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A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: pathology analysis of thyroid cancer cases in Ukraine detected during the first screening (1998-2000).

BACKGROUND: The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening. METHODS: From 1998 to 2000, 13,243 individuals completed the first cycle of screening examinations. Eighty patients underwent surgery between 1998 and 2004. Intraoperative and postoperative pathologic studies were performed at the Institute of Endocrinology and Metabolism, Kyiv. RESULTS: Pathologic analysis revealed 45 thyroid carcinomas, including 43 papillary thyroid carcinomas (PTCs) (95.6%) and 2 follicular thyroid carcinomas (FTCs) (4.4%). TNM classification (5th edition) of the PTCs included 8 T1 tumors (18.6%), 16 T2 tumors (37.2%), and 19 T4 tumors (44.2%). Fifteen PTCs (34.9%) were N1a,N1b, and 3 PTCs (7.0%) were M1. Among the PTCs, 8 exhibited the classical papillary histologic pattern (18.6%), 14 exhibited a follicular histologic pattern (32.6%), 5 exhibited a solid histologic pattern (11.6%), and 16 exhibited a mixed histologic pattern (37.2%). Both FTCs had a microfollicular-solid structure. Eleven of 20 cohort members who underwent surgery before the first screening had PTCs. Regional metastases (63.6%) and distant metastases (18.2%) were more common in this group. CONCLUSIONS: Multifocal growth, lymphatic and blood vessel invasion, extrathyroid spread, and regional and distant metastases were more frequent in less differentiated PTCs (>30% solid structure). Small carcinomas (</=10 mm) comprised 23.3% of PTCs, and most of those (8 of 10 small carcinomas; 80%) were of the papillary-follicular subtype and therefore were more differentiated. The solid subtype of PTC was associated with shorter latency, especially in individuals who were diagnosed before the first screening. The histology of post-Chornobyl cancers is changing with time.

Adenocarcinoma, Follicular↗

Tissue responses to thyroid hormone in a kindred with resistance to thyroid hormone harboring a commonly occurring mutation in the thyroid hormone receptor beta gene (P453T).

Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone (TH) usually due to mutations in the TH receptor beta gene (TRbeta). We studied pituitary and peripheral tissue responses to graded doses of liothyronine (L-T3) in 5 affected members (2 children and 3 adults) of a family with RTH due to the common TRbeta mutation P453T. Overall, the 5 subjects studied exhibited suppressed thyrotropin response to thyrotropin-releasing hormone of 51% +/- 8%, 12.1% +/- 1.5%, and 6.3% +/- 3% of the 100% baseline on 50, 100, and 200 microg/dL L-T3, respectively. This degree of suppression was greater than that observed in subjects with RTH due to other TRbeta mutations, indicating less resistance. Compared with normal subjects, however, the family described here demonstrated less suppression by L-T3, compatible with their RTH, although of a mild magnitude. The 2 children with RTH demonstrated less L-T3-mediated suppression of prolactin and cholesterol than the adults. Patients often receive thyroid ablative therapy before the diagnosis of RTH and are left with variable degrees of hypothyroidism. Our results demonstrate that graded doses of L-T3 can be used to evaluate RTH patients, even under the condition of limited thyroid reserve, when results are compared with their baseline. We demonstrate that RTH patients can be evaluated either on or off thyroid hormone and still be distinguished from hypothyroid subjects without RTH.

Adult↗

The oncogenic activity of RET point mutants for follicular thyroid cells may account for the occurrence of papillary thyroid carcinoma in patients affected by familial medullary thyroid carcinoma.

Activating germ-line point mutations in the RET receptor are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma (MTC), whereas somatic RET rearrangements are prevalent in papillary thyroid carcinomas (PTCs). Some rare kindreds, carrying point mutations in RET, are affected by both cancer types, suggesting that, under specific circumstances, point mutations in RET can drive the generation of PTC. Here we describe a family whose siblings, affected by both PTC and MTC, carried a germ-line point mutation in the RET extracellular domain, converting cysteine 634 into serine. We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. We show that the various RET point mutants, but not wild-type RET, scored constitutive kinase activity and exerted mitogenic effects for thyroid PC Cl 3 cells, albeit at significantly lower levels compared to RET/PTC1. The low mitogenic activity of RET point mutants paralleled their reduced kinase activity compared to RET/PTC. Furthermore, RET point mutants maintained a protein domain, the intracellular juxtamembrane domain, that exerted negative effects on the mitogenic activity. In conclusion, RET point mutants can behave as dominant oncogenes for thyroid follicular cells. Their transforming activity, however, is rather modest, providing a possible explanation for the rare association of MTC with PTC.

Adenocarcinoma, Follicular↗

Goiter prevalence, urinary iodine excretion, thyroid function and anti-thyroid function and anti-thyroid antibodies after 12 years of salt iodization in Shahriar, Iran.

OBJECTIVE: In a previous study in 1983, goiter was found to be endemic in Shahriar, Iran. Iodized salt has been distributed in the region for the past 12 years, and the present study was performed to examine the effect of iodide supplementation on indicators of iodine deficiency (IDD) and thyroid antibodies. DESIGN & METHODS: A total of 3164 people, 58% women and 42% men, were selected by random sampling from the Shahriar area. Goiter was staged according to World Health Organization guidelines. Urinary iodine was measured by a digestion method, and thyroid hormone measurements were done by radioimmunoassay. The results were compared with those of 1983. RESULTS: Goiter prevalence before and after iodine supplementation was 50 and 40% in men, 70 and 51% in women, and 60 and 47% in the whole community, respectively (p < 0.001). A decrease in the prevalence of goiter was observed especially in younger individuals. The mean urinary iodine excretion was 7.6 and 18.5 micrograms/dL, before and after iodine supplementation. In 1983, the urinary iodine in 47.5% of the population studied was between 2 to 5 micrograms/dL, while in 1995, 65% of the population studied had urinary iodine between 10 to 25 micrograms/dL, 12 years after iodine supplementation. Mean serum T4, T3, and thyroid-stimulating hormone (TSH) were normal before and after intervention. There was no significant change in occurrence of positive antibodies, or of hypo- and hyperthyroidism, following iodine supplementation. CONCLUSION: The result of this study shows that the use of iodized salt causes an increase in excreted urinary iodine and a decrease in the prevalence of thyroid goiter, especially in younger age groups. Consumption of iodized salt with 40 parts per million (ppm) iodine has not caused increased prevalence of thyroid dysfunction in this area.

Adolescent↗

[Papillary thyroid carcinoma in a median ectopic thyroid associated with intra-abdominal thyroid tissue].

A 17-year-old female underwent surgical removal of a painless submental lump presumed to be a median cervical cyst. Histology showed a papillary thyroid carcinoma with invasion of the surrounding connective tissue. A 99m-technetium scan, performed in preparation for a planned total thyroidectomy, demonstrated no thyroid tissue. On subsequent 123-iodine scanning there was an area of increased uptake about 3 cm above the larynx, but no normal thyroid tissue. Histological sections, obtained during further surgical exploration of the base of the tongue, showed scattered thyroid cell rests in the lingual muscles. Whole-body scanning, carried out in connection with administration of radioiodine for ablation of remaining thyroid tissue, disclosed an unexpected area of increased uptake in the epigastrium. Sonography and CT scans failed to demonstrate any corresponding morphological abnormality. Following a further dose of radioiodine 4 months later, no areas of increased uptake were noted.

Abdominal Neoplasms↗

Glucocorticoid response in amiodarone-induced thyrotoxicosis resulting from destructive thyroiditis is predicted by thyroid volume and serum free thyroid hormone concentrations.

CONTEXT: Amiodarone-induced thyrotoxicosis (AIT) resulting from destructive thyroiditis (type 2) is commonly treated with glucocorticoids, but time needed to restore euthyroidism may be unacceptable for patients with underlying cardiac disorders. OBJECTIVE: The objective of this prospective study was to identify factors affecting the response to glucocorticoids in a large cohort of patients with type 2 AIT followed prospectively. SETTING: This study was conducted at university centers. PATIENTS: Sixty-six untreated patients with type 2 AIT were enrolled in the study. INTERVENTION: All patients were treated with prednisone (initial dose, 0.5 mg/kg.d) as long as needed to restore euthyroidism, defined as cure of AIT. MAIN OUTCOME MEASURE: The main outcome measure was cure time. RESULTS: The median cure time was 30 d (95% confidence interval, 23-37 d). Serum free T4 concentration (picograms per milliliter) and thyroid volume (milliliters per square meter) (and, to a lesser extent, serum free T3 concentration) at diagnosis were the main determinants of response to glucocorticoids, with a cure hazard ratio of 0.97 (95% confidence interval, 0.95-0.99; P = 0.005) and 0.84 (95% confidence interval, 0.77-0.91; P = 0.000) for unit of increment, respectively. AIT was cured in all patients with a complete follow-up; euthyroidism was reached in 30 d or less in 60% of patients but in more than 90 d in 16%. A prompt control of thyrotoxicosis (<or=30 d of treatment) was more frequent (77%) in patients with serum basal free T4 concentration no greater than 50 pg/ml and thyroid volume (normalized for body surface area) no greater than 12 ml/m2. The cure probability and the mean cure time in an individual patient can be obtained using a formula generated by multiple regression models. CONCLUSIONS: Baseline serum thyroid hormone concentrations and thyroid volume help identify patients with type 2 AIT at risk of a delayed response to glucocorticoids.

Adult↗

Expression of intercellular adhesion molecule-1 on human thyroid cells from patients with autoimmune thyroid disease: study of thyroid xenografts in nude and severe combined immunodeficient mice and treatment with FK-506.

It has been suggested that intercellular adhesion molecule-1 (ICAM-1) may play an important role in the initiation, localization, and perpetuation of autoimmune thyroid diseases (AITD). In an effort to clarify its role, we have investigated the expression of ICAM-1 on thyroid epithelial cells (TEC) of patients with AITD, patients with nontoxic goiter (NTG), and normal subjects (PN) by flow cytometric analysis under basal conditions and after modulation with cytokines, before and after 8 weeks of thyroid tissue xenotransplantation in nude athymic mice (which lyses all passenger lymphocytes), and in severe combined immunodeficient (SCID) mice where these cells survive. Before xenografting, ICAM-1 was expressed on 56% of TEC from Hashimoto's thyroiditis (n = 5), 54% of Graves' disease (n = 6), 15% of NTG (n = 5), and 12% of PN TEC. After the xenografts had been 8 weeks in nude mice, ICAM-1 expression decreased markedly in AITD TEC [from 56% to 10% in Hashimoto's thyroiditis (P < 0.001) and from 54% to 8% in Graves' disease (P < 0.01)], but did not change significantly in NTG or PN. After the xenografts had been 8 weeks in SCID mice, the expression of ICAM-1 was significantly higher on TEC of AITD compared with the same tissue in nude mice. When the SCID mice engrafted with AITD tissue were treated with the anti-CD4+ T (helper) cell agent FK-506, the expression of ICAM-1 was reduced significantly compared with that in the original tissue or that in nontreated mice engrafted with the same tissue. The proportion of TEC that were ICAM-1 positive was up-regulated in all cases by certain cytokines (e.g. interferon-gamma and tumor necrosis factor-alpha applied alone or in combination). We also detected the presence of ICAM-1 in AITD frozen tissues using an immunohistochemical technique. These data suggest a role for ICAM-1 in human AITD. However, the expression of ICAM-1 appears to be a secondary phenomenon in response to the immune assault, rather than a primary event. Our results support the idea that TEC may act as passive captives to immunological events in human AITD.

Animals↗

Existence of nuclear thyroid hormone receptors in the porcine thyroid gland and the rat thyroid cell line FRTL-5.

We have investigated whether nuclear T3 receptors exist in the thyroid cell. Nuclear proteins extracted from porcine thyroid nuclei with 0.4 mol/l KCl were incubated with [125I]T3. The mixture was then analysed by sucrose density gradient ultracentrifugation which revealed that the T3-binding proteins migrated at the same position of 3.6 S as rat liver nuclear T3 receptors. Fractionation by high performance liquid chromatography using a size exclusion column and an ion exchanger column also demonstrated elution patterns of T3-binding similar to those of the rat liver receptor. Scatchard plots of crude nuclear extracts from porcine thyroid represented a curvilinear pattern. However, when the nuclear proteins partially purified by a DEAE column chromatography were analysed, a single binding component was found; the association constant was 4.1 x 10(10) l/mol and the maximal binding capacity was 602 fmolT3/mg protein. Displacement study with several T3 analogues showed a highly selective affinity for L-T3. Cultured rat thyroid cells of the FRTL-5 line also contained a single class of saturable, high affinity T3-binding site. Subconfluent cells in 100-mm dishes were incubated with increasing amounts of [125I]T3 at 37 degrees C for 3 h and radioactive T3 in isolated nuclei was counted. Scatchard analysis of data showed that the association constant and the maximal binding capacity were 3.44 +/- 0.63 x 10(10) l/mol and 63.7 +/- 17.8 fmolT3/mg protein, respectively. These results strongly suggest that there are nuclear T3 receptors, indistinguishable from the hepatic T3 receptors, in the porcine thyroid and rat FRTL-5 cells.

Animals↗

Binding of peripheral blood and thyroidal T lymphocytes to thyroid cell monolayers: possible role of "homing-like" receptors in the pathogenesis of thyroid autoimmunity.

The specific binding of blood lymphocyte populations to non-antigenic receptors on high endothelial cells in peripheral lymphoid organs is well established. Such "homing" receptors in target tissues may also play a role in the early phase of organ specific autoimmunity. In this study binding of peripheral blood and thyroid-derived T cells to human thyroid (THY) cells was examined. Binding was measured as the percentage 51Cr-labelled T cells bound to THY monolayers. Interferon-gamma (IFN-gamma) enhanced the binding of peripheral blood T cells (PBL-T) from patients with Graves' disease (GD) and normals, but not from patients with Hashimoto's thyroiditis (HT), to allogeneic THY monolayers. The binding of T cells from patients with HT to untreated allogeneic THY monolayers was significantly greater than that for T cells from patients with GD or normals. TSH inhibited the IFN-gamma enhancement of binding of PBL-T from 4 normals and one HT patient to both allogeneic (n = 5) and autologous (n = 4) THY monolayers. Intra-thyroid T cells (ITL-T) bound to autologous THY monolayers significantly more than PBL-T from the same patient, while ITL from patients with HT or Graves' disease bound more than their PBL-T to both allogeneic and autologous THY monolayers. ITL-T, but not PBL-T, bound significantly more to autologous THY than to autologous thyroid-derived fibroblast monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up.

The European Organization for Research on Treatment of Cancer (EORTC) Thyroid Cancer Cooperative Group presented a prognostic index in 1979 that included all histologic groups of thyroid carcinomas, and was based on a multivariate analysis of 507 patients with a median follow-up of 40 months. The current report not only uses a multivariate analysis to study the clinical validity and reproducibility of this index on case material consisting of 226 differentiated thyroid carcinomas with a considerably long follow-up (11 years), but also it investigates possible prognostic factors, other than those proposed by the EORTC. Three EORTC variables could be reproduced as important: age at diagnosis, locally advanced disease, and distant metastases. Of the additional histopathologic variables tested, microscopic tumor invasion beyond thyroid capsule (pT4) and marked cellular atypia (MCA) proved to be significant. When the effect of the age-correlated tumor factors pT4 and MCA of differentiated thyroid carcinomas were taken into consideration, age alone lost its prognostic importance as a guide for treatment.

Adult↗

Comparative ultrastructure of thyroid, tongue and eyelid lesions in the neuroma phenotype of medullary carcinoma of the thyroid: association of amyloid with fibroblasts in thyroid tumor and in mucosal neuromas.

Electron-microscopic and histochemical studies of thyroid tumor, tongue neuromas and eyelid neuromas from the lesions of a patient with medullary thyroid carcinoma were compared. In the thyroid tumor, a significant number of the C cells showed heterogeneity of granule types; no C cells, however, were identified in the tongue and eyelid neuromas. Amyloid was clearly shown by Congo red staining in the thyroid neoplasm and in the tongue neuromas. In all tissues, amyloid fibrils were found to be ultrastructurally closely associated with fibroblasts. These fingings suggest that the fibroblast rather than the C cell may have played the important role in the deposition of amyloid in this patient's thyroid carcinoma.

Amyloid↗

Familial form of thyroid dysgenesis: report of thyroid hemiagenesis with accompanying Graves' disease in a woman whose daughter has thyroid agenesis.

The subject is a 44-year-old female with thyroid hemiagenesis, who initially presented with hyperthyroidism. Thyroid peroxide antibody and thyroglobulin antibody levels were high. The scintiscan study and sonographic findings were compatible with thyroid hemiagenesis with accompanying Graves' disease. In reviewing her family history, her daughter was found to have thyroid agenesis, and other thyroid disorders were found in 2 female family members.

Adult↗

[Thyroid hormone metabolism in nonthyroidal illness. I. Changes in thyroid hormone metabolism in dogs with experimental myocardial infarction and effect of thyroid hormone administration on their hemodynamics].

To asses the changes in thyroid hormone metabolism after the onset of acute myocardial infarction (AMI), serum T4 and T3 levels were serially measured for 24 hours after the coronary artery ligation in dogs. The effect of thyroid hormone administration on hemodynamics in these dogs were also studied to clarify the possible usefulness of thyroid hormone therapy in nonthyroidal illness (NTI). Dogs were anesthetized with ketamine using "Micro-Mini" drip administration. Coronary artery ligation was performed in 8 dogs (MI group) Open chest operation was performed in 8 dogs, but their coronary arteries were not ligated and were used as control (cont. group). Blood samples were drawn before and 1, 3, 6, 12, 18 and 24 hours after coronary artery ligation, and serum levels of T4 and T3 were measured using the TDX T4 system and a commercial RIA kit, respectively. Various hemodynamic parameters (heat rate, mean blood pressure, max dp/dt, left ventricular end-diastolic pressure, cardiac output) were measured at the same time mentioned above. All the hemodynamic parameters remained within normal range for 24 hours in the control group. Serum T4 and T3 levels, however, showed slight, but significant decreases due to general anesthesia and open chest operation in the control group. On the other hand, hemodynamic parameters were maintained in the normal ranges only for 12 hours, and gradually deteriorated in the MI group. Moreover, it was remarkable that both T4 and T3 levels were decreased immediately after the ligation in this group, T4 being less than 0.1 micrograms/dl and T3 less than 10 ng/dl. They continued to show the low values thereafter. When T4 (30 micrograms/24 hours), and T3(7, 14 or 21 micrograms/24 hours) were continuously infused intravenously for 24 hours after the coronary artery ligation in 10 dogs, serum T4 levels were maintained in the normal range of the dog (1.5-3.6 micrograms/dl) and the serum T3 levels were increased to the low normal range. However, there were no significant differences in hemodynamic indices between the thyroid hormone treated groups and the non-treated group. These data show that T4 and T3 concentrations decrease prior to the deterioration of cardiac function. Moreover, the present findings also suggest that administration of thyroid hormone has no benefit in patients with NTI associated with low T4 and T3 levels.

Animals↗

Determination of free thyroid hormones and their binding proteins in a patient with severe hyperthyroidism (thyroid storm?) and thyroid encephalopathy.

A patient with severe hyperthyroidism (thyroid storm?) and thyroid encephalopathy is described. During her illness only a slightly raised level of total thyroxine and a normal level of total triiodothyronine was found in contrast with very high levels of free thyroid hormones. Very low levels of thyroxine binding globulin, albumin and low levels of thyroxine binding prealbumin in contrast with nearly normal values of T3 resin uptake were observed. All parameters of thyroid function returned to normal after therapy.

Adult↗

Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma.

Iodine kinetics were studied in patients with differentiated thyroid cancer while euthyroid under exogenous thyroid stimulating hormone (TSH) and while hypothyroid to detect differences in radioiodine uptake, distribution and elimination. Nine patients with total or near-total thyroidectomy on thyroid hormone suppressive therapy received two or three daily doses of 0.9 mg recombinant human TSH (rhTSH) followed by administration of a diagnostic activity of 2 mCi (74 MBq) iodine-131. After the biokinetics assessments had been performed, patients stopped taking thyroid hormones to become hypothyroid. A second 2 mCi (74 MBq) diagnostic activity of 131I was administered, followed by a second set of biokinetics assessments. One week later the patients underwent remnant ablation with a therapeutic activity of 131I. A comparison of the 131I kinetics in the patients while euthyroid and while hypothyroid showed major differences in the doses to the remnant as well as in residence times and radiation exposure to the blood. In the first diagnostic assessment the remnant dose was higher in eight of the nine patients and clearance of the activity from the blood was faster in all of them. The data from this study suggest that radioiodine administration is potent and safe when administered to euthyroid patients following rhTSH administration. Enhanced residence time in the remnant and decreased radiation exposure to the blood were noted when patients were euthyroid compared to when they were rendered hypothyroid. However, all patients received diagnostic activities in the same order: first while euthyroid, followed by hypothyroidism. It is quite possible that "stunning" from the radioiodine administered in the initial uptake study inhibited the subsequent uptake of radioiodine by the remnant lesions in the second uptake study.

Adult↗

Thyroid-specific T cells in the normal Wistar rat. II. T cell clones interact with cloned wistar rat thyroid cells and provide direct evidence for autoantigen presentation by thyroid epithelial cells.

Strains of rat differ in their susceptibility to experimental autoimmune thyroiditis (EAT). We recently observed that the normal Wistar rat has lymph node (LN) T cells which recognize the newly available cloned Wistar thyroid cell line (WRT) and/or rat thyroglobulin (rTg). We have now cloned thyroid-specific T cells and characterized their interaction with the WRT target cell. Twenty-three T cell clones were tested for their reactivity to syngeneic thymocytes, WRT cells alone, or WRT cells with thymocytes. All the clones were of the CD4+CD8- phenotype. Seven of 23 T cell clones proliferated in the presence of WRT cells alone or with the combination of WRT cells and thymocytes, exhibiting stimulation indices of 1.5 to 5. In all but one of the T cell clones responding to WRT cells alone was there no evidence that the additional presence of thymocytes supplied a stronger "second" proliferative signal than the WRT cells. These WRT-reactive clones which were able to be more extensively characterized were MHC class II restricted, secreted rat interferon (IFN)-gamma in response to WRT cell exposure, and one clone showed cross-reactivity with rTg antigen. Induction of WRT cell MHC class II antigen by prior treatment with IFN-gamma failed to further enhance the WRT cell-induced T cell proliferation. These data provide the first evidence for direct antigen presentation by thyroid epithelial cells (TECs) in the absence of other antigen-presenting cells. Furthermore, they provide evidence that TECs are able to provide the appropriate "second" signals required for T cell activation and successful autoantigen presentation.

Animals↗

Estimation of thyroid gland activity in the Snell dwarf mouse by ultrastructural observation of the thyroid gland, measurement of plasma thyroxine concentration and thyroid hormone binding capacity.

An ultrastructural study of the thyroid gland of the Snell dwarf mouse showed cellular activity to be very low. Follicle cell diameters were significantly lower than in controls whilst the nucleocytoplasmic ratio was significantly higher. The observed cellular activity of the thyroid cells was associated with circulating levels of thyroxine which were found to be significantly lower than in controls. Measurement of the free thyroxine index showed very little free hormone available for tissue uptake. No differences in thyroid function due to age or sex in the dwarf mice were seen. Possible endocrine imbalances contributing to the low thyroid activity in the Snell dwarf mouse are discussed.

Animals↗

The relationships between serum T3 index, thyroid volume, and thyroid stimulating, TSH receptor binding and thyroid growth stimulating antibodies in untreated Graves' disease.

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

Adult↗