Biomedical subjects

B Y Cho

Publications and source records attributed to B Y Cho.

At least 55 records · Page 3Linked to original sources

PubMed1994

The tumor necrosis factor beta * 1 allele is linked significantly to HLA-DR8 in Koreans with atrophic autoimmune thyroiditis who are positive for thyrotropin receptor blocking antibody.

The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA-DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed1994

The cytokines, interleukin-1 beta, interleukin-6 and interferon-gamma upregulate the expression of intercellular adhesion molecule-1(ICAM-1) in rat thyroid cell line, FRTL-5.

OBJECTIVES: Recently, the role of adhesion molecules in the immune system has been recognized. ICAM-1 plays an important role in a variety of inflammatory and immune mediated mechanisms, including recruitment and targeting of lymphocytes. We observed the effects of cytokines on expression of rat homologue of human intercellular adhesion molecule-1 in rat thyroid cell line, FRTL-5. METHODS: We have examined expression of rat intercellular adhesion molecule-1 (ICAM-1, CD54), a homologue of human intercellular adhesion molecule-1, by immunocytochemistry (immunoperoxidase staining) in the continuously growing rat thyroid cell line, FRTL-5. RESULTS: Low level of ICAM-1 expression was noted at basal condition and this basal expression was not influenced by thyrotropin. Expression in rat homologue of ICAM-1 is increased by interferon-gamma, interleukin-1 beta and interleukin-6 with a dose dependent manner. CONCLUSION: These results show that a pure line of rat thyroid cells can express an ICAM-1 homologue and this is directly enhanced by cytokines such as rat interferon-gamma, human interleukin-1 beta and interleukin-6. Expression of this homologue is partially responsible for lymphocyte adhesion to thyroid cells, which is likely to be a major event in T cell recognition of thyroid antigens in autoimmune thyroiditis.

Animals↗

PubMed1993

A strong association between thyrotropin receptor-blocking antibody-positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans.

We investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). We analyzed the HLA-A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonucleotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goitrous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was significantly increased in 23 atrophic autoimmune thyroiditis patients that were positive for TSH binding inhibitor immunoglobulin (TBII) compared to 136 controls [52% vs. 16%; chi 2 = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.43. HLA-DQB1*0302 was also increased in patients with TBII-positive atrophic autoimmune thyroiditis (24% vs. 7%; chi 2 = 11.2; Pc = 0.012; relative risk = 4.4; etiological fraction = 0.19). No specific DR antigens or DQB1 alleles were increased in either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. A significant decrease in the frequency of HLA-DR6 antigen was observed in both TBII-positive atrophic autoimmune thyroiditis (0% vs. 32%; chi 2 = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; chi 2 = 23.2; Pc < 0.001) patients. The frequency of the HLA-Cw1 antigen was significantly increased in all patient groups. We conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from both goitrous autoimmune thyroiditis and TRBab-negative atrophic autoimmune thyroiditis. It is possible that HLA-DR8 and/or DQB1*0302 may be related to the susceptibility genes involved in the production of TRBab in Koreans.

Adult↗

PubMed1993

Negative correlation between the conversion of thyrotropin receptor-bound blocking type thyrotropin receptor antibody to the stimulating type by anti-human IgG antibodies and the biological activity of blocking type thyrotropin receptor antibody.

It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Direct relationship between elevated free testosterone and insulin resistance in hyperprolactinemic women.

Women with hyperprolactinemia have been reported to have hyperandrogenemia and/or insulin resistance. However, little is known about the association of hyperandrogenemia and insulin resistance in these women. To investigate whether hyperandrogenemia and/or insulin resistance occur in hyperprolactinemic women, and to assess the relationship between them, we measured basal androgen level and both glucose and insulin levels after oral glucose administration in 20 hyperprolactinemic women and 7 female control subjects. Free testosterone level was higher and estradiol level lower in hyperprolactinemic women than in control subjects (p < 0.05), whereas dehydroepiandrosterone sulfate (DHEAS) and total testosterone levels were similar (p > 0.05). Both fasting glucose and insulin levels didn't differ in the two groups (p > 0.05). However, both serum glucose and insulin levels, after a 75 g glucose load, were significantly increased in hyperprolactinemic women, (p = 0.001, p < 0.001, respectively). In simple linear regression analysis in hyperprolactinemic women, only free testosterone level had a positive correlation with the incremental area under the insulin curve (insulin-IAU) (r = 0.47, p < 0.05). In multiple stepwise regression analysis, free testosterone level, mean blood pressure and DHEAS level were associated significantly with insulin-IAU (beta = 0.98, p < 0.0001; beta = 0.58, p = 0.002; beta = -0.67, p < 0.003, respectively). These results suggest that insulin resistance is closely related to elevated free testosterone level in hyperprolactinemic women.

Adult↗

PubMed1992

Solid-phase immunoassay using a flow cytometer: quantitative and qualitative determination of protein antigens and a hapten.

A fluoroimmunoassay employing a flow cytometer as the fluorescence-detecting device is described. Three kinds of antigens, murine immunoglobulin (Ig), human chorionic gonadotropin (hCG) and progesterone were chosen as examples of the assay using fluorescein-labeled antibodies. Cyanogen bromide-activated agarose beads were used as solid-phase supporters. The flow cytometric immunoassay was applied to both qualitative and quantitative analyses; determination of murine Ig isotypes, quantitative determination of Ig, hCG and a hapten, progesterone. This assay produced very reproducible and less-fluctuating data since thousands of particles in the assay were collected and processed to produce a single value for fluorescence intensities. Furthermore, the working range of the assay in terms of antigen concentration was much broader than that of enzyme immunoassay. Therefore, we believe that microparticles like agarose beads could be useful solid-phase supporters in immunoassay, and the flow cytometer could provide a reliable alternative to the fluorescence-detecting device in immunoassay.

Animals↗

PubMed1992

Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody activities as prognostic markers for discontinuation of antithyroid drug treatment in patients with Graves' disease.

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

Adult↗

PubMed1992

The IgG subclass distribution of TSH receptor blocking antibodies in primary hypothyroidism.

OBJECTIVE: TSH receptor stimulating antibodies are restricted to the IgG1 subclass suggesting an oligoclonal origin. We wished to determine whether thyroid stimulation blocking antibodies, which also bind to the TSH receptor but may cause hypothyroidism, are similarly IgG subclass restricted. DESIGN: Sera containing TSH receptor blocking antibody activity were separated into IgG subclasses by negative depletion of all other subclasses on affinity columns of subclass-specific monoclonal antibodies or protein A as appropriate. PATIENTS: Eleven patients from two centres were studied. All had autoimmune hypothyroidism and TSH receptor blocking antibodies but no thyroid stimulating antibodies. MEASUREMENTS: TSH receptor blocking antibody activity was measured by assessing inhibition of TSH-stimulated cAMP production by human thyroid cells (five Israeli samples) or by the FRTL-5 rat thyroid cell line (six Korean samples). RESULTS: IgG1 was the most important subclass containing TSH receptor blocking antibody activity but complete restriction to this subclass was never seen. Clearly detectable activity was found in the IgG2 subclass in eight patients, in the IgG3 subclass in three patients, and in the IgG4 subclass in six patients. The percentage recovery of activity in the sum of the separated fractions generally corresponded to the activity in whole immunoglobulin, being 117 +/- 66% in the nine patients in whom this could be assessed, although in one of these, the activities in the sum of the fractions was much higher (284%). CONCLUSIONS: Unlike thyroid stimulating antibodies, thyroid stimulation blocking antibodies are not subclass restricted and are therefore likely to have a polyclonal origin. The IgG subclass distribution of these blocking antibodies resembles that of thyroglobulin and thyroid peroxidase antibodies.

Autoantibodies↗

PubMed1991

Cycloheximide inhibits interferon-gamma-induced class II major histocompatibility complex antigen expression in cultured rat thyroid cells.

The effects of the agents that are related to intracellular events on interferon-gamma-induced class II major histocompatibility complex antigen expression were studied using the technique of immunocytochemistry. Rat class II major histocompatibility complex antigen (RT1.B) was expressed in 88.3 +/- 3.3% (n = 3) of the functioning rat thyroid cells (FRTL-5) cultured in a medium containing 100 U/ml recombinant rat interferon-gamma (IFN gamma). Deprivation of bovine TSH had no effect on the expression of RT1.B antigen by IFN gamma. A23187 (1 nM to 2 microM) and/or 10 nM to 10 microM phorbol 12-myristate 13-acetate did not induce the expression of RT1.B antigen. IFN gamma-induced RT1.B expression was not inhibited by either 10 nM to 100 microM 1-(5-isoquinolysulfonyl)-2-methylpiperazine or 200 nM to 200 microM 8-(N,N-dimethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride. It was also not inhibited by either 5-200 microM verapamil or 500 nM to 20 microM trifluoperazine. However, 0.01-10 micrograms/ml cycloheximide inhibited IFN gamma-induced RT1.B antigen expression in a dose-dependent manner. These results suggest that IFN gamma induces RT1.B antigen expression in FRTL-5 cells via de novo protein synthesis independent of the cAMP system, phosphatidylinositide system, and voltage-dependent calcium channel.

Animals↗

PubMed1991

Incidence estimation of thyroid cancer among Koreans.

The medical records of inpatients with diagnoses of either ICD-9 193(malignant neoplasm of the thyroid gland) or 226(benign neoplasm of the thyroid gland) in the claims sent in by medical care institutions throughout the country, to the Korea Medical Insurance Corporation (KMIC) during the period from January 1, 1986 to December 31, 1987 were abstracted. These records were abstracted in order to identify and confirm new cases of thyroid cancer among the beneficiaries of the KMIC. Using these data, the incidence rate of thyroid cancer among Koreans was estimated as of July 1, 1986 through June 30, 1987. The crude rates were estimated to be 0.76(95% Cl: 0.63-0.87) and 3.87(95% Cl: 3.60-4.14) per 100,000 in males and females, respectively, and the cumulative rates for the age spans 0-64 and 0-74 in males were 0.06% and 1.10%, respectively. In females, those were equally 0.35%. The age-adjusted rate for the world population was 0.93 per 100,000 in males, which is one of the lowest levels in the world. However, the adjusted rate in females was 3.96 per 100,000, which is an average level and very similar to that of the Chinese in Singapore and Shanghai. A similar tendency was shown in the case of the truncated rates for the age group of 35-64, which was 1.91 per 100,000 in males and 8.82 per 100,000 in females.

Adolescent↗

PubMed1990

Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism.

To assess the changes in bone mineral density and osteoblastic activity in patients with hyperthyroidism and to investigate the relationship between those changes, we measured bone mineral density and serum osteocalcin in 109 patients with Graves' disease, comprising 75 untreated patients and 34 patients under treatment, and 200 normal controls. The degree of change in bone mineral density was quantified with Z transformation, in which we used means and SDs of bone mineral densities obtained in the process of age- and sex-matched 1:1 pairing developed by ourselves. Bone mineral density was low in female patients with hyperthyroidism in the spine, femur neck, trochanter, and Ward's triangle, but was not low in male patients. Serum osteocalcin was elevated in patients with untreated Graves' disease and correlated negatively with the Z values of bone mineral densities of the spine, femur neck, and trochanter. In conclusion, indices of osteoblastic activity were elevated in patients with hyperthyroidism, probably secondary to a thyroid hormone-induced increase in bone resorption which resulted in reduced bone mineral density. Quantification of the change in bone mineral density by using the parameters derived in the process of age- and sex-matched pairing seems to be an efficient method for statistical analyses.

Adolescent↗

PubMed1990

Changes in thyrotropin receptor antibody after subtotal thyroidectomy in Graves' disease: comparison with the degree of lymphocytic infiltration in the thyroid.

To evaluate changes in TSH receptor antibody after surgery in Graves' disease and its relationship with the degree of lymphocytic infiltration, serial serum levels of TSH receptor antibody were measured before and after the subtotal thyroidectomy in 50 patients with Graves' disease. In 22 (44%) out of 50 patients, thyrotropin binding inhibitor immunoglobulin (TBII) levels gradually decreased and disappeared completely within 12 months after surgery (TBII disappearing group). Twenty-eight (56%) patients showed persistent TBII activity and their levels were not changed until 12 months after surgery (TBII persistent group). The changes of thyroid stimulating antibody (TSab) levels were very similar to those of TBII in both groups. The thyroidal lymphocytic infiltration was more prominent in the TBII disappearing group. The degree of the decrease of TBII levels after surgery correlated with the grade of thyroidal lymphocytic infiltration. There was no significant difference of TSH receptor antibody (both TBII and TSab) levels between the thyroid and peripheral venous blood. These data suggest that the persistence or disappearance of TSH receptor antibody after surgery may reflect the difference between patients in whom the thyroid is the major site of TSH receptor antibody and those in whom additional sites of TSH receptor antibody synthesis exist.

Adolescent↗

PubMed1990

Thyroglobulin synthesis of oxyphilic cells in various types of neoplastic and autoimmune thyroid diseases.

To determine the content of thyroglobulin in oxyphilic cells of the thyroid, which have been considered as non-thyroglobulin producing cells, the degree of stainability of the various oxyphilic cells for thyroglobulin was compared with that of non-oxyphilic follicular cells in either same or different lesion. A total of 13 oxyphilic lesions, including three follicular adenomas containing oxyphilic cell nodules, four pure oxyphilic cell adenomas, and six Hashimoto's thyroiditis were compared with 16 of non-oxyphilic lesions such as, seven follicular adenomas, four chronic lymphocytic thyroiditis, and five Graves' disease. Many oxyphilic cells stained positively for thyroglobulin regardless of their morphologic variation, but less intensely than the usual follicular cells in follicular adenomas, chronic lymphocytic thyroiditis, and Graves' disease. The stainability of oxyphilic cells for thyroglogulin did not show any significant correlation with morphologic features, whereas in follicular adenomas, the non-oxyphilic follicular cells forming microfollicles stained less strongly for thyroglobulin than the same cells lining large mature follicles in a reproducible way. With above findings, we concluded that oxyphilic cells maintain the functional activity in terms of thyroglobulin synthesis, although the content of the thyroglobulin is less than that of non-oxyphilic colloid forming follicular cells.

Adenoma↗

PubMed1990

Poorly differentiated carcinoma of the thyroid retrospective clinical and morphologic evaluation.

Five thyroid carcinomas showing clinically aggressive biologic behavior were retrospectively reviewed to evaluate the possible presence of morphologic differences from conventional thyroid carcinomas. They were originally diagnosed as follicular carcinomas, medullary carcinoma, papillary carcinoma, and mixed papillary and medullary carcinoma. There were three males and two females. The age at the time of initial diagnosis ranged from 36 years to 67 years (mean 56 years). The size of the tumor varied from 4.5cm to 10cm (mean diameter 7cm). One patient died of brain metastasis four years after the initial therapy and the other four patients are still alive with local recurrences and/or metastases to bone, spinal cord, lung, and buttock. Histologically these lesions are categorized into two different groups: insular variant and columnar cell variant. Insular variant was characterized by well-defined nests (insulae) that are composed of small, uniform cells, frequent tumor necrosis, and hyalinization of the stroma. Columnar cell variant was characterized by tall columnar cells with marked nuclear statification. All five cases stained positively for thyroglobulin and negatively for calcitonin. With the above clinical and histopathological findings, we interpreted these lesions as a poorly differentiated carcinoma, biologically in an intermediate position between well differentiated and anaplastic carcinomas. The rapid and often fatal outcome associated with these variants of poorly differentiated carcinoma warrants aggressive treatment at the time of diagnosis.

Adenocarcinoma↗

PubMed1990

Changes in the properties of the thyrotropin receptor antibody in patients with Graves' disease after radioiodine treatment.

We investigated the effect of a single dose of 131I upon thyrotropin receptor antibodies (TRAb) in 21 patients with Graves' disease. The thyrotropin receptor antibodies were assessed by parallel measurements of thyrotropin binding inhibitor immunoglobulin (TBII), thyroid stimulating antibody (TSAb) and thyroid stimulation blocking antibody (TSBAb) in serum by radoreceptor assay, stimulation of adenlate cyclase and inhibition of TSH-stimulated adenylate cyclase activation in FRTL-5 cells, respectively. Prior to radioiodine treatment, TBII was detected in all 21 patients and TSAb in 19 patients. After radioiodine treatment, TBII activities did not change during the 12-months observation period, but in eight patients TSAb activities gradually decreased and were undetectable at the end of the 12-month observation period. Persistence of TSAb was not associated with the clinical outcome. Eight patients developed hypothyroidism within one year after radioiodine treatment. Three of the hypothyroid patients developed TSBAb, and the appearance of TSBAb coincided with the development of hypothyroidism. These results suggest that TSBAb might develop after radioiodine treatment in a minority of patients with Graves' disease and that the appearance of TSBAb, in addition to radiation-induced thyroid destruction, might be involved in the development of hypothyroidism following radioiodine treatment.

Adolescent↗

PubMed1989

Inhibition of thyrotropin-stimulated adenylate cyclase activation and growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema: comparison with activities of thyrotropin-binding inhibitor immunoglobulins.

We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H]thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3, 0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H]thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; P less than 0.01) and the thyroid growth inhibiting immunoglobulin (r = 0.618; P less than 0.01) activity. Thirteen patients whose TSH binding inhibitor immunoglobulin activities were more than 50% had both strong thyroid stimulation inhibiting immunoglobulin (75.1-100%) and thyroid growth inhibiting immunoglobulin (57.4-100%) activities. These data suggest that the vast majority of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibiting TSH-stimulated cAMP generation.

Adenylyl Cyclases↗

PubMed1989

Graves' hyperthyroidism following primary hypothyroidism: sequential changes in various activities of thyrotropin receptor antibodies.

A 40-year-old male who developed Graves' hyperthyroidism following primary hypothyroidism is reported. He presented with clinical signs of hypothyroidism and concomitant myasthenia gravis. The thyroid was not palpable. He was treated with T4, pyridostigmine and prednisolone. One year later he developed hyperthyroidism and goitre. His initial serum IgG had no intrinsic thyroid stimulating activity, but showed almost complete inhibition of TSH-stimulated cAMP generation (99.4%, normal less than 38%) and [3H]thymidine incorporation (99.5%, normal less than 40%) into rat thyroid cells, FRTL-5 cells, with very high activity (80.2%, normal less than 15%) of TSH binding inhibitor immunoglobulin. When he developed hyperthyroidism and goitre, his IgG showed a strong thyroid stimulation, both cAMP production (27-fold increase) and [3H]thymidine incorporation (5.5-fold increase). No inhibitory activities were noted. These findings suggest that clinical states of autoimmune thyroid diseases can be changed in accordance with changes of functional properties of TSH receptor antibodies.

Adult↗

PubMed1989

Role of blocking TSH receptor antibodies on the development of hypothyroidism and thyroid atrophy in primary myxedema.

We studied blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgG to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increases and 3H-thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin (TBII), thyroid stimulation blocking antibody (TSBAb) and thyroid growth blocking antibody (TGBAb) in patients with primary myxedema were 53.6%, 75% and 65.2%, respectively. However, in goitrous Hashimoto's thyroiditis, these were 14.3%, 0% and 17.7%, respectively. These antibodies inhibited the receptor binding of 125I-bTSH dose-dependently, and also inhibited dose-dependently not only TSH-stimulated but also Graves' IgG-stimulated cAMP increase and 3H-thymidine incorporation. TBII activities of patients with primary myxedema were significantly correlated with both their TSBAb (r = 0.665; p less than 0.01) and TGBAb (r = 0.618; p less than 0.01) activities. Thirteen patients whose TBII activities were more than 50% had both strong TSBAb (75.1-100%) and TGBAb (57.4-100%) activities. Transient neonatal hypothyroidism was found in an infant born to a mother having potent TBII activities. Serum of the baby also had potent TBII activities and the baby's IgG inhibited TSH-stimulated cAMP increase and 3H-thymidine incorporation. These data suggest that a significant proportion of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibition of TSH-stimulated cAMP generation.

Adolescent↗