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PubMed1995

Severe but not mild alterations of thyroid function modulate the density of thyroid-stimulating hormone receptors in the rat thyroid gland.

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

Adenylyl Cyclases↗

PubMed1995

Proliferative responses of T-cells to thyroid antigens and synthetic thyroid peroxidase peptides in autoimmune thyroid disease.

We studied the immune responses of 33 patients with autoimmune thyroid disease (AITD; including 17 with Hashimoto's thyroiditis and 16 with Graves' disease), 5 patients with non-AITD, 12 control subjects (CS), and 2 subjects with a family history of autoimmunity to the main thyroid antigens. These antigens included thyroid peroxidase (TPO), thyroglobulin (Tg), TSH receptor (TSH-R), and 13 overlapping TPO peptides. T-cell lines (TCL) were isolated from peripheral blood mononuclear cells (PBMC) after incubation with TPO, Tg, or a protein derivative of tuberculin (PPD). PBMC and TCL were used in a 3- to 5-day microproliferation assay. Peripheral lymphocytes from most AITD patients responded with a stimulation index of 3 or more to TPO, Tg, and/or TSH-R (60-88%) as well as to two or more TPO peptides. Lymphocytes from 3 of 5 patients with non-AITD and 2 subjects with a family history of autoimmunity were also reactive to thyroid antigens. TPO TCL showed a high proliferative response to TPO and its peptides, whereas Tg TCL were less reactive and PPD TCL were nonreactive to these antigens. Six of the 13 peptides tested produced highly significant stimulation in PBMC (CS, 0-17%; AITD, 60-92%) and TPO TCL (73-91%). The amino acid sequences of these putative epitopes were located in TPO regions 100-119, 211-223, 261-275, 420-434, 625-644, and 882-901. These results demonstrate T-cell responses to the main thyroid antigens, including TPO, Tg, and TSH-R, and confirm the heterogeneity of TPO T-cell epitopes in patients with AITD. Amino acid residues 100-119, 420-434, 625-644, and 882-901 are the most common sites recognized by TPO TCL, indicating that they may be immunogenic epitopes in AITD.

Adult↗

PubMed1991

[Effectiveness of iodine prophylaxis and frequency of thyroid enlargement (thyroid goiter) and clinical diagnosis of thyroid diseases in inhabitants of the Szczecin region after the Czernobyl accident].

The study, supported by program MZ-XVII, was carried on 4567 inhabitants of the area of Szczecin (2350 females and 2217 males). The population was chosen randomly, according to a simple drawing scheme. All subjects were clinically examined using standardised questionnaires. In 3468 persons (including 1807 girls and women, 1661 boys and men) apart form clinical examination, the assessment of thyrotropin, thyroxine and triiodothyronine in serum and frequency of antithyroglobulin antibodies and antithyroid membrane antibodies were evaluated. The data indicate that 94% of children in Szczecin's region received the prophylactic dose of iodine, mostly between the 1st and the 5th of May 1986. Only 17% of the adults received iodine. The most common preparation was Lugol solution given in a single dose. Among all persons who received iodine, only in 5% of subjects the side effects were noted (mostly in children), including symptoms of gastrointestinal tract (vomiting, abdomen pain) and occasionally intrathyroid side effects (thyroid pains). In examined population the high frequency of thyroid enlargement, mainly in women (up to 43-44% at the age group 30-50 years) was found. The frequency of clinical diagnosis of thyroid disease was higher in women than in man (most often the diffuse goiter, rarely the nodular goiter). The frequency of thyroid enlargement and clinical diagnosis of thyroid disease was not dependent on prophylactic iodine intake. The iodine prophylaxis did not influence on thyroid hormones and TSH serum levels and on frequency of antithyroid antibodies.

Adult↗

PubMed1991

The effect of xenotransplantation of human thyroid tissue following radioactive iodine-induced thyroid ablation on thyroid function in the nude mouse.

We have attempted to determine whether xenotransplanted human thyroid tissue into nude mice would act as a physiological substitute for the mouse thyroid gland after the mice had been rendered hypothyroid, using radioactive iodine (131I). The dosage of 0.2 millicuries of 131I was given to each mouse. The xenotransplantations of human thyroid tissue, i.e., normal, Graves' and nontoxic multinodular goitre, were carried out three weeks after radioactive ablation. The values of TSH in all mice rose to high levels (71 +/- 15.6 ng/ml, +/- SD) by three weeks after 131I administration. The TSH values in the mice declined rapidly and reached normal levels by 3-5 weeks after xenotransplantation. In addition, the serum T4 values were generally in the euthyroid range by 3-6 weeks after xenotransplantation. There were no marked differences in the changes of serum T4 and TSH when the three groups were compared. These results indicated that the xenografted human thyroid tissue permitted a return to a normal feedback system as reflected by normal serum TSH and T4 values in the animals. The Graves' thyroid tissue reverted to normal physiological function when removed from its human (abnormal) immune environment, signifying that Graves' thyrocytes are mere passive captives to immune events. This model should prove to be useful in the study of human thyroid physiology and pathophysiology.

Animals↗

PubMed2002

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↗

PubMed1991

[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↗

PubMed1995

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↗

PubMed1988

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↗

PubMed1991

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↗

PubMed1986

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↗

PubMed1976

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↗

PubMed2003

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↗

PubMed1988

[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↗

PubMed1984

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↗

PubMed2003

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↗

PubMed1991

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↗

PubMed1980

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↗

PubMed1987

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↗