propylthiouracil and Thyroid-Neoplasms

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

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

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

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

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

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

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

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

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

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

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

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

Thyroid cancers are the most common malignancy of the endocrine system in humans. To understand the molecular genetic events underlying thyroid carcinogenesis, we have generated a mouse model that spontaneously develops follicular thyroid carcinoma similar to human thyroid cancer (Thrb(PV/PV) mouse). This mutant mouse harbors a dominant-negative mutated thyroid hormone receptor β (denoted PV). The PV mutation was identified in a patient with resistance to thyroid hormone (TH). Thrb(PV/PV) mice exhibit highly elevated serum thyroid-stimulating hormone levels and increased TH. We have previously shown that thyroid-stimulating hormone is required, but not sufficient to induce metastatic follicular thyroid cancer in Thrb(PV/PV) mice. However, whether the elevated TH also contributes to the thyroid carcinogenesis of Thrb(PV/PV) mice was not elucidated. To understand the role of TH in thyroid carcinogenesis, we blocked the production of TH by treating Thrb(PV/PV) mice with propylthiouracil (Thrb(PV/PV)-PTU mice) and compared the development of thyroid cancer in Thrb(PV/PV)-PTU and untreated Thrb(PV/PV) mice. We found that thyroid tumor growth was reduced by ∼42% in Thrb(PV/PV)-PTU mice as compared with Thrb(PV/PV) mice. Analysis by bromodeoxyuridine-nuclear labeling showed decreased incorporation of bromodeoxyuridine in thyroid tumor cells of Thrb(PV/PV)-PTU mice, indicative of decreased tumor cell proliferation. However, cleaved-caspase 3 staining showed no apparent changes in apoptosis of tumor cells in Thrb(PV/PV)-PTU mice. Molecular studies identified a marked attenuation of the PI3K-AKT-β-catenin signaling pathway that led to decreased protein levels of cyclin D2, thereby decreasing tumor cell proliferation in Thrb(PV/PV)-PTU mice. Furthermore, matrix metalloproteinase-2, a downstream target of β-catenin and a key regulator during tumor invasion and metastasis, was also decreased. Thus, the present study uncovers a critical role of TH in promoting the thyroid carcinogenesis of Thrb(PV/PV) mice via membrane signaling events. Importantly, these findings suggest that anti-thyroid drugs could be considered as possible therapeutic agents of thyroid cancer.

Topics: Adenocarcinoma, Follicular; Animals; Antithyroid Agents; Cell Proliferation; Cyclin D2; Disease Models, Animal; Mice; Propylthiouracil; Signal Transduction; Thyroid Hormone Receptors beta; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin

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

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

Distant metastases as initial manifestation of follicular thyroid carcinoma is rare. We report a case of an unusual initial presentation of follicular thyroid carcinoma on follow-up. A 52- year-old woman presented with a 12-month history of progressively enlarging mass in the anterior chest wall. The mass was fixed to the chest wall, measuring 12 x 10 cm in diameter. Computed tomography demonstrated a lobulated soft-tissue mass (17 x 11 x 6 cm) destructing sternum and extending into the anterior mediastinum. There was no lung metastasis. Invasion of tumor to the ascending aorta, superior vena cava, and right atrium could not be excluded. Multiple lymph nodes were observed in the supraclavicular regions. Ultrasonography of the thyroid gland showed 46 x 37 mm nodule in the left lobe with milimetric gross calcifications and cystic-necrotic areas. Hyperthyroidism was detected. Biopsy from this nodule and the sternal mass revealed typical histology of follicular carcinoma. She was considered inoperable. Since there was huge tumor burden and iodinated contrast exposure for several times during evaluation, we decided to treat the patient with external beam radiotherapy (EBRT) rather than radioiodine as first-line therapy. After a course of conventional radiation with 50 Gy in 25 fractions over 4 weeks, encompassing the thyroid bed and the gross disease, tumor regressed remarkably in 6 months. In conclusion, when surgical resection is not possible, EBRT may be used for palliative purpose to obtain local control for extensive disease as first-line therapy. The indications of EBRT for differentiated thyroid cancer still remain poorly defined.

Topics: Adenocarcinoma, Follicular; Female; Humans; Iodine Radioisotopes; Mediastinal Neoplasms; Middle Aged; Palliative Care; Propylthiouracil; Thoracic Neoplasms; Thyroid Neoplasms; Thyroxine; Tomography, X-Ray Computed

To investigate the role of copper (Cu)-related cellular responses on thyroid carcinogenesis, the expression of ceruloplasmin (Cp) and metallothionein (MT)-1/2 were examined in relation to the activities of cell proliferation/apoptosis in the thyroid of rats at an early stage of tumor promotion under different dietary Cu levels. Male F344 rats were initiated with N-bis(2-hydroxypropyl)nitrosamine by single subcutaneous injection at 2800 mg/kg body weight, and 1 week later promoted with 6-propyl-2-thiouracil at 12 ppm in the drinking water for 4 weeks. Animals were fed a diet containing Cu at 0.6, 6 or 60 ppm from the time point of initiator-treatment to create marginally deficient, normal, or non-toxic supplementary levels of Cu. At both 0.6 and 60 pm, the multiplicity of preneoplastic focal follicular cell hyperplasias (FFCHs) was decreased as compared with 6 ppm Cu, while adenomas also decreased at 0. 6 ppm Cu. Both 0.6 and 60 ppm Cu levels revealed decreased Ki-67-immunoreactive proliferating cells in both FFCHs and surrounding follicles accompanied by mRNA downregulation of Cdc2a and Ccnb1, while TUNEL-positive apoptotic cells were unaltered with change of dietary Cu. Both Cp and MT-1/2 were immunolocalized in FFCHs and adenomas, with higher distribution in the latter. At both 0.6 and 60 ppm, the immunoreactivities and/or thyroidal mRNA levels of Cp and MT-1/2 were also decreased. Transcript levels of several antioxidant enzymes were up- or downregulated in the same direction at both Cu levels. Serum levels of thyroid-related hormones were unaltered at both Cu levels, except for non-significant reduction of thyroid-stimulating hormone at 0.6 ppm. These results suggest an involvement of Cp and MT-1/2 on the thyroid tumor promotion that can be suppressed by dietary Cu level through inhibition of cell proliferation associated with altered redox balance.

Topics: Animals; Ceruloplasmin; Copper; Diet; Dose-Response Relationship, Drug; Iron; Liver; Male; Metallothionein; Organ Size; Oxidative Stress; Propylthiouracil; Rats; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

The induction of hepatic drug metabolizing enzymes alters not only the metabolism of the xenobiotic substances that induce them but also the metabolism of various endogenous hormones. The xenobiotic receptor constitutive androstane receptor (CAR) (NR1I3) mediates the well-studied induction of CYP2B genes and other drug-metabolizing enzymes by phenobarbital (PB), an antiepileptic drug that has been shown to alter thyroid hormone (TH) levels. Here we show that CAR is required for PB-mediated disruption of TH homeostasis and the induction of thyroid follicular cell proliferation. Treatment with PB or the more potent and more effective CAR ligand 1, 4-bis-[2-(3, 5,-dichloropyridyloxy)] benzene resulted in universal induction of thyroid hormone glucuronidation and sulfation pathways in a CAR-dependent manner. This resulted in a decrease in serum T4 concentration and a concomitant increase in serum TSH levels. CAR activation also decreased serum T3 levels in mice in which T3 production was blocked. The increase in serum TSH levels resulted in the stimulation of thyroid-follicular cell proliferation. These results highlight the central role of the xenosensor CAR in drug-hormone interactions.

Topics: Animals; Anticonvulsants; Blotting, Northern; Cell Proliferation; Constitutive Androstane Receptor; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Male; Mice; Models, Biological; Mutation; Phenobarbital; Proliferating Cell Nuclear Antigen; Propylthiouracil; Pyridines; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Thyroid Hormones; Thyroid Neoplasms; Thyroxine; Transcription Factors; Triiodothyronine; Xenobiotics

We have previously reported that thyroid capsular inflammation induced by sulfadimethoxine (SDM), a goitrogen, might play a role in development of invasive follicular cell adenocarcinomas in rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). The present study was designed to examine the role of cyclooxygenase (COX)-2, widely known to be up-regulated in inflammatory states, during chemically induced rat thyroid carcinogenesis. Male F344 rats received a subcutaneous DHPN (2800 mg/kg) injection, and 1 week later were allowed free access to drinking water containing antithyroidal propylthiouracil (PTU, 0.003%) or SDM (0.1%) for 4 or 10 weeks. Control groups receiving goitrogen alone and no treatment were also included. At week 4, diffuse follicular cell hyperplasia was induced in all PTU- and SDM-treated groups, along with fibrous capsular thickening and capsular thickening with inflammation, respectively. Additionally, multiple focal follicular cell hyperplasias and adenomas were observed in the DHPN + PTU and DHPN + SDM cases. At week 10, adenocarcinomas invasive to the capsule and restricted to the capsular adjacent region, were frequent in the DHPN + SDM group, but not observed in the animals given DHPN + PTU. Western blots and immunohistochemistry revealed constitutive COX-2 expression in non-neoplastic follicular cells of the control and all of the PTU- and SDM-treated rats. However, COX-2 reactivity was significantly reduced or negative in the preneoplastic/neoplastic lesions in the DHPN-treated groups. In fibrous or inflamed thickened capsules, only a few component cells with inflammatory elements were positive for COX-2, and there was no significant difference in this regard between the PTU and SDM treatments. The present results suggest that capsular inflammation could play a role in development of invasive carcinomas, but COX-2 expression does not make a major contribution.

Topics: Adenocarcinoma, Follicular; Animals; Anti-Infective Agents; Antithyroid Agents; Blotting, Western; Carcinogens; Cyclooxygenase 2; Disease Models, Animal; Enzyme Inhibitors; Immunohistochemistry; Inflammation; Iodide Peroxidase; Male; Nitrosamines; Propylthiouracil; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; Sulfadimethoxine; Thyroid Neoplasms

Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylthiouracil (PTU)--a thyrostatic drug--have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA + 4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3--injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3-related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3.

Topics: Animals; Antimetabolites; Antioxidants; Bromates; Dose-Response Relationship, Drug; Indoles; Lipid Peroxidation; Male; Melatonin; Propylthiouracil; Rats; Rats, Wistar; Swine; Thyroid Gland; Thyroid Neoplasms

RET/PTC1 is a rearranged form of the RET proto-oncogene detected in human papillary thyroid carcinomas. We previously showed that thyroid-targeted expression of RET/PTC1 leads to thyroid tumor formation in Tg-PTC1 transgenic mice. Signal transduction pathways mediated by phosphotyrosine 294, 404, or 451 in RET/PTC1 have been shown to be critical for RET-induced transforming activity in vitro. To investigate the contribution of these signaling pathways in RET/PTC1-induced thyroid tumor formation in vivo, we generated and characterized transgenic mice expressing thyroid-targeted RET/PTC1 mutants carrying a site-directed mutation changing tyrosine (Y) to phenylalanine (F) at the residue 294, 404, or 451. In contrast to the 100% tumor formation rate in Tg-PTC1 transgenic mice, tumor formation rates were significantly decreased in Tg-PTC1-Y294F (6%), Tg-PTC1-Y404F (41%), and Tg-PTC1-Y451F (30%) transgenic mice. This indicates that signaling pathways mediated by pY294, pY404, and pY451 do play a role in RET/PTC1-induced tumor formation. However, as tumors are still able to form in some mice within these three mutant transgenic groups, it indicates that none of the signaling pathways mediated by pY294, pY404, or pY451, are solely essential for RET/PTC1-induced tumor formation.

Topics: Amino Acid Substitution; Animals; Antithyroid Agents; Carcinoma, Papillary; Cell Transformation, Neoplastic; Diet; Humans; Iodine; MAP Kinase Signaling System; Mice; Mice, Transgenic; Mutagenesis, Site-Directed; Oncogene Proteins; Oncogene Proteins, Fusion; Phosphorylation; Phosphotyrosine; Propylthiouracil; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Signal Transduction; Thyroid Neoplasms; Tubulin

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

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

The effect of the human TSH-receptor (TSHR) on the growth of human anaplastic thyroid carcinoma cells lacking the endogenous expression of TSHR, was studied both in vitro and in vivo in NMRI nude mice. Cells from a human anaplastic thyroid carcinoma cell line (C643) were transfected with a TSHR cDNA, and clones were isolated after neomycin selection. The expression of a functional receptor protein was ensured by analysis of the specific binding of 125I-TSH and measurement of TSH-induced cAMP. Incorporation of [3H]thymidine and increase in cell number was slightly inhibited by TSH in TSHR-expressing cells in vitro. In order to investigate whether the regained expression of a functional TSHR protein in C643 cells could influence the in vivo growth, cells were injected subcutaneously into NMRI nude mice. To manipulate the endogenous level of TSH, animals were given 6n-propyl-2-thiouracil (PTU; resulting in a high TSH level), T4 (a low TSH level) or no treatment (as a control). There seemed to be a TSH induced inhibition of tumour growth, since tumours in mice treated with PTU grew after a longer take rate and with a slower growth rate. The present results suggest a TSH-mediated growth inhibition in the TSHR-transfected C 643 anaplastic thyroid carcinoma cells.

Topics: Animals; Antithyroid Agents; Carcinoma; Cell Division; DNA, Complementary; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Propylthiouracil; Receptors, Thyrotropin; Thyroid Neoplasms; Transfection; Tumor Cells, Cultured

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

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

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

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

Estrogen receptor (ER) levels were evaluated in thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet (LID) or propylthiouracil (PTU) in intact and estrogen (E2) loaded Long-Evans (LE) rats. MNU at 40 mg/kg body wt was injected in 50 day-old LE rats of both sexes. The animals were killed 17-22 weeks later and the thyroid tissues were subjected to ER assay. In LID-treated groups, cytosolic ER (cER) levels were 6.7 +/- 5.8 (fmol/mg protein, mean +/- SE) in females and 0.7 +/- 1.4 in males, E2 increased the ER levels. In E2-loaded LID groups, cER levels were 12.9 +/- 3.7 in females and 1.7 +/- 1.7 in males. PTU treatment produced almost comparable ER levels as LID treatment. PTU treatment as well as LID treatment increased the serum TSH levels with E2 treatment producing additional elevation. In evaluating ER levels by histological type of thyroid tumors, the level in cER plus nER showed the lowest value of 6 +/- 6.4 (fmol/mg DNA, mean +/- SE) in hyperplasia, followed by 129 +/- 52.3 in adenoma and 289 +/- 51.7 in carcinoma. The rates of BrdU incorporation in thyroid follicles indicated higher proliferation activity in the area of adenoma and carcinoma rather than in the hyperplastic area. These data suggested that E2 treatment increases the ER levels in MNU and LID/PTU-induced thyroid tumors. The level of ER was correlated to the histological type of thyroid tumors.

Topics: Adenoma; Animals; Carcinoma; Estrogens; Female; Hyperplasia; Iodine; Male; Methylnitrosourea; Organ Size; Pituitary Gland; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Estrogen; Thyroid Gland; Thyroid Neoplasms; Thyrotropin

Effects of hormones (E2: estradiol, TP: testosterone) and propylthiouracil (PTU) on the growth of transplantable rat thyroid tumor (F2D1) having estrogen receptors were studied. Rat thyroid neoplasms, induced by N-bis (2-hydroxypropyl) nitrosamine, were inoculated subcutaneously from donor to recipient rats, in order to establish 16 transplantable rat thyroid tumor lines. The grafts were used for histological studies and for the assay of estrogen receptor (ER) and androgen receptor (AR). Of these lines, we designated papillary carcinoma, which was positive for ER (N: 12.5fmol/mg protein, Kd: 0.4nM) but negative for AR, as F2D1. For studies on the effects of sex hormones and PTU on the growth of transplantable tumors, the rats which had been inoculated with tumors were divided into the following 8 groups; (1) Intact, (2) PTU, (3) ovariectomy (OV), and (4) OV + E2 for female, and (5) Intact, (6) PTU, (7) castration (CA), and (8) CA + TP for male.. The growth rate of F2D1 in female rats was decreased by OV, but no change was observed in OV + E2 as compared with Intact. CA and CA + TP in male rats did not influence the growth rate. PTU produced a significant increase in the growth rate in both sexes. These results demonstrate that estrogen and PTU act on the growth of ER-positive rat thyroid tumors.

Topics: Animals; Carcinoma, Papillary; Estradiol; Female; Male; Neoplasm Transplantation; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Estrogen; Testosterone; Thyroid Neoplasms

In the present study, changes in thyroid follicular cell volume and its regulation have been investigated during the early involution of a hyperplastic goitre. Male Wistar rats were administered an iodine deficient diet for 6 months with propylthiouracil (PTU, 0.15%) during the last two months. At the end of iodine deficiency (day 0), some rats were killed and the others received a normal iodine diet. These rats were killed after different periods of iodine refeeding. Thyroid follicular cell volume was very high in hyperplastic gland whereas thyroid protein concentration was low. Thyroid follicular cell volume quickly decreased when rats were normally iodine refed, whereas thyroid protein concentration increased. Electron microscopal observations showed that thyroid follicular cells retained their endocrine aspect in hyperplastic state and throughout the iodine refeeding period. Using concomitant stereological and biochemical techniques, it is shown that the amount of cellular iodide and an unknown iodinated compound strongly increased during the early iodine refeeding. Plasma TSH was high on day 0 and remained at this level until day 8 whereas plasma T3 and T4 were low on day 0 and remained at this low level until day 4. The present data show that the involution of thyroid follicular cell volume is induced by iodide and mediated by an iodinated compound at least in the initial phase, and is independent of plasma TSH, T3, T4, so indicating the involvement of a thyroid autoregulatory mechanism. These changes in cell volume may be of importance in ion transport, i.e. in the metabolism of thyroid follicular cell during the early involution of the hyperplastic goitre.

Topics: Animals; Down-Regulation; Hyperplasia; Iodides; Iodine; Iodine Radioisotopes; Male; Microscopy, Electron; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

The injection of a retrovirus carrying the v-ras-Ki oncogene into the thyroid gland of adult Fischer rats induces thyroid carcinomas when associated with a treatment of the animals with a goitrogenic agent. More than one hundred adult Fischer rats have been treated with the goitrogen agent propylthiouracil in order to induce thyroid hyperplasia. Twenty days after treatment, rat thyroid glands, surgically prepared, were injected with the Kirsten murine sarcoma virus (KiMSV). Within three months more than 90% of the animals developed thyroid tumors. Histologically the tumors had the appearance of well differentiated carcinomas. Thirty animals had lung metastases in addition to the thyroid carcinoma. The presence of KiMSV specific transcripts and the specific transforming protein (p21) in thyroid carcinomas and in the metastases was detected by Northern blot analysis and immunoprecipitation, respectively. Only three rats, among thirty that had not received the goitrogen treatment, but only the injection with KiMSV, developed thyroid carcinomas of very small size and with a very long latency period (almost one year). The results described represent the first instance of thyroid carcinoma induction by retroviruses. This system may be regarded as a useful model to investigate the process of thyroid carcinogenesis in vivo. These results suggest that this model may also be useful for investigating the interaction between hormones and cells harboring the activated oncogene in the development of thyroid carcinoma since activated ras oncogenes have been implicated in human thyroid carcinoma.

Topics: Animals; Carcinoma; Disease Models, Animal; Genes, ras; Kirsten murine sarcoma virus; Neoplasm Metastasis; Oncogene Protein p21(ras); Oncogene Proteins, Viral; Propylthiouracil; Rats; Rats, Inbred F344; Sarcoma Viruses, Murine; Thyroid Neoplasms; Thyrotropin

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

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

The effect of 1000 ppm potassium perchlorate (KClO4), 1000 ppm potassium iodide (KI) or 1000 ppm propylthiouracil (PTU) in the diet on the development of thyroid tumors was studied histologically and biochemically in Wistar rats given a single ip injection of 280 mg of N-bis(2-hydroxypropyl)nitrosamine (DHPN) per 100 g body weight. Basal diet containing 100 ppm KClO4, 1000 ppm KI or 1000 ppm PTU was given for 19 weeks from week 2 to week 20. The incidence of thyroid adenomas at the end of week 20 of the experiment was 100% (20/20) in rats treated with DHPN followed by KClO4, 85% (17/20) in rats given DHPN followed by KI, 95% (19/20) in rats given DHPN followed by PTU, and 5% (1/20) in rats given DHPN alone. The incidence of thyroid cancers was 100% (20/20) in rats treated with DHPN followed by KClO4, 65% (13/20) in rats treated with DHPN followed by KI and 0% (0/20) in rats treated with DHPN followed by or not followed by PTU. Rats given KClO4, KI or PTU alone and untreated rats had no thyroid tumors. The mean values of TSH in serum were 2.94 +/- 0.79 ng/ml in rats treated with DHPN followed by KClO4, 9.40 +/- 16.0 ng/ml in rats treated with DHPN followed by KI and 60.94 +/- 20.60 ng/ml in rats treated with DHPN followed by PTU. It was confirmed that (1) KClO4, PTU and KI promote the development of thyroid tumor in rats treated with DHPN, (2) the promoting effect of KClO4 or KI is stronger than that of PTU and (3) the value of TSH in serum is not parallel to the promoting effect on the development of thyroid tumor.

Topics: Animals; Body Weight; Cocarcinogenesis; Male; Nitrosamines; Organ Size; Perchlorates; Potassium; Potassium Compounds; Potassium Iodide; Propylthiouracil; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroid Neoplasms

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

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

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

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

A patient presenting with hyperthyroidism had a rapidly enlarging thyroid mass that histopathologically was a diffuse histiocytic lymphoma arising in a gland with Hashimoto's thyroiditis. The concurrent development of both hyperthyroidism and lymphoma may have resulted from similar immunologic abnormalities. Appreciation of the relationship between thyroid lymphoma and Hashimoto's thyroiditis, and their presentation with either hypothyroidism or hyperthyroidism should lead to an earlier diagnosis of lymphoma and improved survival.

Topics: Body Weight; Female; Humans; Hyperthyroidism; Lymphoma; Middle Aged; Propranolol; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Thyroiditis

The effect of 0.15% propylthiouracil (PTU) on thyroid tumorigenesis was studied in male Wistar rats given a single i.p. injection of 280 mg of N-bis(-2-hydroxypropyl)nitrosamine (DHPN) per 100 g body weight. The mean weights of the thyroid of rats treated with DHPN followed by PTU and with PTU alone were significantly higher than those of rats treated with DHPN only and control rats. The incidences of follicular adenoma at the end of week 20 of the experiment were 100% (21/21) in rats treated with DHPN followed by PTU, and 19% (4/21) in rats given DHPN alone. Papillary adenoma was observed in one rat treated with DHPN followed by PTU. The incidence of follicular carcinomas with invasive growth into the capsule, adipose tissues or blood vessels was 52% (11/21) in rats given DHPN and then PTU. No papillary carcinomas or solid tumors were found in any rats. Rats given PTU alone and untreated rats had no thyroid tumors. The serum concentration of T4 in rats treated with PTU alone was significantly lower than that in the control group. The serum concentration of T4 in rats treated with DHPN followed by PTU was slightly, but not significantly, lower than that in control rats. The serum concentrations of T3 in rats treated with DHPN followed by PTU, DHPN alone and PTU alone were also slightly, but not significantly, lower than that in controls.

Topics: Adenoma; Animals; Carcinogens; Cystadenoma; Drug Synergism; Male; Nitrosamines; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Neoplasms

The mechanism whereby thyroglobulin (TG) reaches the circulation can involve either the release of newly synthesized TG or the release of colloid-stored TG from the thyroid gland. To distinguish between these possibilities, we have compared the properties of circulating and glandular TG in normal and thyroidectomized thyroid tumor-bearing rats. Circulating TG had the properties of poorly iodinated molecules; it was more susceptible to dissociation into subunits and had a lower density, the latter determined by equilibrium centrifugation in concentrated RbCl. The density of circulating TG was the same as that of glandular TG from propylthiouracil-treated rats, suggesting that circulating TG was nearly or completely devoid of iodine. Circulating TG bound to Concanavalin A-Sepharose and had a normal MCR, indicating that mannose was present and galactose was not in terminal positions, both properties of glandular TG. Since previous studies suggest that these properties cannot arise from differential clearance of TG molecules in the periphery, these data suggest that the TG in the circulation may arise from the direct release of poorly iodinated newly synthesized TG from the thyroid.

Topics: Animals; Kinetics; Male; Neoplasms, Experimental; Propylthiouracil; Rats; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

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

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

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

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

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

Rats treated with 131I and propylthiouracil were shown to develop thyroid tumours 7--9 months after treatment. In this group, the levels of total thyroxine and tri-iodothyronine, and free thyroxine and tri-iodothyronine in the serum were low, and that of TSH was raised. In a group of rats treated with 131I and then propylthiouracil and thyroxine, thyroid tumours were found despite normal concentrations of total and free thyroxine and tri-iodothyronine in the serum. The level of TSH in the serum was significantly raised in this group. Thyroid tumours were not found in the various control groups of rats.

Topics: Animals; Iodine Radioisotopes; Male; Neoplasms, Experimental; Propylthiouracil; Rats; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

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

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

Hyperthyroidism is a clinically dramatic but usually benign syndrome that is most commonly associated with the clinical triad known as Graves' disease. Although the diagnosis and treatment usually are straightforward and clinically rewarding, there are occasional patients in whom considerable clinical and laboratory expertise are required before the problem is identified and solved. Although among the most common endocrine disorders, the etiology of the hyperfunction of the thyroid gland in Graves' disease remains unknown and the mechanism by which thyroid hormones produce their effect is equally obscure. However, if the rate of progress in the past decade is typical, both these questions may well be answered before another 10 years have elapsed.

Topics: Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Thyroid Neoplasms; Thyroxine; Triiodothyronine

To determine if propylthiouracil (PTU) inhibited extrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion in man, PTU was administered to T4-treated hypothyroid patients and serial measurements of T4, T3, and thyrotropin (TSH) carried out. All patients had proven thyroidal hypothyroidism and had been receiving 0.1 or 0.2 mg T4 daily for at least 2 mo before study. Hormone measurements were made for 5 consecutive days before and daily during a 7-day treatment period with PTU, 1,000 mg/day. In eight patients receiving 0.1 mg T4 daily, administration of PTU resulted in a prompt fall in mean serum T3 concentrations from 78 plus or minus 6 ng/100 ml (SEM) to 61 plus or minus 3 ng/100 ml after 1 day. The mean serum T3 concentrations ranged from 55 to 60 ng/100 ml during the remainder of the PTU treatment period (P less than 0.01). The mean control serum TSH concentration was 29.6 muU/ml and it increased to a peak of 40 muU/ml on the 5th and 6th days. In five patients receiving 0.2 mg T4 daily, the mean control serum T3 concentration was 84 plus or minus 7 NG/100ML. It fell to 70 plus or minus 5 ng/100 ml after 1 day and 63 plus or minus 7 ng/100 ml after 2 days of PTU administration and thereafter ranged from 6) to 69 ng/100 ml (P LESS THAN 0.01). Serum TSH concentrations did not increase. No changes in serum T4 concentrations were found in either group. In five patients who received 100 mg methimazole (MMI) daily for 7 days there were no changes in serum T4, T3, or TSH concentrations. These results indicate that PTU, but not MMI, produces a prompt and sustained, albeit modest, reduction in serum T3 concentrations in patients whose sole or major source of T3 is ingested T4. These findings most likely result from inhibition of extrathyroidal formation of T3 from T4.

Topics: Administration, Oral; Adult; Aged; Depression, Chemical; Female; Humans; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine

Over a 7-yr period from January 1967 to January 1974, 141 patients underwent thyroid surgery for various pathology at the Bexar County Hospital - University of Texas Medical School at San Antonio. Of these, 113 patients underwent subtotal thyroidectomy for benign diseases, including 28 of thyrotoxic patients who underwent subtotal thyroidectomy as definitive treatment. In this group of patients special interest and emphasis was placed in the preoperative and intraoperative management of the difficult and complicated hyperthyroid patient. Preoperative treatment was accomplished by the utilization of multiple drug combinations - including antithyroid drugs, adrenergic blocking agents, and iodine - which resulted in significant decrease in preparation time for surgery. Furthermore, this short intensive preoperative management of complicated hyperthyroid patients allowed satisfactory correction of their problems with little or no morbidity which otherwise would have been extremely difficult if not impossible to resolve. At operation, 28 patients were diagnosed to have malignant disease; 23 underwent total thyroidectomy and the other 5 had subtotal thyroidectomy. In addition to total or subtotal thyroidectomy, 23 patients had either classical or modified radical neck dissection including 9 patients who had bilateral neck dissection. The various surgical techniques utilized, the rationale for rapid preoperative preparation of complicated hyperthyroid patients, morbidity, and long-term follow-up are discussed.

Topics: Adolescent; Adult; Aged; Child; Dexamethasone; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Neck Dissection; Potassium Iodide; Propylthiouracil; Reserpine; Thyroid Diseases; Thyroid Neoplasms; Thyroidectomy

Topics: Adenoma; Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodides; Methimazole; Propylthiouracil; Sulfur Isotopes; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Antithyroid Agents; Carbimazole; Chromatography, Paper; Chromatography, Thin Layer; Humans; Imidazoles; Male; Methimazole; Methylthiouracil; Propylthiouracil; Rats; Sulfur Isotopes; Thiouracil; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

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: Adenocarcinoma; Aged; Autoradiography; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Ion Exchange Resins; Neoplasm Metastasis; Propylthiouracil; Radionuclide Imaging; Thyroid Neoplasms; Triiodothyronine

Topics: Adenoma; Animals; Cell Transformation, Neoplastic; Iodine Isotopes; Male; Mitosis; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Propylthiouracil; Rats; Thyroid Neoplasms; Thyrotropin

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: Adenoma; Animals; Iodine Isotopes; Male; Neoplasms, Experimental; Propylthiouracil; Rats; Thyroid Neoplasms

Topics: Animals; Carcinoma, Papillary; Iodine Isotopes; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Propylthiouracil; Rats; Thyroid Neoplasms

Topics: Adenoma, Oxyphilic; Animals; Carcinoma; Iodine Isotopes; Mice; Neoplasms; Neoplasms, Experimental; Pathology; Propylthiouracil; Radiation Effects; Research; Thyroid Neoplasms; Thyrotropin; Transplantation, Homologous

Topics: Adolescent; Antithyroid Agents; Child; Drug Therapy; Humans; Hyperthyroidism; Iodine Isotopes; Neoplasms; Neoplasms, Radiation-Induced; Perchlorates; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Toxicology

Topics: Adenoma; Animals; Carcinogens; Carcinoma; Fluorenes; Methylthiouracil; Neoplasm Metastasis; Neoplasms, Experimental; Propylthiouracil; Rats; Thiouracil; Thyroid Neoplasms

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: Adenocarcinoma; Adolescent; Humans; Infertility; Iodine Isotopes; Lymphatic Metastasis; Neck Dissection; Neoplasm Metastasis; Neoplasms; Pathology; Propylthiouracil; Radiation Injuries; Surgical Procedures, Operative; Thyroid Function Tests; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Toxicology

Topics: Adenoma; Chromatography; Diiodotyrosine; Iodine Isotopes; Metabolism; Mice; Neoplasms, Experimental; Propylthiouracil; Research; Thyroid Neoplasms; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Tyrosine

Topics: Body Weight; Carcinogens; Guinea Pigs; Iodides; Iodine; Neoplasms; Neoplasms, Experimental; Pathology; Propylthiouracil; Research; Thyroid Neoplasms; Thyroiditis; Toxicology

Topics: Animals; Biological Assay; Blood Chemical Analysis; Neoplasms; Neoplasms, Experimental; Pharmacology; Poultry; Propylthiouracil; Rats; Research; Thyroid Neoplasms; Thyrotropin

Topics: Antithyroid Agents; Exophthalmos; Humans; Hyperthyroidism; Iodides; Iodine; Iodine Isotopes; Methylthiouracil; Perchlorates; Propylthiouracil; Radioisotopes; Radionuclide Imaging; Thyroid Neoplasms; Toxicology

Topics: Adenoma; Animals; Joint Diseases; Mice; Pituitary Gland; Pituitary Gland, Anterior; Propylthiouracil; Thyroid Neoplasms

Topics: Iodides; Neoplasms; Pituitary Diseases; Pituitary Gland; Propylthiouracil; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Mice; Neoplasms; Neoplasms, Experimental; Pituitary Gland; Pituitary Neoplasms; Propylthiouracil; Thiouracil; Thyroid Gland; Thyroid Neoplasms