate and blood pressure could be stabilized. Tachycardia of 140 beats x min(-1) persisted, and landiolol was continuously administered at a rate of 5-10 mg x hr(-1) after a 2.5 mg bolus injection. Heart rate became controlled around 120 beats x min(-1) without hypotension during anesthesia. Finally, we noticed thyroid crisis in this case, and diagnosed it with laboratory data after operation. We should be aware that atypical tachycardia is caused by thyroid crisis.

Topics: Adult; Anti-Arrhythmia Agents; Emergencies; Fractures, Bone; Graves Disease; Humans; Intraoperative Complications; Iodine Compounds; Male; Morpholines; Orthopedic Procedures; Propylthiouracil; Tachycardia; Thyroid Crisis; Urea

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

Propylthiouracil (PTU) can induce anti-myeloperoxidase (MPO-ANCA) positive vasculitis. We performed a cross-sectional study to estimate the prevalence of MPO-ANCA in patients with childhood onset Graves' disease (GD) receiving PTU and to assess the relationship between ANCA and clinical manifestations of vasculitis. We studied 60 patients (59 girls and one boy) between 7.3 and 25.0 years of age (mean +/- SD, 14.71 +/- 4.49). GD, diagnosed at the age of 3.0 to 14.5 years (11.3 +/- 2.48), was designated as: newly diagnosed, on PTU therapy, and after PTU discontinuation in 4, 50 and 6 patients, respectively. Manifestations of vasculitis were noted and the patients were tested for MPO-ANCA, antinuclear antibodies, blood urea nitrogen, creatinine and urine analysis. Twenty-six patients (43.3%) reacted positively for MPO-ANCA, 23 were on PTU therapy (0.42 to 6.00, median 3.00 years) and three had discontinued PTU. There were 34 (56.7%) ANCA-negative patients and 27 patients on PTU therapy (0.25 to 5.17, median 1.00 years, p = 0.012). Vasculitis presented in 16 patients (26.7%), all of whom were receiving PTU at the time of the study. The percentage of vasculitis among MPO-ANCA positive patients was 27.6% more than in the negative group, p = 0.017. PTU was discontinued in patients with vasculitis and positive for MPO-ANCA. Our findings show a high prevalence of MPO-ANCA positivity and a significantly higher percentage of vasculitis among these patients, suggesting that patients taking PTU should be closely observed for the appearance of MPO-ANCA and signs of vasculitis, especially patients GD who have been treated for a long time.

Topics: Adolescent; Adult; Age of Onset; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Prevalence; Propylthiouracil; Vasculitis

The present study was undertaken to evaluate the change of circulating visfatin, C-reactive protein (CRP) concentrations, and insulin sensitivity in patients with hyperthyroidism. We studied 19 adult patients (14 women and 5 men aged 32.6 +/- 1.8 years) with hyperthyroidism due to Graves disease and 19 age- and sex-matched euthyroid controls (17 women and 2 men aged 36.7 +/- 2.7 years). All hyperthyroid patients were treated with 1 of 2 antithyroid drugs and were reevaluated after thyroid function normalized. Before antithyroid treatment, the hyperthyroid group had significantly higher visfatin plasma concentration (mean +/- standard error of the mean, 20.7 +/- 1.8 ng/mL) than the control group (16.2 +/- 1.3 ng/mL, P = .044); but the visfatin level dropped significantly after treatment (12.0 +/- 1.4 ng/mL, P < .001). The reciprocal index of homeostasis model assessment of insulin resistance (HOMA-IR) in the hyperthyroid group was higher before treatment (2.06 +/- 0.26 mmol mU/L*L) than after treatment (1.21 +/- 0.16 mmol mU/L*L, P = .027). There was no significant difference in serum glucose, high-sensitivity CRP, and insulin levels between hyperthyroid and control groups and in the hyperthyroid group before and after treatment. Body mass index-adjusted visfatin levels were significantly elevated in the hyperthyroid group. Pearson correlation revealed that visfatin, glucose, insulin, and HOMA-IR values positively correlated with triiodothyronine and free thyroxine levels. However, visfatin did not correlate with insulin and HOMA-IR levels. The results indicated that plasma visfatin concentration was elevated in hyperthyroidism due to Graves disease, but serum CRP levels were not. Plasma visfatin levels were not associated with indicators of insulin resistance in hyperthyroid patients.

Topics: Adult; Antithyroid Agents; Blood Glucose; C-Reactive Protein; Carbimazole; Cytokines; Female; Graves Disease; Humans; Insulin; Insulin Resistance; Male; Nicotinamide Phosphoribosyltransferase; Propylthiouracil; Statistics, Nonparametric; Thyrotropin; Thyroxine; Triiodothyronine

Thionamide induced agranulocytosis is associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) in some patients. This poses a particular challenge when it occurs during pregnancy.. To report a case of a 31-year-old woman with Graves' disease who presented at 11 weeks gestation with propylthiouracil induced agranulocytosis.. After cessation of propylthiouracil the patient developed recurrent thyrotoxicosis, and underwent an elective subtotal thyroidectomy at 23 weeks gestation.. The patient required postoperative thyroxine replacement therapy. Subsequent pregnancy was uneventful and she delivered a healthy baby boy at 41 weeks gestation. As part of our routine work up for agranulocytosis we measured C-ANCA levels, which were significantly elevated.. This case highlights the association of propylthiouracil induced ANCA positivity and agranulocytosis. Second trimester subtotal thyroidectomy was safe and effective in treating this pregnant patient's thyrotoxicosis.

Topics: Adult; Agranulocytosis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Propylthiouracil; Term Birth; Thyroidectomy; Thyrotoxicosis

The optimal treatment for Graves' disease in children is controversial. Antithyroid medications are often used initially, but many children eventually require alternative therapies. We evaluated predictors of remission after 2 years of antithyroid medication use.. We prospectively studied children who had Graves' disease and were treated with antithyroid medications. We compared children who achieved remission after 2 years with those who had persistent disease to determine which variables were associated with remission; multiple logistic regression and binary recursive partitioning analyses were used to evaluate interactions among predictive variables.. Of 51 children who completed the study, 15 (29%) achieved remission. Children who achieved remission had lower thyroid hormone concentrations at presentation than those with persistent disease (free thyroxine: 6.17 +/- 3.10 vs 9.86 +/- 7.54 ng/dL; total triiodothyronine: 431 +/- 175 vs 561 +/- 225 ng/dL). Children who achieved remission were also more likely to be euthyroid within 3 months of initiating propylthiouracil (82% vs 29%). Binary recursive partitioning analysis identified rapid achievement of euthyroid status after initiation of propylthiouracil, lower initial triiodothyronine, and older age as significant predictors of remission. CONCLUSIONS; Thyroid hormone concentrations at diagnosis, age, and initial response to propylthiouracil can be used to stratify patients according to the likelihood of remission after 2 years of antithyroid medication use. These data provide a useful guide for clinical decision-making regarding Graves' disease in children.

Topics: Adolescent; Age Factors; Antithyroid Agents; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graves Disease; Humans; Logistic Models; Male; Multivariate Analysis; Predictive Value of Tests; Propylthiouracil; Prospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Thyroid Function Tests; Treatment Outcome

Topics: Female; Graves Disease; Humans; Middle Aged; Pain; Postmenopause; Propylthiouracil; Remission Induction; Thyroiditis

Topics: Acetaminophen; Adenoidectomy; Adenoids; Analgesics, Non-Narcotic; Analgesics, Opioid; Antihypertensive Agents; Antithyroid Agents; Atenolol; Child; Fentanyl; Follow-Up Studies; Graves Disease; Humans; Hydrocodone; Hypertension; Male; Palatine Tonsil; Propylthiouracil; Sleep Apnea Syndromes; Tachycardia; Thyroid Gland; Tonsillectomy

We describe an unusual case of a patient with eosinophilic pleural effusion (EPE) associated with long-term propylthiouracil (PTU) administration. A 43-year-old woman was admitted to our hospital after complaining of chest pain. She had had Graves' disease, which had been treated with PTU for 11 years. Right-sided pleural effusion was detected and the result of thoracentesis confirmed an EPE. The patient's detailed medical evaluation failed to reveal any other cause of EPE. PTU was terminated since it was thought to be the cause. Despite withdrawal of the medication, however, the pleural effusion persisted for 6 weeks, and steroid therapy was planned for 15 days in decreasing dosages. During the control visit 10 days after the initiation of steroid therapy, no pleural effusion was observed, and the steroid was discontinued. Rechallenge with PTU produced recurrent pleural effusion. Therapy with PTU was again terminated, and treatment with methimazole and a brief course of low-dose corticosteroids were begun. Chest radiography revealed disappearance of the effusion within 10 days and it did not recur during a 1-year follow-up. To our knowledge, there is only 1 other case in the English-language literature describing EPE caused by PTU. Our report is of particular importance because it describes the development of that disorder in the 11th year of PTU treatment. It also shows that steroid therapy can be effective in treating drug-induced EPE.

Topics: Adrenal Cortex Hormones; Adult; Antithyroid Agents; Eosinophilia; Female; Graves Disease; Humans; Pleural Effusion; Propylthiouracil; Treatment Outcome

Propylthiouracil (PTU) has been held responsible for diffuse alveolar hemorrhage (DAH) with positive antineutrophil cytoplasmic antibody (ANCA) and capillaritis. We describe a case of a 23-year-old pregnant female with Grave's disease treated with PTU who presented with flu-like symptoms and progressive dyspnea. Open lung biopsy showed DAH without evidence of capillaritis. All serologies were negative. Five days after PTU withdrawal and intravenous steroid therapy, the patient improved dramatically. She remained symptom free without relapse 9 months after the episode. To the best of our knowledge, this is the first reported case of PTU-related alveolar hemorrhage with negative serologic markers and without capillaritis.

Topics: Adult; Antithyroid Agents; Biomarkers; Female; Graves Disease; Hemorrhage; Humans; Lung; Lung Diseases; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil

A 34-year-old woman with hyperthyroidism, who had been previously treated with propylthiouracil (PTU) is reported. She was admitted because of clumsiness in her left hand and abnormal behavior. A neurological examination demonstrated impairment of higher cortical function, and weakness and hyperreflexia of the left leg. An MRI scan with gadolinium enhancement showed pachyleptomeningeal thickening in the right frontoparietal lobe. Blood tests revealed a high MPO-ANCA titer of 122 EU (normal:<10 EU). After steroid administration, the neurological symptoms and the MRI findings improved markedly. This is the first report of PTU-induced cerebral pachyleptomeningitis associated with a high serum MPO-ANCA titer.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arachnoid; Dexamethasone; Female; Glucocorticoids; Graves Disease; Humans; Magnetic Resonance Imaging; Meningitis; Peroxidase; Pia Mater; Prednisolone; Propylthiouracil

Propylthiouracil (PTU) has been known to induce myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis. Our previous study indicated that the increase of avidity of MPO-ANCA might be associated with the occurrence of clinical vasculitis in patients with PTU-induced ANCA. The current study aimed to follow-up the avidity and titre of anti-MPO antibodies in sequential sera from patients with PTU-induced ANCA-associated systemic vasculitis (AASV).. Six patients with PTU-induced vasculitis were enrolled in the current study. Serial sera in both active phase and in remission were collected. MPO-ANCA avidity was assessed by antigen-inhibition enzyme-linked immunosorbent assays (ELISAs), and avidity constant (aK) was determined as the reciprocal value of the MPO molar concentration in the liquid phase resulting in 50% inhibition of anti-MPO antibody binding to MPO in solid phase ELISA. Titres of MPO-ANCA were determined by using serial serum dilutions in MPO-ELISA.. After cessation of PTU and initiation of immunosuppressive therapy, the avidity and titre of MPO-ANCA decreased significantly during follow-up in sera from all the patients, and the avidity decreased much more quickly than the titres.. Our study indicates that avidity of anti-MPO antibodies might be more closely associated with clinical vasculitis than titre.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antibody Affinity; Antigen-Antibody Reactions; Antithyroid Agents; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glomerulonephritis; Graves Disease; Humans; Peroxidase; Propylthiouracil; Vasculitis; Withholding Treatment

Thyroid dysfunction is recognized in the newborns of mothers affected by Graves' disease during pregnancy. We describe the development of concurrent hyperthyroidism and hypothyroidism in the twin infants of a mother with Graves' disease diagnosed during pregnancy.

Topics: Adult; Antithyroid Agents; Congenital Hypothyroidism; Diagnosis, Differential; Drug Administration Schedule; Female; Graves Disease; Humans; Infant, Newborn; Infant, Premature; Male; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Hormones; Thyroxine; Twins

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. The thyroglobulin (Tg) is a major autoantigen for GD. The human Tg gene polymorphism has specific features that make it important in GD.. This study investigated whether Tg single nucleotide polymorphisms (SNPs) relate to GD development in a Taiwanese population.. This was a case-control association study.. We enrolled 215 Taiwanese patients with GD and 141 controls from the Endocrine Clinic of Kaohsiung Medical University Chung-Ho Memorial Hospital. This study investigated the association between gene polymorphism and relapse of hyperthyroidism after medication was discontinued in three GD patient groups and a control group. We also compared clinical and laboratory data obtained from patients with the three different genotypes with the three different Tg SNPs (E10SNP158, E12SNP, and E33SNP).. We found a significant increase in the T/T genotype of E33SNP compared with the control group (P < 0.001). We also found the E33SNP C/C genotype of the Tg gene was strongly associated with a subgroup of GD patients who were also characterized as having a higher relapse rate, significantly higher levels of persisting TSH-receptor antibody at the end of treatment, a higher frequency in smoking, and a higher incidence of ophthalmopathy (P < 0.05).. This study showed that Taiwanese patients with the C/C genotype of E33SNP, smoking, ophthalmopathy, and positive TSH-receptor antibodies at the end of the treatment were more likely to have a relapse of Graves' hyperthyroidism after antithyroid medication is withdrawn.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Exons; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Propylthiouracil; Receptors, Thyrotropin; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Taiwan; Thyroglobulin

Topics: Congenital Hypothyroidism; Diseases in Twins; Female; Graves Disease; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotropin; Thyroxine

We present the case of a patient who developed deformities of the fingernails and reddish nodules on the nail beds after administration of propylthiouracil (PTU) for 6 months to treat Grave's disease. Histological examination of the lesion revealed a lichenoid tissue reaction. After withdrawal of PTU, she noticed an improvement in the eruption and the growth of the nails. No recurrence of the eruption was detected after the withdrawal of PTU. Thus, we strongly suggest that this was a rare case of PTU-induced lichenoid drug eruption of nail.

Topics: Adult; Antithyroid Agents; Dermis; Drug Eruptions; Female; Graves Disease; Humans; Lichenoid Eruptions; Nail Diseases; Propylthiouracil

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

In this study, we investigated whether the CD40 or cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) polymorphisms, which are associated with the susceptibility of Graves' disease (GD), can predict the clinical outcome after antithyroid drug (ATD) withdrawal. All patients with GD were treated with ATD. GD patients were divided into two groups: remission or failure. The remission group was defined as patients who maintained a euthyroid state for 1 year after ATD withdrawal. The failure group was defined as patients who relapsed within 1 year after the discontinuation of ATD or who could not discontinue their ATD treatment within 24 months. The rate of treatment failure after ATD withdrawal was 72.2%. For the susceptible genes, the CC genotype in the CD40, the GG genotype in the CTLA-4 exon 1, and the CC genotype in the CTLA-4 promoter region have shown no significant association with a clinical outcome after ATD withdrawal. However, clinical parameters, such as male gender, severe thyrotoxicosis, high thyroid-stimulating hormone-binding inhibitory immunoglobulin value, and a large goiter, were related to treatment failure. These findings suggest that the genetic markers associated with the development of GD cannot be used to predict the relapse of GD patients in place of clinical parameters.

Topics: Adult; Alleles; Antigens, CD; Antigens, Differentiation; Antithyroid Agents; CD40 Antigens; CTLA-4 Antigen; Female; Genetic Predisposition to Disease; Graves Disease; Humans; Male; Methimazole; Middle Aged; Polymorphism, Genetic; Prognosis; Propylthiouracil; Recurrence; Treatment Outcome

Graves' disease is the most common cause of thyrotoxicosis in children. Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial.. To review treatment outcome of Graves' disease in Thai children.. Retrospective review of 32 children with Graves' disease, diagnosed between Jan. 1994 and Dec. 2004, at the Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand was performed.. All patients (median age 10.5 yrs, range 2.85-15 yrs) presented with goiter and increased serum T4 (median 18.4 mcg/dL, range 8.8-30 mcg/dL), serum T3 (median 443 ng/dL, range 206-800 ng/dL) and suppressed TSH levels (median 0.009 mU/L, range 0-0.18 mU/L). Anti-thyroglobulin and Anti-microsomal antibodies were positive in 70% and 82% respectively. All patients except two were initially treated with propylthiouracil (PTU). Two patients were initially treated with methimazole. Adverse reaction of PTU occurred in two patients (One girl had arthralgia, positive pANCA, nephritis and another girl had skin rash and arthralgia). Clinical course of 32 patients after treatment with anti-thyroid drugs mainly PTU for 3.4 (range 0.3-11.2) years is as follows: six (18.8%) underwent remission (cessation of PTU > 2 yrs), three (9.4%) relapsed, one (3.1%) underwent subtotal thyroidectomy, and seven (21.9%) had I131 treatment. All patients (6 of 7) who received I131 dose of 100 microCi/g of thyroid tissue required more than a single dose of I131 treatment. Further outcome in fifteen patients (46.9%) is yet to be followed. Among these patients PTU was just discontinued in four and eleven had never been off anti-thyroid drugs (four still had biochemical hyperthyroidism and seven were biochemically euthyroid).. PTU was the most common first line therapy in the presented patients with Graves' disease. Remission rate was only 18.8% after an average 3.5 years of treatment with anti-thyroid drugs. I131 or thyroidectomy was used as second line therapy in the present study. They were offered to those who developed side effects, had poor compliance or failed medication. For those who received I131, higher dose (200 microCi/g of thyroid tissue) seemed to be more effective than the lower dose (100 microCi/g).

Topics: Adolescent; Antithyroid Agents; Body Mass Index; Child; Child, Preschool; Disease Progression; Female; Graves Disease; Humans; Iodides; Male; Propylthiouracil; Retrospective Studies; Thailand; Thyroidectomy; Time Factors; Treatment Outcome

To evaluate the influence of sex as well as pubertal stage at diagnosis on the growth outcome of childhood thyrotoxicosis.. Retrospective, collaborative study.. Longitudinal auxological evaluation in 101 patients (M/F 23/78) for 4.7 +/- 3.1 years subdivided according to pubertal stage at diagnosis into prepubertal (group I) and pubertal (group II).. At diagnosis height and bone age (BA) standard deviation score (SDS) were positive both in girls and boys of groups I and II. In boys of group II, height SDS was significantly higher than in girls of the same group (P = 0.007) and in boys of group I (P = 0.026). During the follow-up, in group I, height SDS remained positive without significant differences between boys and girls, and in group II, height SDS remained significantly lower in girls than in boys. The age at onset of puberty and the age at menarche were within the normal range. Final height (FH) was within target height (TH) range in all groups The FH SDS and the height gain (FH-TH) were similar in girls and in boys in group I and significantly higher in boys than in girls (P < 0.05) in group II. The boys of group II showed a mean height gain significantly greater than that found in all the other groups.. Despite the advancement of BA at presentation, there were no adverse effects on subsequent growth and FH; the growth outcome seems to be better in boys than in girls in group II.

Topics: Adolescent; Antithyroid Agents; Child; Female; Follow-Up Studies; Graves Disease; Growth; Humans; Male; Menarche; Methimazole; Propylthiouracil; Puberty; Regression Analysis; Retrospective Studies; Sex Factors; Statistics, Nonparametric; Thyroidectomy

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Middle Aged; Oral Ulcer; Propylthiouracil; Vasculitis

Palpable purpura is a concerning clinical finding in pediatric patients and can have many causes, including infectious and autoimmune processes. A rare cause, drug-induced vasculitis, may result from the production of antineutrophil cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with Turner syndrome and Graves' disease who presented with palpable purpuric lesions. The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by observation of consistent clinical features, the detection of elevated ANA and ANCA in the blood, and the observed clinical resolution of symptoms following withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with radioablation did not result in an exacerbation of the vasculitis, a complication described in prior case reports.

Topics: Antithyroid Agents; Child; Female; Graves Disease; Humans; Propylthiouracil; Thyroxine; Turner Syndrome; Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis is a potentially life-threatening adverse effect of antithyroid medications. We present a 22-year-old woman with Graves' disease who developed recurrent episodes of arthritis while on treatment with propylthiouracil. A diagnosis of propylthiouracil-induced ANCA-associated vasculitis was established only after exhaustive rheumatological investigations failed to establish a cause for her arthritis. Anti-myeloperoxidase antibody (anti-MPO) titres were grossly elevated at 172.7 RU/mL (0-20). Her arthritis resolved promptly following the withdrawal of propylthiouracil and the anti-MPO titres declined over 16 months to 66.8 RU/mL. While she did not develop the life-threatening renal or respiratory tract complications, there was a delay in establishing the correct diagnosis with its attendant morbidity. This case highlights the need for greater awareness of this relatively rare adverse effect of antithyroid medications so as to allow its early detection, leading to the prompt cessation of the offending medication.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Abdominal Pain; Adolescent; Antithyroid Agents; Diagnosis, Differential; Drug Overdose; Female; Gastrointestinal Hemorrhage; Glomerular Mesangium; Graves Disease; Humans; IgA Vasculitis; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous; Vomiting

Thyrotoxicosis occurs more frequently during the post-partum period than at other times in women of childbearing age. Graves' disease and post-partum thyroiditis are two major causes of thyrotoxicosis in this period. The major task lies in differentiation of these two diseases in the post-partum period; since throtoxicosis caused by post-partum thyroiditis usually does not require treatment. The radioiodine uptake is elevated or normal in Graves' disease and low in post-partum thyroiditis, and TSH-receptor antibodies are positive in Graves' and negative in post-partum thyroiditis. Post-partum thyrotoxicosis due to Graves' disease may be treated with radioiodine but it requires radiation safety measurements for infant and is contraindicated if the mother is breast-feeding. Antithyroid drugs are the mainstay of the treatment of post-partum thyrotoxicosis. Recent investigations conclude that neither propylthiouracil nor methimazole cause any alterations in thyroid function and physical and mental development of infants breast-fed by lactating thyrotoxic mothers, and both can be safely administered in moderately high doses during lactation.

Topics: Antithyroid Agents; Breast Feeding; Female; Graves Disease; Humans; Infant, Newborn; Iodine Radioisotopes; Methimazole; Propylthiouracil; Puerperal Disorders; Radiotherapy; Thyroidectomy; Thyroiditis; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine

This case describes a young girl with Graves' disease, who presented with fulminant hepatic failure 9 months into propylthiouracil (PTU) therapy. Her clinical presentation was consistent with 'probable autoimmune hepatitis,' as defined by the International Autoimmune Hepatitis Group scoring system. Despite discontinuation of PTU and high-dose steroid therapy, she required liver transplantation. Subsequent pathology could not definitively rule out autoimmune hepatitis. PTU is an important cause of drug-related liver failure in children, and clinicians should be mindful that it is frequently used in patients who already have an underlying risk of autoimmune liver disease.

Topics: Antithyroid Agents; Cadaver; Child; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Length of Stay; Liver Failure; Liver Transplantation; Propylthiouracil; Treatment Outcome

Graves' disease (GD) is an autoimmune disease affecting the thyroid gland and eyes and is treated with three therapeutic modalities. This prospective study was designed to find out the outcome of patients with GD treated with thionamides, radioactive iodine (RAI) or surgery in an iodine deficient region.. Fifty-six nonsmoking patients (mean age 38.9 +/- 13.7 years) with GD were enrolled and followed for a mean period of four years. They were analyzed with respect to their treatment options and their outcome.. Remission rate by thionamides was 74.4% in the first year but decreased to 65.1% in the following four years (p=0.0001). Remission rate achieved in the second year did not predict long-term remission with thionamides. Long-term remission rates for RAI and surgery were 100% during about seven years of follow-up. These remission rates for RAI and surgery were reached in the first year and did not reveal a statistically significant change in the following years. Thyroidectomy, both subtotal and total, was carried out without any complication. Graves' ophthalmopathy emergence and progression were not found to be correlated with the preferred therapeutic modality of thyrotoxicosis.. Long-term thionamide therapy offered a relatively low rate of long-term remission in a region with iodine deficiency. Two years of remission achieved by thionamides did not predict long-term remission in patients living in iodine-deficient areas. RAI and thyroidectomy in experienced hands proved to be better therapeutic alternatives that can be carried out safely.

Topics: Adult; Aged; Antithyroid Agents; Disease Progression; Female; Geography; Graves Disease; Humans; Iodine; Male; Middle Aged; Propylthiouracil; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Turkey

Prediction of remission is one of the main problems of antithyroid drug (ATD) therapy for Graves' disease especially in patients who are treated with a minimum maintenance dose of ATD. We evaluated the ability of new sensitive TSH receptor antibody (TRAb) assays to predict remission in Graves' patients using two commercially available kits (TRAb-CT from Cosmic Corporation and TRAb-Dyno from Yamasa Corporation), compared to the original PEG assay. When a euthyroid state was achieved for more than 6 months with methimazole 5 mg/day or propylthiouracil 50 mg/day and thereafter for three months with 5 mg every other day or 50 mg every other day, respectively, we discontinued ATD medication. One year of observation after discontinuation of ATD was completed in 71 patients (60 females, median age 43 years, range 18-71), and TRAb values from these patients were analyzed in relation to prognosis. Twenty-six (37%) of the 71 patients had relapse of thyrotoxicosis and 45 remained euthyroid. The median TRAb levels in the relapse group were significantly higher than those in the remission group (P < 0.05). Relapse occurred in 15/51 patients negative by TRAb-CT, in 11/20 patients positive by TRAb-CT (chi2 = 4.1; P < 0.05), in 11/42 patients negative by TRAb-Dyno and in 15/29 patients positive by TRAb-Dyno (chi2 = 4.8; P < 0.05). By contrast, relapse occurred in 23/64 patients with negative TRAb by PEG assay and in 3/7 patients with PEG assay positive values (n.s.). All patients with TRAb-CT values of 30% inhibition or greater, or TRAb-Dyno values of 3.0 U/L or greater relapsed during the observation period. Thus, measurement of TRAb by the new sensitive assays is useful for prediction of remission in our patients.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Predictive Value of Tests; Propylthiouracil; Reagent Kits, Diagnostic; Recurrence; Thyrotropin; Thyroxine

Topics: Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Middle Aged; Prednisolone; Propylthiouracil; Pyoderma Gangrenosum

Topics: Adult; Child; Female; Graves Disease; Humans; IgA Vasculitis; Propylthiouracil

Topics: Animals; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmunity; Disease Models, Animal; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

To report 4 cases of propythiouracil (PTU)-induced lupus or vasculitis and to review the literature on that subject.. We describe the clinical presentation, course, and outcome of 4 patients and review the medical literature registered in the Medline PubMed database from 1966 to 2004 by using the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis, arthritis, rash, ANA, and ANCA. Cases were classified into drug-induced lupus (DIL) or vasculitis using accepted definitions and evaluated with emphasis on gender, age, origin, duration of treatment, delay in diagnosis, clinical and serological features, and outcome.. We described our 4 patients and analyzed 42 well-documented cases of DIL- and PTU-induced vasculitis (30 had vasculitis and 12 fulfilled the classification criteria of DIL). Patients with vasculitis were significantly older (mean 43 versus 22 years) and had a longer duration of treatment in comparison with DIL (35 versus 24 weeks). Musculoskeletal symptoms were prominent in DIL, while renal and pulmonary involvement was found in a significantly higher proportion of PTU-induced vasculitis. ANA, anti-DNA, and anti-histone were predominantly found in DIL, while p-ANCA was found in a similar proportion of patients in both groups. c-ANCA was detected only in patients with vasculitis. All patients with DIL completely recovered (most after stopping PTU), while about 50% of PTU-induced vasculitis needed steroids or immunosuppressive drugs, including cyclophosphamide and plasmapheresis.. Most of the cases of PTU-induced autoimmune phenomena are due to vasculitis. Despite the common presence of p-ANCA in both DIL- and PTU-induced vasculitis, substantial differences in demographic, clinical, and outcome features of these entities allow an accurate diagnosis and consequent management.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Propylthiouracil; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous; Withholding Treatment

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

Nontraumatic rhabdomyolysis has been associated with alcohol and drug abuse, seizures, strenuous exercise, muscle hypoperfusion, hyperthermia, electrolyte disturbances, diabetic coma, and hypothyroidism. Hyperthyroidism can be associated with several neuromuscular manifestations, such as thyrotoxic myopathy and thyrotoxic periodic paralysis, both associated with weakness and normal creatine phosphokinase levels. There have been only three reported cases of rhabdomyolysis as a result of thyrotoxicosis. We are reporting the fourth case of such association.. The patient is a 26-year-old black woman with history of hypertension. She presented to the clinic with blurred vision, headaches, palpitations, weight loss, weakness, and persistent high blood pressure. She was found to have exophthalmus, lid lag, and a symmetric, smooth, and diffuse goiter. Ptosis and diplopia were absent; neurologic examination findings was normal. The patient had positive TPO antibodies, elevated free T4 level, and low thyroid-stimulating hormone (TSH) level. Graves disease was diagnosed and propylthiouracil was prescribed. The patient then returned to the clinic 2 weeks later with weakness and myalgias. Her physical examination findings were unchanged except for mild muscle weakness. Laboratory evaluation showed normal electrolytes, normal renal function, and negative urine drug screening. Creatine phosphokinase was 1276 U/L. Her free T4 and T3 levels were elevated and TSH level was low. The patient was treated with aggressive oral fluid resuscitation. Propylthiouracil was continued and free T4 and T3 normalized along with creatine phosphokinase with resolution of symptoms.. Hyperthyroidism may, theoretically, cause rhabdomyolysis by means of increasing energy consumption associated with depletion of muscle energy stores and substrates. Our patient constitutes the fourth reported case of rhabdomyolysis associated with hyperthyroidism.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Propylthiouracil; Remission Induction; Resuscitation; Rhabdomyolysis

We present an unusual case of a drug-related hemorrhagic diathesis. One month prior to admission, the patient was diagnosed at another medical center as having Graves' disease and propylthiouracil therapy (PTU) was initiated. Since clinical recovery was not achieved, the PTU was quickly increased to an unconventional daily dose of 1,000 mg. The patient was referred to our hospital because of spontaneous epistaxis, multiple ecchymoses and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), which developed soon after the increase in PTU dose. Drug-related hemorrhagic diathesis was considered, after other possible causes had been eliminated. To the best of our knowledge, this is the first reported case of spontaneous hemorrhage due to PTU use.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Hemorrhagic Disorders; Humans; Partial Thromboplastin Time; Propylthiouracil; Prothrombin Time

Granuloma annulare (GA) is a begin dermatosis characterized, in general, for papular lesions with annular configuration. Its clinical forms comprehend localized GA, generalized GA, perforating GA and subcutaneous GA. With unknown etiology many factors have been responsible, including autoimmune diseases. We describe a case of a 45-year-old man, with characteristic dermatological injuries of localized GA, associated to systemic alterations, compatible with hyperthyroidism (Graves disease). The patient was submitted to an endocrine and dermatological treatment with control of the clinical state. The unusual association of localized GA with hyperthyroidism, not found in the medical literature, stimulated us to publish the case.

Topics: Antithyroid Agents; Granuloma Annulare; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil

A 40-year-old Chinese man was admitted with 1-2 Hz spasmodic truncal flexion resembling myoclonus. He was known to be thyrotoxic, and had defaulted antithyroid therapy. Clinical examination revealed truncal flexion from contraction of the rectus abdominis, with no involvement of limbs or face and no jerking in sleep. He was biochemically thyrotoxic. Treatment with clonazepam and propylthiouracil resulted in resolution of the myoclonic jerks within the next 3 weeks. He stopped taking clonazepam within the next 3 months with no recurrence of myoclonus. He remained well until he stopped taking his antithyroid medications 9 months later, when he developed spasmodic truncal jerking again. Biochemical tests confirmed that he was hyperthyroid at this time. These movements ceased within a month of compliance with antithyroid therapy, and he has been well since. MRI of the brain and thoracic spine were unremarkable. Thyrotoxicosis is known to cause chorea and tremors, and has rarely been described in association with myoclonus.

Topics: Adult; Anticonvulsants; Antithyroid Agents; Clonazepam; Graves Disease; Humans; Male; Myoclonus; Propylthiouracil; Rectus Abdominis; Spasm; Thyrotoxicosis

Topics: Adult; Cyclosporine; Female; Graves Disease; Humans; IgA Vasculitis; Immunosuppressive Agents; Nephritis; Propylthiouracil; Thyroid Function Tests; Treatment Outcome

Topics: Antithyroid Agents; Blood Cell Count; Female; Graves Disease; Humans; Liver Diseases; Middle Aged; Pancytopenia; Propylthiouracil; Recovery of Function; Thyroid Function Tests; Transaminases; Treatment Outcome

Topics: Antithyroid Agents; Female; Graves Disease; Heart Failure; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotoxicosis

Topics: Antithyroid Agents; Female; Graves Disease; Heart Failure; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotoxicosis

Propylthiouracil is a commonly used medication for hyperthyroidism. Though propylthiouracil-induced hepatotoxicity is a rarely encountered problem, death due to fulminant hepatic failure may occur. In the English literature, only 34 cases have been described with severe hepatotoxicity secondary to this drug. Here we report a case of fulminant hepatic failure due to propylthiouracil and review the issues of treatment and management with special emphasis on the use of plasmapheresis in such situations.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Liver Failure, Acute; Plasmapheresis; Propylthiouracil

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

Topics: Antimetabolites, Antineoplastic; Antithyroid Agents; Female; Graves Disease; Humans; Medication Errors; Mercaptopurine; Pharmacists; Pharmacy Service, Hospital; Propylthiouracil

Relapse and exacerbation of Graves' disease during pregnancy is rare, and thionamide induced agranulocytosis is an uncommon side effect. We report a case of a pregnant woman in her 24th week of gestation that experienced a relapse of Graves' disease that was complicated by propylthiouracil induced agranulocytosis. Following the discontinuation of propylthiouracil and administration of a broad-spectrum of antibiotics, agranulocytosis subsided within 10 days. A total thyroidectomy to avoid any future relapse was planned and a short course of a beta-adrenergic blocker and Lugol solution were prescribed before the operation. At the 28th week of gestation, a total thyroidectomy was performed without complications and thyroxine replacement therapy was commenced. At the 40th week of gestation, labor was induced and a 3,370 g healthy male infant was born without clinical features of thyrotoxicosis. We report herein on the patient and the treatment options for this rare and complicated case.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Propylthiouracil; Recurrence; Thyroidectomy

The treatment of Graves' disease (GD) with antithyroid drugs (ATD) leads to remission of the disease in approximately half of patients treated for at least six months, and the overall relapse rate is high, ranging from 60% to 80%. The presence of prognostic features for achieving a remission after medical treatment is a matter of discussion in the literature. The aim of this study is to evaluate the effect of different ATD regimens available in Brazil (propylthiouracil--PTU and methimazole--MMI) on remission and relapse rates of GD, as well as to determine possible predictors of remission and relapse of the disease and the side effects profile. We reviewed the records from all patients submitted to medical treatment of GD (and with no report of prior treatment of the disease) for at least six months and followed for at least 12 months after the drug withdrawal at Hospital Universitário Clementino Fraga Filho (HUCFF), between October 1978 and August 2003. We identified 127 patients, with the age ranging from 18 to 88 years (mean 39.3 +/- 12.8). Remission was observed in 58 patients (45.7%) and relapse occurred in 31 (53.4%), at a mean period of 14.5 +/- 16.1 months. We verified that the duration of symptoms before the beginning of medical treatment, age and gender did not influence the rate of remission and the relapse risk, whereas the presence of large goiter size (> 40 grams), Graves' ophthalmopathy and use of high daily doses of ATD (> or = 600 mg of propylthiouracil/60 mg of methimazole MMI) were associated with a decreased remission rate. Moreover, patients who presented a TSH measurement < 0.4 microIU/mL between 4 to 5 weeks after the drug withdrawal showed an increased relapse cumulative probability. In conclusion, our results confirms that lasting remission rate of GD treated with ATD is relatively low. We concluded that the combination of goiter size > 40 g, ophthalmopathy, and use of daily doses of PTU > or = 600 mg or MMI > or = 60 mg was vigorously related to lack of remission of GD. Furthermore, TSH measurement between 4 to 5 weeks after the drug withdrawal seems to be a useful tool to determine the remission chance and the relapse risk of the disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Cohort Studies; Female; Follow-Up Studies; Graves Disease; Graves Ophthalmopathy; Humans; Male; Methimazole; Middle Aged; Multivariate Analysis; Propylthiouracil; Recurrence; Remission Induction; Thyrotropin; Time Factors; Treatment Outcome

We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39% in groups 1, 2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.

Topics: Adult; Alleles; Antigens, CD; Antigens, Differentiation; Antithyroid Agents; CTLA-4 Antigen; Female; Gene Frequency; Genotype; Graves Disease; Humans; Logistic Models; Male; Methimazole; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Propylthiouracil; Recurrence; Taiwan; Treatment Outcome

Thyroid hormone is essential for fetal neurological development. Among other etiologies, fetal hypothyroidism may be caused by maternal exposure to antithyroid drugs (ATDs). The most common presentation of fetal hypothyroidism is fetal goiter, which can cause dystocia, in addition to airway obstruction in the neonate. Intra-amniotic treatment with levothyroxine normalizes fetal thyroid status and reduces goiter size. We present a case of fetal hypothyroidism diagnosed in a patient who was treated with propylthiouracil (PTU) for Grave's disease. The fetus had marked hydrops fetalis and a large goiter. In addition, anal stenosis, vesicovaginal fistula, bilateral pyelectasia and polydactyly were diagnosed in the neonate. Intra-amniotic treatment with levothyroxine resulted in a regression of the hydrops and a reduction in the goiter size. A euthyroid, non-edematous, non-goitrous neonate was delivered. At the age of 27 months the child's psychomotor development was normal. The present case indicates that hydrops fetalis may be an unusual manifestation of fetal hypothyroidism, caused by intrauterine exposure to maternal antithyroid drugs (ATDs), and that it may be resolved by treatment with intra-amniotic levothyroxine.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hydrops Fetalis; Hypothyroidism; Maternal Exposure; Pregnancy; Pregnancy Complications; Prenatal Care; Propylthiouracil; Ultrasonography, Prenatal

Failure of embryologic development of a lobe of the thyroid gland is a rare anomaly. Usually, this condition is diagnosed when there are some other pathologic conditions in the gland and is often found when a patient presents with a thyroid nodule, which in reality is compensatory hypertrophy of the side that is present, therefore appearing as a nodule. A variety of pathological conditions occur in the remaining thyroid tissue in association with this rare anomaly such as adenoma, carcinoma, subacute thyroiditis, colloid nodule, Graves' disease, simple goiter, and Hashimoto thyroiditis. Association of Graves' disease with ophthalmopathy and thyroid hemiagenesis is quite rare and very few cases are reported in the literature. We report a 29-year-old female presented as Graves' disease and Graves' ophthalmopathy with left lobe hemiagenesis of the thyroid gland.

Topics: Adult; Antithyroid Agents; Biological Transport; Female; Graves Disease; Humans; Propylthiouracil; Radionuclide Imaging; Technetium; Thyroid Gland; Tissue Distribution

We report a case of Graves' disease in a patient on regular hemodialysis. The patient also suffered from Wolff-Parkinson-White (WPW) syndrome and paroxysmal atrial fibrillation, which may both have been manifestations of the Graves' disease because of the increased oxygen demand. To our knowledge, this is the first case to illustrate the usefulness of the antithyroid agent propylthiouracil for Graves' disease complicated by endstage renal disease (ESRD) and WPW syndrome.

Topics: Antithyroid Agents; Atrial Fibrillation; Graves Disease; Humans; Kidney Failure, Chronic; Male; Middle Aged; Propylthiouracil; Renal Dialysis; Wolff-Parkinson-White Syndrome

An 18-year-old woman being treated for Graves disease underwent elective thyroidectomy. Tachycardia was noted before surgery. The patient's heart rate and temperature started to rise 30 minutes into surgery. Malignant hyperthermia was excluded on clinical grounds, and treatment with beta blockers was started. The patient's conditions stabilized, and surgery was completed. A review of the patient's laboratory test results revealed a high free thyroxine level before surgery. Diagnosis and management of thyroid storm are discussed.

Topics: Adolescent; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Intraoperative Care; Nurse Anesthetists; Propylthiouracil; Risk Factors; Thyroid Crisis; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

Thyroidectomy (TX) is no longer the preferred choice for the therapy of hyperthyroid Graves' disease but is an alternative in patients who are noncompliant with or have reactions to antithyroid drugs, have moderate to severe ophthalmopathy, have large goiters, or who refuse (131)I therapy and/or long-term antithyroid drug therapy. Seventeen clinically and biochemically severely thyrotoxic patients (16 female, mean age of 35 yr), all but one with large goiters, underwent TX after rapid preparation. The potent inhibitors of the deiodination of T(4) to T(3), iopanoic acid (IOP) (500 mg twice a day) and dexamethasone (DEX) (1 mg twice a day), were given with propylthiouracil or methimazole, when possible, and beta-blockers. Thyroid function tests were obtained before treatment and at TX. All patients were thyrotoxic (mean +/- SE: T(4), 21.6 +/- 1.2 micro g/dl; free T(4) index (FTI), 10.3 +/- 0.8; total T(3), 510 +/- 48 ng/dl). IOP and DEX rapidly lowered T(3) values (P < 0.0001; total T(3), 147 +/- 13 ng/dl) with a smaller but significant (P < 0.05) decrease in T(4)/FTI (T(4), 17.9 +/- 1.3 micro g/dl; FTI, 7.9 +/- 0.6). All patients were clinically euthyroid before surgery. None developed hypoparathyroidism, laryngeal nerve damage, or worsening of ophthalmopathy after surgery. The restoration of hyperthyroid Graves' disease to euthyroidism is rapidly accomplished with IOP and DEX, beta-blockers, and, when possible, antithyroid drugs. This is especially relevant in noncompliant patients with large goiters.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Dexamethasone; Female; Glucocorticoids; Graves Disease; Humans; Iopanoic Acid; Male; Methimazole; Preoperative Care; Propylthiouracil; Severity of Illness Index; Thyroidectomy; Time Factors; Treatment Outcome; Triiodothyronine

Propylthiouracil treatment of Graves' disease has been postulated to provoke antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We aimed to investigate whether carbimazole therapy was also associated with increased risk of ANCA.. The occurrence of ANCA and the relationship to thionamide treatment was investigated in a cross-sectional study in a consecutive series of 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects.. ANCA was measured by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) for proteinase 3 and myeloperoxidase-ANCA.. The prevalence of ANCA, as measured by IIF, was increased in the Graves' disease cohort (19.9%) compared with euthyroid controls (4.6%; P < 0.001). The prevalence of MPO-ANCA (measured by ELISA) was also increased in Graves' disease (P = 0.019). ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (P = 0.0265), although risk of ANCA was also higher in Graves' patients treated with carbimazole than controls (RR 2.2, P < 0.0001). ANCA positivity was not increased in patients with Hashimoto's thyroiditis.. This study revealed a high prevalence of ANCA in treated patients with Graves' disease but not in those with Hashimoto's thyroiditis. Furthermore, within the Graves' disease population, ANCA development was associated with propylthiouracil usage to a greater extent than carbimazole. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamides is important in promoting ANCA development.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Carbimazole; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil

Antineutrophil cytoplasmic antibody (ANCA)-mediated vasculitis can be induced by propylthiouracil (PTU) and methimazole (MMI) for the treatment of Graves' disease. This study investigated the prevalence of ANCA positivity and its clinical correlates in Taiwanese patients with Graves' disease treated with PTU or MMI.. Eighty nine patients with Graves' disease who were currently being treated with PTU (n = 47) or MMI (n = 42) were included in the study. Sera were screened for ANCA by indirect immunofluorescence. The antigenic specificity of myeloperoxidase or proteinase-3 was measured by enzyme-linked immunosorbent assay. Thyroid autoantibodies against microsomal antibodies (AMA) and thyroglobulin antibodies were detected by indirect passive hemagglutination assays, and thyroid autoantibodies against thyrotropin receptor were detected by a radioreceptor assay. The correlations among ANCAs, clinical manifestations, gender, duration of treatment, and thyroid autoantibodies were analyzed by logistic regression.. 20.2% of patients with Graves' disease receiving PTU and MMI were seropositive for ANCA; all of them were perinuclear-ANCA (p-ANCA)-positive. The frequency of p-ANCA-positive status in the PTU treatment group was significantly higher than in the MMI treatment group (31.9% vs 7.1%; p = 0.01). The mean duration of PTU treatment was 25 +/- 16 months, and was 30 +/- 21 months for the MMI treatment. In the PTU treatment group, the average duration of treatment in p-ANCA-positive patients was significantly longer than in p-ANCA negative patients (32.9 +/- 16.3 vs 19.6 +/- 12.1 months, p = 0.04). In addition, the prevalence of AMA positivity was significantly lower in p-ANCA-positive patients than in p-ANCA negative patients (53.3% vs 90.6%; p = 0.01).. Only p-ANCA positivity was found in long-term treatment with PTU and MMI in Graves' disease. A higher frequency of p-ANCA positivity was found in the PTU treatment group than in the MMI treatment group. However, the presence of AMA was less frequent in p-ANCA-positive patients compared to p-ANCA-negative patients treated with PTU.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prevalence; Propylthiouracil; Taiwan

A 27-year-old woman who had been receiving propylthiouracil for 2 years for Graves' disease presented with painful ulceration on the lower limbs which had first appeared 2 weeks previously. Well-circumscribed hemorrhagic ulcerations with ragged borders were noted on both legs. Skin biopsy demonstrated a florid neutrophilic infiltrate and evidence of leukocytoclasis around small blood vessels in the papillary dermis compatible with the diagnosis of pyoderma gangrenosum. A highly positive perinuclear pattern of antineutrophil cytoplasmic antibody with specificities for IgM myeloperoxidase was observed. The authors think that propylthiouracil is associated with the occurrence of pyoderma gangrenosum in this patient.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Leg Ulcer; Propylthiouracil; Pyoderma Gangrenosum

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Nephritis; Peroxidase; Propylthiouracil; Treatment Outcome

One hundred and forty patients with Graves' disease [32 new patients, 54 treated with propylthiouracil (PTU) for a mean of 27.2 months and 54 treated with methimazole (MMI) for a mean of 48.6 months] were tested for anti-thyroid microsomal antibody (AMA), anti-thyroglobulin antibody (ATA), thyroid binding inhibitory immunoglobulin (TBII), and the non organ specific autoantibodies [i.e., anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA Ab), anti-cardiolipin antibody (aCL Ab) and anti-beta2-glycoprotein I antibody (IgG beta2GPI)]. Treatment with MMI or PTU produced a significant difference in IgG aCL Ab production but not in ANA, dsDNA Ab, IgM aCL or IgG beta2GPI. For those treated with MMI but not those treated with PTU, ANA and anti-dsDNA Ab were positively correlated. IgG and IgM aCL Ab were positively correlated overall and for those on MMI but not PTU treatment. No significant difference was found for any of the four non organ specific antibodies in AMA positive or negative patients but there was a significant difference in IgG aCL positivity rates for ATA positive and negative patients. On the other hand, ANA negative patients were significantly more likely to have higher TBII values. These results suggest that the appearance of the non organ specific autoantibodies is probably largely a coincidental effect of polyclonal activation - except, perhaps, for IgG aCL, which may be related to treatment.

Topics: Adolescent; Adult; Aged; Antibodies, Anticardiolipin; Antibodies, Antinuclear; Antithyroid Agents; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Logistic Models; Male; Methimazole; Middle Aged; Propylthiouracil

We report a patient with antithyroid drug-induced progressive bilateral sensorineural hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). While antithyroid drugs have been linked to MPO-ANCA-associated small-vessel vasculitis, sensorineural hearing loss rarely was noted. A 36-year-old man treated for hyperthyroidism with propylthiouracil (PTU) developed progressive bilateral sensorineural hearing loss accompanied by fever and arthritis. MPO-ANCA were demonstrated in serum. Distortion product otoacoustic emissions test results suggested dysfunction of outer hair cells of the organ of Corti. Inner ear blood flow impairment from ANCA-associated small-vessel vasculitis presumably caused cochlear dysfunction. PTU withdrawal and high-dose methylprednisolone administration greatly improved hearing on both sides.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Graves Disease; Hearing Loss, Bilateral; Hearing Loss, Sensorineural; Humans; Male; Peroxidase; Propylthiouracil

A 3 year old child with Graves' disease and mitral valve prolapse became neutropenic on carbimazole therapy. She was switched to propylthiouracil but the neutropenia recurred. She was treated with radioiodine but required two doses of 113 MBq and then 198 MBq five months later before becoming hypothyroid. The mitral valve prolapse resolved when she was euthyroid on thyroxine replacement. Antithyroid drugs, surgery, and radioiodine all have a place in the management of the thyrotoxic child.

Topics: Antithyroid Agents; Carbimazole; Child, Preschool; Echocardiography; Female; Graves Disease; Humans; Iodine Radioisotopes; Mitral Valve Prolapse; Neutropenia; Propylthiouracil; Thyrotoxicosis

Topics: Adolescent; Female; Graves Disease; Humans; Liver Failure, Acute; Liver Transplantation; Propylthiouracil

A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.

Topics: Adult; Biopsy; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Liver; Propylthiouracil

Topics: Antibodies, Antineutrophil Cytoplasmic; Follow-Up Studies; Graves Disease; Humans; Propylthiouracil; Risk Assessment; Vasculitis

A 54-year-old woman had been administered propylthiouracil (PTU) for Graves' disease for 4 years. Recently, she complained of hemoptysis due to pulmonary alveolar hemorrhage causing anemia, and also had microhematuria. Antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) was positive, and she was diagnosed with PTU-induced vasculitis. Cessation of PTU and the administration of corticosteroids ameliorated these manifestations.

Topics: Antibodies, Antineutrophil Cytoplasmic; Blood Chemical Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graves Disease; Humans; Middle Aged; Peroxidase; Propylthiouracil; Risk Assessment; Severity of Illness Index; Thyroid Function Tests; Tomography, X-Ray Computed; Vasculitis

Topics: Adult; Antithyroid Agents; Clinical Trials as Topic; Evidence-Based Medicine; Expert Testimony; Female; Graves Disease; Humans; Iodine Radioisotopes; MEDLINE; Methimazole; Middle Aged; Patient Compliance; Propylthiouracil; Randomized Controlled Trials as Topic; Thyroid Function Tests

Treatment of maternal hyperthyroidism during pregnancy is complicated by the lack of readily available measures of the thyroid status of the fetus. The aim of this study is to describe the use of serial in utero ultrasound measurements of fetal thyroid in patients being treated for Graves' disease in pregnancy.. Over a 24-month period, all pregnant women with Graves' disease attending our special Fetal Thyroid Unit were followed. Maternal thyroid status was assessed by thyroid function tests. Fetal thyroid size was measured serially by transvaginal ultrasonography between 14 and 17 weeks of gestation and by abdominal ultrasonography between 18 and 37 weeks of gestation in 20 women with Grave's disease.. In 15 fetuses, thyroid width and circumference were within the 95% confidence interval of the normal population. In five fetuses, thyroid size was above the 95th percentile for gestational age. In three of them, thyroid size decreased concurrently with a decrease in maternal thionamide dosage, reaching normal range. These three fetuses were born euthyroid. In two fetuses, thyroid size was unaffected by a decrement in maternal drug dosage. Both had neonatal thyrotoxicosis at birth.. Serial in utero ultrasonography measuring fetal thyroid size in mothers with Graves' disease can serve as an effective noninvasive tool for the early detection of enlarged fetal thyroid. These findings can be used to monitor the maternal antithyroid drug dosage, thereby preventing intrauterine hypothyroidism in some cases. When a dosage reduction does not cause a decrease in fetal thyroid size, transplacental passage of thyroid-stimulating antibodies causing fetal thyrotoxicosis should be suspected.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Follow-Up Studies; Gestational Age; Goiter; Graves Disease; Humans; Longitudinal Studies; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Ultrasonography, Prenatal

Although propylthiouracil inhibits type 1 deiodinase, leading to a more rapid fall in triiodothyronine (T(3)) than thyroxine (T(4)) levels in patients treated for hyperthyroidism, we report a patient with Graves' disease whose free T(3) paradoxically rose during such treatment, despite low free T(4) levels and increasing doses of propylthiouracil. A similar response has previously been associated with high levels of thyroid stimulating antibodies, but it has been unclear why there should be a dichotomy in the circulating thyroid hormone profile. Thyroid tIssue from our patient contained very high levels of type 1 and, especially, type 2 deiodinase, in contrast to other patients treated with Graves' disease, which were most likely secondary to high levels of thyroid stimulating antibodies. This unusual response to propylthiouracil is important to recognise therapeutically, and represents a further situation in which abnormal expression of deiodinase enzymes has clinical significance.

Topics: Adult; Antithyroid Agents; Enzyme Activation; Female; Graves Disease; Humans; Iodide Peroxidase; Isoenzymes; Propylthiouracil; Thyroxine; Triiodothyronine

A 50-year-old Japanese man with Grave's disease had been taking propylthiouracil (PTU) for 10 years prior to the diagnosis of pneumonia. He noticed dyspnea on exertion and had a dry cough for at least 2 years and then suddenly developed high fever and dyspnea at rest. Clinical symptoms, chest radiographs, chest computed tomography and lung function revealed interstitial pneumonia. The symptoms were completely resolved after withdrawal of PTU, and consequently he was diagnosed with PTU-induced interstitial pneumonia. He also showed moderate myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positivity without any signs of vasculitis before as well as after PTU withdrawal. Although PTU-induced interstitial pneumonia is quite rare, with only 3 cases, including the present patient, so far reported, respiratory involvement should be considered in patients treated with PTU.

Topics: Antithyroid Agents; Graves Disease; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Propylthiouracil

A 36-year-old woman presented at our clinic with symmetrical, tender, palpable purpuric lesions on her lower legs and buttocks after restarting PTU therapy for relapsing Graves' disease. PTU-induced vasculitis was diagnosed with remarkable ANCA anti-MPO and anti-PR3 antibody positivity. The purpuric skin lesions resolved immediately after discontinuation of the drug and the ANCA titres lowered. In the presence of activated neutrophils, PTU could induce a high cytotoxity and injure the vessel walls. Treatment of choice is discontinuation of the drug. Sometimes more aggressive therapy as cyclophosphamide or plasmapheresis is warranted.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Female; Graves Disease; Humans; Myeloblastin; Propylthiouracil; Purpura; Serine Endopeptidases; Vasculitis, Leukocytoclastic, Cutaneous

To study the clinicopathological manifestations and target antigens of propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis.. Four hospitalized patients with PTU-induced ANCA positive vasculitis in recent two years were studied. Target antigens and antibody titers were investigated with ELISA using seven highly purified known ANCA antigens as solid phase ligands. The known antigens included proteinase 3 (PR3), myeloperoxidase (MPO), human leukocyte elastase (HLE), lactoferrin (LF), cathepsinG (CG), bactericidal/permeability-increasing protein (BPI) and azurocidin (AZU).. Four patients with Grave's disease, 2 female and 2 male with a mean age of 30 (11 approximately 57) years who had been treated with PTU for 7 approximately 60 months suffered from ANCA positive vasculitis. All the 4 patients had renal, lung, skin, joint, muscle and hematological involvement. Sera from all the 4 patients were ANCA positive and recognized MPO, LF and CG. Sera from 3 patients recognized HLE and AZU and 2 recognized PR3. None of the sera recognized BPI. The majority of the autoantibodies had high titers >/= 1:25 600. All the sera from 30 patients with Grave's disease and PTU treatment but without vasculitis were ANCA negative. All the 4 patients had pauci- immune glomerular lesions in renal biopsy; 2 had crescentic glomerulonephritis and the remaining 2 had minor glomerular abnormalities. All the 4 patients responded to withdrawal of propylthiouracil; 3 patients were treated with immunosuppressive agents. All the patients achieved clinical remission. However, one patient with crescentic glomerulonephritis was dialysis dependent. After withdrawal of PTU and administration of immunosuppressants, ANCA titres declined, but did not turn to negative in 1-6 months in most of the patients.. PTU can induce ANCA positive vasculitis. The autoantibodies were polyclonal and recognized multiple target antigens of neutrophil cytoplasm. Early withdrawal of PTU and administration of immunosuppressive agents might improve the prognosis.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Child; Female; Graves Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Propylthiouracil; Vasculitis

Patients with Graves' disease (n = 61) treated with propylthiouracil (PTU) or thiamazole (MMI) were studied retrospectively to investigate differences in the prevalence of anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) in relation to treatment with anti-thyroid drugs. The patients were divided into two groups: PTU-treated group (n = 32) and MMI-treated group (n = 29). There were no significant differences between the two groups in terms of age, gender distribution, or duration of treatment. In the PTU group, 8/32 (25%) patients were positive for MPO-ANCA, whereas in the MMI group, 1/29 (3.4%) patients were positive. There were no significant differences in age, duration, or dosage between the MPO-ANCA positive and negative patients. Most of the MPO-ANCA positive patients were asymptomatic, except for two patients in whom rheumatic arthritis or membranous glomerulonephritis developed. None of the MPO-ANCA positive patients were diagnosed as having classical ANCA-associated vasculitis. Thus, there is a high frequency of MPO-ANCA in patients with Graves' disease treated with PTU, compared with patients treated with MMI, although classical ANCA-associated vasculitis develops in only a few MPO-ANCA positive patients.

Topics: Adult; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Peroxidase; Propylthiouracil

We describe a patient with Grave's discase who developed purpura fulminans and who was found to have anticardiolipin antibodies after being started on propylthiouracil (PTU). We discuss the potential role of the antiphospholipid antibody in this woman's presentation, and its association to both PTU and autoimmune thyroid disease.

Topics: Adult; Antibodies, Anticardiolipin; Antithyroid Agents; Female; Graves Disease; Humans; IgA Vasculitis; Propylthiouracil

A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Infant, Low Birth Weight; Infant, Newborn; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Thyroidectomy; Vasculitis

Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.

Topics: Adult; Anti-Inflammatory Agents; Antigens, Nuclear; Antithyroid Agents; Autoantibodies; Dermatomyositis; DNA Helicases; DNA-Binding Proteins; Female; Graves Disease; Humans; Ku Autoantigen; Methimazole; Platelet Transfusion; Propylthiouracil; Purpura, Thrombocytopenic, Idiopathic; Scleroderma, Systemic; Steroids

A 13-year-old girl with Graves' disease, whose younger sister had systemic lupus erythematosus, developed polyarthralgia, fever, neutropenia, hypergammaglobulinemia, and microscopic hematuria after treatment with propylthiouracil (PTU) for 2 years. Myeloperoxidase-anti-neutrophil cytoplasmic antibodies were strongly positive. Anti-single- and anti-double-stranded DNA antibodies were positive, whereas LE cells and anti-Sm antibodies were negative. PTU was discontinued and all symptoms subsided gradually. Two years later, the microscopic hematuria had disappeared completely. Both patients had the identical HLA-DR alleles (HLA-DR9). These present two cases in siblings suggest that both sisters had lupus diathesis, and that the elder sister developed a PTU-induced lupus-like syndrome.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Antithyroid Agents; Female; Genetic Predisposition to Disease; Graves Disease; HLA-DR Antigens; HLA-DR Serological Subtypes; Humans; Lupus Erythematosus, Systemic; Propylthiouracil; Siblings

Systemic vasculitis is a rare complication of therapy with antithyroid medication. Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis has been described in patients treated with propylthiouracil (PTU) and methimazole (MMI). The majority of cases have underlying Graves' disease. The authors report 2 children who developed ANCA-associated systemic vasculitis during PTU therapy of Graves' disease. One patient, after PTU treatment for 3 years, developed severe systemic vasculitis. After 3 weeks of arthritis, she abruptly presented with hematuria, proteinuria and edema concomitant with anemia. Her serum creatinine was elevated, to 6 mg/dl. Renal biopsy revealed crescentic glomerulonephritis. After admission, she developed intracerebral hemorrhage and pulmonary hemorrhage. She had positive perinuclear-ANCA (p-ANCA) with a titer of 1:160. Despite intensive therapy with immunosuppressive agents and plasmapheresis, as well as discontinuation of PTU, she died of the complications of severe systemic vasculitis. The other patient developed fever, arthralgia and leukocytoclastic vasculitis of the skin during treatment with PTU for about 2 years. Her symptoms and skin lesions disappeared after discontinuation of PTU. However, she has had a persistently high titer of p-ANCA 1:320 through 17 months follow-up time. Thus, patients who are treated with PTU can develop ANCA-positive vasculitis in a mild or severe form. Therefore, they should be carefully followed and monitored, not only for their thyroid status but also the serious complications of PTU.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Graves Disease; Humans; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

Although antineutrophil antibodies are thought to be involved in drug-induced neutropenia, neither the precise mechanisms nor the particular antigens on the neutrophil surface have yet been clarified. Recently, we examined a patient with Graves' disease who developed antineutrophil cytoplasmic antibodies (ANCA) after propylthiouracil treatment and exhibited neutropenia. Because several target antigens of ANCA are expressed on the surface of neutrophils, it was suggested that ANCA might contribute to neutropenia. The patient's serum bound specifically to neutrophils and HL-60 cells differentiated into granulocytes, and lysed the HL-60 cells via a complement-mediated mechanism. Furthermore, two representative ANCA antigens, proteinase 3 and myeloperoxidase, significantly inhibited both the binding and cytotoxicity of the serum. Finally, tumour necrosis factor-alpha, which is known to up-regulate cell surface expression of several ANCA antigens, enhanced both the binding and cytotoxicity of the serum. These findings suggest that ANCA induced by propylthiouracil contributed to leucopenia through a complement-mediated mechanism.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmunity; Complement Activation; Cytotoxicity, Immunologic; Female; Granulocytes; Graves Disease; HL-60 Cells; Humans; Middle Aged; Neutropenia; Propylthiouracil

Radioactive iodine ((131)I) has become the most widely used therapy for patients with hyperthyroidism caused by Graves' disease in the United States. There remains, however, significant variability among (131)I dosing regimens, and it is clear that most patients ultimately develop hypothyroidism after therapy. To avoid persistent hyperthyroidism, we adopted a high dose (131)I therapy protocol based on measurement of 24-h thyroid (123)I uptake designed to deliver 8 mCi (296 MBq) to the thyroid gland 24 h after (131)I administration. To evaluate the efficacy of this protocol, we reviewed our clinical experience over a 7-yr period. We treated 261 patients (219 women and 42 men) with hyperthyroidism caused by Graves' disease with (131)I [mean dose, 14.6 mCi (540 MBq)] between 1993 and 1999. Before treatment, 207 (79%) had received an antithyroid drug (109 propylthiouracil and 98 methimazole). We determined their thyroid status 1 yr after treatment in relation to age, pretreatment with an antithyroid drug, pretreatment thyroid size, and dose of (131)I retained in the thyroid 24 h after treatment. Among the 261 patients, 225 (86%) were euthyroid or hypothyroid 1 yr after treatment, and 36 patients (14%) had persistent hyperthyroidism and required a second treatment. The patients who had persistent hyperthyroidism were younger (P < 0.01), had larger thyroid glands (P < 0.01), higher pretreatment thyroid (123)I uptake values (P < 0.01), and higher serum T(4) concentrations (P < 0.01) and were more likely to have taken antithyroid medication before administration of (131)I (P = 0.01). Five of these patients developed transient hypothyroidism, followed by thyrotoxicosis. There was an asymptotic, inverse relationship between the retained dose of (131)I at 24 h and persistent hyperthyroidism, revealing a 5-10% failure rate despite delivery of up to 400 microCi (14.8 MBq)/g. A dose of (131)I that results in accumulation of 8 mCi (296 MBq) in the thyroid gland 24 h after administration is an effective treatment for the majority of patients with Graves' hyperthyroidism. Young patients with larger thyroid glands, higher serum T(4) concentrations, and higher 24-h thyroid (123)I uptake values, and those pretreated with antithyroid medication for greater than 4 months are at higher risk for treatment failure. A higher dose of (131)I may be advisable in such patients.

Topics: Adult; Antithyroid Agents; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retreatment; Retrospective Studies; Thyrotoxicosis; Treatment Outcome

A 14-year-old girl developed acute renal failure after 3 years therapy with propylthiouracil (PTU) for Grave's disease. Serologic evaluation showed antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 and myeloperoxidase. Renal biopsy showed a crescentic glomerulonephritis (GN) as well as evidence of IgA nephropathy (IgAN). PTU was discontinued and the patient was treated with prednisone and cyclophosphamide. ANCA became negative and renal function improved, but did not normalize. A second biopsy showed evidence of IgA nephropathy only. Propylthiouracil use has been associated with ANCA positive pauci-immune glomerulonephritis, but not with IgA nephropathy. An overlap syndrome between IgAN and ANCA-positive GN, however, has been described. This patient may have had a preexisting IgAN, with acute pauci-immune GN secondary to PTU, or this may be the first description of an overlap syndrome of IgAN and ANCA vasculitis all caused by PTU therapy.

Topics: Acute Kidney Injury; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Glomerulonephritis; Glomerulonephritis, IGA; Graves Disease; Humans; Propylthiouracil

Graves disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. The autoantibodies mimic the effect of the hormone on thyroid cells, which stimulates autonomous production of thyroxine and triiodothyronine. It has been hypothesized that cross-reactivity of autoantibodies may result in Graves ophthalmopathy and dermopathy. A seldom-recognized feature of Graves disease is thymic hyperplasia. We report 2 patients with Graves disease and incidentally discovered anterior mediastinal masses presumed to be thymic hyperplasia. In both cases, these masses regressed spontaneously after treatment of hyperthyroidism.

Topics: Adult; Female; Goiter; Graves Disease; Humans; Male; Mediastinal Diseases; Propylthiouracil; Thymus Gland; Thymus Hyperplasia; Tomography, X-Ray Computed

In this study, we retrospectively analyzed 18 patients in whom antithyroid drug (ATD)-induced agranulocytosis developed during treatment of Graves' disease. All patients were more than 20 years of age, and we saw no correlation between age and the development of agranulocytosis. In 17 of 18 patients, ATD-induced agranulocytosis developed within 2 to 12 weeks of starting ATD treatment. Development of agranulocytosis was related to the dose of ATD. In some patients, agranulocytosis developed abruptly, and even weekly routine WBC and granulocyte counts failed to predict all case occurrences. Fever and sore throat were the earliest symptoms of agranulocytosis; patients who developed either of these symptoms were closely monitored immediately with WBC and granulocyte count examinations. In this series of patients, treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) increased the granulocyte counts, whereas the effectiveness of glucocorticoid treatment was not confirmed.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Topics: Abdomen; Antithyroid Agents; Congenital Hypothyroidism; Female; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Propylthiouracil; Vasculitis

Oxidative stress parameters and nitric oxide (NO) values were determined in 27 newly diagnosed Basedow patients before and after 1 mo of propylthiouracil (PTU) therapy and in 15 healthy controls. Basedow patients exhibited increased triiodothyronine (T3) and thyroxine (T4) and decreased thyroid-stimulating hormone (TSH) values compared to controls. Significantly higher thiobarbituric acid-reactive substances (TBARS), NO and glutathione (GSH) levels, and CuZn superoxide dismutase (CuZn SOD) activity were found in Basedow patients in comparison to controls, regardless of sex. Treatment with PTU (3 x 100 mg/d for 30 d) was effective in decreasing T1 and T4 and increasing TSH levels. Significantly decreased NO and TBARS and increased GSH and CuZn SOD levels were observed in PTU-treated Basedow patients compared to pre-PTU administration. PTU-treated patients compared to controls still exhibited significantly higher T3 and lower TSH values and higher NO, TBARS, GSH, and CuZn SOD levels. The induced antioxidant defense and decrease in NO) values in response to PTU therapy emphasizes the role of PTU as an antithyroid drug, where the ability to diminish hyperthyroidism results in decreased catabolism and lower oxidant generation.

Topics: Adult; Antithyroid Agents; Erythrocytes; Female; Glutathione; Graves Disease; Humans; Male; Nitric Oxide; Oxidative Stress; Propylthiouracil; Thiobarbituric Acid Reactive Substances; Thyrotropin; Thyroxine; Triiodothyronine

Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex.. The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays.. Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25--36 week) and median B Wt was 1.96 kg (0.50--2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1--16 days) and mean age at commencement of treatment was 12 days (7--26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Four became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supple-mentation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort.. This is a large series of extremely small and premature infants with neonatal thyro-toxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme low birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.

Topics: Antithyroid Agents; Autoantibodies; Carbimazole; Female; Fetal Blood; Fetal Growth Retardation; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Receptors, Thyrotropin; Thyrotoxicosis; Thyrotropin; Thyroxine

A 31-year-old woman presented with neutropenia due to thionamide drug therapy for Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive pregnancy test. Her drug therapy was discontinued and her neutropenia resolved uneventfully. The hyperthyroidism recurred a week later. After consideration of all treatment options, it was decided to observe until 14 weeks when an elective thyroidectomy was planned. Mother and fetus were monitored closely and both tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a total thyroidectomy after rendering her euthyroid with a short course of sodium ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal distress and precipitated a forceps delivery. A 3250 g male infant was born with poor Apgar score and required 2 h of ventilation. At 1 year, the child had reached all developmental milestones at appropriate times. Both mother and fetus may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that should be considered when thionamide drug therapy is contraindicated.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Infant, Newborn; Male; Neutropenia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy Trimester, Second; Propylthiouracil; Thyroidectomy

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO-ANCA in these cases was suspected of being related to PTU because the titres of MPO-ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO-ANCA and vasculitis during PTU therapy, or on the incidence of MPO-ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease.. We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO-ANCA, and for the development vasculitis after starting PTU therapy. Twenty-nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23.6 months (range: 3-37 months).. MPO-ANCA was measured at intervals of 2-6 months.. Before treatment, the MPO-ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U/ml). Three (4.1%) of the 73 patients were positive for MPO-ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO-ANCA titres transiently increased to 12.8 and 15.0 U/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO-ANCA titre increased to 204 U/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO-ANCA titre decreased to 20.7 U/ml by 4 months after discontinuing PTU.. PTU therapy may be related to the appearance of MPO-ANCA, but MPO-ANCA does not appear to be closely related to vasculitis.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Child; Female; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Time Factors; Vasculitis

We report the case of a 31-year-old man with Graves' disease who manifested malignant hyperthermia during subtotal thyroidectomy. His past medical history and family history were unremarkable. Before surgery, his condition was well controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the operation, anesthesia was induced by intravenous injection of vecuronium and thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was maintained with nitrous oxide and sevoflurane. One hour after induction of anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from 40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were administered, which, however, had little effect. Despite the lack of muscular rigidity, the diagnosis of malignant hyperthermia was made based on respiratory acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started to fall to normal levels. His laboratory findings showed abnormally elevated serum creatine phosphokinase and myoglobin but normal thyroid hormone levels. Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia, an immediate intravenous administration of dantrolene should be considered when a hypermetabolic state occurs during anesthesia in surgical treatment for a patient with Graves' disease.

Topics: Acidosis, Respiratory; Adult; Anesthetics; Antithyroid Agents; Carbon Dioxide; Creatine Kinase; Dantrolene; Diagnosis, Differential; Goiter; Graves Disease; Heart Rate; Humans; Male; Malignant Hyperthermia; Methimazole; Methyl Ethers; Muscle Relaxants, Central; Myoglobin; Nitrous Oxide; Propylthiouracil; Sevoflurane; Succinylcholine; Thiopental; Thyroidectomy; Thyroxine; Triiodothyronine; Vecuronium Bromide

A case of 46, XY pure gonadal dysgenesis with very tall stature was investigated. The 24-year-old, phenotypically female patient consulted our clinic because of linear growth persisting into adulthood. The patient was found to have no mutation or deletion of a sex-determining region of the Y chromosome, and also was found to have Graves' disease. Growth was arrested with height remaining at 187 cm after normalization of the thyroid function by treatment with an antithyroid agent, although follow-up to monitor growth was limited to 3 months. In some cases of gonadal dysgenesis, then, Graves' disease may contribute to an abnormally tall stature.

Topics: Adult; Age Determination by Skeleton; Antithyroid Agents; Body Height; Female; Gonadal Dysgenesis, 46,XY; Graves Disease; Humans; Male; Propylthiouracil; Treatment Outcome

Propylthiouracil (PTU)-induced hemolytic anemia is extremely rare. We reported a case of Graves' disease with these unusual clinical manifestations. A 41-year-old female presented with recurrent attacks of severe hemolytic anemia after PTU therapy. Sugar water test and erythrocytes osmotic fragility test revealed no cellular membrane defect of red blood cells. Antinuclear antibody, direct and indirect Coombs' tests were all negative and glucose-6-phosphate dehydrogenase activity was also within normal limits. PTU was not discontinued promptly due to unrecognizableness of such a rare case until two months later with recurrent attacks of severe hemolytic anemia. 1-131 therapy was performed on suspicion of related hemolytic anemia. Unfortunately, challenge of PTU occurred incidentally after discontinuation of PTU followed by severe hemolytic anemia. The diagnosis of PTU-induced hemolytic anemia was established thereafter. A MEDLINE search revealed only one such case reported in English literature. This is the first case report in Taiwan. It should be kept in mind that hemolytic anemia may be a rare complication of PTU therapy.

Topics: Adult; Anemia, Hemolytic; Antithyroid Agents; Female; Graves Disease; Humans; Propylthiouracil

Therapy with anti-thyroid drugs is the initial option mostly used in our country for the treatment of hyperthyroidism due to Graves-Basedow disease. To evaluate the long term results of this kind of therapy, a total of 773 patients were studied who were diagnosed from 1975 to 1994 in three hospitals in Northern Spain (Hospital Central de Asturias, Hospital de Cruces and Hospital de Navarra) after a mean follow-up time after anti-thyroid drug withdrawal of 46 +/- 33.1 months. The results showed a likelihood of hyperthyroidism relapse of 42.9%, 59.8%, 67.9% and 78.9% at one, three, five and ten years, respectively. Goitre size was correlated very significantly with the likelihood of relapse (p < 0.0001). In contrast, only TBII positivity at the end of therapy among the remaining parameters (age, sex, goitre size, length of therapy, positivity of anti-thyroid antibodies and TBII) influenced significantly on the relapse likelihood (p < 0.05). In conclusion, after a long term follow-up after anti-thyroid therapy, a high relapse rate of hyperthyroidism in Graves-Basedow disease, which amounts up to 79% at ten years, was observed. Goitre size was the main predictive factor for this relapse.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Recurrence; Spain

Propylthiouracil (PTU) might theoretically be preferred over methimazole (MMI) during breast-feeding because of its lower milk/serum concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often relapses during the postpartum period, and high doses of PTU are sometimes needed to control maternal hyperthyroidism) during breast-feeding. However, there are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast-feeding.. To investigate whether mothers can breast-feed without adverse effects on infants' thyroid status while taking 300 mg or more daily of PTU.. Eleven infants who were wholly breast-fed while their mothers took PTU 300-750 mg daily for Graves' hyperthyroidism were included in this study. In one of the 11 infants, the mother also took iodine 6 mg daily for a limited period. Thyroid status in these infants was evaluated.. Free T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb) concentrations were examined at least once in the age range 6 days to 9 months. Maternal blood was also examined for FT4 and TBIAb on the same day, or within a week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth were examined, using cord blood, in cases where antithyroid drugs had been continued through delivery.. Three of the 11 infants had TSH concentrations higher than the normal range for adults. In one of the three infants, the TSH concentration, which was determined 19 weeks after birth, was just above the normal range. In the remaining two infants whose mothers had taken PTU through delivery, TSH concentrations, determined within 7 days after birth, were distinctly high, but they became normal while maternal PTU doses were the same as or higher than those at the initial examination. Maternal PTU doses or FT4 concentrations were not significantly correlated with infants' TSH concentrations.. Mothers can breast-feed while taking propylthiouracil at doses as high as 750 mg daily without adverse effects on thyroid status in their infants.

Topics: Adult; Antithyroid Agents; Autoantibodies; Breast Feeding; Drug Administration Schedule; Evaluation Studies as Topic; Female; Fetal Blood; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Infant; Infant, Newborn; Pregnancy; Propylthiouracil; Receptors, Thyrotropin; Thyroid Hormones; Thyrotropin; Thyroxine

We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positive for anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.

Topics: Antithyroid Agents; Autoantibodies; Child; Exophthalmos; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Magnetic Resonance Imaging; Propylthiouracil; Receptors, Thyrotropin; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

The use of propylthiouracil (PTU) for the treatment of Graves' disease is associated with few adverse effects such as skin eruptions, liver dysfunction, and agranulocytosis. Furthermore, recent studies described the development of antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and vasculitis in patients treated with PTU. Here we investigated whether PTU therapy per se is associated with the appearance of ANCA in patients with Graves' disease. We analyzed 119 serum samples from 117 patients with Graves' disease treated with either PTU (n = 56), or methimazole (MMI) (n = 21), as well as untreated patients (n = 42). Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA were tested by enzyme-linked immunosorbent assay (ELISA) kits. MPO-ANCA was negative in all patients treated with MMI therapy and untreated patients. However, MPO-ANCA was detected in 21 (37.5%) of 56 patients treated with PTU therapy. Furthermore, two patients who were negative for MPO-ANCA became positive after PTU therapy. The proportion of patients positive for MPO-ANCA increased with the prolongation of PTU therapy, but did not correlate with age, gender, and positive antithyroperoxidase (TPO) antibody. Among 21 MPO-ANCA positive patients, 12 had no symptoms, but 9 patients complained of myalgia, arthralgia, or common cold like symptoms after the appearance of MPO-ANCA. Three patients developed agranulocytosis or granulocytopenia, but none showed abnormal urinary findings. Our results suggest that PTU per se is associated with the production of MPO-ANCA in patients with Graves' disease.

Topics: Adult; Aged; Agranulocytosis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Iodide Peroxidase; Male; Middle Aged; Myeloblastin; Peroxidase; Propylthiouracil; Serine Endopeptidases

Propylthiouracil (PTU), a drug commonly used for treatment of hyperthyroidism, is associated with various rare side effects. Antineutrophil cytoplasm antibody (ANCA)-positive vasculitis is a relatively unusual complication among them. The pathogenesis of ANCA-positive vasculitis during PTU therapy is still obscure. We present the case of a 12-year-old boy who developed ANCA-positive vasculitis during PTU therapy for Graves' disease. His symptoms and signs were indistinguishable from anaphylactoid purpura, a common small-vessel vasculitis in children. The clinical manifestations improved after discontinuation of PTU and immunosuppressant treatment. He remained symptom-free at 11-months follow-up.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Graves Disease; Humans; IgA Vasculitis; Male; Propylthiouracil; Vasculitis

To stabilize Graves disease and deplete the preformed hormone, the use of antithyroid drugs prior 131I therapy has been suggested, specially in those patients with severe thyrotoxicosis and in the elderly. However, PTU may reduce the effectiveness of 131I.. To study the effects of PTU pretreatment before 131I administration. SUBJETS AND METHODS: A retrospective analysis of the medical records of patients with Graves disease treated with 131I from 1989 to 1997 was made. Of 244 patients with adequate follow-up for at least 12 months after 131I treatment, 142 had not been pretreated and 102 had received PTU prior to 131I therapy. Pretreated patients were distributed according to the number of days that PTU was discontinued before receiving 131I, forming four groups (a = 5 d, b = 6-14 d, c = 15-30 d and d = 31-60 d). Radioiodine was delivered according to our protocol of 120 microCi per gram of thyroid tissue, as estimated by clinical examination. Therapy was considered successful when laboratory evidence of euthyroidism or hypothyroidism after one year of treatment was obtained and as a failure when undetectable TSH values persisted after 12 months of treatment with 131I.. All groups were comparable as to age, gender, goiter size, and 24 h radioiodine uptake. Control of hyperthyroidism was achieved in 76% of the non pretreated group. A similar percentage was observed in groups (b), (c) and (d). However, the disease was controlled in only 50% of group (a) patients (p < 0.003).. The therapeutic efficacy of 131I is significantly reduced when the PTU is stopped for only a few days prior to the use of radioiodine. We postulate that PTU has to be discontinued for at least 10 days before radioiodine administration.

Topics: Adult; Aged; Antithyroid Agents; Cohort Studies; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Time Factors; Treatment Outcome

We have previously reported that serum soluble interleukin-2 receptor (sIL-2R) and IL-12 levels were significantly increased in hyperthyroid Graves' disease. In this study, we investigated serum IL-18 levels in patients with either Graves' disease or Hashimoto's thyroiditis. The serum IL-18 levels in Graves' disease were significantly increased in the hyperthyroid state and were decreased during treatment with methimazole or propylthiouracil. On the other hand, the levels in Hashimoto's thyroiditis in the hypothyroid state showed no significant differences from those in healthy subjects. When liothyronine sodium was administered orally to healthy subjects, serum IL-18 levels were not changed. Positive correlations between serum IL-18 and IL-12, IL-12 and sIL-2R, and sIL-2R and IL-18 levels were noted in Graves' disease. These results suggest that Th1 cytokines might play an important regulatory role in Graves' disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Interleukin-18; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroiditis, Autoimmune; Triiodothyronine

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves' disease. Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves' disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs. These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves' disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves' disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves' disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

Topics: Adolescent; Age of Onset; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodide Peroxidase; Japan; Male; Methimazole; Peroxidase; Propylthiouracil; Thyroglobulin

We report a 35 years old female with left lobe thyroid hemiagenesis who initially was euthyroid and then developed hyperthyroidism due to Graves disease. Hemiagenesis of the thyroid gland is a rare anomaly with an uncertain incidence; up to now 256 cases have been reported. The detection is often made by either clinical symptoms of thyroid dysfunction, by imaginological studies or surgical/pathological procedures. No explanation has been given for the development of this anomaly; left lobe aplasia and predominance of occurrence in women have been most frequently reported.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Propylthiouracil; Radionuclide Imaging; Thyroid Gland; Ultrasonography

Antithyroid drugs adverse effects are varied and rare. Autoimmune disorders (vasculitis, lupus erythematosus, polyarthritis...) are unusual and serious complications of antithyroid drugs. Since 1945, fewer than 100 cases of systemic manifestations related to antithyroid drugs have been reported in the literature, most frequently with propylthiouracil. The outcome is usually good after drug discontinuation, but some fatal cases have been reported. Because possible cross-sensitivity with other antithyroid drugs, the appropriate treatment for hyperthyroidism relapse if a patient has had an antithyroid drug adverse reaction, should be 131I-Iodine or surgery. We report four new cases of systemic manifestations during propylthiouracil therapy.

Topics: Adult; Antithyroid Agents; Arthritis; Diagnosis, Differential; Female; Follow-Up Studies; Graves Disease; Humans; Lupus Erythematosus, Systemic; Middle Aged; Propylthiouracil; Recurrence; Thyroidectomy; Vasculitis

Patient aged 49 who developed hypothyroidism after receiving 1131 for relapsing Graves' disease after treatment with propylthiouracil followed by homeopathy. Substitution with thyroxine (0.05 mg/day) was prescribed. Depressed by the perspective of a life long treatment, the patient swallowed 400 pills (20 mg). The evolution was uncomplicated after betablockers administration at hospital. One year later she became euthyroid without further medication. The occurrence of transient hypothyroidism after curitherapy is discussed. The importance of mutual participation in the patient/physician relationship is underlined in the framework of divergent conceptions of medicine.

Topics: Antithyroid Agents; Brachytherapy; Female; Graves Disease; Humans; Hypothyroidism; Middle Aged; Physician-Patient Relations; Propylthiouracil; Suicide, Attempted; Thyroxine

The association of pyoderma gangrenosum and arthritic symptoms is well documented. We present a rarely reported variant of this in a 44-year-old woman with pyoderma gangrenosum and bilateral large purulent effusions of her knees. She had no evidence of underlying rheumatoid arthritis or a specific seronegative spondyloarthropathy. Of note she had a history of Graves' disease for which she had been treated with propylthiouracil for 3 years and on investigation at this presentation had a markedly elevated perinuclear antineutrophil cytoplasm antibody (P-ANCA) level with specificities for IgM myeloperoxidase, IgG elastase and IgG lactoferrin. We believe this patient had pyoderma gangrenosum with secondary sterile pyarthrosis and a P-ANCA precipitated by propylthiouracil.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Arthritis, Reactive; Female; Graves Disease; Humans; Minocycline; Prednisolone; Propylthiouracil; Pyoderma Gangrenosum; Skin

To evaluate the efficacy of antithyroid medication in the initial treatment of pediatric Graves' disease and the frequency of use and outcome of radioiodine as second-line therapy.. Retrospective review.. Tertiary care children's hospital.. Thirty-three patients (29 female, 4 male; mean age 12.7 years) who started treatment for hyperthyroidism between Jan. 1, 1990, and Dec. 31, 1994.. Initial treatment with propylthiouracil or methimazole (with addition of levothyroxine if needed to maintain euthyroidism); subsequent treatment with radioiodine.. 1) Clinical and laboratory features at the time of diagnosis; 2) doses and duration of antithyroid drug treatment and response to treatment; 3) need for treatment with levothyroxine to maintain euthyroidism during the trial of antithyroid medication; 4) indications for radioiodine therapy, and the dose and number of treatments with 131iodine (131I); 5) thyroid status at last follow-up visit (at least 2 years after diagnosis).. All patients were initially treated with antithyroid drugs, and levothyroxine was added in 16 subjects to maintain euthyroidism. The median duration of drug treatment was 21 months. Ultimately, 24/33 patients (73%) received radioiodine following a trial of antithyroid drugs because of a) side effects of antithyroid medication (in 3 patients); b) inadequate response to medication (in 8 patients); and c) relapse (in 13 patients), which occurred at a median of 6 (range 1 to 16) months following cessation of drug therapy. Five patients required a second dose of radioiodine and 2 patients required 3 doses. Of the 24 patients treated with radioiodine, at last follow-up after the most recent treatment (median 18.5, range 3 to 55 months), 6 patients were euthyroid, 16 required thyroxine replacement, and 2 were-still, or again, hyperthyroid.. In our population of children and adolescents, treatment of hyperthyroidism with antithyroid drugs frequently resulted in either side effects, inadequate response to medication or subsequent relapse, all of which led to radioiodine therapy. We conclude, therefore, that radioiodine could be considered as one of the first-line options in older children and adolescents with hyperthyroidism.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Combined Modality Therapy; Drug Evaluation; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propranolol; Propylthiouracil; Retrospective Studies; Thyroxine; Treatment Outcome

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Drug Eruptions; Female; Graves Disease; Humans; Propylthiouracil; Sweet Syndrome

Thyroid hormones participate in GH synthesis and secretion, and an impaired GH response to many pharmacological stimuli, including GH releasing hormone (GHRH), has been found in thyrotoxicosis. Although the mechanisms involved in this process have not been fully elucidated, there is evidence that thyroid hormones could act at both hypothalamic and pituitary levels. There are no data in the literature about the effect of an acute reduction of circulating T3 levels on GH secretion in hyperthyroidism. The GH responsiveness to GHRH was therefore evaluated in a group of hyperthyroid patients during short-term treatment with iopanoic acid. Iopanoic acid is a compound that induces a rapid decrease in serum T3 levels, mainly by inhibition of peripheral conversion of T4 to T3. To the authors' knowledge, there is no evidence of a direct effect of iopanoic acid on GH secretion.. Hyperthyroid patients were submitted to a GHRH test (100 microg, i.v.) before (day 0), and on days 4, 7 and 15 after oral treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (200 mg every 8 h). A group of normal control subjects was also submitted to a single GHRH test (100 microg, i.v.).. Nine patients with thyrotoxicosis (eight women, one man), with a mean age of 34 years, were studied. All patients had high serum levels of total T3 and total T4, and suppressed TSH levels. None of them had taken any medication for at least 3 months before the study. The patients were compared with a group of nine control subjects (five women, four men) with a mean age of 31 years.. GH and TSH were measured by immunofluorometric assays. Total T3, total T4 and IGF-I were determined by radioimmunoassay. Albumin levels were measured by a colorimetric method.. Iopanoic acid induced a rapid and maintained decrease in serum T3 concentrations, with a significant reduction on days 4, 7 and 15 compared with pre-treatment values. In hyperthyroidism, peak GH levels (mean +/- SE mU/l) after GHRH were significantly higher on day 15 (24.4 +/- 3.8) than those observed on days 0 (14.2 +/- 1.6), 4 (15.2 +/- 3.0) and 7 (19.6 +/- 5.0). There was a 79% increase in this response on day 15 compared with the pre-treatment period. Hyperthyroid patients had a blunted GH response to GHRH on days 0, 4 and 7 in comparison with control subjects. However, on day 15, no differences were observed between the area under the curve (mean +/- SE mU/l.120 min) in thyrotoxic patients (1770 +/- 306) and in the control group (3300 +/- 816). IGF-I and albumin levels did not change during iopanoic acid administration.. The results show that an acute reduction in serum T3 levels elicits an increase in GH responsiveness to GHRH in hyperthyroidism. Although the mechanisms involved in this process are still unknown, it is possible that T3 influences GH responsiveness to GHRH via hypothalamic somatostatin release. Alternatively, T3 could have a direct effect at the pituitary somatotroph, modulating GHRH intracellular pathways.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Female; Graves Disease; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Iopanoic Acid; Linear Models; Male; Middle Aged; Propylthiouracil; Statistics, Nonparametric; Thyrotropin; Thyroxine; Triiodothyronine

We report a case of Graves' hyperthyroidism in a 34-year-old pregnant woman treated with propylthiouracil (PTU) complicated by the development of a fetal goiter. Because of the fetal goiter and normal maternal thyroid function tests, the PTU was discontinued. Over the next 10 weeks, there was a progressive decrease in the fetal thyroid volume as documented by ultrasonography. The fetal neck returned to a normal flexed position, fetal growth and amniotic fluid remained normal, and the patient remained asymptomatic. A normal infant was delivered at term. This is the first report to demonstrate that noninvasive management may be appropriate for fetuses with goiter caused by antithyroid drug therapy.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Propylthiouracil

A 47-year-old man who smelled of alcohol presented with a three-day history of sore throat. He had not had fever, nausea, vomiting, diarrhea, rhinorrhea, cough, chest pain, or palpitations. On evaluation in the emergency department, he was found to have tachycardia and an irregular pulse.

Topics: Alcoholism; Antithyroid Agents; Atrial Fibrillation; Coxsackievirus Infections; Diagnosis, Differential; Electrocardiography; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Thyroid Function Tests

Cardiac tachyarrhythmias are common in thyrotoxicosis. We report an uncommon case of a 53-year-old woman with Grave's disease who developed second degree A-V block while euthyroid on propylthiouracil. The most likely mechanism is an autoimmune response causing infiltration of the cardiac conduction pathways.

Topics: Antithyroid Agents; Female; Graves Disease; Heart Block; Humans; Middle Aged; Propylthiouracil

A 31-year-old woman presented 1993 with fever, painful swelling of cartilaginous portions of the ears and the bridge of nose, polyarthralgia including costochondroral pains, and episcleritis. She has been taking propylthiouracil since 1991 when she was diagnosed as Graves' disease. Laboratory evaluations revealed an elevated erythrocyte sedimentation rate (ESR) of 133 mm/h, a high CRP level of 13.2 mg/dl and positive antinuclear antibodies and anti-type II collagen antibodies. Histopathological findings of the biopsy specimen from the auricular cartilage included chondrocyte degeneration, matrix destruction and inflammatory cell infiltration. She was diagnosed as RP and treatment with 30 mg/day of prednisolone dramatically improved all symptoms and signs, accompanied by a fall in ESR, CRP and autoantibodies. When prednisolone was tapered to 5 mg/day, a clinical relapse occurred. After discontinuation of propylthiouracil, she has been well without prednisolone. Propylthiouracil-induced SLE-like syndrome or antineutrophil cytoplasmic antibodies (ANCA) related angitis has been reported previously. In addition, recent studies demonstrated that about 20% of sera from patients with relapsing polychondritis are P-ANCA positive. This is the first report suggesting a possible association between the development of relapsing polychondritis and propylthiouracil.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Polychondritis, Relapsing; Propylthiouracil

Clinical evaluation was conducted to ascertain whether thyrotropin receptor antibody (TRAb) in the normal range may still be involved in the regulation of thyroid function after prolonged treatment for Graves' disease. All patients (n = 33) were treated with antithyroid drugs for an average of 10.6 years and were under euthyroid conditions in which normal blood levels of tri-iodothyronine (T3) were significantly correlated with blood thyrotropin (TSH) levels, but not with titers of TRAb. A significant correlation was observed between TRAb titer and thyroid-stimulating antibody (TSAb) activity. In contrast, this correlation was not found in normal subjects. After administration of T3 (75 microg daily for 8 days), the patients showed increased levels of T3 with concomitant suppression of TSH levels. Under these conditions, linear regression analysis showed significant correlations of TRAb titer and TSAb activity with 24-h thyroid radioiodine uptake (r = 0.641 and 0.621 respectively, P < 0.01), in contrast to declining blood thyroxine levels. Moreover, the immunoglobulin G (IgG) of the patients precipitated to a greater extent than IgG from normal subjects a peptide consisting of the amino acid sequence near the terminus of the human TSH receptor. These findings indicated that TRAb at normal levels possessed significant unremitting activities on thyroid function despite long-term treatment in euthyroid patients with Graves' disease.

Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Precipitin Tests; Propylthiouracil; Receptors, Thyrotropin; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Prenatal Diagnosis; Propylthiouracil

We evaluated the concentration of epidermal growth factor (EGF) in platelets, serum and plasma obtained from 47 patients with Graves' disease, 7 with hypothyroidism and 20 healthy subjects. The platelets of the subjects were collected from platelet rich plasma and lysed by freezing and thawing. Subsequently the platelet debris was treated with Triton X-100. The EGF concentration was determined by homologous radioimmunoassay. The concentration of EGF in the platelets in 14 patients with untreated Graves' disease was significantly higher than that in the healthy controls. After treating these 14 patients with antithyroid agents, the EGF concentration in the platelets decreased to the level of the healthy controls. The EGF concentration in the platelets in the 7 untreated hypothyroid patients decreased after replacement therapy with thyroxine. The mean volume of the platelets in the 14 patients with untreated Graves' disease was significantly larger than in the control and decreased after treatment with antithyroid agents. The serum and plasma levels of EGF in the 7 untreated hypothyroid increased after replacement therapy. In conclusion, thyroid function affected the concentration of EGF in the platelets of patients with thyroid disorders.

Topics: Adult; Blood Platelets; Epidermal Growth Factor; Female; Graves Disease; Humans; Hypothyroidism; Male; Methimazole; Middle Aged; Platelet Count; Propylthiouracil; Thyroid Diseases; Thyroxine

We measured the soluble cytokine CD27 in a variety of thyroid disorders. Soluble CD27 was increased in untreated Graves' hyperthyroidism and in euthyroid ophthalmopathy. Levels of sCD27 were normal after the establishment of euthyroidism with propylthiouracil (PTU) or radio iodine in primary hypothyroidism, chronic thyroiditis, and the hyperthyroid and euthyroid phases of subacute thyroiditis. Soluble CD27 is a marker for cellular activation as in Graves' hyperthyroidism, but it is not predictive of the outcome of PTU therapy.

Topics: Acute Disease; Adult; Aged; Antithyroid Agents; Biomarkers; Chronic Disease; Female; Graves Disease; Humans; Hypothyroidism; Iodide Peroxidase; Male; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroid Diseases; Thyroiditis; Thyrotropin; Thyroxine; Tumor Necrosis Factor Receptor Superfamily, Member 7

To examine the effects of propylthiouracil (PTU) pretreatment on the outcome of initial I-131 therapy for Graves' disease.. A retrospective chart review was done.. The authors studied 106 patients in an outpatient nuclear medicine setting who were given initial I-131 therapy for Graves' disease from September 1989 to March 1993 and followed for at least 6 months after therapy. These patients were divided into groups based on whether they had ever received PTU or, if they had received PTU, the length of time between the last dose of PTU and the I-131 therapy dose. Measured failure rates of initial I-131 therapy were based on recurrent or continued hyperthyroidism.. Treatment failure rates increased markedly from 2.5% in non-PTU-treated patients (n = 80) to 23.1% (n = 26) in patients pretreated with PTU (P = 0.003). Although not significant, two PTU-pretreated subgroups showed a trend toward increased failure rates. The failure rate was 15.4% (n = 13) in patients whose last dose of PTU was 7-14 days before I-131 therapy, and it increased further to 30.8% (n = 13) in patients whose last dose of PTU was within 1 week of I-131 therapy.. PTU pretreatment within 2 weeks of I-131 treatment is a strong independent risk factor in failure rates after initial I-131 therapy in patients with Graves' disease. Patients should be free of PTU for 2 weeks before I-131 therapy if they are able to tolerate it, otherwise the dose of I-131 may need to be adjusted upward to diminish the risk that the initial I-131 therapy will fail.

Topics: Adult; Antithyroid Agents; Combined Modality Therapy; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Premedication; Propylthiouracil; Retrospective Studies; Risk Factors; Time Factors; Treatment Failure

Two Caucasian patients are described who had destructive postpartum thyroiditis (PPT) before the subsequent onset of Graves' hyperthyroidism (GH). HLA class II DQ typing in these two subjects identified putative susceptibility alleles previously detected in GH and PPT. Although PPT destructive thyroiditis preceding the development of GH is relatively uncommon, the occurrence of both these syndromes in the same patient suggests the possibility of an etiological role for thyroid antigen release and genetic susceptibility as pathogenic factors in the development of Graves' disease.

Topics: Abortion, Therapeutic; Adult; Female; Graves Disease; Humans; Iodine Radioisotopes; Middle Aged; Pregnancy; Propylthiouracil; Puerperal Disorders; Thyroiditis; Thyroxine

To analyse the routine WBC count's effect on predicting antithyroid drugs-induced agranulocytosis developing and risk factors of antithyroid drugs-induced agranulocytosis.. Retrospective analysis of 18 Graves' cases with agranulocytosis induced by antithyroid drugs during 1984-1995.. Most of antithyroid drugs-induced agranulocytosis happens 2-12 weeks after the administration of antithyroid drug, and are related with the drug's doses. Some agranulocytosis happens abruptly, routine WBC and granulocyte count can not predict some agranulocytosis developing. Fever and throat sore are the intitial symptoms of agranulocytosis, if it happens, the WBC and granulocyte count must be checked immediately. The treatment of granulocyte-macrophage colony stimulating factor is effective, the corticosteroid therapy seems not to be useful for the recovery of granulocyte count.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Topics: Adult; Antithyroid Agents; Dose-Response Relationship, Drug; Graves Disease; Humans; Kidney Failure, Chronic; Male; Pancytopenia; Propylthiouracil

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Kidney Failure, Chronic; Male; Methimazole; Pancytopenia; Propylthiouracil

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

Dizygotic twin sisters were born to a woman who, shortly before becoming pregnant, had developed Graves' disease with markedly elevated triiodothyronine (T3) levels and highly positive TSH receptor antibody titres (TRAb: 169 mU/ml). From the second week of life onwards they had a goitre and hyperexcitability, tachycardia and failure to thrive were noted. In addition, twin I had mild exophthalmos. As thyrostatic treatment of the mother was very difficult, intrauterine hypothyroidism or transitory hyperthyroidism had presumably occurred in the twins.. Twin I had maximal thyroxine (T4) concentration of 26.2 micrograms/dl, while it was 24.7 micrograms/dl in twin II with suppressed TSH. Both twins had high concentrations of TRAb and antibodies against thyroid peroxidase.. With the diagnosis of neonatal Graves' disease established, both twins were treated with propranolol (2 mg/kg.d) and phenobarbitone (2-4 mg/kg.d). Twin I, whose symptoms were more severe, also received propylthiouracil (5 mg/kg.d) until euthyroidism had been achieved. Although twin II became euthyroid spontaneously, she gained weight only slowly and microcephaly developed together with definite motor and mental retardation. It remains unclear whether these were consequences of intrauterine hypothyroidism or post-partum hyperthyroidism.. Graves' disease during pregnancy demands interdisciplinary collaboration between gynaecologist, physician and paediatrician to prevent severe sequelae in the children. Early risk assessment is possible by measuring the TSH receptor antibody titre in umbilical blood.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Autoantibodies; Developmental Disabilities; Diseases in Twins; Female; Fetal Blood; Graves Disease; Humans; Hypnotics and Sedatives; Infant, Newborn; Infectious Disease Transmission, Vertical; Iodide Peroxidase; Microcephaly; Phenobarbital; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Receptors, Thyrotropin; Thyroxine; Triiodothyronine; Twins, Dizygotic

Propylthiouracil (PTU) is known to cause vasculitis as a rare complication. We report the case of a patient who developed alveolar haemorrhage and haematuria whilst treated with PTU. The serum was positive for antineutrophil cytoplasmic antibody (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). All symptoms resolved completely after discontinuation of PTU. Alveolar haemorrhage or pulmonary-renal syndrome associated with antineutrophil cytoplasmic antibody with myeloperoxidase specificity may be a new complication of propylthiouracil therapy.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Hemorrhage; Humans; Lung Diseases; Peroxidase; Propylthiouracil; Radiography

Cutaneous reactions to propylthiouracil and methimazole occur in 3%-5% of adults. Generalized maculopapular and papular purpuric eruptions are perhaps the most common thionamide-induced reactions. We report 3 patients who developed cutaneous vasculitis which is a rare and serious side-effect during antithyroid drug therapy. The observation of cutaneous vasculitis during administration of propylthiouracil suggested that clinical awareness of this complication should be of considerable importance.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Skin Diseases; Vasculitis, Leukocytoclastic, Cutaneous

We report a case of propylthiouracil (PTU)-induced cholestatic hepatotoxicity in Graves' disease that developed 1 day after beginning PTU. After clinical recover, liver abnormalities persisted for 5 years. Percutaneous liver biopsy and the eventual normalization of enzyme levels excluded permanent liver damage as a result of PTU therapy. Thus prolonged elevation of serum enzymes is consistent with the diagnosis of PTU-induced hepatotoxicity, which may recover completely.

Topics: Antithyroid Agents; Biopsy; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Female; Graves Disease; Humans; Liver; Liver Function Tests; Middle Aged; Propylthiouracil; Time Factors

Fourteen Graves' hyperthyroid patients who had been prepared for surgery with sodium ipodate (SI) 500 mg orally twice daily for 3 days were retrospectively studied. SI was administered in combination with propylthiouracil (10 cases) and beta blockers (all cases), which had been previously initiated. Free serum thyroxine (T4) and total triiodothyronine (T3) concentrations were measured before and after SI therapy on the morning of surgery. SI treatment significantly reduced total T3 concentration from 445.9 to 193.4 ng/dL (P < 0.0001) and free T4 concentration from 3.874 to 2.800 ng/dL (P = 0.0003). Preoperatively, only one patient had persistent tachycardia, and intraoperatively this same patient required beta blockers. Blood loss was unremarkable or reduced (average blood loss, 121 mL). On clinical examination glands were firm with normal or somewhat decreased vascularity. On histologic study all glands demonstrated changes consistent with treated Graves' disease. Preoperative treatment with SI appears to be a safe and efficacious method of preparing hyperthyroid patients for surgery.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Blood Loss, Surgical; Female; Graves Disease; Humans; Ipodate; Male; Premedication; Preoperative Care; Propylthiouracil; Retrospective Studies; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

This prospective study was designed to investigate the usefulness of granulocyte count measurements 4 hours after injection of granulocyte colony-stimulating factor (G-CSF) for detecting recovery from antithyroid drug (ATD)-induced granulocytopenia or agranulocytosis. Granulocyte and white blood cell counts were measured 4 hours and 24 hours after patients with ATD-induced granulocytopenia had been given an injection of 75 micrograms of G-CSF (1.1 to 1.9 micrograms/kg; 1.5 +/- 0.2 micrograms/kg [mean +/- standard deviation]). Thirty-seven patients were studied and divided into three groups based on their initial granulocytopenic granulocyte count: 28 with mild (granulocyte count 0.501 to 1.0 x 10(9)/L), 6 with moderate (granulocyte count 0.101 to 0.5 x 10(9)/L), and 3 with severe (granulocyte count less than 0.1 x 10(9)/L) ATD-induced granulocytopenia. Twenty-five of the 28 patients with mild granulocytopenia and 4 of the 6 patients with moderate granulocytopenia were found to have recovered from the granulocytopenia both 4 hours and 24 hours after injection, and their granulocyte counts remained normal thereafter. However, the other 3 patients with mild granulocytopenia, 2 patients with moderate granulocytopenia, and all 3 patients with severe granulocytopenia had not recovered by either 4 or 24 hours after the G-CSF injection. Despite daily G-CSF injections, the granulocyte continued to decrease in most cases. It took 2 to 11 days for these counts to recover from granulocytopenia. These results indicate that granulocyte count measurement 4 hours after injection of G-CSF is useful for detecting recovery from ATD-induced granulocytopenia or agranulocytosis and for predicting disease severity. Accordingly, its measurement enables physicians to make an appropriate decision about whether a patient with ATD-induced granulocytopenia should be treated in the hospital or in the outpatient clinic.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Humans; Kinetics; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil; Prospective Studies

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Topics: Agranulocytosis; Angina Pectoris; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Methimazole; Middle Aged; Propylthiouracil; Renal Dialysis

We describe two Caucasian women with the concurrence of Graves' disease and the moyamoya phenomenon (radiological evidence of collateral cerebral blood vessels like "puffs of smoke" due to cerebrovascular occlusive disease). One patient presented with acute cerebrovascular ischemia due to Moyamoya disease shortly after radioactive iodine therapy for Graves' disease and the second presented with Graves' disease 10 years after being diagnosed with moyamoya dysplastic cerebral vessels. The optimal treatment of hyperthyroidism in these patients is unknown; however, careful control of the hyperthyroidism by any modality seems reasonable. Our limited experience suggests that antithyroid drugs and radioactive iodine therapy are rational options. Thyroidectomy appears to be a safe therapeutic alternative, although long-term efficacy may be difficult to assure. Both of our patients had to be treated twice for hyperthyroidism. Whether Graves' disease and Moyamoya coexist because of an aggressive autoimmune mechanism is a concept that remains to be settled.

Topics: Adult; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Iodine Radioisotopes; Middle Aged; Moyamoya Disease; Neutropenia; Propylthiouracil; Thyroidectomy; Triiodothyronine

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Hypokalemia; Male; Periodicity; Propylthiouracil; Quadriplegia; Thyrotoxicosis

Thionamide therapy is a mainstay of the treatment of hyperthyroidism complicated by pregnancy, but it can expose the fetus to hypothyroidism. In terms of fetal thyroid status, propylthiouracil (PTU) has been preferred over methimazole (MMI) based on experimental data on limited transplacental passage, and lower doses have been recommended. However, neither of these practices is supported by convincing clinical evidence. We compared the effect of maternal ingestion of PTU with that of MMI on fetal thyroid status using cord sera at delivery in 77 mothers with Graves' hyperthyroidism who were receiving thionamides and whose free T4 (FT4) levels were within the normal range. We also examined the dose effects on fetal thyroid status in these women. Thirty-four women were taking PTU (group P), and 43 were taking MMI (group M). Neither the mean fetal FT4 nor the mean fetal TSH level was significantly different between the two groups. No significant difference in the occurrence of low FT4 levels or high fetal TSH levels was found between group P and group M (low FT4, 6% vs. 7%; high TSH, 21% vs. 14%). Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU (100 mg daily or less) and MMI (10 mg daily or less) were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses (21%) and in 6 of the 43 fetuses (14%), respectively. Higher doses were associated with normal or low fetal TSH levels. These findings demonstrate that in terms of fetal hypothyroidism-inducing potential, there is little reason to choose PTU over MMI. Individualized, not uniformly low, doses of these drugs may prevent fetal hypothyroidism.

Topics: Female; Fetal Blood; Fetal Diseases; Graves Disease; Humans; Hypothyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotropin; Thyroxine

Topics: Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Middle Aged; Necrobiosis Lipoidica; Propylthiouracil; Thyroiditis, Autoimmune; Thyroxine

Antithyroidal drugs (ATD) are used in the management of Graves' disease either as primary therapy for several months while awaiting remission of the disease or as pretreatment for several weeks prior to definitive radioactive iodine therapy (RAI). We have reported previously that pretreatment with propylthiouracil (PTU) before definitive RAI therapy is associated with a higher RAI treatment failure rate than RAI therapy alone. The objectives of the current study were 2-fold. First, to verify the results of our prior study regarding the effect of PTU used as pretreatment before RAI in a cohort of patients from a different institution and, secondly, to better define the relationship between the number of days off PTU before RAI therapy and therapeutic efficacy of RAI dosing.. A retrospective review of Graves' disease patients treated from 1980 to 1994.. Study patients had to meet the following inclusion criteria: radionuclide studies and thyroid hormone values consistent with Graves' disease, at least 1 year of follow-up data available and discontinuation of the ATD at least 4 days before RAI administration. Exclusion criteria included therapy with any ATD other than PTU or ATD therapy during or following RAI dosing.. Effectiveness of RAI therapy, days on PTU, days off PTU and calculated RAI dose to the thyroid were recorded for each subject. We compared the efficacy of RAI therapy in patients treated with PTU (used either as pretreatment in preparation for RAI therapy or as primary long-term therapy) before RAI administrations to those treated with RAI alone with special attention to the number of days on and off PTU before RAI dosing. Patients were considered RAI treatment failures if a second dose of RAI was required to achieve a euthyroid or hypothyroid state.. One hundred and sixteen patients met our study criteria. Forty patients received PTU therapy for a mean of 221 +/- 59 days. The PTU was discontinued for a mean of 60 +/- 25 days before RAI dosing. Persistent hyperthyroidism was seen in 9% (7/76) of patients treated with RAI alone. The failure rate of a single dose of radioactive iodine was significantly increased when PTU was discontinued between 4 and 7 days before the administration of RAI (29% vs 9% for RAI alone, P = 0.039). PTU discontinued for at least 1 week before RAI dosing was associated with a nearly 2-fold increase in failure rate, but this difference did not achieve significance (17% vs 9% for RAI alone, P = 0.24). Examining only those patients receiving PTU, patients who had successful single dose RAI therapy tended to receive a higher dose of RAI than patients failing RAI therapy (480 +/- 30 vs 410 +/- 40 MBq administered dose, P = 0.18; and 8.0 +/- 0.9 vs 5.5 +/- 1.1 MBq/g thyroid tissue calculated dose, P = 0.21). Furthermore, total serum thyroxine at diagnosis was significantly higher in patients failing RAI therapy after PTU administration than in patients successfully treated with RAI after receiving PTU (316 +/- 40 vs 225 +/- 13 nmol/L, P = 0.03).. Propylthiouracil discontinued 4-7 days before radioiodine dosing is associated with a significant increase in the failure rate of a single dose of radioiodine. Discontinuation of the propylthiouracil for at least a week before radioiodine administration is associated with a higher, although not statistically significant, radioiodine failure rate. In patients that require treatment with propylthiouracil before radioiodine therapy, a higher total serum thyroxine level at diagnosis is associated with an increased rate of radioiodine failure. Consideration should be given to increasing empirically the dose of radioiodine administered to Graves' disease patients that have received propylthiouracil within a week of radioiodine administration in an effort to decrease the radioiodine failure rate to an acceptable level.

Topics: Adult; Antithyroid Agents; Chi-Square Distribution; Combined Modality Therapy; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Propylthiouracil; Retrospective Studies; Statistics, Nonparametric; Time Factors; Treatment Failure

We recently observed 2 lactase-deficient women with Graves' disease who consistently developed severe diarrhea after ingestion of thionamide (methimazole and propylthiouracil) tablets containing lactose as carrier. The strict temporal relationship between ingestion of lactose-containing tablets and appearance of intestinal symptoms, as well as the absence of side effects following ingestion of methimazole tablets without lactose as carrier, provided the clue for the diagnosis. To our knowledge, severe diarrhea resulting from carrier lactose has not been previously reported for antithyroid drugs, and should be considered in occasional cases of patients with gastrointestinal symptoms on thionamide therapy.

Topics: Adult; Antithyroid Agents; beta-Galactosidase; Diarrhea; Drug Carriers; Female; Graves Disease; Humans; Lactase; Lactose; Lactose Intolerance; Methimazole; 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

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

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Hypokalemia; Male; Periodicity; Propylthiouracil; Quadriplegia

Topics: Adult; Antithyroid Agents; Biopsy; Chemical and Drug Induced Liver Injury; Female; Graves Disease; Humans; Liver Failure, Acute; Liver Function Tests; Propylthiouracil

This brief report presents a patient with isolated right heart failure and two rare underlying causes, hyperthyroidism and dysplastic tricuspid valve. Repair of the tricuspid valve and treatment of the hyperthyroidism were both essential for successful treatment of the right heart failure. Most important, recrudescence of hyperthyroidism in this patient was associated with reappearance of florid right heart failure. This report provides further information about a potential linkage of hyperthyroidism and severe right heart failure.

Topics: Antithyroid Agents; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Graves Disease; Heart Failure; Humans; Male; Middle Aged; Propylthiouracil; Tricuspid Valve; Tricuspid Valve Insufficiency

Topics: Antithyroid Agents; Female; Fetal Diseases; Graves Disease; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Diseases

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with propylthiouracil. We have experienced three adult cases of Graves' disease with main features being renal derangements. All three patients, who were between the ages of 22 and 82 years, had been treated with propylthiouracil for 2 to 5 years after a diagnosis of Graves' disease. After several weeks of upper respiratory tract infection or flu-like symptoms, they abruptly began to manifest proteinuria and hematuria concomitant with severe anemia. Their serum creatinine increased from normal levels to 1.2 to 3.6 mg/dL. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes (ie, pauci-immune type). Crescent formations were observed in 40% to 60% of the glomeruli in all three cases. The serum from the patients revealed positive perinuclear-ANCA and negative cytoplasmic-ANCA (C-ANCA) pattern, and myeloperoxidase (MPO)-ANCA titers were 120 to 502 ELISA Units/mL (normal, < 10 ELISA Units/mL). A withdrawal of propylthiouracil with or without immunosuppressive therapy ameliorated their renal derangements. Graves' disease patients should be placed under vigilant observation by monitoring their urinalysis and serum creatinine, especially when being treated with antithyroid drugs and when suffering from flu-like symptoms.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Glomerulonephritis; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil

Older reports have suggested that the use of antithyroid drugs with radioactive iodine-131 (RAI) results in higher rates of persistent hyperthyroidism than treatment with RAI alone. Our objective was to determine if propylthiouracil (PTU) given prior to RAI would be associated with a higher single dose RAI failure rate than treatment with RAI alone. Patients were considered treatment failures if a second dose of RAI was required to produce euthyroidism or hypothyroidism. All study patients stopped PTU at least 4 days before RAI therapy and did not receive PTU after RAI. The overall failure rate of one course of treatment in the 86 study patients was 17% (15/86). Persistent hyperthyroidism was seen in 4% of patients (2/48) treated with only RAI and in 34% of patients (13/38) receiving RAI after pretreatment with PTU (p = 0.003). Patients were treated with PTU for a mean of 151 +/- 32 days. There were no significant differences in race, gender, thyroid size, RAI dose, or days of follow-up between patients receiving RAI alone and those receiving PTU before RAI therapy. These data suggest that pretreatment with PTU leads to a higher failure rate even if PTU is discontinued at least 4 days before RAI therapy and not restarted after RAI dosing. Consideration should be given to increasing the dose of RAI in patients pretreated with PTU to ensure adequate treatment of Graves' disease.

Topics: Adult; Combined Modality Therapy; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Thyroid Gland; Treatment Failure

There are few reported convincing cases of hyperthyroid depressed patients receiving electroconvulsive therapy (ECT). We describe a depressed 66-year-old woman with catatonic depression diagnosed with new-onset hyperthyroidism due to Grave's disease. After commencing propylthiouracil, her Grave's disease was partially treated, but her depression was no better. She subsequently received a course of seven ECT with resolution of her depression and no adverse sequelae.

Topics: Aged; Antithyroid Agents; Catatonia; Depressive Disorder; Electroconvulsive Therapy; Female; Graves Disease; Humans; Propylthiouracil

We present a case of maternal Grave's disease associated with fetal goitrous hyperthyroidism. Fetal goiter was diagnosed by ultrasound and diagnosis of fetal hyperthyroidism was established by umbilical blood sampling. Fetus was successfully treated by increasing maternal propylthiouracil dosage. Fetal thyroid status was normal at birth. Role of sonography and umbilical blood sampling in management of fetal goiter complicated with maternal Grave's disease is discussed.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Prenatal Diagnosis; Propylthiouracil; Ultrasonography

Thionamides are often used acutely to control the symptoms of thyrotoxicosis associated with Graves' disease before definitive treatment with radioiodine. Several reports have suggested that pretreatment with thionamides reduces the efficacy of radioiodine therapy in patients with Graves' disease, but other data refute this. This study retrospectively reviewed the records of 95 patients with Graves' disease treated with radioiodine. Pretreatment with thionamides resulted in significantly greater (2 1/2-fold) treatment failure rate than in patients not pretreated with thionamides but given a comparable dose of radioiodine. Higher serum thyroxine concentration at the time of diagnosis was also an independent factor associated with radioiodine treatment failure.

Topics: Adult; Chi-Square Distribution; Contraindications; Discriminant Analysis; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Thyrotoxicosis; Thyroxine; Treatment Failure

A maternal history of Graves' disease places the fetus at risk for thyrotoxicosis in utero via the placental transfer of thyroid-stimulating immunoglobulins. Methods for prediction of fetal hyperthyroidism are available, but are not widely used. Clinical assessment of fetal thyroid status by monitoring of fetal heart rate and growth may be inaccurate. This raises some uncertainty in the initial diagnosis of fetal thyrotoxicosis and complicates the assessment of fetal response to maternal propylthiouracil therapy. A case illustrating these pitfalls in the diagnosis and management of fetal hyperthyroidism is presented. The condition was correctly diagnosed, but treatment based on fetal heart rate resulted in biochemical hypothyroidism in the infant at birth. Current recommendations for diagnosis and treatment of fetal hyperthyroidism are reviewed along with recent developments in the field. A modified approach is proposed.

Topics: Adult; Algorithms; Female; Fetal Diseases; Graves Disease; Heart Rate, Fetal; Humans; Pregnancy; Prenatal Diagnosis; Propylthiouracil; Thyrotoxicosis; Triiodothyronine

Drug induced hepatitis is a rare complication of thiourea antithyroid drugs. In some patients, the hepatotoxicity may be severe and lead to submassive hepatic necrosis (SHN). Submassive hepatic necrosis is a potentially fatal complication which is usually recognized on the liver biopsy and histological examination or autopsy. In the case presented here, SHN was identified on Tc-99m SC liver images. Sharply defined intrahepatic photopenic abnormalities without significant colloid shift were noted. SPECT images were most remarkable and exhibited extensive liver necrosis. Resolution of hepatic abnormalities correlated with clinical and biochemical resolution of SHN. In patients with propylthiouracil hepatotoxicity, serial liver SPECT images with Tc-99m SC appear helpful for the diagnosis and follow up of SHN and, in an appropriate clinical context, may obviate the need for liver biopsy.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Graves Disease; Humans; Liver; Necrosis; Propylthiouracil; Technetium Tc 99m Sulfur Colloid; Tomography, Emission-Computed, Single-Photon

Thyroid-stimulating hormone (TSH) levels obtained one month after the cessation of anti-thyroid drug treatment were assessed retrospectively for possible use in predicting outcome in 50 patients with a clinical diagnosis of Graves' disease. Thirty-four patients remained in remission at the end of the follow-up period and 16 patients relapsed. Although a TSH level of < 1.2 mU/1 did not discriminate between the two groups, none of the 24 patients who had TSH levels of > 1.2 mU/1 relapsed during the follow-up period, making early discharge from the thyroid clinic possible for these patients.

Topics: Adult; Carbimazole; Female; Graves Disease; Humans; Male; Middle Aged; Predictive Value of Tests; Propylthiouracil; Recurrence; Retrospective Studies; Thyrotropin; Time Factors; Treatment Outcome

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

A fetal goitre is a potentially dangerous phenomenon because of mechanical obstruction and possible fetal thyroid function disorders. In this report we describe a patient with Graves' disease diagnosed in early pregnancy and treated with propylthiouracil, which resulted in a large fetal goitre and fetal hypothyroidism. The diagnostic problems are discussed and we focus on the need for fetal thyroid hormone serum evaluation. The only reliable way to obtain information about the fetal thyroid status is percutaneous fetal umbilical cord blood sampling, since amniotic fluid levels do not properly represent the fetal thyroid function. Fetal hypothyroidism can thus be diagnosed in utero and treated with intra-amniotic injections of thyroxine. The recommended dose and frequency of injections are only based on a few case reports and for that reason we performed a second fetal blood sampling 1 week later to evaluate our therapy. Weekly intra-amniotic injections of 250 micrograms of thyroxine seem to be sufficient to reduce a fetal goitre and give a normal thyroid hormone level.

Topics: Adult; Dose-Response Relationship, Drug; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hypothyroidism; Injections; Maternal-Fetal Exchange; Pregnancy; Prenatal Diagnosis; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Traditionally, Basedow-Graves disease was considered a protection against thyroid cancer. However, recent reports suggest that cancer occurs with a higher frequency than expected and is more aggressive in this disease. We report six patients with hyperthyroidism due to a Basedow Graves disease that presented a palpable thyroid nodule, which was cold in the scintiscan and solid in the ultrasound examination. Fine needle cytology disclosed cancer in five cases (two with cytological features of greater aggressiveness) and a nodular hyperplasia in one. The diagnosis was confirmed in the surgical piece in all patients. We conclude that Basedow-Graves disease and thyroid cancer, which can have an increased aggressiveness, may coexist.

Topics: Adolescent; Adult; Carcinoma, Papillary; Female; Graves Disease; Humans; Male; Middle Aged; Propranolol; Propylthiouracil; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography

A 30-year-old woman with hyperthyroidism due to coexisting Graves' disease and struma ovarii is described. Physical examination revealed a diffusely enlarged thyroid and an abdominal mass. CT scan of the abdomen showed a 25-cm predominantly cystic right ovarian mass. 123I uptake and scan showed 75% thyroid uptake at 4 h and a focus of intense uptake in the left upper quadrant of the abdomen. Preoperative treatment for the hyperthyroidism included propylthiouracil, propranolol, and ipodate. Surgery was performed and pathologic examination of the ovarian mass revealed struma ovarii.

Topics: Adult; Antihypertensive Agents; Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Ovarian Neoplasms; Propranolol; Propylthiouracil; Radionuclide Imaging; Struma Ovarii; Tomography, X-Ray Computed

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: Adult; Carbimazole; Female; Fetus; Graves Disease; Humans; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyrotoxicosis

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

Topics: Adolescent; Appetite; Behavior Therapy; Body Weight; Bulimia; Combined Modality Therapy; Female; Graves Disease; Humans; Propylthiouracil

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

We examined the effects of anti-thyroid drug treatment on serum autoantibodies against thyroid hormones (thyroid hormone autoantibodies, THAA), thyroglobulin (Tg) and thyroid peroxidase (TPO) in patients with Graves' disease by measuring each autoantibody level before and after treatment. Six patients among 40 untreated patients with Graves' disease had anti-thyroxine (T4) antibodies. One patient had both anti-T4 and anti-triiodothyronine (T3) antibodies. Thus the prevalence of THAA in untreated Graves' disease was 7 out of 40 (17.5%). Changes in T4-Ab levels after treatment varied. In five cases (cases 3-7) levels decreased 4-7 months after treatment. However, in the other two cases levels fluctuated 1, 3, 6 and 12 months after treatment. None of the previously THAA-negative patients became positive after treatment. Anti-Tg antibody (Tg-Ab) was positive in 34 out of 40 (85%) untreated cases and its level decreased in both THAA positive and negative patients after treatment. Anti-thyroid peroxidase antibody (TPO-Ab) was positive in 32 of the 40 (80%) untreated Graves' patients and its level significantly decreased after treatment. Our findings suggest that treatment with anti-thyroid drugs does not produce THAA in Graves' disease.

Topics: Adult; Autoantibodies; Female; Graves Disease; Humans; Iodide Peroxidase; Male; Methimazole; Propylthiouracil; Reference Values; Thyroglobulin; Thyroid Hormones; Thyroxine; Triiodothyronine

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

A 17-year-old Japanese woman developed a lupus erythematosus-like syndrome during treatment for Graves' disease with thiamazole and propylthiouracil. Erythema, arthralgia, and low grade fever developed during therapy with thiamazole; purplish-red erythema developed during therapy with propylthiouracil. Antinuclear antibodies, anti-single-stranded DNA antibodies, and anti-double-stranded DNA antibodies were positive throughout the administration of these two drugs. Eruptions and other symptoms improved after their discontinuation. The titers of autoantibodies also decreased two months after withdrawal. The patient had HLA DR4.

Topics: Adolescent; Antibodies, Antinuclear; DNA; DNA, Single-Stranded; Female; Graves Disease; Humans; Immunoglobulin M; Lupus Erythematosus, Systemic; Methimazole; Propylthiouracil; Skin Tests

IL-2 production by mitogen-induced peripheral blood mononuclear cells was reported to be reduced in several autoimmune diseases, including Graves' disease (GD). This production defect in hyperthyroid GD was restored to normal by antithyroid drug therapy or during remission. However, its underlying mechanism and role in the autoimmune process are still uncertain. The present study was undertaken in order to screen the in vitro IL-2 generating system for putative factors responsible for its failure, and to see to what extent this was reversible. Thyroid hormone or antithyroid drugs had no effect on IL-2 production in vitro. Cultures were found to be free of soluble inhibitors of IL-2 production or action. IL-1 deficiency as a cause of the IL-2 defect was ruled out; rather, Graves' adherent cells were found to be activated in being capable of secreting large amounts of IL-1 and prostaglandin E2 (PGE2). The latter was not found to be responsible for the decreased IL-2 production. IL-2 production by Graves' mononuclears was completely restored to normal by: (i) adherent cell depletion, irradiation or substitution with normal adherent cells; (ii) preincubation of mononuclears for 24-72 h before mitogen stimulation; (iii) the synergistic action of a phorbol ester and a calcium ionophore. These data indicate that inhibition by activated adherent cells accounts for the in vitro IL-2 production defect in GD. This inhibition is not mediated by soluble factors, but probably through direct interaction with the producing cells, and is reversible in rested cultures or through a bypassed signal transduction.

Topics: Cell Adhesion; Cells, Cultured; Dose-Response Relationship, Drug; Graves Disease; Humans; Interleukin-1; Interleukin-2; Leukocytes, Mononuclear; Methimazole; Orbit; Propylthiouracil; Tetradecanoylphorbol Acetate; Triiodothyronine

Two premenopausal female patients with Graves' hyperthyroidism and propylthiouracil (PTU)-induced agranulocytosis are presented. The first patient, age 47, received 300 mg of PTU per day and developed agranulocytosis within 6 weeks of the commencement of therapy. There were no granulocytes in the peripheral smear and a bone marrow biopsy demonstrated an absence of the entire myeloid cell line as well as the presence of many granulomas. The second patient, age 39, received PTU 1600 mg per day for two and half weeks and then 2 days of methimazole, 200 mg per day. She developed complete agranulocytosis on peripheral smear within 3 weeks of the initiation of therapy. Her bone marrow biopsy demonstrated maturation arrest of the granulocytic cell line at the myelocyte stage. In addition to discontinuing their antithyroid drugs, both patients were treated with G-CSF subcutaneously. The first patient received 300 micrograms of G-CSF on days 2 and 4 after discontinuing PTU with the appearance of 4.7 x 10(9)/L granulocytes and granulocyte precursors on day 4. The second patient received 575 micrograms of G-CSF for 2 days and 300 micrograms for 1 additional day beginning on the third day after discontinuing antithyroid drugs. On the second treatment day there were 5.8 x 10(9)/L granulocytes and granulocyte precursors on the peripheral smear. A comparison to previously published cases on antithyroid drug induced agranulocytosis suggests that the use of G-CSF decreased the amount of time required for marrow recovery after the cessation of the offending drug.

Topics: Adult; Agranulocytosis; Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Hematopoietic Stem Cells; Humans; Middle Aged; Propylthiouracil; Recombinant Proteins

The primary objective of this study was to ascertain the effectiveness of granulocyte colony-stimulating factor in the treatment of antithyroid drug-induced granulocytopenia of varying degree. Sixteen patients with Graves' disease with antithyroid drug-induced granulocytopenia (granulocyte counts < 1.0 x 10(9)/L) each received a daily dose of 75 micrograms of granulocyte colony-stimulating factor administered subcutaneously. Within 24 hours of the first injection, the granulocyte count increased (0.6 to 12.3 x 10(9)/L) in all 10 patients with mild granulocytopenia (granulocyte counts between 0.5 and 1.0 x 10(9)/L) and all three with moderate granulocytopenia (granulocyte counts < 0.5 x 10(9)/L). The three remaining patients with severe granulocytopenia (agranulocytic), whose granulocyte counts were zero, did not recover from granulocytopenia until the 6th, 7th, and 14th days of treatment with granulocyte colony-stimulating factor. Examination of bone marrow taken at the onset of the disease in all three agranulocytic patients showed a prominent decrease in granulocytic series, while identical examination in six of eight patients with mild to moderate granulocytopenia showed close to normal granulocytic series. There was no elevation of serum granulocyte colony-stimulating factor concentration in four patients with mild granulocytopenia and one with moderate granulocytopenia at the onset of their disease, whereas those of the remaining three patients with severe granulocytopenia (agranulocytic) increased at onset of agranulocytosis. This information led us to conclude that: (1) granulocyte colony-stimulating factor is effective in the treatment of antithyroid drug-induced mild to moderate granulocytopenia and (2) in severe agranulocytic cases, granulocyte colony-stimulating factor is not effective. Accordingly, we were again reminded of the importance of early diagnosis and treatment of antithyroid drug-induced agranulocytosis.

Topics: Adult; Aged; Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Recombinant Proteins

The effect of radioiodine therapy in Graves' disease is gradual in onset and the subjects continue to be hyperthyroid for several weeks after such therapy. In a prospective study of 112 patients, we compared the usefulness of two commonly employed antithyroid drug regimens in controlling hyperthyroidism in the period immediately following radioiodine therapy. They received propylthiouracil (PTU, 100 mg orally three times a day), saturated solution of potassium iodide (10 drops once a day) or no drugs starting 5 days after radioiodine therapy. Thyroid status was monitored clinically and by serum thyroxine index and TSH measured at 4-6 week intervals over a 6-month period. The control or drug-treated groups did not differ in thyroid status 6 weeks after radioiodine. The PTU-treated group had greater incidence of hyperthyroidism and a lower incidence of hypothyroidism at 6 months. However, the differences were explained on the basis of a greater incidence of large goiters that appeared to confer relative radioresistance in the PTU group. We conclude that patients with mild to moderate hyperthyroidism do not benefit from adjunctive treatment with PTU or potassium iodide immediately after radioiodine therapy.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Potassium Iodide; Propylthiouracil; Prospective Studies; Thyrotropin; Thyroxine

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 serum soluble interleukin 2 receptor (sIL2R) was measured in 38 first visited patients with Graves' disease and 29 normal controls. The serum sIL2R in 17 patients with Graves' disease was determined after treatment with antithyroid drugs (propylthiouracil) for a short period (1.2 +/- 0.5 months). The serum sIL2R was measured by sandwich enzyme linked immunosorbent assay. The sIL2R was significantly higher in patients before (3.04 +/- 0.19 U/ml) and after treatment (2.56 +/- 0.41 U/ml) than in normal controls (2.20 +/- 0.27 U/ml, P < 0.01). The mean value of serum sIL2R in 17 patients after treatment (2.56 +/- 0.41 U/ml) was substantially decreased as compared with that before treatment (2.99 +/- 0.14 U/ml, P < 0.01). The serum level of sIL2R in pretreatment patients was correlated significantly with T3(r = 0.5032, P < 0.05), but was not obviously related to T4 or rT3. These findings suggest that the human lymphocytes in patients with Graves' disease were activated in vivo and that sIL2R may be an useful immunological indicator of disease activity.

Topics: Adolescent; Adult; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Receptors, Interleukin-2; Thyroxine; Triiodothyronine

We report a case of 26-year-old woman with Graves' disease and idiopathic hypoparathyroidism diagnosed at 11 years of age, who subsequently developed insulin-dependent diabetes mellitus (IDDM) at 17 years of age. Treatment with antithyroid agents had failed to control her Graves' disease and her IDDM was unmanageable despite insulin therapy. Surgical intervention was carried out, resulting in an improvement of both her hyperthyroidism and IDDM. This case is the first report of polyglandular autoimmune (PGA) syndrome, presenting the association of IDDM, Graves' disease and idiopathic hypoparathyroidism.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycosuria; Graves Disease; Humans; Hypoparathyroidism; Insulin; Propylthiouracil; Thyroid Hormones

Graves' disease is an organ-specific autoimmune disease, and intrathyroidal lymphocytes seem to be the major source of thyroid autoantibodies. Consequently, the intensity of the intrathyroidal lymphocytic infiltration is generally believed to reflect the activity of the autoimmune process. We, therefore, investigated the correlation of microsomal (enzyme immunoassay), thyroglobulin (RIA), and TSH receptor antibodies (RRA) with the degree of intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T-cells, antigen-presenting cells, and the total number of lymphocytes. The immunocompetent cells were identified immunohistologically with monoclonal antibodies for immunoglobulins kappa and lambda, UCHL1, and the S100 antibody, respectively, in 26 thyroid glands of patients suffering from Graves' disease. The intensity of lymphocytic infiltration was determined by the point-counting method and by counting all lymphocytes and the labeled lymphocytes in 3 x 51 visual fields or 3 slides/thyroid gland. Microsomal antibodies correlated significantly (P = 0.001) with the total number of lymphocytes (r = 0.86), kappa (r = 0.71), lambda (r = 0.71), UCHL1 (r = 0.9), and S100 (r = 0.9) positive cells. These correlations were also significant for thyroglobulin antibodies. However, TSH receptor antibodies showed no significant correlations with any of the populations of immunocompetent cells. Patients with preoperatively undetectable TSH receptor or microsomal antibodies showed a broad variation of intrathyroidal infiltration by the immunocompetent cells investigated. Microsomal antibody titers, therefore, seem to reflect the intensity of the intrathyroidal autoimmune process in Graves' disease better than TSH receptor antibodies. However, the broad baseline variation in intrathyroidal infiltration observed with nondetectable thyroid antibodies will not always allow determination of the intensity of the intrathyroidal autoimmune process from microsomal or thyroglobulin antibody titers.

Topics: Adult; Antigen-Presenting Cells; Autoantibodies; Autoimmune Diseases; Carbimazole; Graves Disease; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Lymphocytes; Microsomes; Plasma Cells; Propylthiouracil; Receptors, Thyrotropin; T-Lymphocytes; Thyroglobulin; Thyroid Gland; Thyrotropin

We report a patient who developed eosinophilic pleuritis due to propylthiouracil. Although immunologic side effects associated with thionamides previously have been described, this is the first reported case of an isolated eosinophilic pleural reaction.

Topics: Emergencies; Eosinophilia; Graves Disease; Humans; Male; Middle Aged; Pleurisy; Propylthiouracil; Time Factors

Topics: Drug Therapy, Combination; Graves Disease; Humans; Infant, Newborn; Infant, Premature, Diseases; Ipodate; Male; Propranolol; Propylthiouracil

Intrauterine diagnosis and treatment of fetal goitrous hyperthyroidism due to maternal Graves disease has not been reported.. A case of fetal goitrous hyperthyroidism caused by maternal Graves disease was diagnosed and treated in the second trimester. High concentrations of both thyroid-stimulatory immunoglobulins (Igs) and thyrotropin-binding inhibitory Igs were detected in both maternal and fetal umbilical venous blood. Maternal propylthiouracil (PTU) treatment resulted in normalization of fetal thyroid function and a decrease in the size of the fetal thyroid goiter. Although euthyroid immediately after birth, the infant later became hyperthyroid and required treatment with PTU.. The relatively high frequency of fetal thyroid disorders in maternal Graves disease warrants complete maternal and fetal evaluation. Fetal diagnosis and treatment of either hyperthyroidism or hypothyroidism are feasible and necessary to prevent fetal morbidity and mortality.

Topics: Adult; Female; Fetal Blood; Fetal Diseases; Goiter; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Propylthiouracil; Ultrasonography, Prenatal

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

Topics: Adult; Graves Disease; Humans; Infusions, Intravenous; Male; Paralysis; Potassium; Propranolol; Propylthiouracil; Thyrotoxicosis

The well documented ability of immunoglobulins G (IgGs) from Graves' patients to stimulate cAMP production is believed to be involved in the pathophysiology of this disease. It is still under discussion whether other intracellular messengers known to regulate thyroid function might play a similar role. This study shows that phospholipase-A2, a signal pathway unrelated to cAMP, is activated by Graves' IgGs. The IgGs from 67 patients with active Graves' disease, 8 patients with Graves' disease in remission, 5 patients with idiopathic myxedema, 2 patients with Hashimoto's thyroiditis, 57 patients with nonautoimmune thyroid disease, and 65 normal subjects were tested for their ability to stimulate phospholipase-A2 activity, as measured by arachidonic acid release from FRTL5 thyroid cells. The IgGs from patients with active Graves' disease caused a significant increase in arachidonic acid release compared to those from normal subjects, patients with nonautoimmune thyroid diseases, and patients with Graves' disease in remission (P less than 0.0001). The IgGs from active Graves' patients were also able to increase cAMP accumulation in FRTL5 cells. This effect did not correlate with the ability of the same IgGs to induce arachidonic acid release, suggesting that Graves' IgGs stimulate these two pathways by separate mechanisms. Moreover, a subgroup of IgGs that stimulated phospholipase-A2 did not increase the cAMP levels in FRTL5 cells. Our data suggest a novel mechanism of action of Graves' IgGs, the activation of phospholipase-A2, well distinguishable from the known effect on cAMP accumulation. The assay we describe could be helpful in improving the diagnosis and therapy of Graves' disease and in distinguishing it from nonautoimmune thyroid diseases. It also supplies the basis for a prospective subclassification of the Graves' patients, which might become useful to clarify the pathophysiology of this disease.

Topics: Adolescent; Adult; Aged; Animals; Arachidonic Acids; Cell Line; Cyclic AMP; Female; Graves Disease; Humans; Immunoglobulin G; Male; Methimazole; Middle Aged; Phospholipases A; Phospholipases A2; Propylthiouracil; Rats; Reference Values; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyrotropin

Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

Topics: Adult; Female; Graves Disease; Humans; Peripheral Nervous System Diseases; Propylthiouracil

Using a rapid (whole blood lysis) single laser microfluorocytometric technique that permitted the simultaneous analysis of two monoclonal antibody surface markers tagged with different fluorescent dyes, the intrathyroidal (IT) and peripheral blood (PB) activated [Ia+ = DR+] T-lymphocyte CD3+ subsets and [F(ab')2+] B cells were studied in hyperthyroid patients with Graves' disease (GD) before and after 1-4 months of propylthiouracil (PTU) therapy. IT lymphocytes were obtained by serial fine needle aspiration. In untreated patients a marked quantitative (approximately < 10 fold) increase in activated (Ia+ CD3+) T-lymphocytes as well as CD4+ and CD8+ subsets, for IT compared to PB sites, was found. The percentages of Ia+ CD4+ and Ia+ CD8+ within Ia+ CD3+ were not significantly different between the two sources of T cells. F(ab')2+. B cells were significantly increased (approximately 2-3 fold) in IT compared to PB. In hyperthyroid GD patients, PTU therapy induced rapid and specific changes within the Ia+ CD3+ subsets, namely a reduction in the Ia+ CD4+ subset and an increase in the Ia+ CD8+ subset, resulting in a marked decrease in the Ia+ CD4+/Ia+ CD8+ ratio. These changes occurred in association with a reduction in serum T4 and T3 concentration. No significant changes could be detected within the total (predominantly non-activated) CD3+, CD4+ or CD8+ lymphocyte subsets within PB and only a small decrease in the CD4+/CD8+ ratio was demonstrated in IT, following PTU treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; B-Lymphocytes; Biopsy, Needle; Female; Flow Cytometry; Graves Disease; Histocompatibility Antigens Class II; Humans; Lymphocyte Activation; Male; Middle Aged; Propylthiouracil; T-Lymphocyte Subsets

An adolescent with Graves' disease presented with acute painful swelling of the thyroid gland and overlying erythema simulating acute suppurative or subacute thyroiditis. She had an elevated radioactive iodine uptake, thyroid stimulating antibodies, thyrotrophin binding inhibiting immunoglobulins, and a normal sedimentation rate and leucocyte count. The course of the thyrotoxicosis and painful thyroid was protracted, and the pain and tenderness of the thyroid recurred on two subsequent relapses.

Topics: Adolescent; Erythema; Female; Graves Disease; Humans; Iodine Radioisotopes; Pain; Propylthiouracil; Thyroid Function Tests; Thyroid Gland

Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Graves Disease; Humans; Intelligence; Methimazole; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Propylthiouracil

Recently, we identified significant amounts of thyroxine sulfate (T4S) in fetal sheep serum, meconium, bile, and amniotic and allantoic fluids. Little is known, however, about sulfate conjugation of thyroxine in humans. In this study, we employed a novel, sensitive T4S RIA to address this question. The rabbit antiserum was quite specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reactivity. Other analogs cross-reacted less than 0.0001%. Only rT3S and T3S cross-reacted significantly (9.9% and 2.0%, respectively). The mean serum T4S concentration (ng/dL) was 8.6 in euthyroid subjects, 14.4 in hyperthyroid subjects, 5.0 in hypothyroid subjects, 5.9 in pregnancy, and 4.5 in patients with nonthyroid illnesses. T4S concentration in amniotic fluid from women at 18-19 weeks of gestation (25.5 ng/dL) was higher than that at 14-15 weeks of gestation (14.3 ng/dL). A significant rise in serum T4S was detected in hyperthyroid patients 1 day after ingestion of 1 g of ipodate. These data suggest that T4S is a normal component of human serum and amniotic fluid, and it is mostly derived from T4 peripherally and accumulates when type I 5'-monodeiodinating activity is low in fetuses or inhibited by drugs, such as ipodate.

Topics: Amniotic Fluid; Analysis of Variance; Female; Graves Disease; Humans; Ipodate; Pregnancy; Propylthiouracil; Radioimmunoassay; Sensitivity and Specificity; Thyroxine

Reactive oxygen species are generated in tissues by activated mononuclear cells and macrophages. These cells infiltrate the thyroid gland in Graves' disease (GD), as well as the retroocular and pretibial space in Graves' ophthalmopathy and pretibial myxedema (PTM). Because a 72 kilodalton heat shock protein (HSP 72) is associated with autoimmune thyroid disease and is selectively expressed in fibroblasts derived from involved sites of patients with Graves' ophthalmopathy and pretibial myxedema, we studied the influence of oxygen free radicals (OFR), oxygen radical scavangers (ORS), and antithyroid drugs on HSP 72 expression in Graves' retroocular fibroblasts. Fibroblast monolayers were exposed to hydrogen peroxide (H2O2) or heat stress with simultaneous treatment, or pretreatment, with the ORS diaminobenzidine, nicotinamide, glutathione, propylthiouracil (PTU), or methimazole (MT). HSP 72 expression was determined by sodium dodecylsulfate polyacrylamide-gel electrophoresis, followed by immunoblotting with an anti-HSP 72 monoclonal antibody and densitometric quantitation of HSP 72 immunoreactivity. Baseline HSP 72 expression in Graves' retroocular fibroblasts was strongly enhanced by H2O2 and heat stress. Both pretreatment and simultaneous treatment with the ORS and any of the antithyroid agents significantly reduced the abundance of H2O2-induced (P less than 0.01), and to a lesser degree heat-induced (P less than 0.05), HSP 72 expression. These results demonstrate that, in Graves' retroocular fibroblasts, H2O2-induced HSP 72 expression is diminished both by classical ORS and by the antithyroid agents PTU and MT. In addition, heat-induced HSP 72 expression appears to be mediated in part by OFR. Stimulation of immunogenic 70 kilodalton HSPs by OFR, derived from immunocompetent cells infiltrating the affected tissues in GD, may play a role in the autoimmune process. The beneficial effect of MT and PTU on the clinical course and immune status of patients with GD may be related to their OFR-scavanging properties.

Topics: 3,3'-Diaminobenzidine; Cells, Cultured; Connective Tissue; Electrophoresis, Polyacrylamide Gel; Eye; Fibroblasts; Fluorescent Antibody Technique; Free Radicals; Gene Expression; Glutamine; Graves Disease; Heat-Shock Proteins; Humans; Hydrogen Peroxide; Immunoblotting; Methimazole; Niacinamide; Oxygen; Propylthiouracil

Graves' disease was initially diagnosed in an 11-year-old Chinese boy in March 1989. After regular propylthiouracil (PTU) and thyroxine, he achieved a euthyroid state. Heavy proteinuria with class IV lupus glomerulonephritis, anemia, arthralgia, low serum complement and anti-dsDNA (+) appeared 15 months later. Thyrotoxicosis also relapsed at this time. His condition fitted the diagnostic criteria of systemic lupus erythematosus. His antimicrosomal antibody titer was 1:1,600 (+) thyroid-stimulating hormone receptor antibody level was strongly positive, and the titer of antiinsulin antibody was high as well. These clinical, laboratory and histological findings indicate that class IV lupus nephritis may be associated with Graves' disease.

Topics: Carbimazole; Child; Chlorambucil; Graves Disease; Humans; Lupus Nephritis; Male; Prednisolone; Propylthiouracil; Thyroxine

We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens.

Topics: Adolescent; Adult; Autoantibodies; Drug Therapy, Combination; Eye Diseases; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroglobulin; Triiodothyronine

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

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

Topics: Autoantibodies; Congenital Abnormalities; Female; Fetus; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Gland

We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497 +/- 649 (mean +/- SD), 641 +/- 137 vs 221 +/- 63 10(3) U/l, p less than 0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r = 0.684, p less than 0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411 +/- 148 vs 221 +/- 63 10(3)U/l, p less than 0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.

Topics: Adult; Aged; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Goiter, Nodular; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Receptors, Interleukin-2; Thyroglobulin; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine

This retrospective study serves as an inquiry into the common practice of long-term administration of small maintenance doses of either methyl-mercaptoimidazole (MMI) or propylthiouracil (PTU) to Graves' hyperthyroid patients who became euthyroid with primary large doses of the same drugs. One hundred and two patients with Graves' hyperthyroidism treated with antithyroid drug (ATD) were studied. Sixty-one were treated with conventional long term therapy and 41 were treated with short-term therapy. Small maintenance doses of ATDs were not administered to the short-term therapy patients. The duration of long-term therapy was 28.6 +/- 20.2 months (from 12 to 48 months) and that of short-term therapy was 8.4 +/- 1.8 months (from 5 to 11). Post therapy and follow-up observation continued for 19.0 +/- 2.7 months (16-25 months) in both long-term and short-term patients. Of the 61 long-term therapy patients, 20 were relapsed and 41 (67.2%) continue to remain in remission. So too, of the 41 short-term therapy patients, 14 relapsed and 27 (65.9%) still remain in remission. There was no statistical difference between the long-term and short-term therapy group in age, sex, duration of symptoms before diagnosis, antithyroid antibodies, radioactive iodine uptake, free thyroid hormone levels or goiter size before treatment or in TBII levels at cessation of ATD. It is concluded that 'short-term ATD therapy' without a maintenance dose is sufficient and saves several months of the patient's and clinician's time.

Topics: Adult; Autoantibodies; Drug Administration Schedule; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Propylthiouracil; Remission Induction; Retrospective Studies; Thyroid Gland; Thyrotropin; Triiodothyronine

To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.

Topics: Adolescent; Adult; Autoantibodies; CD4 Antigens; CD8 Antigens; Female; Flow Cytometry; Graves Disease; HLA-DR Antigens; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine; Male; Methimazole; Middle Aged; Propylthiouracil; T-Lymphocyte Subsets; Thyroiditis, Autoimmune; Thyroiditis, Subacute

A 56-year-old man presented with clinical and biochemical hyperthyroidism with high thyroid 99mTc uptake, positive result for antimicrosomal antibody (MCHA; 1:8,100) and markedly high activities of thyrotropin-binding inhibitory immunoglobulin (TBII; 90.0%) and thyroid-stimulating antibody (TSAb; 2,400%). Fifty days after the initiation of antithyroid drug therapy, he developed a painful tender enlarged thyroid and an accelerated erythrocyte sedimentation rate (ESR), which were followed immediately by hypothyroidism with a transient increase in MCHA titer (peak; 1:218,700) despite of maintenance of high TBII and TSAb activities. Two and a half months after the recovery from hypothyroidism, recurrent hyperfunction was observed with further elevation of TSAb activity (4,643%). After about 2 weeks, recurrences of a painful tender enlarged thyroid and an accelerated ESR, which were followed by abrupt progression to hypothyroidism, were found. Specimens obtained when he had still slightly tender goiter after the first and second episodes of neck pain showed microscopically extremely extended interstitial fibrosis with collapsed follicles and moderate lymphocytic infiltration. Thyroid-stimulation-blocking antibody was not detected at either onset of hypothyroidism. Thus, it is possible that Graves' disease, subacute aggravation of chronic thyroiditis and hypothyroidism coexist in the same individual. In such patients, thyroid status may be determined by the degree of each of the stimulating factors (TSH, TSAb and/or unknown factors) and suppressive or destructive factors (humoral and/or cellular) and may be changed in a very short interval.

Topics: Autoantibodies; Biopsy, Needle; Blood Sedimentation; C-Reactive Protein; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

In three separate studies, members of the American Thyroid Association (ATA), the European Thyroid Association (ETA), and the Japan Thyroid Association (JTA) were surveyed by questionnaire on their management of Graves' disease. The aim was to determine how expert clinical thyroidologists employ diagnostic procedures and the three different therapies that are available for this disorder. In this report, we identify, summarize, compare, and contrast similarities and differences in the results of these surveys in these three different regions of the world. In general, ATA members used fewer diagnostic tests than did their European or Japanese colleagues. For the index patient, radioiodine was the therapy of choice for 69% of ATA respondents but only 22% and 11% of ETA and JTA respondents, respectively. In contrast, only 30.5% of ATA respondents chose antithyroid drugs as first-line therapy compared to 77% of ETA and 88% of JTA respondents. There was consensus on the relative lack of a role for thyroidectomy except for narrow indications. The implications of these differing approaches for the diagnosis and treatment of hyperthyroidism due to Graves' disease are discussed.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Cholesterol; Europe; Female; Graves Disease; Humans; Iodine; Japan; Male; Methimazole; Propylthiouracil; Severity of Illness Index; Surveys and Questionnaires; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; United States

A new commercially available human thyrotropin immunochemiluminometric assay (ICMA) kit was evaluated. The BeriLux assay (Hoechst Co., Germany) was compared with two other non-radioisotopic methods (AIA-1200 and IMx) and two other immunoradiometric assays (RIA-gnost TSH IRMA and EIKEN IRMA kits) in 32 normal subjects and 104 patients with Graves' disease, divided into seven groups: 1) untreated hyperthyroidism; 2) hyperthyroidism during treatment; 3) euthyroid with negative thyroliberin test (subclinical hyperthyroidism); 4) euthyroid with low thyroliberin test; 5) euthyroid with normal thyroliberin test; 6) euthyroid with high thyrotropin level (subclinical hypothyroidism); and 7) primary hypothyroidism. Patients in groups 2-6 were undergoing treatment with mercazole and propylthiouracil. The new immunoluminometric assay (ILMA) BeriLux kit was shown to have a remarkably improved analytical and clinical sensitivity. The minimal detectable level of thyrotropin in the assay was 0.006 mU/l. The precision was 2.8% and 6.1% at 0.093 +/- 0.003 mU/l and 0.028 +/- 0.002 mU/l, respectively, whereas the precision of the other methods was above 17.2% and 59.4% respectively. Seven patients from the untreated hyperthyroid group were given 500 micrograms thyroliberin i.v. (the thyroliberin test). The thyrotropin pattern before and after thyroliberin administration was always less than 0.006 mU/l with the BeriLux kit, whereas the other methods showed random fluctuations indicating their low accuracy at this concentration. Using the BeriLux kit, 7 of the 16 overt hyperthyroid patients undergoing treatment showed a measurable thyrotropin level below 0.01 mU/l but a negative thyroliberin test.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Evaluation Studies as Topic; Female; Graves Disease; Humans; Immunoassay; Immunoenzyme Techniques; Immunoradiometric Assay; Luminescent Measurements; Male; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Severe adverse reactions to propylthiouracil occur in 1-5% of patients. Three major side effects, namely agranulocytosis, hepatotoxicity and drug-induced hypersensitivity, have been described though these syndromes are not distinct entities and there can be overlaps in the clinical manifestations. The drug-induced hypersensitivity may be an immune-mediated reaction with multiorgan involvement in which a combination of polyarthritis, cutaneous vasculitis and fever is common. We report a patient with propylthiouracil-induced hypersensitivity with an unusual combination of high spiking fever, migratory polyarthritis, reversible sensorineural deafness, normochromic normocytic anaemia, leucocytosis and hepatotoxicity associated with polyclonal activation of multiple autoantibodies. This case illustrates the highly variable clinical manifestations of the syndrome. The prompt recovery upon withdrawal of the drug indicates the importance of early diagnosis.

Topics: Adult; Arthritis; Carbimazole; Drug Hypersensitivity; Female; Graves Disease; Hearing Loss, Sensorineural; Humans; Propranolol; Propylthiouracil; Thyroxine

It has been proposed that intrathyroid lymphocytes, localized in specific anatomical sites might have distinct, pathophysiologically relevant functions in Graves' disease. However, most studies of intrathyroidal lymphocytes were restricted to two lymphocyte locations and used semiquantitative methods. Therefore we used seven anatomically different lymphoid compartments to classify and evaluate by quantitative representative methods the total intrathyroidal lymphocytic infiltration and the staining indexes for immunoglobulin-producing plasmocytes and primed T cells (CD45RO), which provide maximum help to pokeweed mitogen-stimulated immunoglobulin synthesis in 36 thyroid glands from patients with Graves' disease. We found only 3.4% of all intrathyroidal lymphocytes intraepithelially. However, only intraepithelial lymphocytes showed a significantly higher staining index for primed T cells compared with several other compartments. There was also a high staining index for immunoglobulin-producing lymphocytes in this compartment. Kappa- and lambda-positive plasmocytes were found in a polyclonal distribution (kappa:lambda = 64.1: 35.9) in all compartments. This increased incidence of CD45RO-positive T lymphocytes and of immunoglobulin-producing lymphocytes among the intraepithelial lymphocytes suggests a distinct pathophysiological function of lymphocytes in peripolesis in Graves' disease. Furthermore, there is a polyclonal intrathyroidal immunoglobulin synthesis.

Topics: Adult; Antigens, CD; Carbimazole; Epithelium; Graves Disease; Histocompatibility Antigens; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulins; Iodine; Leukocyte Common Antigens; Plasma Cells; Pokeweed Mitogens; Propranolol; Propylthiouracil; T-Lymphocytes; Thyroid Gland

Topics: Adult; Graves Disease; Humans; Methimazole; Propylthiouracil; Thrombocytopenia

Topics: Adult; Agranulocytosis; Graves Disease; Humans; Liver; Methimazole; Propylthiouracil

The case of a 43-year-old female with propylthiouracil-induced hepatitis is reported. The case is unique because the patient's liver function deteriorated 2 weeks after medication was discontinued.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Graves Disease; Humans; Liver Function Tests; Propylthiouracil

Thirty-six patients with hyperthyroid Graves' disease were treated with low doses of antithyroid drugs until thyroid function test results indicated euthyroidism or mild hypothyroidism (median treatment period three months, range 1.5-8 months). Less than one-half (42%) of the patients remained hyperthyroid after two months of treatment, but 21% were still thyrotoxic after three months of treatment. Of 32 patients who completed treatment and entered the observation period after treatment was withdrawn, 27 (84%) have relapsed, two have remitted for one year or more and three have been followed for less than one year without relapse. Although once daily, low dose, short term antithyroid drug treatment of patients with Graves' disease in the Wellington area satisfactorily controls the hyperthyroidism in the majority of cases, it is followed by an unacceptably high relapse rate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbimazole; Drug Administration Schedule; Drug Evaluation; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Recurrence; Remission Induction; Thyroid Function Tests; Time Factors

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

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroiditis, Autoimmune

Members of the American Thyroid Association were invited to participate in a survey of the management of Graves' disease. One primary case and several variations were provided, which differed in respect to age, sex, goiter size, severity, etc. The questionnaire was based on the format used in a similar survey of members of the European Thyroid Association. The aim of the survey was to determine 1) how expert thyroidologist employ diagnostic procedures for this disorder, and 2) the choice of therapy of the three treatment options and its manner of implementation. Questionnaires were sent only to clinically active members. The overall response rate was 62%. Data analysis was possible on 52% of members surveyed and was performed using SPSS and a specific Fortran program. In the laboratory evaluation of the primary case a radioiodine uptake, scan, serum total T4, and basal TSH were requested by 92%, 47%, 83%, and 66%, respectively, with 84% of respondents using an ultrasensitive TSH assay. For management of the primary case, radioiodine treatment was the first choice of 69% of the respondents. Antithyroid drugs were used briefly (3-7 days) before 131I by 28%, whereas 41% said they would employ thioureas after 131I. Of those using 131I, 66% tailored the dose to achieve euthyroidism as the goal of therapy, while 34% aimed for hypothyroidism requiring T4 replacement. Only 30% of respondents chose thioureas as a first line of treatment (72% propylthiouracil; 28% tapazole). The duration of drug therapy was a predetermined fixed interval for 80% of the respondents, with 90% treating for 1-2 yr. Other specific trends in diagnostic approach and therapeutic preferences were identified for the eight variations on the primary case problem.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Propylthiouracil; Surveys and Questionnaires

Topics: Agranulocytosis; Antithyroid Agents; Depression, Chemical; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Tablets; Thyroid Hormones

We studied interrelationships between maternal and neonatal thyroid function, TSH receptor binding inhibiting immunoglobulins (TBII), and dose of thionamide antithyroid drugs in 44 women with active Graves' disease presenting during 46 pregnancies, and their 48 infants. The women were treated with propylthiouracil (PTU) or carbimazole (CBZ). In 30 pregnancies (30 infants) treatment was withdrawn from 3 to 18 weeks before delivery (Group A). Drug treatment (PTU, n = 10, dose 50-400 mg/day or CBZ, n = 6, dose 5-45 mg/day) was continued throughout pregnancy and delivery in 16 pregnancies producing 18 infants (Group B). The maternal TBII at delivery was well correlated with maternal free thyroxine index (FTI) averaged over the third trimester (r = 0.603, P less than 0.001) and umbilical venous serum TBII (r = 0.940, P less than 0.001). Neonatal FTI was independently related to umbilical vein TBII (t = 2.29, P = 0.03) and maternal dose of antithyroid drug (t = -2.21, P = 0.03). Neonatal thyrotoxicosis was seen in all four infants (8% of births) of women whose TBII levels at delivery exceeded 70%. No child was born with a subnormal FTI but 7/18 infants in group B had raised TSH at birth. This was more likely to occur (P = 0.05) if maternal TBII was less than 30% (6/10) than if maternal TBII was greater than 30% (1/8). Four Group B women with FTI in the lower half of the reference range delivered infants with raised TSH compared with 3/14 (21%) women whose FTI was in the upper half of the reference range or above (P = 0.05). In pregnant women with active Graves' disease TBII levels reflect stimulatory TSH receptor antibody activity. TBII measurements are of use in the prediction of neonatal thyrotoxicosis and impaired neonatal thyroid function in infants of women treated with antithyroid drugs.

Topics: Autoantibodies; Carbimazole; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine

With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

Topics: Birth Weight; Carbimazole; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Growth; Humans; Infant, Newborn; Intelligence; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Administration, Rectal; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Thyroid Crisis

This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment.

Topics: Adult; Agranulocytosis; Female; Granulocytes; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Propylthiouracil

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

The efficacy of 131I therapy in achieving euthyroidism has been studied in a group of 264 patients followed for up to 10 yr. One hundred and eighty-six were given a dose adjusted for thyroid size and radioactive iodine uptake (Protocol 1), and a second group received the same dosage followed by antithyroid drug therapy plus potassium iodide for 15 days (Protocol 2). At 10-yr follow-up, 50-60% of patients were euthyroid. 25-29% of patients required 2 doses of 131I, and 4-5% required 3 doses. Fewer patients became hypothyroid when their pretreatment FTI was above the average value. More patients became hypothyroid, if their pretreatment test for antimicrosomal antibodies was positive. Patients who required a second dose of radioactive iodide had a significantly greater chance of having worsening of their ophthalmopathy than those who became hypothyroid after the first dose. Treatment with radioactive iodide under either protocol appears to achieve euthyroidism at 10 yr with an incidence higher than that achieved by antithyroid drugs and comparable to that reported for subtotal thyroidectomy.

Topics: Combined Modality Therapy; Eye Diseases; Female; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Middle Aged; Potassium Iodide; Propylthiouracil; Thyroid Gland; Thyroxine

Antidouble stranded DNA (dsDNA) antibodies have been detected by a sensitive RIA in the sera of 28-100% of patients with Graves' disease, but it remains unclear whether these assays have detected authentic dsDNA antibodies. We have obtained sera from 42 patients with active Graves' disease and no known connective tissue disorders. All sera were tested for dsDNA antibodies by 2 quantitative RIAs (Farr assay and Millipore filter assay; normal, less than 20% for both assays) and by an enzyme-linked immunosorbant assay for antibodies to dsDNA and to single stranded DNA (ssDNA). All sera were negative for dsDNA antibodies by the Farr assay and by enzyme-linked immunosorbant assay, 2 of 42 had mildly elevated levels (33% and 23%) by the Millipore filter assay, and 7 of 42 were positive for ssDNA antibodies. The 2 positive sera for dsDNA antibodies were also tested using the Crithidia luciliae indirect immunofluorescence assay, and both were negative. Patients with Graves' disease have been reported to have an increased prevalence of antinuclear antibodies, but the more recent findings of dsDNA antibodies in these patients is of interest because dsDNA antibodies are considered to be specific for systemic lupus erythematosus. Our data suggest that true immunoglobulin G dsDNA antibodies are not elevated during active Graves' disease, and positive assay results may be due to measurement of ssDNA antibodies, immunoglobulin M dsDNA antibodies, or nonantibody DNA binding.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; DNA; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil

Topics: Adult; Female; Graft Rejection; Graves Disease; Hepatic Encephalopathy; Humans; Liver Transplantation; Lymphoma; Pregnancy; Pregnancy Complications; Propylthiouracil

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

We studied 4 cases of Graves' disease with anti-thyroid hormone antibodies. Changes in the serum levels of triiodothyronine(T3), thyroxine(T4), free T4, thyrotropin(TSH), and thyroglobulin(Tg), as well as titers of anti-Tg antibodies, anti-thyroid hormone antibodies, anti-TSH receptor antibodies(TRAb) and anti-microsomal antibodies(MCHA) during 2 10 years' treatment periods were examined in each case. Case 1; A woman, who was diagnosed as having Graves' disease when she was 10 years old, had been treated with methimazole(MMI) or propylthiouracil(PTU). Treatment with the antithyroid drug had been discontinued by herself when she was 19 years old until she was 24 years old, when she was pregnant and consulted our hospital. Since her serum levels of T3 were unusually high, examination of her serum for the presence of anti-T3 antibodies was done. The presence of anti-T3 antibodies in her serum was confirmed. Case 2; A woman, who was diagnosed as having Graves' disease at the age of 41, had been treated with MMI or PTU. Presence of serum anti-T3 antibodies was found in a screening test for the antibodies. Serial sera were obtained during the 5 year observation period when she was treated with MMI, PTU, and subtotal thyroidectomy. Titers of anti-Tg antibodies in her sera were in the normal range. Case 3; A woman, who was diagnosed as having Graves' disease at the age of 11, had been treated with MMI or PTU. Presence of anti-T3 and anti-T4 antibodies were found in her sera in a screening test. Serial sera obtained during the 4 year treatment period were tested. Case 4; A woman, who was diagnosed as having Graves' disease at the age of 14, had been treated with MMI. Presence of anti-T3 and anti-T4 antibodies was found in her sera in a screening test. Serial sera obtained during the 2 year treatment period were tested. Titers of anti-Tg were increased when the levels of TSH or titers of TRAb were increased. The results suggested that TSH and TRAb, which are thyroid stimulating substances, increased serum levels of Tg, which resulted in the increase of titers of anti-Tg. Because of the possibility that administration of PSL could modify B lymphocyte functions, periods during which PSL was administered were excluded from the examination of the correlation between Tg concentrations or titers of anti-Tg and titers of anti-thyroid hormone antibodies, as in Cases 2 and 4, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Autoantibodies; Autoantigens; Child; Female; Graves Disease; Humans; Methimazole; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroglobulin; Thyroid Hormones; Thyrotropin

Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change. All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red-cell membrane. In addition LSH is a general radical scavenger and SOD a specific O2- scavenger. In Graves' disease the increased oxidative stress and increased general radical scavenging may result from raised free-radical activity. These changes, which have not previously been reported in Graves' patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect.

Topics: Adult; Carbimazole; Ceruloplasmin; Female; Free Radicals; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Oxidation-Reduction; Oxygen; Propylthiouracil; Sulfhydryl Compounds; Superoxide Dismutase; Thyroxine; Triiodothyronine

We assessed the post-natal thyroid function in eight infants of mothers with Graves' disease whose thyroid function at birth was suppressed by maternal ingestion of propylthiouracil during pregnancy. These mothers continued taking propylthiouracil after delivery and breast-fed exclusively (two mothers supplemented their breast milk with a small amount of baby food). The cord free T4 level was slightly but uniformly below the normal range in all eight infants, and the cord TSH level was above the normal in seven infants. The dose of propylthiouracil after delivery ranged from 50 to 300 mg daily, which was equal to, or higher than, that before delivery. All these abnormal values normalized in the infant after birth. Serum samples, from seven of the eight mothers, taken at delivery were examined for TSH receptor antibodies; all were positive. The antibody titre, however, was too low, and/or free T4 and TSH levels were examined too long after delivery, for the antibodies to be the cause of the restoration of the infants' thyroid function. These results assure the safety of breast-feeding for the infants of mothers with Graves' disease taking propylthiouracil.

Topics: Adult; Breast Feeding; Female; Fetal Diseases; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine

This study examined the abilities of methimazole, propylthiouracil (PTU) and propranolol to exert an immunosuppressive effect in vitro. Incubation of peripheral blood lymphocytes (PBL) with propranolol showed the drug to have no effect on either B- or T-cell activity. Methimazole or PTU at concentrations of greater than or equal to 10(-5)M resulted in significantly lower amounts of IgG and IgM being released into the culture medium. Both drugs were also found to have a direct effect on T-cell function as they caused the percentage of total and suppressor cells to increase towards normal levels. The three drugs were all found to have some free radical scavenging ability. These ranked PTU greater than methimazole greater than propranolol. These in-vitro findings would suggest that both methimazole and PTU have some direct effect on the immune system. It would seem more likely however that these effects are mediated via interleukin 2 rather than by their ability to act as free radical scavengers.

Topics: Antithyroid Agents; B-Lymphocytes; Culture Media; Free Radicals; Graves Disease; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppression Therapy; In Vitro Techniques; Methimazole; Propranolol; Propylthiouracil; T-Lymphocytes

Cultures of human thyroid follicles embedded in collagen gel were performed to investigate certain functional properties under bovine thyrotropin (TSH) stimulation. Follicles obtained from normal glands responded to increasing concentrations of TSH administered on day 4 in culture and for 3 days by increased amounts of cyclic AMP (cAMP), thyroglobulin (Tg) and triiodothyronine (T3) and by decreased levels of thyroxine (T4). Effect was maximal at 2000 microU/ml TSH (cAMP) or 200 microU/ml (Tg, T3, T4). When methimazole or propylthiouracil (PTU) were added, the T3 levels decreased. Follicle lumens contained a periodic acid-Schiff substance which was identified by immunoreaction as Tg. Thyroid follicles obtained from Graves' disease glands gave modified results with an earlier and intensified T3 response and no increase in Tg. These data show that (1) Tg and T3 are secretory products of functional follicles giving a cAMP-mediated response to TSH. (2) The detected T3 also derives from T4 5'-deiodination inhibited by PTU. (3) Intensified T3 response in Graves' follicles is probably due to enhanced conversion of T4 to T3.

Topics: Cells, Cultured; Collagen; Cyclic AMP; Graves Disease; Humans; Kinetics; Methimazole; Propylthiouracil; Thyroglobulin; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Interleukin-2 is a lymphokine which is believed to play a central role in the regulation of the immune response. The production of and response to interleukin-2 were determined in hyperthyroid Graves' patients together with thyroid function and serum thyrotropin receptor antibody, a marker of autoimmune activity. Interleukin-2 production by mitogen-induced peripheral blood mononuclears was markedly low in 24 of 29 patients when compared to controls. Five patients in remission had normal values. In nine patients followed during antithyroid drug therapy, interleukin-2 production returned gradually to normal levels within 4-6 months. This rise and the concomitant decrease in serum thyrotropin receptor antibody correlated with the decline in the free thyroxin index. Antithyroid drugs and triiodothyronine had no effect on interleukin-2 production in vitro. Mitogen-activated mononuclears from hyperthyroid Graves' patients did not proliferate as well as the controls in response to interleukin-2. However, seven patients treated with antithyroid drugs and three in remission responded normally. Flow cytometry using anti-Tac antibody revealed that the interleukin-2 receptor density on mononuclears from five patients was low. This parameter was normal in treated patients and those in remission. We conclude that the production of and response to interleukin-2 by peripheral blood mononuclears from hyperthyroid Graves' patients are poor, the latter being due to impaired receptor expression. Both aberrations are restored to normal by antithyroid drug therapy or in remission. The relative roles of the autoimmune process and thyroid function in modulating the interleukin-2 pathway and the question of whether antithyroid drugs act directly or through thyroid inhibition remain to be clarified.

Topics: Adult; Antibody Formation; Cell Line; Cell Line, Transformed; Female; Graves Disease; Humans; Interleukin-2; Male; Methimazole; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Thyroxine

To investigate the natural killer (NK) cell mediated immunity in Graves' disease (GD) and the effect of antithyroid drugs upon NK cell activity, 51Cr release assay for NK cytotoxicity against K562 cells was examined in patients with GD before and during antithyroid medication and after drug withdrawal. Fifty-eight patients were divided into three groups: the untreated thyrotoxic patients (n = 33), the euthyroid patients under antithyroid treatment (n = 19) and the euthyroid patients after drug withdrawal (n = 6). The results of the three groups were compared to 23, 15 and 5 sex- and age-matched controls, respectively. The data revealed a significant NK dysfunction in the untreated hyperthyroid patients, although the number of the NK cells was not decreased. NK function was normal when patients were no longer taking antithyroid medication and in euthyroid state. However, euthyroid patients under antithyroid medication had markedly depressed NK activity, suggesting an immunosuppressive effect of the antithyroid drugs. This study demonstrated that both the hyperthyroid state and the antithyroid drugs exerted immunosuppressive effects upon the NK cells. Since such an immunosuppressive effect on NK cells might be associated with a decreased immune surveillance against tumour growth, this study implies that a long-term follow up of GD patients treated with antithyroid drugs may be indicated to guard against a possible increased incidence of malignancy.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Killer Cells, Natural; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Hormones; Time Factors

A 67 year old man presented with a well differentiated follicular carcinoma of the thyroid 17 years after he had been given radioactive iodine for Graves' disease. As this was insufficient to cure him he had continued to take propylthiouracil regularly. The tumour, which had completely replaced the thyroid, was apparently maintaining thyrotoxicosis. The implications of this management are discussed and it is concluded that antithyroid drugs should not be given on a long term basis after therapeutic radioiodine has been administered.

Topics: Adenocarcinoma; Aged; Graves Disease; Humans; Iodine Radioisotopes; Male; Neoplasms, Radiation-Induced; Propylthiouracil; Thyroid Neoplasms; Thyrotoxicosis

Carbimazole and Propylthiouracil (PTU) are widely used in the treatment of Graves' disease, although controversy still exists as to whether or not they have any direct effect on the immune system. While many previous studies have investigated the possible effects of one or other of these drugs on the immune system only a few have directly compared the effects of equivalent doses of each drug. This study aimed to examine the effects of both drugs, during the initial 8 weeks of treatment, on various biochemical and immunological parameters. The results obtained showed that while thyroid hormone levels fell at similar rates in both treatment groups, TRAb levels and T cell subset abnormalities returned towards normal more rapidly in patients receiving Carbimazole compared to PTU. These results indicate that the effects of Carbimazole on TRAb levels and T cell subset abnormalities are not due solely to its action in controlling the biochemical features of Graves' disease and provide indirect evidence of an action on the immune system in vivo.

Topics: Adult; Autoantibodies; Carbimazole; Female; Graves Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; T-Lymphocytes; Thyroxine; Triiodothyronine

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

The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.

Topics: Adult; Agranulocytosis; Bone Marrow; Colony-Forming Units Assay; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Stem Cells

We describe the endocrine, psychiatric, and neuropsychological assessments of 10 untreated, newly diagnosed Graves' disease subjects who were studied longitudinally at three stages: hyperthyroid (stage 1), after 2 weeks of propranolol treatment (stage 2), and after 6 months of antithyroid treatment (stage 3). Major depression, generalized anxiety disorder, and hypomania were diagnosed at stage 1. Elevations on psychiatric symptom rating scales and in motor activity monitoring at stage 1 were significantly decreased at stage 2 and again at stage 3. Psychiatric improvements paralleled improvements in endocrine symptoms. Neuropsychological improvements were noted on the more challenging memory and attention tasks at stage 3, whereas propranolol treatment was not associated with changes on attention tests. Results are discussed in relation to catecholamine-thyroid hormone interactions, in particular, the beta-adrenergic system.

Topics: Adult; Female; Graves Disease; Humans; Male; Middle Aged; Neurocognitive Disorders; Neuropsychological Tests; Propranolol; Propylthiouracil; Psychiatric Status Rating Scales; Thyroid Hormones

The pharmacokinetics of propylthiouracil (PTU) was studied in 7 patients having Graves' disease when they were hyperthyroid and then again when they were euthyroid. Two additional euthyroid patients were also studied. The t1/2, Ke, Ka, apparent Vd, AUC and clearance were calculated. Serum T3 and T4 were also measured. PTU had an immediate effect in reducing T3 levels. Although there were intraindividual variations, the mean PTU elimination half-time did not change from the hyperthyroid state (1.47 h) to the euthyroid state (1.53 h). The mean Ka when hyperthyroid (2.12 h-1) was significantly increased (p less than 0.005) compared to when euthyroid (1.00 h-1). The calculated kinetic information indicates that the disposition of PTU in children is similar to that reported in adults.

Topics: Adolescent; Child; Female; Graves Disease; Humans; Kinetics; Male; Propylthiouracil; Thyroid Function Tests; Thyroxine; Triiodothyronine

The pregnancy of a women with diabetes mellitus was complicated by Graves' disease and maternal allergies to propylthiouracil and methimazole. Preparations for surgical removal of the thyroid gland were being made until pregnancy intervened. Several well-documented mechanisms of hyperthyroidism, including increased intestinal absorption of glucose, decreased insulin responsiveness, and increased glucose production may exacerbate glucose intolerance; the daily insulin requirement of this patient rose 80% from her pregestational dosage. When large doses of propranolol failed to control her thyrotoxic symptoms and led to severe, recurrent hypoglycemic episodes, subtotal thyroidectomy was performed. A 42% decrease in insulin requirements was observed postoperatively, with return to the euthyroid state. A propensity for symptomatic postoperative hypoglycemia should be anticipated in diabetic patients undergoing thyroidectomy.

Topics: Adult; Drug Hypersensitivity; Female; Graves Disease; Humans; Insulin Coma; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Propranolol; Propylthiouracil; Thyroidectomy

Topics: Adolescent; Adult; Antibodies, Antinuclear; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Hypothyroidism; Male; Middle Aged; Propylthiouracil

The iodine organification in thyroid gland was inhibited by application of Thyrostatic (Methimazole, Carbimazole) and consequently, thyroid hormone production and excretion were diminished. Carbimazole is converted to Methimazole in vivo and in vitro. Equivalent doses of Carbimazole and Methimazole are 0.6 to 1.0. Methimazole penetrates through the placenta, therefore established therapy with Methimazole (or Carbimazole) and thyroid hormone are contradicted in states of gravidity. In hyperthyroidism, preferred therapy strategy is accepted as Methimazole and/or Carbimazole only and in low doses, respectively (40-60 mg Methimazole as first step, consequently to doses down to 5-10 mg daily); accompaning rates of hematopoetic damage are dose responded.

Topics: Antithyroid Agents; Carbimazole; Dose-Response Relationship, Drug; Graves Disease; Humans; Methimazole; Propylthiouracil

The monocyte procoagulant activity (PCA) production assay has been shown to be a good parameter of cell-mediated immunity. We have studied antigen-specific PCA production in peripheral blood mononuclear cells from patients with Graves' disease to determine the effect of the treatment on the cell-mediated immune response. Peripheral blood mononuclear cells from patients with untreated or relapsed Graves' disease produced significantly greater PCA with thyroid antigen stimulation than those from normal subjects. Patients both on antithyroid drugs in the hyperthyroid state and within 3 months post-131I therapy also produced significantly larger amount of PCA than normal subjects. However, there was no significant difference in PCA production with thyroid antigen stimulation between normal subjects and patients on anti-thyroid drugs in the euthyroid state, or patients over 3 months post-131I therapy. The ratio of positive to negative PCA production in patients on anti-thyroid drugs in the euthyroid state or over 3 months post-131I therapy was significantly lower than in untreated or relapsed Graves' disease patients. Mononuclear cells from patients on propylthiouracil responded to propylthiouracil in vitro by production of PCA. Cells from normal subjects, untreated Graves' disease patients, or patients with Hashimoto's thyroiditis did not produce PCA with propylthiouracil stimulation. Mononuclear cells from patients who were on propylthiouracil for more than 3 months produced greater PCA than those on the drug for less than 3 months, suggesting sensitization of lymphocytes to propylthiouracil during the course of treatment. However, after 131I therapy, they gradually became unresponsive to propylthiouracil. This study has shown that the activity of the antigen-specific response assessed by PCA production in mononuclear cells from Graves' disease patients declined after treatment, suggesting that the treatment exerted immunomodulatory effects.

Topics: Adolescent; Adult; Aged; Blood Coagulation Factors; Epitopes; Female; Graves Disease; Humans; Immunity, Cellular; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil

Natural killer (NK) activity of peripheral blood lymphocytes from hyperthyroxinemic patients (Graves' disease or thyroxine (T4)-treated) is severely depressed. In order to study the relationship of thyroid hormone to NK activity, a model for hyperthyroxinemia was induced in mice by addition of T4 to the drinking water. Control mice were hypothyroid (fed propylthiouracil) or normal. Serum T4 levels were elevated (within 2 wk) in mice fed thyroid hormone. Six weeks after initiation of the diets, in vitro NK activity was undetectable in the peripheral blood, spleen, or lung mononuclear cell populations harvested from hyperthyroxinemic mice. Control mice had NK activity within the normal range. Spleen cells from mice fed thyroid hormone and control mice were tested for their ability to release lytic factors (natural killer cytotoxic factors). Lymphoid cells were incubated for 20 hr with unlabeled Yac-1 cells. Supernatants were tested for their capacity to lyse 51Cr-labeled Yac-1 cells in a 20-hr chromium release assay. Unlike controls, supernatants from hyperthyroxinemic spleen cells incubated with Yac-1 targets were unable to lyse 51Cr-Yac-1 cells. The NK cells from the mice fed T4 synthesized lytic factors because nonspecific stimuli, such as 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore A23187, induced release of lytic factors capable of lysing Yac-1 targets into the media. These data support the hypothesis that excess thyroid hormone interferes with the triggering mechanism used by NK targets to cause release of lytic molecules from NK cells.

Topics: Animals; Cytotoxicity Tests, Immunologic; Disease Models, Animal; Female; Graves Disease; Hypothyroidism; Interleukin-2; Killer Cells, Natural; Killer Factors, Yeast; Leukocyte Count; Mice; Mice, Inbred C57BL; Propylthiouracil; Proteins; T-Lymphocytes; Thyroxine

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

The effects of methylmercaptoimidazole (MMI) and propylthiouracil (PTU) were compared in patients with Graves' hyperthyroidism. Firstly, the duration of action of the drugs was studied by the perchlorate discharge test, which was performed 2, 12, or 24 h after administering a single dose of 15 mg MMI or 300 mg PTU. After 2 h, the 9 MMI-treated patients who were tested had marked discharge (mean +/- SD, 65.0 +/- 15.8%), as did the 6 patients treated with PTU (57.6 +/- 26.6%). The mean values for the percent discharge 12 and 24 h after drug administration were 34.9 +/- 31.9% (4 patients) and 36.5 +/- 26.9% (69 patients), respectively, in the MMI group and 19.1 +/- 11.7% (11 patients) and 8.6 +/- 10.5% (7 patients) in the PTU group, indicating that the effect of MMI lasted longer. Secondly, the clinical effects of long term administration of the drugs were compared in a different group of patients with Graves' hyperthyroidism. Within 5 weeks after the onset of treatment, 34 (52%) of 66 patients treated with MMI (10 mg, 3 times daily) were euthyroid, while only 1 of 17 patients treated with PTU (100 mg, 3 times daily) was euthyroid. The average time required to achieve euthyroidism, namely normal serum T3 and T4 levels, was significantly shorter in the MMI group [6.7 +/- 4.6 (+/-SD) weeks] than in the PTU group (16.8 +/- 13.7). In spite of the well known effect of PTU on the extrathyroidal conversion of iodothyronines, the serum T3 level normalized much faster with MMI than with PTU. These results indicate that in our patient population 15 mg MMI had a longer inhibitory effect on the organification of iodide than did 300 mg PTU, and that MMI was more rapidly effective in the treatment of Graves' hyperthyroidism.

Topics: Adult; Female; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Thyroid Hormones; Time Factors

Sequential changes in thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) during antithyroid drug treatment were studied in 17 patients with Graves' disease. Before treatment, TSAb and TBII were detected in 17 (100%) and 13 (76.5%) patients, respectively, with a significant correlation between the two activities (r = 0.600, n = 17, P less than 0.02). In 9 patients who became euthyroid as early as after 1-4 months of treatment, the TSAb and TBII activities both gradually decreased, and there was a good correlation between the changes of these activities during treatment. Among the 7 patients in whom small changes in TSAb and TBII activities were observed, 4 showed poor control of the thyrotoxicosis during the whole observation period (7 months-2 years). One patient who showed a marked dissociation between the changes in TSAb and TBII activities developed hypothyroidism, when his TBII became remarkably high. These potent TBII inhibited cAMP production induced by bTSH. These findings indicate that 1) changes in TSAb and TBII activities reflect the clinical course of hyperthyroidism in most patients with Graves' disease, and 2) development of a blocking-type of TBII may induce hypothyroidism in some patients after the treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Propylthiouracil

We compared fetal and maternal serum indexes of thyroid status at delivery in 70 patients with Graves' disease who required therapy with thionamides (such as propylthiouracil) during pregnancy. Forty-three mothers required thionamides until delivery (Group 1), whereas the drugs were discontinued during pregnancy after remission in 27 mothers (Group 2). Maternal free thyroxine levels were closely correlated with cord levels in both groups, being essentially identical in Group 2 but slightly lower in fetuses than in mothers in Group 1. Normal maternal free thyroxine levels did not preclude fetal hypothyroidism. The mothers and fetuses in Group 1 had a significantly higher incidence of antibodies that inhibit thyrotropin binding than did those of Group 2. However, a significant correlation between maternal levels of these antibodies and cord levels of free thyroxine or triiodothyronine was found only in Group 2, in which some maternal and cord thyroxine levels were in the thyrotoxic range at delivery, presumably because therapy was discontinued. These findings indicate that high free thyroxine levels and the presence of antibodies that inhibit binding of thyrotropin are useful indexes of the fetal need for antithyroid treatment, and that the thionamide dosage that maintains maternal free thyroxine levels in a mildly thyrotoxic range seems appropriate for maintaining euthyroid status in the fetus.

Topics: Antibodies; Antithyroid Agents; Female; Fetal Blood; Fetal Diseases; Fetus; Graves Disease; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

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

We studied the effects of high doses of methimazole (MMI) or propylthiouracil (PTU) on thyroid-stimulating antibody (TSAb), antithyroid microsomal (MCHA) and antithyroglobulin (TGHA) levels in Graves' disease and Hashimoto's thyroiditis. Thirty Graves' hyperthyroid patients were treated for 14 +/- 8 months (mean +/- SD) with MMI, 60-80 mg daily or PTU, 900-1200 mg daily plus T3, 50-75 micrograms daily. Fifteen Hashimoto's thyroiditis patients (4 of whom hypothyroid) received 100-200 micrograms of T4 daily for 4-8 weeks prior to MMI, 60-90 mg daily or PTU, 900 mg daily for 12-16 weeks. In Graves' disease a decrease (p less than 0.001) in TSAb activity (20/25 patients) was observed: before therapy, 0.424 +/- 0.506 pmoles/mg wet wt and at the end of treatment, 0.189 +/- 0.23 pmoles/mg wet wt. The MCHA titers also fell (18/26 patients) from 1:10,403 +/- 20,197 to 1:3,476 +/- 5,252 (p less than 0.01) and was associated with a decrease in free T4 values (1.23 +/- 0.69 vs. 0.51 +/- 0.36 ng/dl; p less than 0.01). A fall of MCHA titers in T4-treated Hashimoto's thyroiditis patients (1:10,416 +/- 25,576) was found when compared with the value before T4 (1:25,920 +/- 39,973; p less than 0.001). However, the titers of MCHA (1:13,280 +/- 25,992) did not change on MMI or PTU plus T4 treatment. The TGHA titers fell in a single patient. No alterations were observed in serum immunoglobulins. Serum concentrations of the complement factor C'3 remained higher (p less than 0.01) than normal values in both Graves' disease and Hashimoto's thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Isoantibodies; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Thyroiditis, Autoimmune

Changes in titers of serum thyroid hormone autoantibodies (THAA) and anti-thyroglobulin (Tg) antibodies during treatment with antithyroid drugs (methimazole and propylthiouracil) were examined in two cases of Graves' disease. Effects of prednisolone and subtotal thyroidectomy were also investigated in one case (case 1). Initially both cases had only anti-T4 autoantibodies in their serum. During methimazole therapy, the titer of anti-T4 autoantibodies increased in both cases, and anti-T3 autoantibodies became detectable and their titer increased in case 2. The influence of propylthiouracil on the titer of THAA was not clear. Both prednisolone plus methimazole therapy and subtotal thyroidectomy decreased the level of anti-T4 autoantibodies in case 1. There was a significant correlation between titers of THAA and anti-Tg antibodies in both cases, although titers of anti-Tg antibodies in case 1 stayed within the normal range throughout the investigation period. These results indicate that methimazole treatment could induce and/or enhance the production of THAA and THAA are antibodies against thyroid hormone-containing Tg molecule.

Topics: Autoantibodies; Child; Female; Graves Disease; Humans; Methimazole; Middle Aged; Prednisolone; Propylthiouracil; Thyroglobulin; Thyroid Hormones; Thyroidectomy; Thyroxine; Triiodothyronine

Thyroid function was tested in mother and her son. The mother was taking propylthiouracil for treatment of hyperthyroidism, and she was breast-feeding. Thyroid function was normal in both.

Topics: Adult; Breast Feeding; Female; Graves Disease; Humans; Hypothyroidism; Infant; Male; Propylthiouracil

Peroxidase activity in thyroid tissue from 25 patients with Graves' disease was measured by Mini assay method (J. Biochem. 98, 637-647, 1985) employing guaiacol or iodide as a second substrate. The mean values of protein-based specific activity were 0.496 guaiacol unit/mg protein and 0.187 iodide unit/mg protein, reaching 16 fold and 28 fold those of normal thyroids, respectively. The mean value of ratio of iodide unit to guaiacol unit in each thyroid, 0.68, was also much higher than that of normal human thyroid, 0.16. No significant difference in peroxidase activity was observed between patients treated with methylmercaptoimidazole and those with propylthiouracil, but the activities of those groups were significantly higher than those of patients treated with potassium iodide, suggesting that inorganic iodine therapy plays some role in suppressing the synthesis of thyroid peroxidase in vivo.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Peroxidases; Potassium Iodide; Propylthiouracil; Thyroid Gland

Anti-thyroid drugs are widely used to treat diffuse toxic goiter (Graves' disease). Of the two drugs currently available in the United States, propylthiouracil is prescribed far more often than is methimazole (Tapazole). However, compared with propylthiouracil, methimazole can be given as a single daily dose, is cheaper, and, at low doses, is associated with less major toxicity; for these reasons, methimazole should be used for the routine management of Graves' disease when anti-thyroid drugs are selected as primary therapy. On the other hand, because of certain pharmacologic factors, propylthiouracil should be used in selected situations, particularly in patients with "thyroid storm" and in pregnant or lactating women.

Topics: Drug Administration Schedule; Female; Graves Disease; Humans; Metabolic Clearance Rate; Methimazole; Pregnancy; Propylthiouracil

Aplasia cutis congenita, the localized absence of skin at birth, usually is an isolated scalp defect. We examined an infant with aplasia cutis congenita associated with maternal Grave's disease and the use of methimazole during pregnancy. This association was reported twice before. It has certain implications with respect to therapy of pregnant hyperthyroid women.

Topics: Abnormalities, Drug-Induced; Adult; Female; Graves Disease; Humans; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Skin Abnormalities

Topics: Female; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; 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

In a patient with active Graves' disease an infiltrative ophthalmopathy developed during antithyroid drug therapy. Her eye symptoms were effectively treated with a large dose of prednisolone (PD), plasma exchanges (PE), cyclophosphamide, orbital irradiation, antithyroid drug and a supplemental dose of triiodothyronine. Before, during and after these treatments thyrotropin binding inhibitor immunoglobulin (TBII) activities in a unit serum immunoglobulin (IgG) were measured after adjusting the IgG concentration by adding normal IgG. Relative TBII concentrations were calculated by extrapolating individual data on a standard curve constructed from serial dilutions of the most potent IgG. Approximately a 5 fold increase in the TBII concentration was observed during the 2 months of progression of the ophthalmopathy, while TBII activity revealed only a 13.3% increase. After treatment TBII concentrations decreased gradually showing a close relation with the severity of the eye symptoms. Every PE was found to remove 48.5 +/- 7.9 (s.e.m.) % of TBII. After PE TBII returned to the preexchange level very rapidly and then overshot it in 2 to 3 weeks. Sixty mg of PD failed to prevent the overshoot but a 100 mg initial dose of PD after 5 PEs inhibited it to some extent. The effectiveness of combined therapy with PE, PD and cyclophosphamide appeared to confirm a role of humoral factors in the pathogenesis of Graves' ophthalmopathy. Serial determinations of TBII in a relative concentration were considered quite useful in analyzing the effectiveness of treatment in Graves' ophthalmopathy.

Topics: Eye Diseases; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Plasmapheresis; Propylthiouracil; Radiography; Skull

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

Patients with Graves disease were prospectively followed by means of three 99mtechnetium thyroid uptake ratios. These three ratios were greater than 90% sensitive and specific for the detection of hyperthyroidism in the patient with untreated Graves disease. Twelve of 15 patients experienced prolonged remission after normalization of the ratios. These ratios exhibit significant linear correlation with serum thyroxine and triiodothyronine concentrations (r = 0.4-0.6, P less than 0.01) and are a very sensitive index of medical oversuppression of thyroid function.

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Prospective Studies; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Thyroid Gland; Time Factors

Two groups of patients with newly diagnosed thyrotoxicosis were treated with propylthiouracil (PTU) 400 mg every 6 h for 4 days followed by methimazol (MMI) 40 mg every 6 h for 4 days or by MMI for 4 days followed by PTU for 4 days. The shift from MMI to PTU induced a considerable decrease in serum T3 while shift from PTU to MMI led to an increase in serum T3. Serum T4 decreased gradually during the whole treatment period. The opposite variations in serum T3 were accompanied by similar opposite variations in basal metabolic rate (BMR) (P less than 0.001). Hence the rapid variations in serum T3 which can be induced by PTU in thyrotoxic patients, are followed by rapid alterations in the thyrotoxic state as evaluated by BMR.

Topics: Achilles Tendon; Adult; Basal Metabolism; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Pulse; Reflex; Thyroid Hormones; Thyroxine; Triiodothyronine

Patients with hyperthyroidism may develop osteopenia associated with fractures; however, there has been no general agreement on the incidence of osteopenia in hyperthyroidism or the recovery of the mineral loss after treatment of hyperthyroidism. We conducted a longitudinal prospective study on the effect of hyperthyroidism and its treatment on bone mineral content (BMC) using photon absorptiometry. We observed that both young and older hyperthyroid patients showed a significantly decreased baseline BMC compared with age- and sex-matched controls. We also observed a slight recovery of BMC in hyperthyroid patients at the two-year interval after a euthyroid state had been achieved. However, the BMC was still much lower than that of controls, and we did not find any significant restoration of BMC following "cure" of hyperthyroidism.

Topics: Adult; Bone and Bones; Calcium; Graves Disease; Humans; Iodine Radioisotopes; Longitudinal Studies; Male; Middle Aged; Minerals; Osteolysis, Essential; Propylthiouracil; Prospective Studies; Thyroxine

The coupling of iodotyrosine (coupling reaction) is one of the least studied in the formation of thyroid hormone, particularly in human thyroid diseases. This paper describes a method of measuring iodotyrosine coupling catalyzed by human thyroid peroxidase (TPO) in vitro. There were two important requirements to demonstrate the coupling reaction: 1) thyroglobulin with a low thyroid hormone content, and 2) partially purified TPO. Thyroglobulin with low thyroid hormone content was obtained from Grave's and follicular adenoma tissues after propylthiouracil (PTU) therapy and L-T4 therapy, respectively. TPO was prepared from Graves' thyroid by solubilizing the 100,000 X g pellet of thyroid homogenate with sodium deoxycholate and trypsin, followed by Sephacryl S-300 gel filtration. Before the coupling reaction, thyroglobulin was iodinated with chloramine-T and potassium iodide, followed by dialysis. The coupling reaction was carried out by incubating newly iodinated thyroglobulin with TPO, diiodotyrosine, a coupling stimulator, and a H2O2-generating system (glucose and glucose oxidase) for 20 min at 37 C. After thyroglobulin was digested with Pronase, the thyroid hormone content of the thyroid digest was measured by RIA. Coupling activity was measured by the amount of newly formed T3 (nanograms of T3 per mg thyroglobulin). The time course of coupling reaction showed a progressive increase in coupling activity up to 30 min, and the reaction was temperature and pH dependent, with a pH optimum of 7.0. Coupling activity in the presence of H2O2 and TPO was 43 +/- 5.0 ng T3/mg thyroglobulin (mean +/- SD of triplicate samples), and addition of diiodotyrosine to the H2O2-TPO system caused a nearly 3-fold increase in coupling activity. This method has potential utilization for measurement of peroxidase coupling activity, since there was a linear relationship between the measured coupling activity and the amount of added TPO when the TPO concentration was over 3 micrograms/300 microliter. Methimazole (MMI) and PTU had similar potencies in inhibiting the TPO-catalyzed coupling reaction, whereas MMI was distinctly more potent than PTU as an inhibitor of TPO-mediated iodination in vitro. The different potencies of MMI in the two reactions suggest that different inhibitory mechanisms may be involved in iodination and coupling. The reducing agent, sodium metabisulfite, was also found to be a more potent inhibitor of the TPO-mediated coupling reaction than of the TPO-mediated

Topics: Catalysis; Chemical Phenomena; Chemistry; Chromatography, Gel; Graves Disease; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Iodide Peroxidase; Methimazole; Monoiodotyrosine; Peroxidases; Propylthiouracil; Sulfites; Temperature; Thyroglobulin; Thyroxine; Triiodothyronine

Thyroid surgery in the pediatric age patient accounts for a small minority of all thyroid surgery. Batsakis and Nishiyama reported only 136 patients under the age of 18 who underwent thyroid surgery in 27 years at the University of Michigan. In most series involving the pediatric age group, the majority of thyroid procedures are performed on adolescents. Thyroid surgery in the young child requires special precautions in addition to those routinely associated with thyroidectomy in the adult. The techniques and perioperative management of the pediatric thyroidectomy employed at our institution has evolved as experience is gained. Our experience with five such patients with adequate follow-up will be presented.

Topics: Adenoma; Adolescent; Age Factors; Child; Child, Preschool; Drainage; Female; Follow-Up Studies; Graves Disease; Humans; Hypothyroidism; Iodine; Male; Postoperative Care; Postoperative Complications; Preoperative Care; Propylthiouracil; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy

A 38-year-old man with Graves' disease taking propylthiouracil (PTU) for 6 years developed neutropenia and marked splenomegaly. After subtotal thyroidectomy with discontinuance of PTU the patient remained asymptomatic for the last two and half years. The serum obtained during the period of neutropenia demonstrated opsonic activity to neutrophils of the patient as well as of normal volunteers. This opsonic antineutrophil activity was located in the IgG fraction of the serum. Furthermore, PTU at the concentration (0.1-1.0 micrograms/ml) attainable in the patient's serum significantly stimulated [3H] thymidine incorporation in the patient's lymphocytes. These findings indicate that the patient developed autoimmune neutropenia by producing opsonic antineutrophil antibodies in association with the PTU therapy.

Topics: Adult; Agranulocytosis; Autoantibodies; Autoimmune Diseases; Graves Disease; Humans; Lymphocytes; Male; Neutropenia; Neutrophils; Propylthiouracil; Splenomegaly; Thyroidectomy

Pancreatic alpha and beta cell hormone secretion was studied in 11 patients with thyrotoxicosis before and in 7 patients after thyroid function was normalized with either prophylthiouracil or methimazole and propranolol (R). All had IV arginine and IV glucose infusions. Forty control subjects had IV arginine; 21 had IV glucose tests. After arginine, untreated patient had blunted serum insulin at both 15 and 30 minutes (p less than 0.05, p less than 0.001) compared to control subjects, blunted glucagon at 30 minutes (p less than 0.05) and blunted glucose at both 15 and 30 minutes (p less than 0.001, p less than 0.01) compared to control subjects. After glucose, untreated patients had lower nadir glucagon than in the studies with both arginine and glucose infusions. These data document blunted glucagon, suppressed glucose and insulin peaks after arginine in thyrotoxicosis, indicate that both alpha and beta cell hormone secretion may be abnormal, and that the preferential abnormality follows protein rather than carbohydrate loading.

Topics: Adolescent; Adult; Aged; Arginine; Blood Glucose; Child; Child, Preschool; Female; Glucagon; Glucose; Graves Disease; Growth Hormone; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Methimazole; Middle Aged; Propranolol; Propylthiouracil

In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 +/- 47 nmol/l (mean +/- SD) to 40 +/- 9 nmol/l after 6 weeks of PTU treatment and continued to be below the normal range during the next 4 months. In group 2 serum T4 decreased from 190 +/- 35 to 88 +/- 47 nmol/l and stayed in the normal range. Serum T3 was normalized in both groups after 6 weeks but increased to values above the normal range in group 1 after that time. In spite of unmeasurable TSH during the 6 months of treatment in group 1, thyroid volume, determined ultrasonically, increased significantly from 60 +/- 29 to 93 +/- 68 ml (P less than 0.05), but was unaltered in group 2 about 25 ml. Thyroid stimulating antibodies (TSAb) measured by adenylate cyclase activation (normal below 109%) decreased in group 2 from 117 +/- 23 to 90 +/- 17% (P less than 0.01) (6 months of therapy), but increased significantly in group 1, from 201 +/- 47% to a maximum value of 234 +/- 69% (P less than 0.05). TSH binding inhibitory immunoglobulins (TBII) (given as per cent inhibition, normal below 26%) decreased in group 2 from 43 +/- 29 to 29 +/- 27% (P less than 0.05) but were unaltered high in group 1, 66 +/- 25% before therapy and 57 +/- 26% after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antibodies; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Middle Aged; Propylthiouracil; Thyroid Gland; Thyroxine; Triiodothyronine

Previous studies have shown that serum titers of thyroid-specific antibodies such as thyroid-stimulating immunoglobulins (TSI), TSH-displacing antibodies (TDA), or microsomal antibodies (MAb) decrease in patients with Graves' disease during therapy with thionamide drugs (TD). In keeping with some in vitro results it was postulated that TD have an immunosuppressive action which may be partly responsible for the beneficial effects. To further elucidate this theory, we compared the changes in TSI during treatment with TD such as methimazole (MMI) and propylthiouracil (PTU) as well as with perchlorate (PC), an unrelated compound with a different mode of therapeutic action. Of 69 patients with hyperthyroidism due to Graves' disease, serum from 62 (90%) was positive for TSI, as measured by cAMP accumulation in a thyroid tissue culture assay. Six patients had to be excluded due to noncompliance. Of the remaining 56 patients, those 41 subjects (73%) with good control of the disease were followed up to 24 months during dose-adjusted antithyroid treatment. All patients with an uncomplicated course of treatment had a decline in the initially increased TSI values on either drug regimen. Five of 10 patients receiving PTU and 8 of 13 patients receiving MMI reached normal TSI levels; so did 11 of 18 patients receiving PC. There was no individual correlation between TSI decrease and drug dosages or the serum T4 and T3 levels. In all 3 groups, however, a decrease in mean T4 and T3 levels preceded the fall in TSI. By grouping the patients according to whether they had more than a 20% decrease in the initial TSI values after either 2 months or more than 4 months of treatment, it could be shown that the late responders had significantly higher T4 and T3 levels after 2 months of treatment. The similar patterns of change in TSI during treatment with TD and PC are strong evidence against an immunosuppressive effect of TD. If any direct interference occurs, a toxic effect on intrathyroidal lymphocytes by intrathyroidal drug accumulation could be the cause of the disappearance of TSI with both drug types. On the other hand, the data provide indirect evidence for the theory that the restoration of the euthyroid state is the cause of decreasing TSI levels and normalization of the immune regulation in many patients during treatment with antithyroid drugs.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Perchlorates; Propylthiouracil; Thyroxine; Time Factors; Triiodothyronine

Studies of in vitro immunoreactivity to propylthiouracil (PTU), methimazole (MMI), and carbimazole (CARB), as assessed by peripheral blood lymphocyte transformation and 2 antibody tests, were carried out in 12 patients with Graves' hyperthyroidism who had developed agranulocytosis during treatment with PTU (11 patients) or CARB (1 patient) from 1 week to 10 yr earlier. Significant lymphocyte transformation responses to antithyroid drugs (stimulation indices greater than mean +/- 2 SD for normal subjects) were found in 5 of 6 patients tested, in 1 patient to PTU only, in 3 patients to MMI only, and in 1 patient to both PTU and MMI, but in none of 10 patients currently being treated with PTU who did not develop agranulocytosis. Circulating antibodies causing neutrophil agglutination in the presence of antithyroid drugs were demonstrated, using the indirect Coombs test, in 5 of 7 patients tested, in 2 patients to PTU only, in 3 patients to CARB only and in 1 patient (the only one tested with MMI) to PTU and MMI. Lymphocyte transformation and antibody tests to PTU were both carried out in 6 patients. Of these, both tests were positive in one patient, both negative in 3 patients, and 1 negative and 1 positive in 2 patients. In the 1 patient in whom both tests were carried out with CARB (patient 3), tests were negative, whereas in the 1 patient in whom both tests were carried out with MMI (patient 3), 1 test was positive, whereas the other was negative. Thus, in patients in whom both tests were carried out using the same drug, correlation between lymphocyte transformation responses and the detection of neutrophil antibodies was found in 5 of 6 cases. Antibodies reactive with neutrophils were also detected in 2 of the 5 patients tested using an enzyme-linked immunosorbent assay. In this test antibodies to PTU or MMI were not demonstrated. Possible mechanisms for the neutrophil depression in relation to these findings are discussed. It is concluded that patients with Graves' disease may be prone to develop this complication of antithyroid drug therapy because of underlying immunological abnormalities.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antithyroid Agents; Autoantibodies; Carbimazole; Female; Graves Disease; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Methimazole; Middle Aged; Neutrophils; Propylthiouracil

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

A 44-year-old man subjected to Hardy's operation for a treatment of acromegaly developed hyperthyroidism right after surgery. He had a normal thyroid function with a slightly suppressed TSH response to TRH before operation. Sudden onset of hyperthyroidism after surgery and suppressed TSH were compatible with Graves' disease. Hyperthyroidism was effectively treated with propylthiouracil (PTU) with slightly increased basal TSH level and normal response of TSH to TRH. Plasma GH level also increased after he attained euthyroidism, but inappropriate GH response to TRH persisted. It is suggested that increased endogenous TRH stimulated both TSH and GH release, but inappropriate GH response to TRH occurred irrespective of endogenous hypothalamic TRH. Bromocriptine, 5.0 mg/day, suppressed plasma GH level to a normal range with a concomitant suppression of PRL and TSH, both basal levels and responses to TRH.

Topics: Acromegaly; Adult; Bromocriptine; Graves Disease; Growth Hormone; Humans; Male; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone

Triiodothyronine (T3)-predominant Graves' disease is characterized by persistently high serum T3 level, normal serum thyroxine (T4) level, and high (greater than 20) serum T3/T4 ratio (nanograms/micrograms) during thionamide drug therapy. We studied the clinical course of 30 patients with T3-predominant Graves' disease. After receiving drug therapy for 1 to 4 years, 27 patients with T3-predominant Graves' disease had relapses, whereas only 9 control patients with Graves' disease whose serum T3/T4 ratio had become persistently normal (less than 20) had relapses. The T3-predominant patients had greater serum TSH receptor antibody activity, thyroid T4 5'-deiodinase activity, and decreased T3 content of thyroglobulin when compared with the control patients. Our findings show that patients with T3-predominant Graves' disease are unlikely to have a long-term remission with drug therapy. The cause of high serum T3/T4 ratio is due, in part, to the more active thyroid T4 5'-deiodinase that may be mediated by high levels of Graves' immunoglobulin.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Male; Methimazole; Prognosis; Propylthiouracil; Recurrence; Thyroxine; Time Factors; Triiodothyronine

We asked 54 thyroidologists how they would treat each of four patients having moderate hyperthyroidism of Graves' disease and a thyroid gland weighing 70 g (three to four times normal). For a 19-year-old woman, 67% of thyroidologists recommended an initial course of therapy with antithyroid drugs, usually for 1 year; 24% favored radioiodine treatments; and 9%, surgery. Choices for treating a 19-year-old man were similar. For a 29-year-old man, 44% of thyroidologists preferred drug therapy; 50%, radioiodine; and 6%, surgery. For a 29-year-old woman, choices were similar to those for the 29-year-old man, except for a slight preference for drugs over radioiodine. If hyperthyroidism recurred after a first course of antithyroid drugs, the consultants favored radioiodine treatments and surgery about equally, except in the 29-year-old man, in whom radioiodine was preferred. This survey shows considerable variation among experts in treating hyperthyroidism in young adults.

Topics: Adult; Drug Administration Schedule; Female; Genes; Graves Disease; Humans; Internal Medicine; Iodine Radioisotopes; Male; Medicine; Methimazole; Propylthiouracil; Specialization

Topics: Adult; Agranulocytosis; Autoimmune Diseases; Graves Disease; Humans; Lupus Erythematosus, Systemic; Male; Neutropenia; Propylthiouracil; Splenomegaly

Symptoms and signs of severe hypothyroidism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received L-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroidism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Female; Goiter; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroxine

Cough productive of sputum, exertional dyspnea, and hypoxemia developed in two patients with Graves' disease after six months (patient 1) or three weeks (patient 2) of treatment with propylthiouracil, 300 mg/day. Chest roentgenograms and transbronchial lung biopsy specimens revealed diffuse interstitial pneumonitis. Lymphocyte transformation by phytohemagglutinin was highly stimulated by propylthiouracil. Symptoms and signs improved after cessation of the drug therapy and administration of prednisolone acetate. These cases represent the first report of a complication of diffuse interstitial pneumonitis induced by propylthiouracil.

Topics: Aged; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Pulmonary Fibrosis

A T4 suppression test involving 24-h thyroidal 131I uptake was carried out on patients with Graves' disease during therapy with an antithyroid drug. Thirty-three patients received propylthiouracil (PTU) for at least 1 year. Each patient was given 75 micrograms L-T3 daily for 8 days in conjunction with PTU (50 mg/day) at the time of the experiment and then the 24-h thyroidal 131I uptake (post T3 uptake was measured). Twenty-two patients had normal levels of serum T3 and T4-I before L-T3 administration and were divided into 2 groups, positive T3 suppression (post T3 uptake less than or equal to 35%, group I) and negative T3 suppression (post T3 uptake greater than 35%, group II). Eleven patients showed elevated serum T3 or T4-I concentrations before L-T3 administration (group III). The T4 suppression test was then performed on the same patients. Each patient was given 300 micrograms L-T4 daily for 8 days in conjunction with PTU and the 24-h thyroidal 131I uptake (post T4 uptake) was measured. Some patients receiving PTU (50 mg/day) were switched to MMI (5 mg/day) and the T4 suppression test was done one month later. A significant correlation between the two suppression tests during PTU therapy was observed (r = 0.961, p less than 0.01). None of the patients complained of side effects during the T4 suppression test. The mean post T4 uptake in group I was 18.8 +/- 3.3% during PTU therapy and 5.4 +/- 1.3% during MMI therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroxine; Triiodothyronine

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

The variable clinical course of Graves' disease has been followed in 27 patients each studied for 2 years from the time of diagnosis. Thyroid hormone synthesis was blocked with large doses of antithyroid drugs for the first 12 months while euthyroidism was maintained with triiodothyronine. The latter was given alone from 12 to 18 months, and for the last 6 months the patients received no treatment. The activity of the disease was determined by repeated measurements of thyroid uptake of pertechnetate and by assay of thyrotrophin receptor antibodies (TSH binding inhibitory immunoglobulins). Retrospectively there were no features on presentation which singly or in combination indicated the clinical outcome: 16 patients remained in remission (Group 1) whilst in 11 hyperthyroidism had recurred before the end of the study (Group 2). Both measures of disease activity (thyroid uptake and antibody levels) fell during the first 12 months in patients of both groups. Recurrence of Graves' disease could be predicted in some but not all patients of Group 2 at 12 months by higher thyroid uptakes and levels of thyrotrophin receptor antibodies. There was, however, evidence of abnormal thyroid function, from which we infer continuing activity of the disease, 12 to 18 months after diagnosis in all patients of Group 1, even though these patients had normal TRH tests during the last phase of the study. The difference in the course of Graves' disease 12 to 24 months after diagnosis between those patients who remained in remission and those who did not was relative: in no patient was completely normal physiological control of thyroid function re-established. Clinical remission from hyperthyroidism at this time is a level of disease activity at which the normal physiological output of thyroid hormones is not exceeded.

Topics: Carbimazole; Drug Therapy, Combination; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Propylthiouracil; Prospective Studies; Sodium Pertechnetate Tc 99m; Technetium; Thyroid Gland; Triiodothyronine

To obviate several problems inherent in indirect thyroid-stimulating hormone (TSH) receptor antibody assays, we developed an enzyme-linked immunosorbent assay (ELISA) that measures antibodies binding to guinea pig fat cell membrane, which contain high concentrations of TSH receptors. Solubilized guinea pig fat cell membranes were adsorbed to plastic microtiter plates and served as the solid-phase antigen. Test sera and affinity-purified alkaline phosphatase-conjugated anti-human IgG were co-incubated with membranes, after which p-nitrophenyl phosphate was added. Results were read when a positive control reached a standard color change (OD405nm). Specificity of this assay was demonstrated by the inability of albumin, insulin, TSH subunits, propranolol, or dexamethasone to block binding 30. normal subjects had a mean OD value of 0.080 +/- 0.050 (SD). 23 of 25 untreated Graves' patients had OD values at least 2 SD above the normal mean (Grave's mean +/- SD; 0.46 +/- 0.33, P less than 0.001) and in each case 10(-6) M TSH inhibited the binding by at least 60%, suggesting that the immunoglobulins were directed at the TSH receptor. Seven of 25 serum samples from patients with Hashimoto's disease, seven of 23 serum samples from patients with transient hyperthyroidism (subacute thyroiditis or painless thyrotoxic thyroiditis), and two of 10 samples from patients with thyroid carcinoma had significant elevations in the titers of membrane-directed immunoglobulins. Graves' patients who were treated with ablative therapy at least 6 mo earlier and who were euthyroid when restudied continued to have abnormally elevated membrane-directed immunoglobulins in six of eight samples studied. Further studies involved the substitution of affinity-purified alkaline phosphatase anti-IgM antisera for the anti-IgG antisera routinely used. Seven of 12 serum samples from patients with Graves' disease had significant elevations in binding which in every instance was inhibited by greater than 60% by 10(-6) M TSH. In sum, the present results indicate that (a) we have developed a sensitive, specific, reproducible, convenient ELISA for the measurement both of the total amount of circulating membrane-directed antibodies and of TSH-displaceable membrane-directed immunoglobulins. (b) This ELISA detected significant elevations in TSH-displaceable guinea pig membrane binding in 23 of 25 untreated Graves' patients as well as in approximately 30% of patients with Hashimoto's thyroiditis and subacu

Topics: Adipose Tissue; Animals; Antigen-Antibody Reactions; Binding, Competitive; Cell Membrane; Chorionic Gonadotropin; Enzyme-Linked Immunosorbent Assay; Graves Disease; Guinea Pigs; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Lupus Erythematosus, Systemic; Propylthiouracil; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroiditis, Autoimmune; Thyrotropin

Thyroid stimulating immunoglobulins were measured in 43 patients with Graves' disease both before and at the end of longterm antithyroid treatment. Parallel determinations were performed of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb). Before treatment 33 patients were TBII positive and 32 TSAb positive, and at the end of treatment 19 remained TBII positive and 14 TSAb positive. The frequency of relapse was about 70% in the positive patients and about 40% in the patients, who became negative in either test for thyroid stimulating immunoglobulins. By combination of the two assays 23 patients were positive in both before treatment. In these patients 5 relapsed of the 6 who remained positive for both, while none relapsed of the 5 patients, who became negative during treatment. In the remaining 12 patients either TBII or TSAb became negative during treatment and 7 of these relapsed. It is concluded, that the combined measurement of TBII and TSAb in this study seemed superior to the separate determinations of either activity in predicting relapse after medical treatment of Graves' disease, though this evaluation was only possible in part of the patients.

Topics: Adenylyl Cyclases; Adolescent; Adult; Aged; Antibodies; Carbimazole; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Middle Aged; Prognosis; Propylthiouracil; Thyroid Gland

Topics: Adolescent; Adult; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Recurrence; Thyroxine; Triiodothyronine

The T3 suppression test by the 24-hr thyroidal 131I uptake was reevaluated in patients with Graves' disease before and after withdrawal of antithyroid drug. Fifty patients had been treated with propylthiouracil (PTU) or methylmercaptoimidazole (MMI) for 12 to 70 months. They were prescribed a maintenance dose of antithyroid drug (PTU, 50 mg/day; MMI, 5 mg/day) at the time of investigation and regarded as euthyroid on the basis of serum T3, T4 and TSH levels. Each patient was given 75 micrograms T3 daily for 8 days in conjunction with PTU or MMI. The 24-hr thyroidal 131I uptake was then measured (post T3 uptake). In 30 patients whose post T3 uptake was below 35%, treatment was stopped and the T3 suppression test was repeated at one and 3 months later. During the two-year follow up, 24 remained well, while 6 relapsed within 4 to 12 months. In patients with sustained remission, the post T3 uptake was significantly lower in the MMI-treated group (13 cases, 7.7 +/- 1.0%) than in the PTU-treated group (11 cases, 18.6 +/- 1.9%). MMI withdrawal produced a marked rebound in the post T3 uptake, whereas none of the patients showed the rebound after PTU withdrawal. In patients who relapsed later, there was no difference in the post T3 uptake during treatment and the rebound occurred in the both groups following goitrogen withdrawal. Serum T3, T4 and TSH levels were within normal ranges at one and 3 months after cessation of antithyroid drug. From the results of the present study, it is concluded that criteria for T3 suppressibility by the 24-hr uptake should be determined by the antithyroid drug employed and by the time of investigation. There is a dissociation in the post T3 uptake values following withdrawal of the two different antithyroid drugs.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Thyroid Gland; Time Factors; Triiodothyronine

Topics: Adolescent; Adult; Aged; Female; Follow-Up Studies; Graves Disease; Humans; Immunologic Techniques; Male; Middle Aged; Propylthiouracil; T-Lymphocytes; T-Lymphocytes, Regulatory

The effects of TSH on iodothyronine 5- and 5'-deiodinations were investigated using cultured thyroid tissues from patients with Graves' disease. The addition of TSH to the culture medium stimulated all of the iodothyronine-deiodinating activities of thyroid tissues cultured for more than 4 days. Peak TSH-induced activities were found on the fifth day of culture, and increased activities were found up to 9 days. On the fifth day of culture, TSH enhanced both outer and inner ring monodeiodinations in a dose-responsive manner between 62.5 and 250 microU/ml. This stimulation by TSH was blocked by the addition of actinomycin D or propylthiouracil. Incubation of thyroid tissues with (Bu)2cAMP mimicked the action of TSH, and theophylline potentiated the action of TSH. These results suggest that TSH, in an action probably mediated by cAMP, induces synthesis of iodothyronine deiodinases in the thyroid gland.

Topics: Bucladesine; Culture Techniques; Dactinomycin; Enzyme Induction; Graves Disease; Humans; Iodide Peroxidase; Kinetics; Peroxidases; Propylthiouracil; Theophylline; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Although the activity of lysosomal protease in Graves' thyroid is considered to be increased, there has been no quantitative method to estimate the protease activity in the thyroid tissue due to the contamination of thyroglobulin (Tg) which varies in susceptibility to the protease. In the present study, the proteolytic activity (PA) of thyroid lysosomal protease preparation (P25) separated from Tg was assayed using 125I labeled rat Tg. More than 95% of 125I-Tg was hydrolyzed at pH 4.0 without deiodination, and the pattern of liberated iodoamino acids resembled that of pronase digest except for a higher T3/T4 ratio. Thirty-seven Graves' thyroids and 15 paranodular thyroid tissues were assayed. PA, the specific PA (SPA; calculated as PA per mg P25 protein) and PA per DNA content in Graves' thyroids were significantly higher than those in controls. There were good correlations among PA, SPA and PA per DNA content of the thyroid tissue. PA and SPA in the thyroid from 29 patients with Graves' disease treated with propylthiouracil or methimazole did not correlate with serum thyroid hormone level immediately before surgery. In 8 patients treated with KI, PA from 5 patients whose serum thyroid hormone levels had been normalized were significantly lower than those from 3 patients who were still thyrotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aspartic Acid Endopeptidases; Endopeptidases; Graves Disease; Humans; Hydrolysis; In Vitro Techniques; Lysosomes; Male; Methimazole; Potassium Iodide; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroglobulin; Thyroid Gland

The records of all patients with antithyroid drug-related agranulocytosis at two Boston hospitals (Group 1, 14 patients), as well as the published case reports of 36 patients with this syndrome (Group 2) were reviewed. The clinical characteristics of these patients were then compared with those of 50 hyperthyroid patients who had taken antithyroid medication without untoward hematologic reactions (Group 3). The mean ages of patients in Group 1 and Group 2 were significantly greater than that of Group 3 (50.6 +/- 16 years versus 35.7 +/- 13.7 years, p less than 0.001; 46.3 +/- 18.7 years versus 35.7 +/-- 13.7 years, p less than 0.02). By chi-square analysis, the relative risk of developing agranulocytosis in patients over age 40 was 6.4 times that among younger patients (p less than 0.001). The mean doses of methimazole in Group 1 and Group 2 were significantly higher than that in Group 3 (43.8 +/- 9.9 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.001; 40.7 +/- 15.7 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.02), with and 8.6-fold increased risk of agranulocytosis with doses greater than 40 mg/d (p less than 0.01). In contrast, the mean doses of propylthiouracil did not differ among the three groups. These data suggest that antithyroid drugs should be administered cautiously to patients over age 40. Because no cases of agranulocytosis were seen with methimazole doses less than 30 mg/d, low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil.

Topics: Adolescent; Adult; Age Factors; Aged; Agranulocytosis; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Sex Factors

Presented are two case studies which investigate the adverse effects of Graves' disease in pregnant women. Particular attention has been paid to the therapeutic regimen and its implications for the maternal, fetal and neonatal well-being. The first case study illustrates that Graves' disease complicating pregnancy can be treated by bed rest and careful observation of mother and fetus. The first pregnancy of our second case study confirms these results. Her second pregnancy, in which the symptoms of Graves' disease were far more severe, illustrates that it is possible to treat fetal hyperthyroidism by treating the pregnant mother with antithyroid drugs. If great care is taken to avoid overtreatment of the fetus, the treatment with antithyroid drugs is superior to surgical treatment, since surgery completely neglects the problem of fetal hyperthyroidism.

Topics: Abortion, Spontaneous; Adult; Female; Fetal Diseases; Graves Disease; Humans; Hypothyroidism; Intellectual Disability; Pregnancy; Pregnancy Complications; Propylthiouracil

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

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Male; Pregnancy; Propylthiouracil; Radioimmunoassay

Topics: Adult; Female; Fever; Graves Disease; Humans; Propylthiouracil

Pharmacokinetics of propylthiouracil after a single oral dose were studied in six pediatric patients with Graves disease, with respect to influence of food intake. Propylthiouracil administration in the fasting state induced a rapid rise of plasma level reaching a peak of 30 to 60 min. Peak values ranged from 7.2 to 18 micrograms/ml with administered dose (100 to 280 mg/m2 BSA) and plasma half-life was 1.3 +/- 0.41 hr (mean +/- SD). Single compartment model with first order absorption showed excellent fit to the data obtained in the fasting state, but not in the fed state. Most individuals showed marked difference in the pattern of propylthiouracil concentration-time curves between the fasting and the fed state. Food intake prior to the drug ingestion was associated with lower and delayed peak and variable AUC values. These results indicate that propylthiouracil administration in the fasting state is more advisable for obtaining a consistent bioavailability.

Topics: Administration, Oral; Adolescent; Biological Availability; Child; Female; Graves Disease; Half-Life; Humans; Intestinal Absorption; Kinetics; Male; Propylthiouracil

In order to investigate the incidence of side effects of antithyroid drugs and to study if there were any factors related to the onset of the side effects, clinical and laboratory findings were examined in 71 untreated Graves' patients. The overall incidence was 28.2% among 71 cases who were initially administered methimazole or propylthiouracil. The incidences were 23.2% (13 of 56 cases) for methimazole and 46.7% (7 of 15 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Seventeen of 20 cases with side effects under the drug of first choice were administered the another antithyroid drug. Four of 17 (23.5%) cases successively had side effects. The side effects were observed within 1.5 months of administration of less than 150 tablets in total in most of the cases. The serum concentration of Ig-E and peripheral eosinophils(/mm3) at the onset of the side effects were significantly higher than those before treatment. These results suggest that allergic mechanism rather than accumulating may concern the onset of side effects. Since in cases without the side effects the peripheral eosinophils at 3 to 4 weeks after administration were significantly higher than those before treatment and 19 of 51 (38.0%) cases without side effects had a high concentration of Ig-E of more than 500 u/ml, it is suggested that allergic mechanism may be triggered in most of Graves' patients who were administered methimazole or propylthiouracil. Thus, immunological disturbances in Graves' disease seems to be the cause of the side effects of antithyroid drugs, although there was no correlation between antithyroid autoantibodies and development of the side effects.

Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Eosinophils; Female; Graves Disease; Humans; Immunoglobulin E; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil

Using peripheral blood lymphocytes from 8 healthy individuals and 5 patients with untreated Graves' disease, direct effects of methimazole (MMI) and propylthiouracil (PTU) on lectin-induced lymphocyte proliferative response were studied. Lymphocytes were cultured for 72 hr in the presence of lectins and antithyroid drugs. Lymphocyte DNA synthesis was counted by incorporation of 3H-thymidine. MMI at 1,000 microM enhanced lectin-induced lymphoproliferation of peripheral blood lymphocytes from both patients with Graves' disease and healthy individuals, at every point of culture time, while PTU showed a tendency toward suppression. These results suggest that this lympho-stimulation by MMI may be a causative factor related to insulin autoimmune syndrome, as deduced from the clinical reports that insulin autoimmune syndrome is, sometimes, found in patients with Graves' disease treated with MMI. This lympho-stimulation was evident regardless of the time of MMI addition, thus indicating that MMI is, by its action, a lymphoid stimulator and may lead to the insulin autoimmune syndrome in predisposed subjects with underlying Graves' disease.

Topics: Autoimmune Diseases; Concanavalin A; Graves Disease; Humans; Insulin Antibodies; Lymphocyte Activation; Methimazole; Phytohemagglutinins; Pokeweed Mitogens; Propylthiouracil; Syndrome

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

In the present study we have measured in parallel thyrotrophin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cylase stimulating immunoglobulins (TACSI) in patients with Graves' disease (GD) both before and during long-term antithyroid treatment. A statistical model based on the calculation of the differences (TACSI-TBII) is presented, comparing the changes in this parameter to the analytical variation. The correlation between TBII and TACSI in 52 patients with GD before treatment was: r = 0.58, P less than 0.0001. During long-term antithyroid treatment of GD the 2 activities changed in parallel in 39 of 45 patients followed. In a few patients discrepancies were observed, and 1 patient, initially TACSI positive, developed adenylate cyclase inhibiting IgG during treatment but without detectable TBII. In conclusion, 1) TBII and TACSI are significantly correlated in patients with GD both before and during long-term antithyroid treatment, 2) in some patients discrepancies between TBII and TACSI suggest, that these IgGs are heterogeneous with varying capacity for stimulation of the adenylate cyclase and receptor binding, and 3) adenylate cyclase inhibitory IgG without TBII activity was demonstrated in GD.

Topics: Adenylyl Cyclases; Adult; Aged; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins; Male; Middle Aged; Propylthiouracil; Receptors, Cell Surface; Receptors, Thyrotropin-Releasing Hormone; Thyrotropin-Releasing Hormone; Time Factors

We have treated 68 thyrotoxic patients with Graves' disease with a single daily dose of 30 mg methimazole until they were clinically euthyroid and their plasma thyroid hormone concentrations were within normal limits. Sixteen of 56 patients (29%) treated 4.8 +/- 0.2 months (mean +/- SEM; range, 1.5-8.5 for their initial attack of thyrotoxicosis have remained in remission for 54.4 +/- 7.7 months (range, 12-105). Twenty-seven of the patients who relapsed were treated with a subsequent 1-yr course of methimazole. Five of these patients (19%) have maintained a remission for 29.6 +/- 10.8 months (range, 3-66); the remainder relapsed after 7.1 +/- 2.3 months (range, 1-50). If the patients lost to follow-up while known to still be in remission are excluded, the sustained remission rate is 12 of 52 (23%) for initial short term therapy and 3 of 25 (12%) for the subsequent 1-yr of antithyroid treatment. The results of short term antithyroid drug treatment in 12 patients previously treated with long term antithyroid drugs or thyroidectomy were similar, but the follow-up period was not as long. Short term antithyroid drug therapy is a potentially long lasting, innocuous, and relatively inexpensive program for the treatment of Graves' disease, especially for patients with small goiters.

Topics: Antithyroid Agents; Drug Administration Schedule; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Propylthiouracil; Recurrence; Thyroidectomy

The aims of the present study were to investigate the incidence of adverse effects of thioureylene antithyroid drugs and to see if there were any factors related to the development of the adverse effects. Methimazole or propylthiouracil was administered to 151 patients with Graves disease; 76 untreated cases and 75 treated cases. The overall incidence was 22.4% among the 76 untreated cases. The incidences were 26.7% (13/45 cases) for methimazole and 16.1% (5/31 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Fourteen out of 17 cases with the adverse effects were given the other thioureylene. The successive incidence of the adverse effects was 28.6% (4 cases), which was not significantly different from that under the drug of first choice. The result suggests that methimazole and propylthiouracil may not have cross-reaction each other. On the other hand, antinuclear antibody and anti-DNA antibody became positive in 2 out of the 4 cases. It would be a significant phenomenon, since antinuclear antibody was positive in only 3% of cases before the drug treatment. Thus, an immunological mechanism seemed to be involved in the problems, although there was no correlation between antithyroid autoantibodies and the development of the adverse effects. The adverse effects were observed within 2 months of administration of less than 250 tablets in total in most of the cases. The results imply that allergic mechanism rather than accumulating or toxic effect may concern the development of adverse effects of the thioureylenes.

Topics: Adult; Autoantibodies; Drug Eruptions; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland

Topics: Adult; Graves Disease; Humans; Lymphocyte Activation; Lymphocytes; Methimazole; Propylthiouracil; T-Lymphocytes, Regulatory

Topics: Adult; Female; Graves Disease; Humans; Iodine; Iodine Radioisotopes; Kinetics; Male; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of [99mTc]pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

Topics: Adult; Carbimazole; Graves Disease; Humans; Immunoglobulin G; Propylthiouracil; Prospective Studies; Sodium Pertechnetate Tc 99m; Technetium; Thyroid Gland; Thyrotropin

Monoclonal antibodies reacting with cell surface antigens of helper (T4), suppressor (T8) T cells and common T-cell antigen (T3) were used by an immunofluorescence technique to enumerate peripheral T-lymphocytes in 42 patients with Graves' disease and 16 patients with Hashimoto's thyroiditis. The percentages of total T cells (cells which react with anti-T3) and helper/inducer cells (cells which react with anti-T4) among peripheral mononuclear cells in Graves' and Hashimoto's patients were not significantly different from those found in normal controls, except for a decrease in cells which react with anti-T3 in toxic Graves' disease without medication. The most important finding was a decrease in the percentage of cytotoxic/suppressor T cells (cells which react with anti-T8) in toxic Graves' disease and Hashimoto's thyroiditis. In patients with Graves' disease who were hyperthyroid or euthyroid on propylthiouracil treatment and euthyroid after radioactive iodide treatment, the percentage of cells which react with anti-T8 was also decreased, but this did not reach statistical significance. These findings support the hypothesis of defects in suppressor T-lymphocytes in autoimmune thyroid diseases.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Cell Count; Female; Fluorescent Antibody Technique; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; T-Lymphocytes; T-Lymphocytes, Regulatory; Thyroiditis, Autoimmune

Topics: Adult; Blood Pressure; Body Weight; Female; Graves Disease; Humans; Ipodate; Kinetics; Male; Middle Aged; Propylthiouracil; Pulse; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

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

Measurement of serum thyroglobulin (Tg) and its autoantibody (TgAb) by radioimmunological methods was performed in 48 patients with Graves' disease during treatment with radioiodine (n = 16) or propylthiouracil (PTU) (n = 32). Twenty-five of the 48 patients were TgAb positive, their sera being inaccessible to measurement of serum Tg. TgAb showed only minor changes during PTU treatment, whereas TgAb fell rapidly after radioiodine, in 5 of 16 patients to unmeasurable levels, followed by a secondary rise to 4.5 times pre-treatment level after 20 weeks. Serum Tg showed a steady increase during the first weeks after radioiodine treatment, but fell to lower levels after one year. PTU caused only minor changes in the serum Tg concentration. There was no shift in molecular sizes of either Tg or TgAb during the course of the treatments. Five of 16 131I-treated patients developed myxoedema, 4 of whom were TgAb positive. Another 3 patients had high increases in TgAb without myxoedema. Six of 18 patients had relapse of thyrotoxicosis after withdrawal of PTU-treatment. There was no significant difference in serum concentrations of TgAb or Tg between those developing relapse and those remaining in remission, and it is concluded that serum Tg is a poor predictor of relapse in medically treated thyrotoxicosis.

Topics: Adult; Aged; Autoantibodies; Female; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Prospective Studies; Thyroglobulin

Topics: Adolescent; Female; Graves Disease; Humans; Propylthiouracil; Thymus Gland; Thyroxine; Triiodothyronine

Between 1969 and 1979 a course of either propylthiouracil or carbimazole was given to 102 patients with Graves' disease. Ten of the patients discontinued the therapy because of adverse reactions or persisting symptoms, and 40 relapsed at some time after cessation of the therapy, giving a proportion of total failures of 49%. The proportion of such failures increased from 45% in 1969-72 to 57% in 1973-79. The probability of relapse was significantly higher in 1973-79 than in the earlier period (p less than 0.01). Patients aged 30-39 years had the highest proportion of failures (55%), but the mean time until relapse (6 months) was shortest in patients older than that. Adverse reactions--agranulocytosis, leukopenia, urticaria and elevated serum levels of liver enzymes--were seen in 12 patients. Six patients developed hypothyroidism after a mean time of 3.5 years after termination of thionamide therapy.

Topics: Adolescent; Adult; Age Factors; Carbimazole; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Recurrence; Time Factors

Topics: Adolescent; Adult; Child; Female; Graves Disease; Humans; Male; Middle Aged; 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: Adult; Aspirin; Blood Sedimentation; Diagnosis, Differential; Female; Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Function Tests; Thyroiditis; Thyroiditis, Autoimmune; Thyroxine

Topics: Female; Fetus; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Pregnancy Complications; Propylthiouracil; Prospective Studies; Thyroid Function Tests; Thyroid Hormones; Thyrotropin

Ten patients with hyperthyroidism due to Graves' disease were treated with sodium ipodate (1 g daily) in addition to propranolol (P) plus propylthiouracil (PTU; 100 mg every 8 h) and were compared with a control group of 8 patients treated with P and PTU. Patients on P and PTU had a mean (+/- SEM) basal free T3 index of 387 +/- 59 (normal, 70--160) compared with that of 409 +/- 47 (P greater than 0.05) in the sodium ipodate group. The respective basal free T4 index values (normal, 4.5-10.9) were 21.3 +/- 2.8 for the controls and 25.9 +/- 2.8 for the ipodate group (P greater than 0.5), and the basal rT3 values were 192 +/- 49 and 210 +/- 41 (normal, 16--50 ng/dl; P greater than 0.05). The average percent changes in each thyroid index and rT3 were calculated. The first 3 days on P and PTU served as the basal period for the control group, and comparisons were made to the following 9 days. The ipodate group received P and PTU for 2.7 +/- 3.0 days, and comparisons were made with the interval on ipodate, P, and PTU (mean, 9.1 +/- 0.9 days). For the free T3 index, the control group showed a mean decrement of 20.5 +/- 4.4% compared with 50.2 +/- 3.1% for the ipodate group (P less than 0.001). The respective free T4 index decrements were 14.5 +/- 4.4% and 18.5 +/- 2.7% (P greater than 0.05). The respective changes in rT3 were -13.4 +/- 7.6% and +140 +/- 26.9% (P less than 0.001). In patients with hyperthyroidism, short term daily therapy with sodium ipodate plus P and PTU produces a greater reduction of free T3 index values than that caused by P and PTU alone.

Topics: Female; Graves Disease; Humans; Ipodate; Kinetics; Male; Propranolol; Propylthiouracil; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In a study of fifty-two patients with Graves' disease followed for 1 year after stopping antithyroid drugs, a strong relationship has been found between serum LATS-P and relapse. In those with serum LATS-P activity on stopping therapy, twenty-one (88%) out of twenty-four relapsed. In those with no LATS-P activity on stopping antithyroid drugs only eight (29%) out of twenty-eight relapsed and in five LATS-P was detectable at relapse. The overall prevalence of positive assays for LATS-P at relapse (90%) was similar to that seen in untreated Graves' disease.

Topics: Adolescent; Adult; Carbimazole; Female; Graves Disease; Humans; Immunoglobulin G; Long-Acting Thyroid Stimulator; Male; Middle Aged; Propylthiouracil; Recurrence

Topics: Abnormalities, Drug-Induced; Adult; Female; Fetus; Graves Disease; Humans; Infant, Newborn; Japan; Maternal-Fetal Exchange; Methimazole; Pregnancy; Propylthiouracil

A patient with Graves' disease who experienced various allergic reactions to both PTU and MMI is reported. She developed fever, skin rash, lymphadenopathy, liver damage and moderate leukopenia during PTU administration. Furthermore, she developed an MMI-induced lupus-like syndrome characterized by generalized lymphadenopathy, migrating, polyarthritis and myalgia, and results of tests for anti-DNA antibody and anti-nuclear antibody, and LE were positive. All these abnormalities reverted to normal upon discontinuation of medication after subtotal thyroidectomy.

Topics: Adult; Autoantibodies; Dexamethasone; Female; Graves Disease; Humans; Lupus Erythematosus, Systemic; Methimazole; Propranolol; Propylthiouracil; Thyroidectomy

Propylthiouracil (PTU) concentrations were measured in blood and milk from nine lactating women after oral administration of 400 mg of PTU. 1 1/2 h after PTU ingestion mean serum-PTU reached 7.7 microgram/ml and the mean concentration of PTU in milk reached only 0.7 microgram/ml. The mean total amount of PTU excreted during 4 h was 99 microgram--i.e., 0.025% of the administered dose. One of the suckling babies was studied for 5 months during which the mother received 200-300 mg of PTU daily: there were no changes in any of the thyroid parameters. PTU is not concentrated in human breast milk and recommended dosages to the mother result in minimal and presumably clinically insignificant doses to the suckling infant.

Topics: Adult; Breast Feeding; Female; Graves Disease; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk, Human; Propylthiouracil

The effects of long-term treatment with antithyroid drugs, carbimazole (CMI) or propylthiouracil (PTU), on serum reverse triiodothyronine (rT3) levels were studied in 23 patients with Graves' disease. Nineteen patients were given CMI and four PTU for a minimum of six months. After one month of treatment the serum levels of thyroxine (T4), triiodothyronine (T3) and rT3 had normalized in both groups. When L-thyroxine was added to the regimens after two months of therapy, both serum T4 and rT3 levels increased, whereas serum T3 level continued to fall. The serum levels of rT3 seemed to be dependent on and followed the T4 levels so closely that determinations of rT3 in the medical management of patients with Graves' disease will be of little clinical use.

Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Thyroid Hormones; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

In some children, psychological events have appeared to be important in the triggering of Graves' disease. This report examines the case histories of three children in whom the appearance of symptomatology of Graves' disease was associated with depression following the death of a loved one. An analysis of neuroendocrine and immunologie pathways suggests that depression, set off by bereavement, causes low levels of norepinephrine in the brain. The latter in turn may mediate an increase in ACTH and cortisol, leading to reductions in immune surveillance and resultant production of thyroid-stimulating immunoglobulins, hence the development of Graves' disease.

Topics: Adolescent; Adrenocorticotropic Hormone; Child; Depression; Female; Graves Disease; Humans; Hydrocortisone; Male; Norepinephrine; Propylthiouracil; Psychophysiologic Disorders; Stress, Psychological; Thyroglobulin

Topics: Adolescent; Biological Assay; Child; Child, Preschool; Cyclic AMP; Female; Graves Disease; Humans; Infant; Male; Methimazole; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine

Thyroid-stimulating antibodies (TSAb) were found in 51 patients (83.6%) with untreated Graves' disease. The mean TSAb index reached the normal level after 6 months of antithyroid drug therapy. In 9 patients (14.8%), TSAb remained persistently positive during and after antithyroid drug therapy, and relapse occurred in all. In 42 patients (68.8%), TSAb indices gradually returned to the normal range after drug treatment was started; in 38% of these, remission was maintained after treatment was stopped, in another 40.5%, relapse occurred when they were TSAb-positive, and the remaining 21.5% relapsed despite return of TSAb indices to the normal range. A positive TSAb index at the end of drug treatment was a useful indicator in predicting subsequent relapse because, with 1 exception, all patients who were still TSAb positive at drug withdrawal relapsed subsequently.

Topics: Adult; Antibodies; Carbimazole; Female; Graves Disease; Humans; Male; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy.

Topics: Adult; Biopsy; Blood Vessels; Complement C3; Female; Graves Disease; Humans; Immunoglobulin M; Leukopenia; Propylthiouracil; Skin; Splenomegaly; Vasculitis, Leukocytoclastic, Cutaneous

The present study was undertaken to investigate whether there is a rational basis for the usual long periods of thionamide therapy in patients with hyperthyroid Graves' disease. Eighty untreated patients were given the minimum dose of thionamide drug needed to maintain serum thyroxine, triiodothyronine, and thyrotropin (TSH) concentrations within their normal ranges. Thyrotropin-releasing hormone (TRH) tests were done at 6 monthly intervals for 2 years. Among patients who had positive responses of TSH to TRH, approximately 10 patients every 6 months were asked to stop thionamide therapy and were followed up for at least 1 year after discontinuation of drugs. In the groups treated for 6, 12, 18, and 24 months, relapses occurred in nine of 13, five of nine, three of 12, and two of 11 patients, respectively. Values for thyroid function tests before and at the end of treatment were not different among these four groups of patients. The overall remission rates were not ascertained. However, a minimum of 1 year's treatment is recommended, at least in Japan.

Topics: Adolescent; Adult; Child; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Recurrence; Thyroid Function Tests; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

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

Thyroid stimulating immunoglobulins (TSAb) were measured in fifty-four patients with Graves' disease before treatment with either radioiodine (seventeen patients) or propylthiouracil (PTU) (thirty-seven patients), and followed during treatment. After radioiodine TSAb increased to levels exceeding pretreatment values, and became detectable in three of six originally TSAb negative patients. In most patients TSAb decreased during treatment with PTU, and became undetectable after a mean of 12 months in patients above 40 years, and after a mean of 6 months in patients below 40 years. In order to eliminate the presumed causative agent in Graves' disease, antithyroid treatment should be at least 18 months in patients above 40 years, and at least 12 months in patients below 40 years of age. In twenty-nine patients TSAb were measured at cessation of 2 years antithyroid drug therapy. Ten patients were TSAb positive and all except one relapsed. Five of nineteen TSAb negative patients relapsed. Although TSAb positivity predict relapse, it is not an ideal index of prognosis after antithyroid therapy.

Topics: Adult; Autoantibodies; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil

Topics: Adult; Endoplasmic Reticulum; Epithelium; Female; Golgi Apparatus; Graves Disease; Humans; Iodides; Lithium; Lysosomes; Male; Methimazole; Microscopy, Electron; Microvilli; Middle Aged; Propylthiouracil; Thyroid Gland

Suppressor cell function of peripheral mononuclear cells has been examined in patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer, as well as in healthy subjects. Suppressor cell function was assessed through two methods: 1) measurement of enhanced blastogenesis after 24-h preculture and 2) concanavalin A-inducible suppressor activity. The results from the two tests were coincident and indicate that suppressor cell function was significantly decreased in the Graves' disease population but not changed in either the Hashimoto's thyroiditis or the thyroid cancer groups compared to healthy controls. The impairment of suppressor cell function in the Graves' disease population was still observed when patients became euthyroid by treatment with antithyroid drugs, although the treated patients had improved suppressor cell function compared to untreated patients (P = NS). Low activity of suppressor cell function in the Graves' disease population might be a constitutional character based on an inherited abnormality specific for the disease population.

Topics: Adolescent; Adult; Cells, Cultured; Concanavalin A; DNA; Female; Graves Disease; Humans; Male; Propylthiouracil; T-Lymphocytes; Thyroid Neoplasms; Thyroiditis, Autoimmune; Time Factors

Topics: Adolescent; Adult; Age Factors; Aged; Child; Female; Graves Disease; Humans; Iodine; Male; Methimazole; Middle Aged; Propylthiouracil; Sex Factors; Thyroid Function Tests; Thyroid Gland; Triiodothyronine

Topics: Graves Disease; Humans; Long-Acting Thyroid Stimulator; Propylthiouracil; Thyroid Diseases; Thyrotropin

Topics: Adult; Aged; Female; Graves Disease; Humans; Immunoglobulin G; Long-Acting Thyroid Stimulator; Male; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Hyperthyroidism of Graves' disease may be treated very effectively by antithyroid pills, such as PTU and Tapazole, by radioactive iodine therapy, and by subtotal thyroidectomy. Each form of therapy has advantages and disadvantages, and thus treatment should be individualized. While therapy with radioactive iodine would appear to be ideal since it does not require an operation and is less expensive than surgical management, it suffers from a high rate of progressive hypothyroidism and from the fact that the time until a euthyroid state is obtained is often prolonged. In addition, the long-term carcinogenic risk of the therapy for thyroid neoplasia has never been completely defined since the data most often quoted have a mean follow-up time of only eight years. Furthermore, new "low-dose" radioiodine regimens may be more dangerous in this regard. Subtotal thyroidectomy, while not totally without complications, remains a rapid, safe, and effective treatment for Graves' disease. The careful use of propranolol has facilitated the preparation of some patients and has lessened the risk of operation. Thyroidectomy should remain the treatment of choice for young adults with this disease.

Topics: Graves Disease; Humans; Iodine Radioisotopes; Leukemia, Radiation-Induced; Methimazole; Neoplasms, Radiation-Induced; Premedication; Propranolol; Propylthiouracil; Risk; Thyroid Neoplasms; Thyroidectomy

Topics: Adolescent; Child; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Iodine Radioisotopes; Male; Propylthiouracil; Thyroid Hormones; Thyroid Neoplasms; Thyroiditis, Autoimmune

Topics: Adult; Aged; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Time Factors

The correlations between serum triidothyronine (T3), thyroxine (T4), 131I-triiodothyronine resin sponge uptake (RT3U) or free thyroxine index (T7) and the basal metabolic rate (BMR) during antithyroid drug treatment in 86 patients with Graves' disease were investigated. Although serum T3, T4, RT3U and T7 during therapy with MMI showed significant positive correlations with BMR, the coefficient of correlation (r = 0.6088, P less than 0.001) between T3 and BMR was the highest of all. While the normal range of BMR in control subjects was between -1.9 and +14.9 (the range of mean +/- SD), the corresponding values of T3, T4, RT3U and T7 calculated from the regression lines, ranged from 94.2 to 184.0 ng/dl, from 5.32 to 8.75 microgram/dl, from 26.5 to 28.9% and from 1.57 to 2.47 respectively. On the other hand, when the corresponding values of BMR to normal values of T3 (100-170 ng/dl), T4 (7.6-12.2 microgram/dl), RT3U (26.7-36.5% and T7 (2.29-3.49) in control subjects were calculated from the regression lines, the range of value obtained from the regression line of T3 coincided better with normal value of BMR in control subjects that those calculated from other regression lines (T4, RT3U and T7). These results suggest that serum T3 level would be a better index of evaluation of the thyroid function that T4 or RT3U in patients with Graves' disease under antithyroid drug treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Basal Metabolism; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroxine; 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

Serum thyroglobulin (Tg), triiodothyronine (T3), and thyroxine (T4) concentrations were measured in sera from selected patients with hyperthyroidism due to Graves' disease and with subacute thyroiditis. In agreement with previous reports, the concentration of serum Tg was elevated in untreated hyperthyroidism due to Graves' disease, being 132 +/- 124 ng/ml (mean +/- SD) as opposed to 11 +/- 6.4 ng/ml in normal subjects. During treatment of hyperthyroidism with antithyroid drugs with or without iodide, reductions in thyroid hormone concentrations were not associated with a change in serum Tg. On the other hand, marked elevations in serum Tg to concentrations as high as 7000 ng/ml were observed within 24-48 hr after subtotal thyroidectomy or 131I treatment of patients with Graves' disease. These abrupt 10-50-fold increases in serum Tg were not associated with changes in serum T3 and T4. As previously demonstrated, patients with subacute thyroiditis may have elevated serum Tg concentrations that are not associated with elevations in serum T3 and T4. Serum Tg may remain elevated long after clinical and other biochemical mainfestations of this disease have disappeared. These data suggest that the disruption in thyroid function in patients with subacute thyroiditis may persist in a subclinical form for longer periods than previously suspected. Serum Tg appears to be a sensitive indicator of acute thyroidal damage due to surgical, radiation, or inflammatory trauma. The absence of parallel changes in serum Tg, T3, and T4 indicates that release of these thyroidal components can occur by different mechanisms and that nonthyroid tissues cannot efficiently generate T3 and T4 from circulating Tg. Accordingly, local or systemic stimulation of thyroidal Tg hydrolysis may be involved in the generation of hyperthyroidism sometimes seen in patients with subacute thyroiditis.

Topics: Child, Preschool; Female; Graves Disease; Humans; Potassium Iodide; Propylthiouracil; Thyroglobulin; Thyroidectomy; Thyroiditis; Thyroxine; Triiodothyronine

We report here six pregnancies in 5 women with juvenile diabetes and Graves disease. The diabetes was managed in a standard fashion. The Graves disease was managed with propylthiouracil when required. The course of neither the diabetes nor Graves disease was different than expected. When established guidelines for therapy are followed the two have no interaction with one another. One infant was mildly hypothyroid. None developed neonatal Graves disease. Four of the infants had hyperbilirubinemia.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Infant, Newborn; Insulin; Jaundice, Neonatal; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Propylthiouracil

Topics: Adrenal Glands; Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Sympatholytics; Thyroid Crisis; Thyroxine; Triiodothyronine

Since 1946 104 children and adolescents with toxic diffuse goiter have been treated. Sixty-seven were treated with a thioamide for more than 12 months. Remission occurred in 61%. Twenty-five patients had a 12-hour perchlorate discharge test to determine the least frequent dose schedule required for disease control: 68% could be controlled on a single daily dose and an additional 25% on an every 12-hour schedule. A one-hour radioiodine uptake on combined therapy and change in thyroid gland size during treatment were found to be highly correlated with the presence of a spontaneous remission. Thirty-six patients have been treated by subtotal thyroidectomy. To date 65% have developed permanent hypothyroidism. In the author's opinion, thoamides are the treatment of choice for the majority of children and adolescents.

Topics: Adolescent; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Drug Administration Schedule; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Perchlorates; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine

We investigated whether thyrotoxic patients treated with short-term antithyroid therapy would achieve prolonged remissions. Thirty-one previously untreated and nine previously treated patients with thyrotoxic Graves's disease received a single daily dose of methimazole or propylthiouracil. The drug was stopped at, or shortly after, the time they became euthyroid. Twelve of the 31 previously untreated patients remained in remission for 29 +/- 3.5 months (mean +/- S.E.) after treatment for 4.5 +/- 0.3 months. Four of the nine previously treated have remained in remission of 13.0 +/- 2.1 months after treatment for 3.0 +/- 0.3 months. Of various possibilities analyzed, only a small goiter at the onset of therapy and tri-iodothyronine toxicosis were significantly favorable prognostic indicators that a remission would be maintained. The lasting remission rate is as good when antithyroid drugs are stopped as soon as the patient is euthyroid as when they are continued for one year or more.

Topics: Administration, Oral; Adolescent; Adult; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Remission, Spontaneous; Thyroidectomy; Thyroxine; Time Factors; Triiodothyronine

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

Thyroid tissue obtained from 12 patients with Graves' disease and treated with thionamide drugs for 3-7 mo before subtotal thyroidectomy, from 12 patients with Graves' disease, similarly treated, and given 50 mug of triiodothyronine (T3) for 10 days before surgery, and from 12 euthyroid patients with solitary cold nodules was investigated to compare in vitro iodination of thyroglobulin in toxic diffuse goiter and in normal thyroid tissue. The supernates of the homogenates (105,000g) were subjected to sucrose density gradient centrifugation (5--28%) to separate the thyroglobulin fraction. The precipitates were treated with 1% digitonin and centrifuged to collect the supernate (particulate fraction). When thyroglobulin and particulate fractions obtained from the same patient were incubated with 125I-, iodide, glucose, and glucose oxidase, the amount of iodine bound to thyroglobulin was several times greater in toxic diffuse goiter than in normal thyroid tissue; administration of T3 did not affect iodination in toxic diffuse goiter. When the thyroglobulin fraction from each patient was incubated with a standardized quantity of peroxidase instead of the individual particulate fraction, the amount of iodine bound to thyroglobulin was the same among the three groups of patients. Finally, when bovine serum albumin was substituted for thyroglobulin from each of the patients, iodination of bovine serum albumin was several times greater with the particulate fraction obtained from toxic diffuse goiter tissue than with that obtained from normal tissue. The guaiacol-oxidizing activity oty. These results suggest that in vitro iodination of thyroglobulin is increased in toxic diffuse goiter even when patients are made euthyroid by treatment with thionamide drugs as well as when they are given additional T3 for 10 days before operation. The increase in iodination of thyroglobulin appears to be due to an increase in peroxidase activity in the particulate fraction.

Topics: Adult; Female; Graves Disease; Guaiacol; Humans; Iodide Peroxidase; Iodine; Male; Methimazole; Middle Aged; Propylthiouracil; Protein Binding; Serum Albumin, Bovine; Thyroglobulin; Thyroid Gland; Triiodothyronine

One hundred simultaneous determinations of serum T4 and T3 were performed during the course of treatment of 23 children and adolescents with Graves' disease. Five patients were previously untreated and six were experiencing relapse after treatment was discontinued. During relapse, increased T3 concentration is frequently present when serum T4 concentration is normal and T3 measurement is therefore more reliable for early detection of relapse. During therapy with thionamides, T4 measurement alone is often misleading in assessing adequacy of control achieved by therapy. Commonly, patients who clinically have hyperthyroidism have serum T4 concentrations within the normal range but continue to have elevated T3 concentrations (T3 toxicosis). Similarly, T4 can be suppressed into the hypothyroid range in the clinically euthyroid patient with either a normal or high T3 concentration. In these patients, determination of serum T3 often prevents premature reduction of thionamide dosage. When T4 and T3 concentrations do not clearly demonstrate presence or absence of hypothyroidism, measurement of serum thyroid stimulating hormone can be of value.

Topics: Graves Disease; Humans; Infant; Methimazole; Propylthiouracil; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Previous studies have suggested that there is an overproduction of triiodothyronine (T(3)) relative to thyroxine (T(4)) in patients with thyrotoxicosis associated with Graves' disease. To evaluate whether or not an increased ratio of T(3) to T(4) in thyroidal secretion could be contributing to this relative T(3) hyperproduction, T(3), T(4), and iodine were measured in thyroglobulin (Tg) from controls and patients with Graves' disease who had been treated either with propranolol only or with antithyroid drugs plus iodide before surgery. To avoid possible artifacts associated with pulse labeling and chromatography, T(3) and T(4) were determined by radioimmunoassay of Pronase hydrolysates of purified Tg. Results of analyses of Tg from six control patients and seven with Graves' disease, not receiving thiourea drugs or iodide, showed that the iodine content of Graves' disease Tg was not different from normal. Both contained 3.4 residues of T(4)/molecule Tg, but there was 0.39+/-0.08 (mean+/-SD) residue of T(3)/molecule Tg in Graves' Tg as opposed to 0.23+/-0.07 residue T(3) molecule Tg in controls matched for iodine content (P < 0.01). This difference resulted in a significantly lower T(4)/T(3) molar ratio (9+/-2) in Graves' Tg as opposed to control (15+/-2, P < 0.001). In Tg from patients with treated Graves' disease, iodine, T(3), and T(4) were reduced, but the reduction in the latter was more substantial, resulting in a T(4)/T(3) molar ratio of 3.4+/-1. Fractionation of Tg from all groups by RbCl density gradient ultracentrifugation indicated that at physiological levels of Tg iodination, the molar ratio of T(3)/Tg was consistently higher in Graves' disease. The specific mechanism for this difference is not known, but it is not due to iodine deficiency. If T(3) and T(4) are secreted in this altered ratio in patients with Graves' disease, the magnitude of the difference could explain the relative T(3) hyperproduction which is characteristic of this state.

Topics: Drug Therapy, Combination; Graves Disease; Humans; Iodides; Iodine; Methimazole; Propranolol; Propylthiouracil; Thyroglobulin; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine

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: Adult; Dexamethasone; Drug Synergism; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Middle Aged; Potassium Iodide; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Adrenal Cortex Hormones; Child; Female; Graves Disease; Humans; Hyperthyroidism; Pregnancy; Prognosis; Propylthiouracil; Recurrence; Thyroxine; Triiodothyronine

A method has previously been described which detected xenogeneic and allogeneic antibodies to human granulocytes by their inhibition of the normal phagocytosis-associated hexose monophosphate shunt (HMS) activity. This method was used to study three patients with acute agranulocytosis secondary to antithyroid drug administration. Two patients with methimazole and one patient with propylthiouracil induced agranulocytosis were studied. Serum samples from each of these three patients taken during the acute phase of agranulocytosis had inhibitory effects on phagocytosis-associated HMS activity in leukocytes from both normal donors and the patients after their full recovery from agranulocytosis. IgM but not IgG prepared from acute sera in two patients was also inhibitory. Disruption of IgM disulfide bonds by dithiothreitol destroyed its inhibitory activity. The possibility of drug-dependent immune destruction of leukocytes in these patients is discussed.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Drug Hypersensitivity; Female; Granulocytes; Graves Disease; Humans; Immunoglobulin M; Leukopenia; Methimazole; Phagocytosis; Propylthiouracil; Remission, Spontaneous

To understand why some patients with hyperthyroidism due to Graves' disease remain euthyroid after a course of antithyroid drug therapy, pituitary-thyroid regulation was studied in 20 such patients who had remained well for six months or longer after the withdrawal of antithyroid drugs. Only patients who were clinically euthyroid and had normal serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were studied. Serum TSH responses to thyrotropin-releasing hormone (TRH) and thyroid suppression were determined in all patients. Seven patients had normal responses to both tests. Six patients had a subnormal response to TRH and abnormal suppression. Five patients had a subnormal response to TRH and normal suppression, and two patients had a normal TSH response to TRH and abnormal suppression. There were no differences in the mean serum T4, T3 or TSH concentrations between any of the groups. The mean duration of time after antithyroid drug withdrawal was 19 months in the patients in whom both tests were abnormal, whereas it was 58 months in those in whom both tests were normal and 45 months in those with a subnormal TSH response to TRH and a normal suppression test. Thus, in 13 of the 20 patients studied, various degrees of abnormality of pituitary-thyroid regulation were demonstrable. These results suggest that, in most patients with Graves' disease who remain clinically and biochemically euthyroid after a course of antithyroid drug therapy, the disease persists in a mild or subclinical form.

Topics: Adolescent; Adult; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pituitary Gland; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; 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

Fasting plasma gastrin levels measured by radioimmunoassay were found to be elevated in patients with hyperthyroidism. The intravenous injection of arginine caused an increase of plasma gastrin in hyperthyroid patients as in normal subjects. The elevated gastrin level in patients with hyperthyroidism was significantly lowered after the thyroid function was normalized by treatment.

Topics: Adolescent; Adult; Arginine; Blood Glucose; Fasting; Female; Gastrins; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil

A possible in vitro immunosuppressive role of propylthiouracil (PTU) was investigated by culturing peripheral blood lymphocytes (PBL) from normal subjects with plant lectins in the presence of PTU added at the onset of culture or near the time of peak cell division. When added at the onset of culture PTU caused a dose-related suppression of lectin stimulated 3H-thymidine uptake with an average of approximately 50% suppression at a PTU concentration of 100 mug/ml. When added at the time of peak cell division however, marked suppression was produced by 10 mug/ml of PTU. Prolonged remissions in patients with Graves' disease treated with PTU, and possibly other anti-thyroid drugs, may thus be due to an immunosuppressive role of the drug rather than the natural evolution of the disease.

Topics: Graves Disease; Humans; Immunosuppression Therapy; Lectins; Lymphocyte Activation; Propylthiouracil; Time Factors

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

Topics: Animals; Cyclic AMP; Female; Graves Disease; Humans; Immunoglobulin G; Long-Acting Thyroid Stimulator; Lymphocyte Activation; Lymphocytes; Male; Prolactin; Propylthiouracil; Rats; Stimulation, Chemical; Stress, Psychological; Thymidine; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine

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

Topics: Chemical and Drug Induced Liver Injury; Child; Female; Graves Disease; Humans; Jaundice; Liver; Propylthiouracil

Chronic idiopathic thrombocytopenic purpura (ITP) and hyperthyroidism coexisted in two children. In one, hyperthyroidism developed nine years after the onset of purpura. In the other, the two diseases appeared concomitantly. It is important to distinguish the thrombocytopenia due to ITP from that due to antithyroid drugs.

Topics: Azathioprine; Child; Female; Graves Disease; Humans; Prednisone; Propylthiouracil; Purpura; Purpura, Thrombocytopenic; Splenectomy; Thrombocytopenia

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

Topics: Adult; Asthma; Female; Graves Disease; Humans; Hypothyroidism; Infant; Male; Potassium Iodide; Propylthiouracil; Thyroxine

Topics: Adult; Antithyroid Agents; Collagen Diseases; Female; Graves Disease; Humans; Propylthiouracil

Topics: Aged; Bone Marrow; Female; Graves Disease; Humans; Leukemia, Myeloid, Acute; Propylthiouracil

Topics: Animals; Antithyroid Agents; Child; Goiter; Graves Disease; Humans; Hyperthyroidism; Methimazole; Phenylthiourea; Propylthiouracil; Rats; Sulfaguanidine; Thioglycosides; Thyroid Gland; Vegetables

Topics: Carbimazole; Graves Disease; Humans; Immune Adherence Reaction; Iodine; Iodine Radioisotopes; Propylthiouracil; Remission, Spontaneous; Thyroid Gland; Thyroxine; Time Factors; Triiodothyronine

Topics: Fundus Oculi; Graves Disease; Humans; Male; Middle Aged; Optic Atrophy; Optic Neuritis; Propylthiouracil; Retinal Vein; Thrombosis; Tonometry, Ocular; Visual Acuity

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: 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

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: 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: Adult; Diet; Female; Graves Disease; Humans; Iodine; Male; Methimazole; Middle Aged; Propylthiouracil; Remission, Spontaneous; Thyroxine; Time Factors; Triiodothyronine

Topics: Adult; Chromatography, Paper; Depression, Chemical; Diiodotyrosine; Female; Goiter, Nodular; Graves Disease; Humans; Iodine; Iodine Isotopes; Male; Metabolic Clearance Rate; Methimazole; Middle Aged; Potassium Iodide; Propylthiouracil; Thyroid Function Tests; Thyroid Gland

Topics: Antithyroid Agents; Graves Disease; Humans; Iodine Isotopes; Methimazole; Propylthiouracil; Remission, Spontaneous

Topics: Adult; Female; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

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: Adolescent; Adult; Aged; Child; Estradiol; Follicle Stimulating Hormone; Graves Disease; Gynecomastia; Humans; Long-Acting Thyroid Stimulator; Luteinizing Hormone; Male; Middle Aged; Propylthiouracil; Radioimmunoassay; Thyroxine

Topics: Esterases; Fasting; Female; Glycerides; Goiter; Graves Disease; Heparin; Humans; Hyperthyroidism; Insulin; Iodine Isotopes; Lipase; Lipoprotein Lipase; Male; Methimazole; Propranolol; Propylthiouracil; Triglycerides

Topics: Adult; Blindness; Dexamethasone; Female; Graves Disease; Humans; Middle Aged; Prednisone; Propylthiouracil; Visual Acuity

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: Apgar Score; Bone Diseases, Developmental; Cesarean Section; Electroencephalography; Female; Fetus; Goiter; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Iodides; Labor Presentation; Male; Maternal-Fetal Exchange; Potassium Iodide; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Tracheal Stenosis; Triiodothyronine

Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Methimazole; Methylthiouracil; Propylthiouracil; Radioimmunoassay; Thyroxine; Triiodothyronine

Topics: Adult; Amniocentesis; Amniotic Fluid; Female; Fetal Diseases; Graves Disease; Humans; Hypothyroidism; Pregnancy; Propylthiouracil; Thyroid Function Tests; Thyroxine; 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: Adolescent; Adult; Aged; Analysis of Variance; Graves Disease; Humans; Immunoglobulin G; Iodine Radioisotopes; Ion Exchange Resins; Long-Acting Thyroid Stimulator; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Eye Manifestations; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Propylthiouracil; Skin Manifestations; Thyroid Diseases

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests

Topics: Adult; Corneal Ulcer; Diplopia; Emergencies; Female; Glucocorticoids; Graves Disease; Humans; Hypophysectomy; Iodine Isotopes; Keratitis; Male; Middle Aged; Orbit; Papilledema; Propylthiouracil; Thyroidectomy; Vision Disorders

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: Adult; Anemia, Aplastic; Graves Disease; Humans; Male; Propylthiouracil

Topics: Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Long-Acting Thyroid Stimulator; Propylthiouracil; Thyroid Function Tests; Triiodothyronine

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: Drug Therapy; Female; Goiter; Graves Disease; Hormones; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Iodine; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Reserpine; Thyroid Function Tests; Thyroid Gland; Thyrotropin

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: 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: Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Patient Selection; Propylthiouracil; Thiouracil

Topics: Edema; Graves Disease; Hyperthyroidism; Myxedema; Propylthiouracil; Thiouracil

Topics: Graves Disease; Humans; Propylthiouracil; Thiouracil

Topics: Agranulocytosis; Goiter; Graves Disease; Humans; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Graves Disease; Humans; Hyperthyroidism; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Disease Management; Goiter; Graves Disease; Propylthiouracil; Thiouracil

Topics: Graves Disease; Humans; Propylthiouracil; Thiouracil

Topics: Child; Exophthalmos; Goiter; Graves Disease; Humans; Propylthiouracil

Topics: Graves Disease; Propylthiouracil; Thiourea; Thyroid Diseases

Topics: Eye Diseases; Goiter; Graves Disease; Graves Ophthalmopathy; Humans; Propylthiouracil; Thyrotoxicosis

Topics: Eye Diseases; Goiter; Graves Disease; Graves Ophthalmopathy; Humans; Propylthiouracil; Thyrotoxicosis

Topics: Goiter; Graves Disease; Graves Ophthalmopathy; Humans; Propylthiouracil; Thiouracil

Topics: Exophthalmos; Goiter; Graves Disease; Humans; Propylthiouracil; Thiourea

Topics: Goiter; Graves Disease; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Goiter; Graves Disease; Humans; Hyperthyroidism; Paralyses, Familial Periodic; Propylthiouracil

Topics: Goiter; Graves Disease; Propylthiouracil; Thyrotoxicosis