propylthiouracil and Goiter

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

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

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

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

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

Topics: Animals; Carbimazole; Choanal Atresia; Ectodermal Dysplasia; Female; Goiter; Guinea Pigs; Humans; Hypothyroidism; Methimazole; Mice; Pregnancy; Propylthiouracil; Rabbits; Rats; Teratogens; Thyroid Gland

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

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

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

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

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

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

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

Goiter with hypothyroidism occurs in several thyroid diseases. Xiao-Luo-Wan (XLW), which contains Scrophularia ningpoensis Hemsl., Fritillaria thunbergii Miq. and Ostrea gigas Thunberg, has been used as an effective Chinese medicine for the treatment of goiters in China for hundreds of years. Based on clinical observations and experimental studies, XLW also exerts a certain effect on hypothyroidism. However, the therapeutic mechanism of XLW remains unclear.. The present study aimed to investigate the therapeutic effect of XLW on propylthiouracil (PTU)-induced goiter with hypothyroidism in rats and to uncover the underlying molecular mechanism using ultra high-performance liquid chromatography-mass spectrometry (UPLC/MS), network pharmacology, and molecular docking simulations.. After successful modeling, the remaining rats were randomly divided into a model group, an Euthyrox group, an XLW group, and a control group. The corresponding drugs were given by gavage for four consecutive weeks. The growth status was monitored, the relative thyroid weight was calculated, and the total serum T3, T4, and TSH content were detected. Hematoxylin-eosin (H&E) staining was used to observe the pathological changes in the thyroid glands. The chemical components of the XLW were identified by UPLC/MS and the putative targets of XLW were predicted using multiple databases. We performed network pharmacology based on the intersection of goiter/hypothyroidism-related targets and XLW targets. Then, we performed KEGG pathway enrichment analysis, and key targets were further screened using protein-protein interaction (PPI) networks. Finally, molecular docking was used to predict the binding ability of XLW identified components and the key targets.. XLW significantly increased the levels of T3 and T4, and reduced TSH, increased body weight, and decreased swollen thyroid glands in PTU-induced rats. XLW promoted the morphological recovery of thyroid follicles and epithelial cells. Twenty-one main chemical components of XLW were identified using UPLC/MS. 270 potential gene targets of XLW and 717 known targets of goiter/hypothyroidism disease were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction, and UniProt databases. A total of 83 KEGG pathways were enriched with phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) and RAS signaling pathways. PPI analysis revealed nine key targets of kinase-protein kinase B (AKT) 1, interleukin (IL) 6, vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), epidermal growth factor receptor (EGFR), GTPase HRas (HRAS), matrix metalloproteinase (MMP) 9, and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Molecular docking verified which drug components had good binding ability to key targets (all ≤5 kcal/mol).. For PTU-induced goiter with hypothyroidism in rats, XLW improves thyroid function, reduces goiter, increases body weight, and promotes the recovery of thyroid follicles and epithelial cells. The underlying molecular mechanism suggests that XLW may regulate thyroid hormone signaling by regulating the PI3K-AKT, RAS, and other signaling pathways. This study provides a pharmacological and biological basis for using XLW to treat goiter with hypothyroidism.

Topics: Animals; Chromatography, High Pressure Liquid; Disease Models, Animal; Drugs, Chinese Herbal; Goiter; Hypothyroidism; Male; Mass Spectrometry; Molecular Docking Simulation; Network Pharmacology; Phosphatidylinositol 3-Kinase; Propylthiouracil; Proto-Oncogene Proteins c-akt; ras Proteins; Rats; Rats, Wistar

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

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

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

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

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

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

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

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

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

A 40 year old male victim of a road traffic accident presented to our emergency trauma services with multiple limb injuries and a Glasgow Coma Score (GCS) of 15/15. Soon after admission, he became confused, stuporous, febrile and tachycardic. A clinical diagnosis of thyrotoxic crisis precipitated by trauma was confirmed by relevant investigations, with appropriate therapeutic response. A review of the clinical features and management of this rare medical emergency, with only few cases reported worldwide, is presented.

Topics: Accidents, Traffic; Adult; Anti-Inflammatory Agents; Antithyroid Agents; Glasgow Coma Scale; Goiter; Humans; Hydrocortisone; Male; Multiple Trauma; Propranolol; Propylthiouracil; Thyroid Crisis; Treatment Outcome; Ultrasonography

Goiter is associated with increased oxidative stress (OS). We studied the effects of an anti-inflammatory agent, 15 deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) and an antioxidant, N-acetylcysteine (NAC), on OS, thyroid function, and goiter expansion in a model of goiter induced by propylthiouracil (PTU) or perchlorate. OS was assessed by the immunodetection of 4-hydroxynonenal, thyroid function by measuring thyroxin (T4) and thyrotropin (TSH) plasma levels and detecting T4-rich thyroglobulin (Tg-I), and goiter expansion by weighing the thyroids and measuring cell proliferation (PCNA and cyclin D1 immunodetection). In both PTU and perchlorate-induced goiters, OS, TSH plasma levels, thyroid weight, and cell proliferation were strongly enhanced, whereas Tg-I expression was negative. All these parameters were reversed by NAC and 15dPGJ2 in PTU-goiters. In perchlorate-goiters, TSH plasma levels remained elevated and Tg-I-negative after NAC or 15dPGJ2 treatment. OS was reduced by NAC, but not by 15dPGJ2. In addition, NAC reduced PCNA and cyclin D1 immunostainings, as well as thyroid weight, whereas 15dPGJ2 influenced neither thyroid weight nor cell proliferation. In conclusion, NAC and 15dPGJ2 overcome PTU- but not perchlorate-induced effects. The retrieval of hormonal synthesis may result from direct chemical interactions between PTU and NAC/15dPGJ2. Although 15dPGJ2 has no effect in perchlorate-goiters, the reduction of OS by NAC is associated with altered goiter development, making OS a required condition for the growth of the thyroid gland.

Topics: Acetylcysteine; Animals; Cell Nucleus; Cell Proliferation; Cyclin D1; Female; Goiter; Organ Size; Oxidative Stress; Perchlorates; Peroxiredoxins; Proliferating Cell Nuclear Antigen; Propylthiouracil; Prostaglandin D2; Rats; Rats, Wistar; Thyroid Gland; Thyroxine

A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.

Topics: Acidosis, Renal Tubular; Adult; Antithyroid Agents; Diabetes Insipidus, Nephrogenic; Female; Goiter; Humans; Hypokalemic Periodic Paralysis; Medication Adherence; Polyuria; Propylthiouracil; Recurrence; Thyrotoxicosis; Vasopressins; Water Deprivation

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

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

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

C cells are primarily known for producing calcitonin, a hypocalcemic and hypophosphatemic hormone. Nevertheless, besides their role in calcium homeostasis, C cells may be involved in the intrathyroidal regulation of follicular cells, suggesting a possible interrelationship between the two endocrine populations. If this premise is true, massive changes induced by different agents in the activity of follicular cells may also affect calcitonin-producing cells. To investigate the behaviour of C cells in those circumstances, we have experimentally induced two opposite functional thyroid states. We hyperstimulated the follicular cells using a goitrogen (propylthiouracil), and we suppressed thyroid hormone synthesis by oral administration of thyroxine. In both scenarios, we measured T(4), TSH, calcitonin, and calcium serum levels. We also completely sectioned the thyroid gland, specifically immunostained the C cells, and rigorously quantified this endocrine population. In hypothyroid rats, not only follicular cells but also C cells displayed hyperplastic and hypertrophic changes as well as increased calcitonin levels. When exogenous thyroxine was administered to the rats, the opposite effect was noted as a decrease in the number and size of C cells, as well as decreased calcitonin levels. Additionally, we noted that the two cell types maintain the same numerical relation (10 +/- 2.5 follicular cells per C cell), independent of the functional activity of the thyroid gland. Considering that TSH serum levels are increased in hypothyroid rats and decreased in thyroxine-treated rats, we discuss the potential involvement of thyrotropin in the observed results.

Topics: Animals; Body Weight; Calcitonin; Calcium; Cell Size; Goiter; Hypothyroidism; Male; Paracrine Communication; Propylthiouracil; Rats; Rats, Wistar; Thyrotropin; Thyroxine

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

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

We 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

N,N,N',N'-Tetramethylthiourea (TMTU) is a rat goitrogen inducing thyroid hyperplasia, hypertrophy, and tumor formation. Little is known about the exact underlying mechanism of action. As thyroid peroxidase (TPO) and type I iodothyronine deiodinase (ID-I) have been established as targets of goitrogenic thiourea derivatives, we investigated interactions of TMTU with target enzymes using a partially purified fraction from hog thyroids or solubilized hog thyroid microsomes and 10,000g supernatant from rat liver homogenate, respectively, as enzyme sources. For comparison, comprehensively characterized goitrogenic thiourea derivatives were studied as well. In contrast to propylthiouracil (PTU), and like ethylenethiourea (ETU), TMTU only marginally affected TPO-catalyzed oxidation of guaiacol. TMTU, like ETU, concentration-dependently suppressed TPO-catalyzed iodine formation with concomitant oxidative metabolism. Suppression ceased upon consumption of thiourea derivatives, the rate of the reappearing iodine formation was similar to that of controls. TMTU, like ETU, also suppressed non-enzymatic and TPO-catalyzed monoiodination of l-tyrosine with a stoichiometry of 2:1, i.e., one molecule of thiourea derivative suppressed two times monoiodination. TMTU and ETU were unable to irreversibly inhibit TPO. In contrast to PTU, TMTU did not inhibit ID-I. These findings provide evidence that TMTU interferes with thyroid hormone synthesis at the level of iodination and demonstrate a metabolic route for the oxidative detoxification of TMTU in the thyroid suggesting that low-level or intermittent exposure to TMTU would have only minimal effects on thyroid hormone synthesis. Finally, it can be concluded that meaningful toxicological studies on TPO inhibition can be performed without a need for highly purified TPO.

Topics: Amitrole; Animals; Antithyroid Agents; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ethylenethiourea; Goiter; Guaiacol; Hydrogen Peroxide; Iodide Peroxidase; Iodine; Oxidation-Reduction; Propylthiouracil; Rats; Swine; Thiourea; Time Factors; Tyrosine

The aim of this study was to evaluate in vivo the antiproliferative effect of an inhibitor of isoprenoids metabolism, lovastatin, in an experimental model of propylthiouracil-induced goiter. In thyroid cells, thyrotropin (TSH)-induced proliferation requires active isoprenoid synthesis, and the HMG-CoA reductase inhibitors have antiproliferative effects in vitro. Propylthiouracil treatment (PTU) of rats led to thyroid hypertrophy and hyperplasia by TSH-induced activation of the mitogen-activated protein kinase (MAPK) pathway. Immunohistochemistry showed an increased number of proliferating cell nuclear antigen (PCNA)-positive cells in the thyroid gland of PTU-treated rats. Moreover, the phosphorylation of ERK1 and ERK2 was increased in the extract from goiter tissue as compared with the thyroid tissue of untreated rats. To determine whether the inhibition of selected pro-survival pathways (i.e., p21ras-MAPK) was sufficient to affect goitrogenesis, thyroids from 12 PTU-treated rats were injected in vivo with an adenovirus transducing a dominant-negative ras gene (Rad-L61.S186) and another set of 12 rats were injected with a pharmacological inhibitor of MAPK (PD98059). Both Rad-L61.S186 and PD98059 were able to inhibit the PTU-induced goiter. It is interesting to note that lovastatin, when administered in drinking water, significantly prevented the thyroid gland enlargement. Therefore, lovastatin-treated thyroid glands were significantly smaller than those treated with PTU alone. In addition, the lovastatin-treated glands also showed a decreased expression of phosphorylated ERK1/2 and a number of PCNA-positive cells. Our data suggest that lovastatin is an efficient inhibitor of goitrogenesis and provide a rationale for innovative therapeutic strategies employing statins in the treatment of nodular goiter in humans.

Topics: Animals; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Gene Transfer Techniques; Goiter; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperplasia; Hypertrophy; Lovastatin; Male; MAP Kinase Signaling System; Phosphorylation; Proliferating Cell Nuclear Antigen; Propylthiouracil; Protein Kinase Inhibitors; Protein Prenylation; ras Proteins; Rats; Rats, Wistar; Terpenes; Thyroid Gland; Thyrotropin

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

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

We have investigated immunohistochemically the effect of dl-alpha-tocopherol (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats. The animals were divided into four groups. Rats in group I were designated as control, rats in group II were treated with injections of PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with injections PTU for 15 days and kept for 15 next days after cessation of PTU treatment. At the end of experiment, the animals were killed by decapitation, blood samples were obtained, thyroid tissues were collected and processed for quantitative evaluation of immunohistochemical PCNA (marker of cell proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker) staining. There was an increase in the number of PCNA-immunopositive cells in follicular epithelial cells of group II rats compared with other groups (p<0.05). After vitamin E treatment, the number of PCNA-immunopositive cells decreased (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The number of Bcl-2-positive follicular epithelial cells of group IV rats was higher than in those of other groups (p<0.05). The results of this study indicate that hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may promote involution of the gland.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Biomarkers; Cell Division; Down-Regulation; Epithelial Cells; Goiter; Hypothyroidism; Immunohistochemistry; Male; Proliferating Cell Nuclear Antigen; Propylthiouracil; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Signal Transduction; Thyroid Gland; Up-Regulation; Vitamin E

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

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

Previously, we observed that excess iodide rapidly suppressed the elevated ornithine decarboxylase activity in the thyroid of propylthiouracil (PTU)-pretreated rats. Excess iodide also induces involution of goitrous thyroids. These findings led us to study effects of excess iodide on apoptosis of rat thyroids. When given to PTU-pretreated rats, excess potassium iodide (KI) (13 mg/kg body weight, 10 mg as iodine) induced DNA fragmentation in the thyroid at the first 3 hours after its treatment. The percentage of DNA fragmentation was also maximal at 3 hours after KI treatment. In methimazole-pretreated rats, the kinetic of DNA fragmentation was nearly the same; apoptosis increased for the first 6 hours and then decreased at 12 hours after KI administration. Other iodinated compounds such as amiodarone and diiodotyrosine have also shown apoptosis-inducing activity, but their effect was observed later than KI. Iopanoic acid had no such effect. Apoptotic changes were also observed with the use of flow cytometry. PTU or methimazole alone had some stimulatory effect on thyroid apoptosis. Iodine effect was not observed in rats treated with either perchlorate or thiocyanate. These results suggest that excess iodine induces thyroid involution in goitrogen-treated rats at least partially by apoptosis.

Topics: Amiodarone; Animals; Antithyroid Agents; Apoptosis; Diiodotyrosine; DNA Fragmentation; Goiter; Male; Methimazole; Potassium Iodide; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland

Excess iodine and some iodine-containing compounds are known to affect various parameters of thyroid function. Lecithin-bound iodine (LBI) is a compound which induces involution of an enlarged thyroid. LBI was tested for its ability to affect thyroid ornithine decarboxylase (ODC) activity and apoptosis.. LBI was given orally to propylthiouracil-pretreated rats and the changes in ODC activity and apoptosis were observed. The thyroid apoptosis was detected by DNA laddering and flow cytometry.. LBI suppressed the thyroid ODC activity within one hour after its administration and lowered slightly but significantly the thyroid putrescine levels at 3 h. The DNA cleavage ladder was evident at 3-6 h after LBI treatment. Propylthiouracil induced thyroid enlargement was reduced significantly at 3 days after chronic treatment with LBI. The thyroidal content of putrescine was also decreased after chronic treatment. These effects of LBI were essentially the same as those of excess iodide, while other iodinated compounds including amiodarone, iopanoic acid and erythrosine had no effect on the thyroid ODC activity.. These results suggest that LBI may exert its anti-goitrous effects, consisting of the inhibition of ODC activity and apoptosis, in the form of inorganic iodide in vivo.

Topics: Animals; Apoptosis; DNA Fragmentation; Flow Cytometry; Goiter; Male; Ornithine Decarboxylase; Phosphatidylcholines; Propylthiouracil; Putrescine; Rats; Rats, Wistar; Thyroid Gland

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

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

Apoptosis, a physiological process of cell death, may modulate the mass of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis during goiter formation and involution in a rat model of goiter. Rats were fed a low iodine diet and a goitrogen, 6-propyl-2-thiouracil, to induce goiter. Rats with goiter were then fed a high iodine diet to study the phase of involution. We examined the presence of apoptosis by electron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL). We also investigated the association between Fas and FasL expression and thyrocyte apoptosis using immunohistochemistry and Western blotting. To evaluate the proliferation of thyrocytes, proliferating cell nuclear antigen was examined immunohistochemically. The number of apoptotic cells increased during goiter formation and the early stage of involution, which were also associated with increased number of Fas-positive thyrocytes, and some of these cells contained TUNEL-positive nuclei. However, the expression of FasL was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly increased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis of thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the induction of apoptosis of these cells. Moreover, the delicate balance between apoptosis and cell proliferation may play an important role in the control of thyroid gland mass.

Topics: Animals; Apoptosis; Blotting, Western; Diet; fas Receptor; Goiter; Immunohistochemistry; Male; Microscopy, Electron; Organ Size; Proliferating Cell Nuclear Antigen; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland; Thyroxine; Triiodothyronine

To evaluate the possible antigoitrogenic effect of somatostatin, the influence of long-acting somatostatin analog--octreotide--on experimental goiter developed in rats treated with propylthiouracil was examined. Goiter formation was assessed by measurement of the main histological compartments of the thyroid as well as by morphometric analysis of the vascularization and blood supply of the gland. Although treatment with octreotide did not prevent the goiter formation, it clearly reduced blood supply and vascularization of the thyroid and counteracted propylthiouracil-induced increase in the relative volume of follicular epithelium. To conclude, the somatostatin analog--octreotide--is effective in reduction of goiter vascularisation. This finding provides a rationale for the clinical trials of the treatment of hypervascular goiter by somatostatin analogs.

Topics: Animals; Antithyroid Agents; Goiter; Hormones; Male; Octreotide; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

Topics: Animals; Blotting, Northern; Cattle; Goiter; Hyperplasia; Male; Propylthiouracil; Rats; Rats, Wistar; RNA, Messenger; Thyroid Gland; Thyrotropin; Time Factors; Transforming Growth Factor beta

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

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

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

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

Fetal goiter is a rare disorder, usually associated with maternal thyroid disease. Antenatal diagnosis of fetal goiter is crucial for the immediate postpartum management of these neonates. A case report is presented of an antenatally diagnosed fetal goiter induced by antithyroid medications. Color Doppler was used to demonstrate a high flow pattern that, unlike in the adult goiter, was associated with hypothyroidism in the neonate. A scan of fetal neck region is recommended in patients with current or previous history of thyroid disease, or if neck extension is noted on routine examination of fetal spine.

Topics: Adult; Female; Fetal Diseases; Goiter; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotoxicosis; Ultrasonics; Ultrasonography, Prenatal

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

Myeloperoxidase (MPO), which displays considerable amino acid sequence homology with thyroid peroxidase (TPO) and lactoperoxidase (LPO), was tested for its ability to catalyze iodination of thyroglobulin and coupling of two diiodotyrosyl residues within thyroglobulin to form thyroxine. After 1 min of incubation in a system containing goiter thyroglobulin, I-, and H2O2, the pH optimum of MPO-catalyzed iodination was markedly acidic (approximately 4.0), compared to LPO (approximately 5.4) and TPO (approximately 6.6). The presence of 0.1 N Cl- or Br- shifted the pH optimum for MPO to about 5.4 but had little or no effect on TPO- or LPO-catalyzed iodination. At pH 5.4, 0.1 N Cl- and 0.1 N Br- had a marked stimulatory effect on MPO-catalyzed iodination. At pH 4.0, however, iodinating activity of MPO was almost completely inhibited by 0.1 N Cl- or Br-. Inhibition of chlorinating activity of MPO by Cl- at pH 4.0 has been previously described. When iodination of goiter thyroglobulin was performed with MPO plus the H2O2 generating system, glucose-glucose oxidase, at pH 7.0, the iodinating activity was markedly increased by 0.1 N Cl-. Under these conditions iodination and thyroxine formation were comparable to values observed with TPO. MPO and TPO were also compared for coupling activity in a system that measures coupling of diiodotyrosyl residues in thyroglobulin in the absence of iodination. MPO displayed very significant coupling activity, and, like TPO, this activity was stimulated by a low concentration of free diiodotyrosine (1 microM). The thioureylene drugs, propylthiouracil and methimazole, inhibited MPO-catalyzed iodination both reversibly and irreversibly, in a manner similar to that previously described for TPO-catalyzed iodination.

Topics: Animals; Catalysis; Cattle; Goiter; Humans; Iodide Peroxidase; Iodides; Kinetics; Lactoperoxidase; Methimazole; Peroxidase; Propylthiouracil; Serum Albumin, Bovine; Swine; Thyroglobulin; Thyroid Gland

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

Generalized resistance to thyroid hormone (GRTH), or Refetoff syndrome, is a disease in which peripheral tissues show resistance to thyroid hormone. Three patients with this disease were investigated. Cases 1 and 2 involved identical 7-year-old female twins and case 3, a 5-year-old girl. All three patients had goiters, and cases 1 and 2 had sensorineural deafness. In all three, the blood levels of T4, free T4, and T3 were high, while the blood levels of TSH were normal or slightly elevated. The responses shown by blood levels of the thyroid hormone and TSH to administration of propylthiouracil and T3 suggest that the regulating mechanism in the hypothalamic-pituitary-thyroid system was functional. Upon administration of T3, no sign of hyperthyroidism was observed.

Topics: Child; Child, Preschool; Female; Goiter; Humans; Pedigree; Prednisone; Propylthiouracil; Syndrome; Thyroid Hormones; Thyrotropin; Triiodothyronine

Goitre growth was investigated in rats receiving a low iodine diet (less than 0.1 microgram iodine/g) and either 1 g/l KClO4 or 1 g/l propylthiouracil (PTU), or a combination of KClO4 or PTU with 50.82 nmol/1 T3 in tap water for 3 weeks. To investigate goitre involution, rats with iodine-deficient goitres were treated for 3 weeks either with T3 (0.5 microgram T3/day = 0.768 nmol/day), iodide (0.5 or 2.7 micrograms KI/day) or a combination of T3 with both iodide doses. Histology together with total DNA distinguished between hypertrophy and hyperplasia of the gland. During goitre growth there was highly significant correlation between goitre weight and TSH serum level (r = 0.93, P less than 0.001). Thyroid total DNA, however, was only weakly correlated to TSH but was inversely related to the degree of iodine deficiency. During goitre regression, TSH levels were normalized, histological signs of hypertrophy had disappeared, and thyroid weight was nearly normalized in all therapy groups. Total DNA, however, was normalized only with 2.7 micrograms KI/day (95 +/- 18 micrograms DNA/gland), and still elevated in all other groups. The highest DNA levels were found under T3 therapy (143 +/- 21 micrograms DNA/gland) and under 0.5 microgram KI/day (161 +/- 19 micrograms DNA/gland). Reduction of total DNA was independent of TSH, but followed replenishment of the iodine content of the glands. We conclude that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.

Topics: Animals; DNA; Female; Goiter; Hyperplasia; Hypertrophy; Iodine; Male; Organ Size; Potassium Chloride; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Gland; Thyrotropin; Triiodothyronine

The aim of this work was to investigate some aspects of the thyroid epithelial cell kinetics during the iodide-induced involution of a hyperplastic goitre in the rat. Rats were made iodine-deficient for 6 months, and propylthiouracil (PTU) (0.15%) was added to the diet during the last 2 months. Thereafter, rats were refed with iodide and PTU was removed (day 0). Forty-eight hours previously, all the rats were injected with tritiated thymidine ([3H]TdR) (1 microCi/g). Some animals were killed 1 hr or 24 hr after [3H]TdR injection (i.e. on day -2 and -1, day 0 corresponding to the restoration of a normal iodine diet); the other animals were killed after different delay periods and following [3H]TdR injection. Autoradiography of thyroid sections, iodine determination of plasma iodide and protein-bound iodine (PBI), and RIA of plasma thyroid stimulatory hormone (TSH) were performed. Plasma TSH concentration was very high on day 0 of iodide refeeding (3000 +/- 330 ng/ml) and remained at this level until day 8. Plasma PBI was very low on day 0, remained so until day 4 and greatly increased on day 8. Plasma iodide was also very low on day 0, but markedly increased on day 1, then did not vary significantly until day 43 of iodine refeeding. Thyroid weight, elevated on day 0, decreased relatively quickly until day 30, then more slowly until day 73. The [3H]TdR labelling index (LI) of the thyroid epithelial cells (TEC) was high on day 0 (56 +/- 3 labelled cells/10,000 cells), and 24 hr thereafter increased to 104 +/- 3, by division of the labelled cells. On day 1 of iodine refeeding, the LI had abruptly decreased to about half this value and then remained stable for 3 more days. Between day 4 and day 16, a progressive decline in the LI, (by about 3-4 per day), was observed. The LI showed no further modification, up to day 73, the longest period investigated. The decrease in LI occurred without any significant changes in the labelling intensity (grain count) of the remaining labelled cells between day 1 and 16, this indicates that no cell division took place during this period. The data are therefore interpreted as showing a biphasic elimination after iodide refeeding, of cells that were actively proliferating during the goitrous state.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Cell Division; Diet; Epithelium; Goiter; Hyperplasia; Iodine; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Function Tests; Thyroid Gland; Thyrotropin

Delayed morphological changes induced in mouse hyperplastic thyroid by refeeding iodine were analyzed by light and electron microscopy, stereology, and autoradiography. Thyroid hyperplasia was induced by a low iodine diet supplemented with 0.25% propylthiouracil for 10 days. Involution was obtained by discontinuing the propylthiouracil and returning either to a moderate iodine diet [(MID) 1 microgram I/day] or to an iodine-rich diet [(HID) 10 micrograms I/day] for 40 days. In other experiments, three cycles of hyperplasia (8 days) and subsequent involution (8 days) with MID or HID were brought about. Control animals were fed MID or HID. All animals were killed when 12-14 weeks old after injection of 10-50 microCi 125I. Double labeling, with repeated injections of [3H]thymidine from day 0 to day 7 of involution followed by 125I injection 4 h before killing, was also performed. When involutions were performed with MID, most morphological variables returned to control values. However, when involution was brought about with HID, the glandular weight, the number of follicles, and the relative volume of follicular lumina remained larger than in controls. Moreover, the 125I-labeling pattern of the follicles was altered. The proportions of unlabeled, and unevenly or partly labeled, follicles, which were fewer than 5% in control groups, represented 25-35% of all follicles after involution with HID, whereas they were unchanged with MID. In unlabeled follicles the epithelium was flattened, with a reduced number of microvilli. Partly labeled follicles were of two types. In some follicles a persistent ring reaction was observed, suggesting an abnormally slow mixing of thyroglobulin. In others, the 125I labeling was restricted to areas adjacent to the apex of a reduced number of cells, suggesting that some cells were iodinating thyroglobulin, whereas others were not. There was no relationship between the follicular 125I labeling and the frequency of [3H]thymidine-labeled cells. These results indicate that refeeding iodine excess after hyperplasia leads to the formation of a colloid goiter with new follicles, and to an increased heterogeneity of iodine metabolism among follicles and among cells.

Topics: Animals; Cytoplasm; Endoplasmic Reticulum; Epithelium; Female; Goiter; Hyperplasia; Iodine; Mice; Mice, Inbred C3H; Microscopy, Electron; Microvilli; Organ Size; Propylthiouracil; Thyroid Gland

Rats on iodine deficient diet for 6 months received propylthiouracil (PTU) (0.15%) during the last 2 months. At the end of this treatment, PTU was withdrawn and the rats were iodine refed. 48 hrs. before the iodine refeeding all rats were injected with 3H thymidine. The results showed that some prelabelled cells in the hyperplastic goitre preferentially disappeared during its involution and therefore are more sensitive to iodine.

Topics: Animals; Goiter; Iodides; Iodine; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Thymidine; Thyroid Gland; Thyrotropin

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

In this study we investigated further the antigoitrogenic effect of ClO4 in rats on a low iodine diet (LID) and 6-propyl-2-thiouracil (PTU). The thyroid weight of rats on the mixed goitrogen was initially similar to that of animals on PTU, decreasing to values obtained in rats treated with ClO4 alone by 10 days. Despite the differences in thyroid weight, rats treated during an identical period with PTU or mixed goitrogen develop hypothyroidism to a comparable degree as far as can be assessed by the thyroidal 127I content, plasma T4, T3 and TSH concentrations, and pituitary TSH content. Moreover, it was observed that there were differences in plasma insulin and glucose levels in these hypothyroid animals. The plasma insulin and glucose levels of rats on PTU are comparable to those found in control rats. In rats on mixed goitrogen, both plasma insulin and glucose levels are initially maintained within the normal ranges, and then decline over the subsequent days of treatment. Within the treatment period studied here, plasma insulin and glucose levels were higher for rats on PTU than for animals on ClO4, PTU + ClO4, or thyroidectomized (Th) animals. We have obtained further evidence of the hypothyroid state of rats on these goitrogen regimens based on measurements of pituitary and plasma GH levels and liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). The PTU-treatment decreased the liver alpha-GPD activity to a comparable degree to that of mixed goitrogen. Moreover, both PTU + ClO4 and PTU-treatment resulted in a state of hypothyroidism intense enough to induce effects on growth, and plasma and pituitary GH levels comparable to that of Th animals. However, the values for rats on mixed goitrogen appear to be below the PTU data. The present findings appear to be consistent with the view that TSH is not the unique factor determining the size of the resulting goitre. The results are discussed in relation to the hypothesis that: 1) the antigoitrogenic effect of ClO4 could be associated with changes in the ability of the thyroid tissue to bind TSH, or with a step beyond TSH binding, and 2) the different endocrine and metabolic states of rats on PTU or PTU + ClO4, shown by their different plasma insulin, GH and glucose levels, may play an important role in determining the thyroid weight response to TSH.

Topics: Animals; Blood Glucose; Goiter; Growth Hormone; Hypothyroidism; Insulin; Male; Organ Size; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroid Hormones

Topics: Anemia; Arrhythmias, Cardiac; Female; Goiter; Humans; Hypercalcemia; Hyperthyroidism; Iodine Radioisotopes; Middle Aged; Propranolol; Propylthiouracil; Thyroxine

To investigate a possible role of TSH in the regulation of its own receptor, a sensitive assay of [125I]TSH tropin binding to rat thyroid membranes was used. With 1 mM MgCl2 in the buffer, Scatchard analysis of displacement of TSH gave a curvilinear plot with a high affinity, low capacity (K1, 3.4 nM; Q1, 3.1 pmol/microgram) and a low affinity, high capacity binding site (K2, 0.54 microM; Q2, 1.2 X 0.1 nmol/microgram). Feeding rats propylthiouracil led to a decrease in [125I]TSH binding (expressed either per U protein or per wet wt of tissue) that was related to the duration of treatment. Evaluation by Scatchard analysis showed that this was due to a loss of binding sites, e.g. a 50-60% decrease after 1 month of propylthiouracil treatment; affinity was actually slightly increased in the goitrous tissue. This change in the number of TSH-binding sites was readily reversed in association with the suppression of TSH in vivo either by injections of T3 for 3 days or more by feeding a normal diet for 1 month. Thus, the data are compatible with TSH, that is in high concentration in the serum of rats fed propylthiouracil, exerting a downregulatory influence on its own receptors.

Topics: Adenylyl Cyclases; Animals; Cell Membrane; DNA; Goiter; Kinetics; Magnesium; Male; Propylthiouracil; Rats; Receptors, Cell Surface; Thyroid Gland; Thyrotropin

The sonographic diagnosis of a fetal goiter, confirmed at delivery, is described in a fetus exposed to large doses of propylthiouracil, which was administered to the mother. The pregnancy was also complicated by recalcitrant premature labor secondary to polyhydramnios. The intraamniotic instillation of thyroxine decreased the size of the fetal goiter, and numerous therapeutic amniocenteses permitted continuation of the pregnancy, so a mature infant with a goiter but no airway obstruction was delivered. Amniotic fluid reverse-T3 assays confirmed fetal utilization of the thyroxine. Fetal thyroid physiology is discussed briefly along with the benefits of the antenatal sonographic diagnosis of fetal goiter.

Topics: Adult; Female; Fetal Diseases; Goiter; Goiter, Nodular; Humans; Lung; Maternal-Fetal Exchange; Polyhydramnios; Pregnancy; Propylthiouracil; Thyroxine

The critical time of onset of the reciprocal relationship between the pituitary and the thyroid in fetal rats was assessed by the appearance of goiters in fetuses after maternal treatment with goitrogen, propylthiouracil (PTU), on various days of gestation. The assessment was based on changes in the weight and histology of the fetal thyroids. The day following overnight mating was regarded as day 1 of gestation. Pregnant rats were treated with 40 mg PTU each day for two days and autopsied on the third day. The various experimental periods were days 16--18, 17--19, 18--20, 19--21, and 20--22. PTU given to pregnant rats on days 16 and 17 did not cause any change in the fetal thyroids. PTU given on days 17 and 18 caused only a slight increase of fetal "thyroid weight/body weight" ratio. In all other experimental periods (days 18--20, 19--21, and 20--22), PTU induced conspicuous goiters in fetuses, which was reflected by an increased weight of thyroids, an increased height of follicular cells, and a decreased amount of colloid stored in follicles. The results suggest that in fetal rats, the reciprocal relationship between the pituitary and the thyroid is established on approximately days 19--20 of gestation.

Topics: Animals; Female; Fetal Diseases; Goiter; Maternal-Fetal Exchange; Organ Size; Pituitary Gland; Pregnancy; Propylthiouracil; Rats; Thyroid Gland

Topics: Animals; Coturnix; Female; Goiter; Male; Organ Size; Propylthiouracil; Thyroid Gland; Thyroxine; Triiodothyronine

Most of the cyclic AMP-dependent protein kinase activity in propylthiouracil-induced goiters and control rat thyroid glands was found in the soluble fraction. The activity in the particulate fractions was cyclic AMP-independent. Protein kinase activity was 2--3-fold higher in all the subcellular fractions of goitrous tissue than of control tissue. In the presence of Triton X-100, both groups showed a significant increase in kinase activity in all subcellular fractions, and the kinase activity in the particulate fractions could now be slightly stimulated by cyclic AMP. Again, enzyme activity in fractions from goiters was significantly higher than in control tissue. Two major peaks, Types I and II, of soluble cyclic AMP-dependent protein kinase activity could be separated by DEAE-cellulose chromatography. Chronic in vivo stimulation by TSH was associated with a selective increase in Type II isoenzyme activity. Elution and pH profiles, dissociation of subunits with 0.5 M NaCl, and activity ratios (-cyclic AMP/+cyclic AMP) for various substrates for Type II isoenzyme in goitrous and control tissue were similar. The elevated activity in goitrous tissue was manifested by an increase in V for histone, ATP, Mg2+ and cyclic AMP, with no change in the apparent Km.

Topics: Animals; Cyclic AMP; Goiter; Hydrogen-Ion Concentration; Isoenzymes; Kinetics; Male; Propylthiouracil; Protein Kinases; Rats; Subcellular Fractions; Substrate Specificity; Thyroid Gland; Thyrotropin

Topics: Alkaloids; Animals; Antithyroid Agents; Goiter; Iodine; Liver; Male; Nitriles; Organ Size; Plants, Toxic; Propylthiouracil; Rats; Ricinus; Ricinus communis; Thyroxine; Triiodothyronine

Topics: Animals; Cathepsins; Diet; Glucuronidase; Goiter; In Vitro Techniques; Lysosomes; Organ Size; Propylthiouracil; Rats; Rats, Inbred Lew; Thyroid Gland

The treatment of benign forms of thyroid disease is reviewed. Endemic goiter is a public health problem preventable by the addition of iodine to the food or water supply. Endemic and familial goiters are treated with replacement doses of I-thyroxine, as are sporadic colloid goiters and goiters resulting from chronic thyroiditis. Hyperfunctioning autionomous nodules without thyrotoxicosis and cystic nodules require no specific therapy. Prophylaxis against diffuse or nodular goiter after radiation to the head or neck for therapeutic purposes with thyroxine replacement therapy is debatable. All forms of hypothyroidism, including incipient types, require replacement thyroxine therapy, but this should be undertaken cautiously in older patients and in those with evidence of ischemic myocardial disease. Myxedema coma requires vigorous treatment and detailed supervision because of dismal mortality rates. Iodine 131 is the treatment of choice in diffuse toxic goiter, but alternative forms.

Topics: Adolescent; Adult; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Radiation Dosage; Thyroid Diseases; Thyroxine

Topics: Animals; Cyclic AMP; Goiter; Iodine; Male; Organ Size; Propylthiouracil; Rats; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

Topics: Animals; Body Weight; Calcitonin; Calcium; Diet; Female; Goiter; Iodine; Male; Organ Size; Phosphates; Propylthiouracil; Rats; Thyroid Gland; Thyrotropin

Topics: Adenylyl Cyclases; Animals; Calcium; Fluorides; Goiter; Guanosine Triphosphate; Kinetics; Magnesium; Male; Manganese; Propylthiouracil; Prostaglandins E; Rats; Thyroid Gland

A patient with malignant lymphoma developed goiter and thyrotoxicosis during the course of her disease. A thyroid biopsy revealed involvement of the thyroid gland with a malignant lymphoma. This was associated with the high levels of circulating thyroglobulin and thyroid hormones. The patient was treated with propylthiouracil, local radiotherapy, and nitrogen mustard and prednisone. The patient became euthyroid with the disappearance of goiter. Circulating levels of thyroglobulin and thyroid hormones returned to the normal range.

Topics: Adult; Female; Goiter; Humans; Hyperthyroidism; Lymphoma, Non-Hodgkin; Propylthiouracil; Thyroglobulin; Thyroid Function Tests; Thyroid Neoplasms; Thyrotropin; Thyroxine

The protein metabolism and [3H]-uridine uptake of thyroid and adenohypophysis and the kinetics of pituitary TSH rebound (PTR) were studied in goitrous female rats (fed propylthiouracil, PTU: for 7-12 weeks) following single, iv injections of L-thyroxine (T4: 0.8 to 200 mug). Goitrogenesis was associated with reduced protein concentration and enhanced uptake of [3H] uridine in both glands. Plasma levels of TSH were invariably elevated but stores in the adenohypophysis were consistently reduced. Small doses of T4 (4 mug) induced significant TSH repletion in the pituitary within 2-6 h following injection. Accumulations of pituitary TSH to supranormal levels (15-fold increases) were achieved with 20 mug T4 at 6 and 24 h; higher doses (100-200 mug) inhibited the PTR at all time intervals tested (0.5-24 h). Administration of puromycin or actinomycin D did not influence the PTR. Protein content and labeled uridine uptake of the pituitary bore no apparent relationship to T4-induced TSH repletion in the gland. Blood clearance rate of exogenous rat TSH was measured prior to and during PTR. Plasma half-life was determined to be 13.6 and 19.9 min in euthyroid and chronically hypothyroid rats, respectively; it was not significantly altered from the latter during rebound (18.7 min). Calculations of theoretical TSH secretory rates prior to (50.5 +/- 4.4 mU/h) and after rebound with 20 mug T4 (25.4 +/- 4.2 mU/H) revealed that the reaccumulation of TSH in the pituitary induced with T4 cannot be attributed solely to inhibition of release, but may also involve enhancement of synthesis. It is concluded that T4 administration at high dose levels inhibits both synthesis and release of TSH from pituitary thyrotrophs, whereas low critical doses of T4 suppress release, but augment synthesis and/or facilitate conformational change in a pituitary precursor(s) molecule which renders it detectable by bioassay.

Topics: Animals; Dactinomycin; Female; Goiter; Kinetics; Metabolic Clearance Rate; Pituitary Gland; Pituitary Gland, Anterior; Propylthiouracil; Puromycin; Rats; Secretory Rate; Thyroid Gland; Thyrotropin; Thyroxine; Uridine

Administration of propylthiouracil (PTU) to pregnant, third trimester sheep led to decreasing serum thyroxine and increasing serum thyroid-stimulating hormone in both mothers and fetuses. Hypothyroidism appeared more pronounced in the fetuses than in the ewes, and goiter formation was observed in all fetuses exposed to PTU. Concomitant administration of triiodothyronine failed to protect the fetuses from the effects of PTU.

Topics: Animals; Disease Models, Animal; Female; Fetal Diseases; Goiter; Hypothyroidism; Organ Size; Pregnancy; Propylthiouracil; Sheep; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Twenty-one women were studied who had received propylthiouracil or methimazole during 26 pregnancies. Four of the infants had a goiter at birth, and 3 of these had neonatal thyrotoxicosis. In 2 children neonatal thyrotoxicosis was not evident at birth because of maternal antithyroid therapy. Five children had congenital defects. Two mothers were responsible for 4 of the children with abnormalities, and both mothers had been treated with thiourea drugs for long periods, ranging from 7 to 11 years. The majority of children who are exposed to these drugs in utero appear to have no subsequent ill effects. However, prolonged therapy with these agents may be undesirable.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Female; Fetal Blood; Fetal Death; Goiter; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Long-Acting Thyroid Stimulator; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Scalp; Thyroid Function Tests; Thyroxine

From 1959 to 1970, 272 operations for thyrotoxicosis were performed. Most of the patients received anti-thyroid drugs and thyroid hormones preoperatively. The patients were continuously followed up. The primary results with low morbidity and no mortality as well as the long term results with a low rate of recurrence and a relatively high incidence of thyroid substitution are discussed. A safe and effective programme for surgical treatment of thyrotoxicosis is described. Anti-thyroid drugs and thyroid hormones should be administered as the method of choice in preparing these patients for surgery.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Child; Female; Goiter; Humans; Hyperthyroidism; Hypocalcemia; Hypothyroidism; Laryngoscopy; Length of Stay; Male; Methimazole; Middle Aged; Paralysis; Postoperative Complications; Preoperative Care; Propylthiouracil; Recurrent Laryngeal Nerve; Thyroxine; Triiodothyronine

Topics: Female; Goiter; Humans; Imidazoles; Iodine; Perchlorates; Propylthiouracil; Radionuclide Imaging

The potentiation of the propylthiouracil (PTU)-induced goitrogenesis after chronic administration of small doses of thyroid hormone has been attributed to the high circulating level of thyrotrophin (TSH) or to the re-instatement of insulin. In re-examining this problem radioimmunoassayable concentrations of TSH, thyroxine (T4), insulin, and growth hormone (GH) were observed in sera of rats at sequential intervals after surgical or chemical thyroidectomy and after thyroidectomy and replacement therapy with GH or T4. In addition, TSH, GH or a combination of both hormones were injected into hypophysectomized recipients in a further attempt to delineate the effect of either hormone on the thyroid. As expected, the rate of body growth was inversely proportional to the apparent severity of the hypothyroidism achieved in the several experimental groups. Goitrogenesis was enhanced after T4 treatment but evidently was not the exclusive result of increased blood levels of TSH or insulin. Evidence is presented that suggest the enhancement of goitrogenesis may be a growth phenomenon involving the additive or synergistic action of GH and TSH and possible of other hormones.

Topics: Animals; Body Weight; Female; Goiter; Growth Hormone; Insulin; Male; Organ Size; Propylthiouracil; Rats; Stimulation, Chemical; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine

Topics: Adolescent; Adult; Antithyroid Agents; Drug Therapy, Combination; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Triiodothyronine

Topics: Antithyroid Agents; Congenital Hypothyroidism; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Male; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Twins

Topics: Animals; Antithyroid Agents; Child; Goiter; Graves Disease; Humans; Hyperthyroidism; Methimazole; Phenylthiourea; Propylthiouracil; Rats; Sulfaguanidine; Thioglycosides; Thyroid Gland; Vegetables

Topics: Adolescent; Adult; Aged; Blood Proteins; Calcium; Carbimazole; Cholesterol; Female; Goiter; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Middle Aged; Perchlorates; Phosphorus; Propylthiouracil; Recurrence; Serum Albumin; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine

Topics: Adult; Female; Goiter; Humans; Iodides; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland; Time Factors; Triiodothyronine

Topics: Adrenal Glands; Animals; Body Weight; Goiter; Hypothalamo-Hypophyseal System; Male; Morphine; Organ Size; Pituitary Gland; Propylthiouracil; Rats; Testis; Thyroid Gland; Thyrotropin; Time Factors

Topics: Adrenal Glands; Age Factors; Animals; Blood Glucose; Body Weight; Chlorates; Diet; Female; Goiter; Gonads; Growth Hormone; Insulin; Iodine; Male; Organ Size; Pituitary Gland; Potassium; Propylthiouracil; Rats; Sex Factors; Thyroid Function Tests; Thyroid Gland; Thyrotropin

Topics: Animals; Cattle; Cross Reactions; Goiter; Guinea Pigs; Half-Life; Iodine; Iodine Isotopes; Male; Pituitary Gland; Propylthiouracil; Radioimmunoassay; Rats; Secretory Rate; Thyrotropin; Thyroxine; Time Factors

Topics: Adolescent; Female; Goiter; Hemorrhage; Humans; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Iodine; Methylthiouracil; Postoperative Care; Postoperative Complications; Potassium Iodide; Preoperative Care; Propylthiouracil; Thyroid Diseases; Thyroidectomy; Thyroiditis; Time Factors; Vocal Cord Paralysis

Topics: Abortion, Spontaneous; Adolescent; Adult; Cesarean Section; Cholesterol; Female; Fetal Death; Gestational Age; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Iodine; Iodine Radioisotopes; Maternal Mortality; Methimazole; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Triiodothyronine

Topics: Abnormalities, Drug-Induced; Age Factors; Animals; Cochlea; Deafness; Disease Models, Animal; Female; Gestational Age; Goiter; Hypothyroidism; Iodine; Male; Mice; Mice, Inbred C57BL; Organ of Corti; Pregnancy; Propylthiouracil; Thyroxine

Topics: Adrenal Glands; Animals; Animals, Newborn; Body Weight; Female; Goiter; Gonads; Humans; Male; Morphine Dependence; Organ Size; Pituitary Gland; Pituitary-Adrenal System; Propylthiouracil; Thyroid Gland; Thyrotropin; Time Factors

Topics: Adenoma; Antithyroid Agents; Buffers; Centrifugation; Chromatography, Paper; Evaluation Studies as Topic; Goiter; Humans; Hydrolysis; Imidazoles; Iodine; Iodine Radioisotopes; Methods; Pronase; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroid Neoplasms; Thyroxine

Topics: Animals; Auditory Cortex; Cell Nucleus; Chick Embryo; Cochlea; Cochlear Nerve; Cytoplasm; Ear; Ear Diseases; Ear, Inner; Ear, Middle; Goiter; Hypothyroidism; Propylthiouracil; Thyroid Gland; Thyroxine

Topics: Adrenalectomy; Animals; Body Weight; Corticosterone; Cyanates; Goiter; Growth Hormone; Insulin; Male; Organ Size; Potassium; Propylthiouracil; Rats; Stimulation, Chemical; Thyroid Gland; Thyrotropin

Topics: Animals; Bile; Chromatography, Thin Layer; Circadian Rhythm; Goiter; Guinea Pigs; Half-Life; Iodine; Iodine Isotopes; Kinetics; Mice; Organ Size; Propylthiouracil; Protein Binding; Spectrum Analysis; Sulfur Isotopes; Thyroid Gland; Thyrotropin; Ultraviolet Rays

Topics: Esterases; Fasting; Female; Glycerides; Goiter; Graves Disease; Heparin; Humans; Hyperthyroidism; Insulin; Iodine Isotopes; Lipase; Lipoprotein Lipase; Male; Methimazole; Propranolol; Propylthiouracil; Triglycerides

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: Animals; Blood Proteins; Goiter; Iodine; Iodine Isotopes; Male; Metabolic Clearance Rate; Propylthiouracil; Protein Binding; Rats; Thyroid Gland; Thyroid Hormones; Time Factors

Topics: Adolescent; Audiometry; Child; Cochlea; Deafness; Female; Goiter; Humans; Hyperthyroidism; Labyrinth Diseases; Lupus Erythematosus, Systemic; Propylthiouracil; Tinnitus

Topics: Animals; Goiter; Male; Nitrates; Perchlorates; Propylthiouracil; Rats; Thiocyanates

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Brain; Diencephalon; Female; Fetus; Gestational Age; Goiter; Hypophysectomy; Hypothalamus; Maternal-Fetal Exchange; Organ Size; Pituitary Gland; Pregnancy; Propylthiouracil; Rats; Thiourea; Thyroid Gland; Thyrotropin-Releasing Hormone; Vitamin A

Topics: Animals; Choline; Dextrans; Drug Evaluation; Goiter; Male; Organ Size; Propylthiouracil; Rats; Thiouracil; Thyroid Gland

Topics: Aminoglutethimide; Aniline Compounds; Animals; Anticonvulsants; Antithyroid Agents; Blood Proteins; Chromatography, Paper; Depression, Chemical; Diiodotyrosine; Female; Goiter; Iodine; Iodine Isotopes; Male; Monoiodotyrosine; Organ Size; Propylthiouracil; Protein Binding; Pyridones; Rats; Thyrotropin; Thyroxine

Topics: Animals; Antithyroid Agents; Blood Proteins; Body Weight; Goiter; Hypothyroidism; Insulin; Iodine; Male; Methimazole; Organ Size; Perchlorates; Propylthiouracil; Protein Binding; Rats; Rhenium; Thiocyanates; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine

Topics: Adult; Aged; Basal Metabolism; Ethchlorvynol; Female; Goiter; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Serum Globulins; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Animals; Goiter; Iodine; Iodine Isotopes; Leucine; Male; Perchlorates; Propylthiouracil; Proteins; Rats; Thyroid Gland; Thyroxine; Tritium; Ultracentrifugation

Topics: Adolescent; Adult; Aged; Goiter; Humans; Hyperthyroidism; Immunoglobulin G; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Triiodothyronine

Topics: Animals; Feedback; Goiter; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Pituitary Gland; Propylthiouracil; Rats; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine

Topics: Animals; Antithyroid Agents; Anura; Depression, Chemical; Female; Follicle Stimulating Hormone; Goiter; Metamorphosis, Biological; Pigmentation; Pituitary Gland; Propylthiouracil; Stimulation, Chemical; Thyroid Gland; Thyrotropin

Topics: Aminophylline; Animals; Antithyroid Agents; Blood Proteins; Caffeine; Cyclic AMP; Drug Synergism; Goiter; Hypophysectomy; In Vitro Techniques; Iodine; Male; Propylthiouracil; Protein Binding; Rats; Theobromine; Theophylline; Thyroid Gland

Topics: Animals; Colloids; Cricetinae; Disease Models, Animal; Goiter; Hyperplasia; Iodine; Male; Microscopy, Electron; Propylthiouracil; Thyroglobulin; Thyroid Hormones; Thyrotropin

Topics: Animals; Autoradiography; Cell Nucleus; Chick Embryo; Goiter; Hypothalamo-Hypophyseal System; Iodine; Iodine Isotopes; Karyotyping; Organ Size; Pituitary Gland; Propylthiouracil; Thyroid Gland; Thyrotropin; Transplantation, Homologous

Topics: Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Long-Acting Thyroid Stimulator; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adolescent; Anesthesia, General; Carbimazole; Female; Follow-Up Studies; Goiter; Halothane; Horner Syndrome; Humans; Hyperthyroidism; Hypoparathyroidism; Laryngeal Edema; Male; Nitrous Oxide; Oxygen; Postoperative Complications; Preoperative Care; Propylthiouracil; Thyroidectomy; Thyroxine; Tracheotomy

Topics: Animal Nutritional Physiological Phenomena; Animals; Calcium; Cricetinae; Female; Goiter; Iodine Radioisotopes; Male; Potassium Iodide; Propylthiouracil; Sex Characteristics; Thyroid Function Tests; Thyroid Neoplasms; Thyrotropin

Topics: Antithyroid Agents; Female; Goiter; Humans; Hyperthyroidism; Iodine Isotopes; Pregnancy; Propylthiouracil; Thyroidectomy; Thyroxine

The present studies demonstrate that iodine depletion increases the sensitivity of the thyroid to the goitrogenic effects of thyrotropin. Iodine depletion was induced by feeding rats a low iodine diet containing propylthiouracil for 10-14 days before hypophysectomy. Accumulation of iodine in the thyroid after hypophysectomy was prevented by continuing the antithyroid drugs in the diet. Doses of thyrotropin as low as 3 mU/100 g of body weight per day produced significant thyroid enlargement in 3-7 days in iodine-depleted rats. Adding propylthiouracil or perchlorate to the diet during treatment with thyrotropin did not reduce or augment the goitrogenic response to thyrotropin in iodine-depleted rats. Increasing the level of circulating iodide also did not reduce the goitrogenic response to thyrotropin. The increased sensitivity of the iodine-depleted thyroid gland may provide an explanation for the development of thyroid enlargement without requiring an increased level of circulating thyrotropin.

Topics: Animals; Deficiency Diseases; Diet; Goiter; Hypophysectomy; Iodine; Perchlorates; Pituitary Gland; Propylthiouracil; Rats; Thyroid Gland; Thyrotropin

Topics: Animals; Deficiency Diseases; Feedback; Goiter; Hyperplasia; Iodine; Iodine Isotopes; Iodoproteins; Male; Perchlorates; Propylthiouracil; Rats; Thyroid Hormones; Thyrotropin

Topics: Animals; Depression, Chemical; Diiodotyrosine; Dinitrophenols; Goiter; Iodine; Iodine Isotopes; Male; Monoiodotyrosine; NADP; Propylthiouracil; Rats; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Animals; Feces; Feedback; Goiter; Male; Pituitary Gland; Propylthiouracil; Rats; Thyroid Gland; Thyroxine

Topics: Animals; Female; Goiter; Hypophysectomy; Hypothalamo-Hypophyseal System; Hypothalamus; Pituitary Gland; Propylthiouracil; Rats; Stereotaxic Techniques; Thyrotropin-Releasing Hormone; Thyroxine; Transplantation, Homologous

Topics: Child, Preschool; Female; Goiter; Growth; Humans; Hyperthyroidism; Infant; Intelligence; Intelligence Tests; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Propylthiouracil; Psychological Tests; Thyroid Function Tests

Topics: Animals; Body Weight; Goiter; Male; Organ Size; Oxygen Consumption; Pituitary Gland; Propylthiouracil; Rats; Thyroidectomy; Thyrotropin; Triiodothyronine

Topics: Animals; Castration; Drug Antagonism; Estradiol; Female; Goiter; Male; Propylthiouracil; Rats; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Animals; Diet; Female; Goiter; Homeostasis; Iodine; Iodine Isotopes; Male; Organ Size; Propylthiouracil; Rats; Thyroid Gland; Thyrotropin; Thyroxine

Topics: Animals; Colloids; Deficiency Diseases; Diet; Female; Goiter; Hyperplasia; Iodine; Male; Organ Size; Propylthiouracil; Rats; Thyroglobulin; Thyroid Gland; Thyrotropin

Topics: Animals; Body Weight; Goiter; Inbreeding; Male; Mice; Organ Size; Propylthiouracil; Secretory Rate; Thyroid Gland; Thyroid Hormones; Thyroxine

Topics: Adolescent; Adult; Antithyroid Agents; Blood Cell Count; Diagnosis, Differential; Diagnostic Errors; Female; Goiter; Heart Auscultation; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methylthiouracil; Myxedema; Nervous System Diseases; Neurotic Disorders; Propylthiouracil; Radioisotope Dilution Technique; Thiazoles; Thiouracil; Thiourea; Thyrotropin

Topics: Adolescent; Aminoglutethimide; Animals; Anticonvulsants; Child; Child, Preschool; Chromatography; Female; Goiter; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Propylthiouracil; Rats; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Animals; Antithyroid Agents; Goiter; Male; Methylthiouracil; Microscopy; Neoplasms, Radiation-Induced; Organ Size; Propylthiouracil; Radiation Effects; Rats; Thyroid Gland; Triazoles

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: Animals; Antithyroid Agents; Body Weight; Fluorides; Goiter; Hypophysectomy; In Vitro Techniques; Iodides; Iodine; Nitrates; Perchlorates; Propylthiouracil; Rats; Rhenium; Thyroid Gland; Thyrotropin

Topics: Animals; Chromatography, Paper; Diiodotyrosine; Electrophoresis; Goiter; Humans; Immunoelectrophoresis; In Vitro Techniques; Iodine Isotopes; Male; Propylthiouracil; Rats; Thyroglobulin; Thyroid Gland; Thyroid Hormones; Thyronines; Thyrotropin; Thyroxine-Binding Proteins; Tyrosine; Ultracentrifugation

Topics: Adrenal Glands; Animals; Atrophy; Female; Fetal Diseases; Goiter; Guinea Pigs; Hyperplasia; Hypertrophy; Pituitary Gland; Pregnancy; Pregnancy, Animal; Propylthiouracil; Thyroid Gland

Topics: Animals; Body Weight; Female; Goiter; Male; Poultry; Propylthiouracil; Secretory Rate; Species Specificity; Thyroid Gland; Thyroxine

Topics: Female; Goiter; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Iodine Isotopes; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Toxicology

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: Adenoma; Goiter; Hyperthyroidism; Pathology; Propylthiouracil; Rats; Research; Thyroid Neoplasms; Thyrotropin; Toxicology

Topics: Blood Chemical Analysis; Chromatography; Geriatrics; Goiter; Hyperthyroidism; Iodine Isotopes; Monoiodotyrosine; Myxedema; Neoplasms; Propylthiouracil; Thiourea; Thyronines; Thyroxine; Tyrosine

Topics: Adolescent; Antithyroid Agents; Child; Female; Goiter; Graves Disease; Guanethidine; Heart Diseases; Humans; Hyperthyroidism; Infant; Iodides; Iodine Isotopes; Myxedema; Ophthalmology; Perchlorates; Pituitary Gland; Potassium; Pregnancy; Pregnancy Complications; Propylthiouracil; Radiotherapy; Reserpine; Thyroid Function Tests; Thyroidectomy; Thyrotoxicosis; Toxicology

Topics: Adrenocorticotropic Hormone; Digoxin; Female; Genetics, Medical; Goiter; Graves Disease; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Propylthiouracil; Thymus Gland; Thyroid Gland; Thyrotoxicosis

Topics: Adrenal Cortex Hormones; Blood Transfusion; Goiter; Hyperthyroidism; Hypoprothrombinemias; Iodine Isotopes; Propylthiouracil; Prothrombin Time; Reserpine; Toxicology; Vitamin K

Topics: Biomedical Research; Blood; Female; Goiter; Humans; Menstrual Cycle; Ovary; Ovulation; Physiology; Propylthiouracil; Rats; Research; Statistics as Topic; Thyroid Gland; Thyrotropin

Topics: Biological Assay; Goiter; Guinea Pigs; Hypophysectomy; Immune Sera; Iodine Isotopes; Metabolism; Mice; Pharmacology; Physiology, Comparative; Pituitary Hormones, Anterior; Propylthiouracil; Rats; Research; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine

Topics: Aging; Animals; Animals, Newborn; Goiter; Hypothalamo-Hypophyseal System; Male; Pituitary Gland; Propylthiouracil; Rats; Thyrotropin

Topics: Goiter; Iodides; Iodine; Iodine Radioisotopes; Propylthiouracil; Thiouracil

Topics: Goiter; Propylthiouracil; Thiouracil; Thyroxine

Topics: Goiter; Guinea Pigs; Hypothalamus; Pituitary Gland; Propylthiouracil; Thiouracil; Thyrotropin

Topics: Animals; Biomedical Research; Goiter; Iodides; Iodine; Propylthiouracil; Rats; Thiouracil

Topics: Goiter; Leadership; Prednisolone; Propylthiouracil; Thiouracil

Topics: Child; Disease; Diseases in Twins; Female; Goiter; Humans; Hyperthyroidism; Infant; Pregnancy; Propylthiouracil; Thiouracil; Twins

Topics: Goiter; Propylthiouracil; Thiouracil; Thyroxine

Topics: Child; Eating; Goiter; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Mothers; Propylthiouracil; Thiouracil

Topics: Child; Goiter; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Propylthiouracil; Thiouracil

Topics: Adrenocorticotropic Hormone; Goiter; Propylthiouracil; Thiouracil

Topics: Analgesics; Animals; Goiter; Propylthiouracil; Rats; Thiouracil

Topics: Animals; Goiter; Propylthiouracil; Rats; Thyroxine

Topics: Goiter; Hyperthyroidism; Propylthiouracil; Thiouracil

Topics: Agranulocytosis; Goiter; Graves Disease; Humans; Propylthiouracil; Thiouracil; Thyrotoxicosis

Topics: Animals; Goiter; Guinea Pigs; Propylthiouracil; Rats; Thiouracil

Topics: Disease Management; Goiter; Graves Disease; Propylthiouracil; Thiouracil

Topics: Child; Exophthalmos; Goiter; Graves Disease; Humans; Propylthiouracil

Topics: Goiter; Humans; Propylthiouracil; Thiourea

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; Humans; Hyperthyroidism; Propylthiouracil; Thyroid Gland

Topics: Goiter; Graves Disease; Propylthiouracil; Thyrotoxicosis