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Journal articles on the topic 'Thyroid stimulating immunoglobulin'

Author: Grafiati

Published: 7 June 2025

Last updated: 16 July 2025

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Zhou, Yulin, Mengxi Zhou, Yicheng Qi, Weiqing Wang, Xinxin Chen, and Shu Wang. "The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves’ disease." Therapeutic Advances in Endocrinology and Metabolism 12 (January 2021): 204201882110449. http://dx.doi.org/10.1177/20420188211044943.

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Background: The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines. Methods: A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves’ disease. Results: A total of 77 patients with Graves’ disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves’ disease ( p < 0.001). Under anti-thyroid drugs treatment, thyroid-stimulating immunoglobulin value decreased gradually. A total of 21 patients had positive thyroid-stimulating immunoglobulin at the end of treatment. According to clinical fate of patients with Graves’ disease after withdrawal of anti-thyroid drugs, thyroid-stimulating immunoglobulin value and positivity in patients with relapse were significantly higher than that reported in patients with remission ( p = 0.001, p < 0.001). After adjustment for age, gender, initial thyroid receptor antibody, initial thyroid-stimulating immunoglobulin, and thyroid receptor antibody at the end of treatment, the odds ratio of positive thyroid-stimulating immunoglobulin for the risk of relapse was 33.271 (95% confidence interval: 4.741–233.458, p < 0.001) and odds ratio of quantitative thyroid-stimulating immunoglobulin was 1.009 (95% confidence interval: 1.002–1.015, p < 0.001). Conclusion: Thyroid-stimulating immunoglobulin is a good predictor of relapse in patients with Graves’ disease treated with anti-thyroid drugs. It might be safer to discontinue anti-thyroid drugs when thyroid-stimulating immunoglobulin and thyroid receptor antibody were both negative.

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Tamai, Hajime, Kanji Kasagi, Osamu Mizuno, et al. "Thyroid-stimulating antibody and thyrotropin-binding inhibitory immunoglobulin activity in hypothyroid patients who subsequently developed thyrotoxicosis." Acta Endocrinologica 122, no. 4 (1990): 499–504. http://dx.doi.org/10.1530/acta.0.1220499.

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Abstract. Although abnormal thyroid-stimulating and -blocking antibodies have been demonstrated in hyperthyroid and hypothyroid patients with autoimmune thyroid disorders, a direct correlation is not always observed. Thyroid-stimulating antibody, thyrotropinbinding inhibitory immunoglobulin, and thyroid-stimulating blocking antibody levels were determined in three hypothyroid patients who subsequently developed hyperthyroidism. Thyroid-stimulating antibodies levels were normal in one, elevated in another, and unmeasured in the third hypothyroid patient, but became elevated in all patients with the onset of hyperthyroidism. There was discordance, however, in one patient who had markedly elevated thyroid-stimulating antibodies and TSH-binding inhibitory immunoglobulin levels when she was hypothyroid. The data indicate that thyroidal responses to the abnormal stimulating antibodies may differ among patients with autoimmune thyroid disease.

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Jiang, Nai-Siang, Virgil F. Fairbanks, and Ian D. Hay. "Assay for Thyroid Stimulating Immunoglobulin." Mayo Clinic Proceedings 61, no. 9 (1986): 753–55. http://dx.doi.org/10.1016/s0025-6196(12)62778-5.

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Woeber, K. A. "Relationship between thyroid stimulating hormone and thyroid stimulating immunoglobulin in Graves’ hyperthyroidism." Journal of Endocrinological Investigation 34, no. 3 (2010): 222–24. http://dx.doi.org/10.1007/bf03347070.

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OCHI, YUKIO, TAKEHIRO INUI, TSUYOSHI KOUKI, KEI YAMASHIRO, TAKASHI HACHIYA, and YOSHIHIRO KAJITA. "Thyroid Stimulating Immunoglobulin(TSI) in Graves' Disease." Endocrine Journal 45, no. 6 (1998): 701–8. http://dx.doi.org/10.1507/endocrj.45.701.

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ANDO, Michiyasu, Kazuyuki YAMAUCHI, Hiroshi TANAKA, et al. "Thyroid Stimulating Immunoglobulin Bioassay Using Cultured Normal Human Thyroid Cells." Folia Endocrinologica Japonica 61, no. 8 (1985): 847–58. http://dx.doi.org/10.1507/endocrine1927.61.8_847.

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Berardo, Jeronimo, Leon A. Fogelfeld, Dan V. Mihailescu, Maria E. Padilla Sorto, and Donald W. Trepashko. "PSAT275 A Rare Case of Thyroid-Stimulating Immunoglobulin-Induced Thyrotoxicosis in Poorly Differentiated Metastatic Thyroid Cancer." Journal of the Endocrine Society 6, Supplement_1 (2022): A884. http://dx.doi.org/10.1210/jendso/bvac150.1830.

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Abstract We report case of a rare of hyperthyroidism secondary to functional metastatic thyroid carcinoma, which is an infrequent phenomenon that can be challenging to diagnose and treat, as low thyroid-stimulating hormone (TSH) levels can suppress the development and growth of differentiated thyroid carcinoma cells. Previous studies have reported that hyperfunctioning thyroid carcinoma may present as autonomous functioning thyroid nodules (AFTN) within the thyroid gland, or as functioning lesions in metastatic foci, which is our case. Functional thyroid carcinomas are capable of absorbing iodine, as well as synthesizing and releasing thyroxine, are often associated with follicular thyroid carcinomas. Potential mechanisms for the thyrotoxicosis include a large aggregate tumor mass, as well as the presence of thyroid-stimulating immunoglobulins (TSIs) that are able to stimulate the thyroid-stimulating hormone (TSH) receptors of the thyroid carcinoma. In this clinical case, patient presented with high titers of TSIs, and metastatic thyroid carcinoma, with persistent hyperthyroidism after thyroidectomy and with a remarkable radioactive iodine treatment response. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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Baek, Han-Sang, and Dong-Jun Lim. "Interpretation of Thyroid Autoantibodies in Hyperthyroidism." Korean Journal of Medicine 98, no. 3 (2023): 132–36. http://dx.doi.org/10.3904/kjm.2023.98.3.132.

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Thyrotoxicosis is a clinical state with a variety of various etiologies that results from excess thyroid hormones, including hyperthyroidism and thyroiditis. Graves' disease (GD) is a well-known autoimmune thyroid disease that causes hyperthyroidism, and its pathogenesis is mainly driven by the thyroid-stimulating hormone receptor antibody (TSHRAb), which is highly specific for GD. Measuring the TSHRAb is a fast and accurate diagnostic tool for GD and has been used to monitor disease activity and the treatment response. However, conventional TSH-binding inhibitory immunoglobulin (TBII) does not differentiate between stimulating, blocking, or neutral antibodies. In contrast, thyroid stimulatory immunoglobulin bioassays differentiate between stimulating and blocking antibodies and have comparably high sensitivity and specificity to TBII for GD. We also discuss the role of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) in thyrotoxicosis, although they are less specific than TSHRAb for GD. TPOAb is associated with autoimmune thyroiditis, while TgAb appears with TPOAb in patients with autoimmune thyroid disease. In addition, TPOAb or TgAb may be associated with a low recurrence of GD after discontinuing anti-thyroid drugs. Clinicians should interpret thyroid autoantibodies in the context of the patient's clinical presentation and consider their implications to manage and monitor thyrotoxicosis.

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Nishikawa, Mitsushige, Masayoshi Yoshimura, Nagaoki Toyoda, et al. "Correlation of orbital muscle changes evaluated by magnetic resonance imaging and thyroid-stimulating antibody in patients with Graves' ophthalmopathy." Acta Endocrinologica 129, no. 3 (1993): 213–19. http://dx.doi.org/10.1530/acta.0.1290213.

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To evaluate the relationship between eye changes and autoantibody to the thyrotropin receptor in patients with Graves' disease, we evaluated the eye changes using magnetic resonance imaging and the results were correlated with thyroid-stimulating antibody, thyrotropin binding inhibitor immunoglobulin and thyroid growth activity. Subjects were 15 patients with Graves' disease who had Graves' ophthalmopathy, including exophthalmos and other signs and symptoms, and nine patients without ophthalmopathy; all were maintained in a euthyroid state by antithyroid drugs. The thyrotropin-binding inhibitor imunoglobulin was measured by a kit, and thyroid-stimulating antibody and thyroid growth activity were evaluated by cyclic adenosine 3′,5′-monophosphate production and [3H]thymidine incorporation, respectively, by cultured functional rat thyroid lined cells. The sum of the swelling ratios (muscle thickness to the diameter of the optic nerve) of the four extraocular muscles correlated well with the degree of exophthalmos. The thyrotropin-binding inhibitor immunoglobulin was positive in nine out of 15 patients with ophthalmopathy; however, no correlation was observed between the activity and exophthalmos or muscle swelling. No significant correlation was observed between muscle changes and thyroid growth activity either. On the other hand, thyroid-stimulating antibody (642±91%) in Graves' patients with ophthalmopathy was significantly (p<0.02) higher than that (315±84%) in patients without ophthalmopathy. Moreover, the level of the stimulating activity in Graves' patients with ophthalmopathy showed a significant (p < 0.02) positive correlation with the sum of the swelling ratios of the individual eight eye muscles. These results suggest that thyroid-stimulating antibody has a close relation to Graves' ophthalmopathy.

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Goretzki, Peter E., Michael West, Rainer Koob, Christine Koller, K. Joseph, and Hans-Dietrich Röher. "Adenylate cyclase stimulation and [3H]thymidine incorporation in human thyroid tissues and thyrocyte cultures: The effect of IgG preparation from patients with different thyroid disorders." Acta Endocrinologica 116, no. 1_Suppl (1987): S281—S287. http://dx.doi.org/10.1530/acta.0.114s281.

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Abstract. Primary cell cultures of normal and adenomatous human thyroid tissues were incubated with TSH or ammonium sulphate precipited IGG fractions (1 mg/ml) of sera from patients with different thyroid diseases (Graves' disease: active n = 7 in remission n = 12; thyroid autonomy n = 39; simple euthyroid goitre n = 15) and were compared to controls (n = 26). [3H]thymidine incorporation in primary thyrocyte cultures demonstrated a typical bell shape curve after incubation with EGF and TSH with a maximal effect at 10–100 μIU/ml. This effect, however, was inconsistent and positive only in 2 of 7 primary cultures. Only TSH positive cultures were used for IgG studies. 16–28% of IGG fractions from sera of thyroid patients caused high (more than X + 5 sd of controls) stimulation of [3H]thymidine incorporation. Dose response curves of IgG fractions of 19 additional patients (Graves' disease in remission n = 15; thyroid autonomy n = 4) showed an increase in [3H]thymidine incorporation at 0.1 mg protein/ml for 10 patients and at low concentrations of 10–5 mg/ml for 5 patients. There was a good correlation (r = 0.72) (P < 0.0001) between positive findings in TSH-binding inhibition (TBII) and AC-stimulation (TSI) IGG fractions but none between stimulation of [3H]thymidine incorporation and any other thyroid specific immunoglobulin nor thyroid function nor any other available data. Immunoglobulins stimulating [3H]thymidine incorporation differ therefore from TBII and TSI. The growth effect of these immunoglobulins, however, has yet to be determined.

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Murakami, Masami, Kazuya Miyashita, Satoru Kakizaki, et al. "Clinical usefulness of thyroid-stimulating antibody measurement using Chinese hamster ovary cells expressing human thyrotropin receptors." European Journal of Endocrinology 133, no. 1 (1995): 80–86. http://dx.doi.org/10.1530/eje.0.1330080.

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Murakami M, Miyashita K, Kakizaki S, Saito S, Yamada M, Iriuchijima T, Takeuchi T, Mori M, Clinical usefulness of thyroid-stimulating antibody measurement using Chinese hamster ovary cells expressing human thyrotropin receptors. Eur J Endocrinol 1995;133:80–6. ISSN 0804–4643 Human thyrotropin (TSH) receptors were expressed in Chinese hamster ovary (CHO) cells using eukaryotic expression plasmid pCXN2, which contains β-actin promoter. We measured cAMP stimulation in CHO cells expressing human TSH receptors (CHO-hTSH-R cells) by immunoglobulin G (IgG) of patients with Graves' disease and Hashimoto's thyroiditis, and compared the results with a conventional thyroid-stimulating antibody (TS-Ab) assay using porcine thyroid cells and a TSH-binding inhibiting immunoglobulin (TBII) assay. Nineteen untreated patients with Graves' disease, including a case who developed hyperthyroidism after interferon -α therapy for chronic hepatitis C, and 13 treated patients with Graves' disease, 10 patients with Hashimoto's thyroiditis and 8 control subjects were studied. In 19 untreated patients with Graves' disease, 17 patients showed positive CHO-hTSH-R cell stimulation, 11 patients showed positive porcine thyroid cell stimulation and 15 patients showed positive TBII. All the untreated patients showed positive results in at least one assay, Although significantly positive correlations were observed among CHO-hTSH-R cell stimulation, porcine thyroid cell stimulation and TBII activities, the IgG of several patients showed significant discrepancy in the assay results. In a patient with interferon-induced hyperthyroidism only CHO-hTSH-R cell stimulation was positive, while porcine thyroid cell stimulation and TBII were negative. After the treatment with propylthiouracil for 6 months, CHO-hTSH-R cell stimulation became negative. The IgG of patients with Hashimoto's thyroiditis did not show significant stimulation of CHO-hTSH-R cells. These results suggest that the CHO-hTSH-R cell stimulation assay is clinically useful for the diagnosis and follow-up of patients with Graves' disease. Masami Murakami, First Department of Internal Medicine, Gunma University, School of Medicine, Maebashi 371, Japan

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Ikenoue, Hiroshi, Ken Okamura, Kaori Sato, et al. "Prediction of relapse in drug-treated Graves' disease using thyroid stimulation indices." Acta Endocrinologica 125, no. 6 (1991): 643–50. http://dx.doi.org/10.1530/acta.0.1250643.

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Abstract. Thyroid stimulation indices such as high thyroidal radioactive iodine uptake, increased estimated thyroid weight, presence of TSH-binding inhibitor immunoglobulin or thyroid-stimulating antibody, and elevated serum thyroglobulin level, were evaluated in 148 patients with Graves' disease who had been treated with antithyroid drugs for two years or more before the drugs were withdrawn. In all 19 patients in whom three or more indices were positive, early relapse, within 12 months, occurred after reducing the dosage of antithyroid drugs. Other 129 patients were followed after the drug was withdrawn and in 77 patients with one or two positive indices, early relapse occurred in 65-71% and late relapse, after 12 months or later, occurred in 2-11%. In 52 patients in whom none of the indices were positive, 86% remained in remission, but 10% developed an early relapse, and 4% a late relapse. We conclude that a combined analysis of thyroid stimulation indices is useful in predicting relapse in Graves' disease whereas it remains difficult to predict permanent remission.

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Kraiem, Z., R. Alkobi, and O. Sadeh. "Sensitization and desensitization of human thyroid cells in culture: effects of thyrotrophin and thyroid-stimulating immunoglobulin." Journal of Endocrinology 119, no. 2 (1988): 341–49. http://dx.doi.org/10.1677/joe.0.1190341.

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ABSTRACT Using an in-vitro system of cultured human thyroid cells and cyclic AMP (cAMP) accumulation as an index of cell stimulation, we compared TSH and thyroid-stimulating immunoglobulin (TSI) with regard to thyrocyte sensitization and desensitization. The smallest dose of TSH (0·05 mU/ml) capable of stimulating thyroid cells was the same as the minimum dose required to induce desensitization upon subsequent rechallenge with the hormone. In contrast, about 30-fold higher doses of TSI were needed to cause cell refractoriness compared with doses capable of eliciting stimulation. Moreover, significant stimulation of the thyroid with TSI was apparent much later than with TSH. A longer time-lapse was also necessary for TSI to induce densensitization. Likewise, thyrocytes recovered more slowly from TSI compared with TSH desensitization. Although at high doses TSI induced homologous desensitization, at lower doses the antibody, unlike TSH, potentiated the cAMP response to subsequent exposure to the antibody. The stimulatory doses of TSI were in the range usually encountered in active Graves' disease, which may explain why prolonged TSI in vivo sustains a hyperthyroid condition. In addition, we found that under conditions in which TSH leads to desensitization of the cAMP response, the thyroid cells maintained their responsiveness in terms of triiodothyronine secretory activity. Pre-exposure of human thyrocytes to TSI induced heterologous desensitization towards the TSH-stimulated cAMP response. Moreover, addition of the antibody to maximally desensitizing doses of TSH decreased cell sensitivity to the hormone even further. In sharp contrast, preincubation of cells with TSH, or TSH plus TSI, potentiated by four- and twofold respectively the cAMP response to subsequent challenge with TSI. Taken together, the data reveal marked differences between the action of TSH and TSI, and raise interesting questions concerning the mechanism whereby TSH potentiates the cAMP response to TSI. J. Endocr. (1988) 119, 341–349

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Niedzialkowska, Ewelina, Ashbita Pokharel, and Ajaz Banka. "Thyroid dermopathy and thyroid eye disease associated with hypofunctional autoimmune thyroid disease with high TSI/anti-TSHR antibodies improved with teprotumumab." BMJ Case Reports 17, no. 12 (2024): e260129. https://doi.org/10.1136/bcr-2024-260129.

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Thyroid dermopathy (TD) and thyroid eye disease (TED) are rare clinical entities in patients with hypofunctional autoimmune thyroid disease; however, these can be present in patients with thyroid-stimulating immunoglobulin (TSI)/anti-thyroid-stimulating hormone receptor (TSHR) antibodies. TED is believed to be associated with antibodies stimulating TSHRs and cross-talk with IGF-1 receptor (IGF-1R) pathway, prompting tissue proliferation. Teprotumumab (monoclonal antibody targeting IGF-1R) has been proven to improve symptoms of TED. It is proposed that TD share the same pathophysiology as TED. We present a case of a patient with hypofunctional autoimmune thyroid disease with high TSI/anti-TSHR antibodies who experienced significant improvement of symptoms of both TED and TD after six doses of teprotumumab. We postulate that further studies regarding the efficacy of teprotumumab in patients with TD are needed.

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Sachmechi, MD, FACE, FACP, Issac, and Rachelle Bitton, MD. "ROLE OF THYROID-STIMULATING IMMUNOGLOBULIN IN AGGRESSIVENESS OF WELL-DIFFERENTIATED THYROID CANCER." Endocrine Practice 6, no. 2 (2000): 139–42. http://dx.doi.org/10.4158/ep.6.2.139.

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SHECHNER, CARMELA, ZAKI KRAIEM, ELIMELECH ZUCKERMAN, and GABRIEL DICKSTEIN. "Toxic Graves' Disease with Thyroid Hemiagenesis: Diagnosis Using Thyroid-Stimulating Immunoglobulin Measurements." Thyroid 2, no. 2 (1992): 133–35. http://dx.doi.org/10.1089/thy.1992.2.133.

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Weetman, A. P., M. E. Yateman, P. A. Ealey, et al. "Thyroid-stimulating antibody activity between different immunoglobulin G subclasses." Journal of Clinical Investigation 86, no. 3 (1990): 723–27. http://dx.doi.org/10.1172/jci114768.

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Kasagi, Kanji, Hiroto Hatabu, Yasutaka Tokuda, Keisuke Arai, Yasuhiro Iida, and Junji Konishi. "Comparison of thyroid stimulating activities measured by cyclic AMP production, those by radioiodine uptake in FRTL-5 cells and TSH-binding inhibitory activities in patients with hyperthyroid and euthyroid Graves' diseases." Acta Endocrinologica 117, no. 3 (1988): 365–72. http://dx.doi.org/10.1530/acta.0.1170365.

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Abstract. By using an assay measuring cAMP production in FRTL-5 thyroid cells, thyroid stimulating antibodies (TSab) were detected in all of 15 patients with euthyroid Graves' disease (EG) and of 26 patients with hyperthyroid Graves' disease (HG). There was no significant difference between TSab activities in EG and in HG. In an effort to elucidate why EG patients remain euthyroid in spite of having TSab, we investigated the effect of the patient's crude immunoglobulin fractions on 125I uptake in FRTL-5 thyroid cells, one of the indices of stimulation subsequent to cAMP production. The 125I uptake stimulating (IUS) activity was positive in 46.7% (7/15) of EG patients and 88.5% (23/26) of HG patients, being significantly lower in the former than in the latter (P < 0.02). Although the IUS activities significantly correlated with TSab activities in 41 patients with EG and HG (r = 0.784, P < 0.001), the ratio of IUS to TSab in EG tended to be lower than that in HG. TSH-binding inhibitor immunoglobulins (TBII) activities in EG patients were negative or weakly positive, being significantly lower than those in HG patients (P < 0.001). Thus, the ratios of TBII to both TSab and IUS activities were significantly higher in HG than in EG (P < 0.01, P < 0.001, respectively). The in vitro IUS activities also correlated with TBII activities (r = 0.441, P < 0.001) and in vivo 99mTc thyroid uptake (r = 0.401, P < 0.001) in both EG and HG patients. The EG patients with positive IUS activities displayed smaller goitre size and lower 99m thyroid uptake in comparison to 19 HG patients with a similar range of IUS activities. There was a good correlation between thyroid weight and 99mTc thyroid uptake (r = 0.827, P < 0.001). In conclusion, lower IUS activity and/or smaller goitre size in EG than in HG, which may lead to lower thyroidal uptake of 99mTc and presumably radioiodine in vivo, might be a factor responsible for keeping EG patients euthyroid despite the presence of TSab.

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Gärtner, R., C. Tsavella, G. Bechtner, and W. Greil. "Evidence that thyroid growth promoting activity of immunoglobulin preparations is due to contamination with EGF." Acta Endocrinologica 116, no. 1_Suppl (1987): S256—S259. http://dx.doi.org/10.1530/acta.0.114s256.

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Abstract. Immunoglobulin (IG) preparations may be contaminated with growth factors. Therefore, we investigated whether the growth promoting activity in IG preparations (thyroid growth stimulating immunoglobulins = TGI) from patients with sporadic goitre may be caused by contaminating EGF (epidermal growth factor). EGF in sera as well as in indifferently prepared IG of patients with recurrent goitre (n = 23), Graves' disease (n = 19) and normals (n = 17) was determined by EGF receptor assay. Comparatively, the ability for stimulating thyroid cell growth was determined in these IG preparations (2 mg/ml). EGF in ammoniumsulphate (AS) precipitates was about 2-fold higher than serum EGF. The growth promoting activity of indifferent IG preparations correlated with the EGF content. After additional purification on protein A-sepharose, neither EGF, nor a growth promoting activity was found in these IG preparations. We therefore conclude, that the growth promoting activity of crude IG preparations may be due to a contamination with EGF.

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Andre, Emanuilov Manov, Badi Yasra, B. Wang Andrew, and Walid Haddadin Rakahn. "Description of a patient with Graves' disease post COVID-19 with negative serology." World Journal of Advanced Research and Reviews 22, no. 2 (2024): 332–35. https://doi.org/10.5281/zenodo.14554456.

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We are presenting a 62-year-old African-American female who was admitted to our Emergency Department (ED) with septic shock due to pneumonia and diverticulitis. After improvement of the admitting conditions, we found out that the patient developed 1-month post-COVID-19 pneumonia Graves’ disease. The diagnosis was challenging because the patient was negative for thyroid-stimulating immunoglobulin (TSI) and thyroid receptor antibodies (TRAb). The clinical picture was highly suggestive of GD. The patient complained of increased sweating, palpitation, lower extremities weakness, and lack of sleep before the septic shock and after the COVID-19 infection. We palpated a trill and we heard a bruit on her thyroid gland which was a specific finding for the hypervascular gland as in GD. Our physical findings were confirmed by the laboratory findings of thyrotoxicosis with increased free thyroxin levels (Ft4) and very low thyroid stimulating hormone (TSH). The Doppler flow ultrasound of the thyroid confirmed bilateral hypervascular thyroid gland suggestive of hyperthyroidism without nodules. The patient did not have any thyroid disease or complaints before her COVID-19 infection. This is as far as we know the first described patient post-COVID-19 induced GD without TSI and TRAb.

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Kasagi, Kanji, Junji Konishi, Yasuhiro Iida, et al. "A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells." Acta Endocrinologica 115, no. 1 (1987): 30–36. http://dx.doi.org/10.1530/acta.0.1150030.

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Abstract. A sensitive, precise and practical assay for thyroid stimulating antibodies was developed in which poorly differentiated rat thyroid cells (FRTL-5) were exposed to crude immunoglobulin fractions precipitated from serum with 15% polyethylene glycol under hypotonic conditions. After the incubation at 37°C for 2 h, cAMP released into Hank's medium without NaCl was determined by radioimmunoassay. The removal of NaCl from the isotonic Hank's medium greatly enhanced cAMP production in response to both TSH and thyroid stimulating antibodies. The assay was sensitive enough to elicit an approximately 30-fold increase in cAMP at 10 mU/l bovine TSH. Thyroid stimulating activities measured using FRTL-5 cells significantly correlated with those measured using cultured porcine (r = 0.918, N = 72) or human (r = 0.830, N = 23) thyroid cells. Thyroid stimulating activities were detected in all of the 50 patients with hyperthyroid Graves' disease, the 14 patients with recurrent hyperthyroid Graves' disease, and the 25 patients with ophthalmic Graves' disease. Thyroid stimulating activity was also detected in some patients (9/24, 37.5%) with Hashimoto's thyroiditis whose serum TSH concentrations were higher than 30 mU/l. However, it was completely abolished by pre-treatment of the sera with anti-TSH antibodies. Although thyroid stimulating activities were detected in one of the patients with simple goitre (N = 10) and in one with thyroid cancer (N = 10), none of the patients with silent thyroiditis (N = 7), adenomatous goitre (N = 11), and thyroid adenoma (N = 9) were positive for thyroid stimulating antibodies.

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Andre Emanuilov Manov, Yasra Badi, Andrew B Wang, and Rakahn Walid Haddadin. "Description of a patient with Graves’ disease post COVID-19 with negative serology." World Journal of Advanced Research and Reviews 22, no. 2 (2024): 332–35. http://dx.doi.org/10.30574/wjarr.2024.22.2.1371.

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Mills, F., J. Jeffery, P. Mackenzie, A. Cranfield, and R. M. Ayling. "An immunoglobulin G complexed form of thyroid-stimulating hormone (macro thyroid-stimulating hormone) is a cause of elevated serum thyroid-stimulating hormone concentration." Annals of Clinical Biochemistry: An international journal of biochemistry and laboratory medicine 50, no. 5 (2013): 416–20. http://dx.doi.org/10.1177/0004563213476271.

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Fontes, Rosita, Mauricio Massucati Negri, Suemi Marui, Yolanda Schrank, and Andrea Faria Dutra Fragoso Perozo. "A higher cut-off for Thyroid-stimulating immunoglobulin (TSI) could better predict relapse in Graves’ disease?" Journal of Clinical and Laboratory Research 3, no. 2 (2021): 01–05. http://dx.doi.org/10.31579/2768-0487/035.

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Background: TSH receptor (TSHr)-stimulating immunoglobulins (Igs) can be used as diagnostic markers of Graves’ disease (GD). Thyroid-stimulating immunoglobulin (TSI) assays exclusively detect these specific Igs. Materials and Methods: This was a prospective longitudinal study in which hyperthyroid patients with GD and toxic nodular goitres were evaluated at diagnosis. GD patients were also evaluated at antithyroid drug (ATD) withdrawal. An automated chemiluminescent assay measured TSI. According to the manufacturer TSI less than 0.55 IU/L was a non-reactive result. The authors evaluated the Se and Sp of the cutoff point provided by the TSI assay manufacturer, and tested other cutting points through a ROC curve, to assess relapse risk of Graves’ disease. Results: At diagnosis, were evaluated 92 (85.2%) GD patients aged 41.2 ± 2.0 years, and 16 patients (14.8%) with toxic multinodular goiter (TMNG) or toxic adenoma (TA), aged 60.8 ± 4.8 years. They were re-evaluated after 18 ± 4 months with methimazole (MMI) treatment. The follow-up after treatment suspension was of 20 ± 6 months. At diagnosis, the TSI (Se) and (Sp) were 98.9% and 100%, respectively. At ATD withdrawal, despite a high Se (95.5%), Sp was low (59.6%). By adjusting the cut-off to 1.11 (TSI <1.11 IU/L non-reactive), TSI presented the best Sp (89.4%) with a small decrease in Se (93.3%) in predicting GD relapse. Conclusions: TSI had high Se and Sp in GD differential diagnosis with nodular goiters. In the assessment for GD relapse, by raising the cutting point to 1.11 IU/L, a better Sp was obtained at the expense of a small drop in Se. A larger sample is needed to support a higher TSI cut-off point in the clinical routine to assess GD relapse after ATD.

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Tariq, Alkhansaa, Hayfaa Mahmood, and Maha Majeed. "Evaluating the patient's serum for thyroid stimulating immunoglobulin and Cytotoxic -T-lymphocyte associated protein 4 in Graves hyperthyroidism." University of Thi-Qar Journal of Science 11, no. 2 (2024): 104–7. https://doi.org/10.32792/utq/utjsci/v11i2.1259.

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Graves' disease (GD) is a common autoimmune disorder that causes an excess of thyroid hormone production. It is mainly due to the production of IgG antibodies that activate the thyrotropin receptor. The aim of this study is to measure the levels of Cytotoxic -T-lymphocyte associated protein 4 and thyroid stimulating immunoglobulin in individuals with GD. It also seeks to establish the connection between thyroid stimulating immunoglobulin and thyroid stimulating hormone (TSH), as well as to assess the predictive value of CTLA4 for Graves' disease. The study was a case-control investigation conducted at the Alrusafa Center for Diabetes and Endocrinology. It involved a total of 45 people diagnosed with Graves' illness. The healthy group consisted of 45 individuals who had no previous medical history or clinical indications of hyperthyroidism or any other chronic condition. Blood samples from 90 individuals diagnosed with Graves' illness and a control group were analyzed to measure the levels of CTLA4, TSI by ELISA. The findings indicated a robust and statistically significant association (P.value<0.01) serum levels of CTLA4 in the patients for Graves' disease comparing to the control group. The patient samples included 13 men (28.89%) and 32 women (71.11%). There was no significant relationship found between TSI and TSH.

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Ning Purwani, Ni Putu Ayu Elistya, and Anak Agung Made Sucipta. "Penyakit Graves pada Anak Perempuan Usia 10 Tahun." Cermin Dunia Kedokteran 49, no. 5 (2022): 280–83. http://dx.doi.org/10.55175/cdk.v49i5.234.

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Penyakit Graves (PG) adalah penyakit autoimun akibat pembentukan antibodi TSH receptor-stimulating immunoglobulin (TSI) yang menyebabkan produksi hormon tiroid meningkat. Seorang anak perempuan, usia 10 tahun, dengan benjolan pada leher bagian kanan dan kiri depan yang baru disadari sejak 3 hari, tidak nyeri. Prestasi belajar seperti biasa. Tangannya bergetar ringan saat menulis. Penyakit Graves didiagnosis berdasarkan pemeriksaan fisik dan ultrasonografi tiroid, fungsi tiroid, dan pemeriksaan antibodi tiroid. Terapi dengan methimazole tablet 5 mg setiap 12 jam dan kontrol FT4 dan TSH setelah 1 bulan. Graves’ disease is an autoimmune disease with formation of TSH receptor-stimulating immunoglobulin (TSI) antibodies resulting in increased thyroid hormone production. A 10 year-old girl with a painless lump in the right and left side of her anterior neck, noticed since 3 days ago. Learning achievement is still good. Her hands were slightly trembling while writing. Graves’ disease was diagnosed based on physical examination and thyroid ultrasound, thyroid function, and thyroid antibody tests. The treatment was methimazole 5 mg tablets every 12 hours and laboratory check for FT4 and TSH after 1 month.

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Lee, Je Sang, Si Hyung Lee, Bo Yeon Kim, and Sun Young Jang. "Relationship between Serum Thyroid-stimulating Hormone Receptor Autoantibodies and Activity and Severity of Thyroid Eye Disease." Journal of the Korean Ophthalmological Society 62, no. 11 (2021): 1459–64. http://dx.doi.org/10.3341/jkos.2021.62.11.1459.

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Purpose: To study the relationship between the levels of serum thyroid-stimulating hormone (TSH)-receptor autoantibodies (TRAbs) and thyroid eye disease (TED) activity and severity scores.Methods: A cross-sectional study was performed. The medical records of 315 patients diagnosed with TED between March 2014 and December 2019 were reviewed. The clinical activity score (CAS) was used to assess TED activity and a modified NOSPECS score was used for severity grading. The serum TRAb level was measured using two assays: a TSHR binding inhibitory immunoglobulin (TBII) assay and thyroid stimulating immunoglobulin (TSI) bioassay.Results: The TBII and TSI assay results were significantly positively correlated with the CAS (R = 0.113 and 0.211, respectively; p < 0.05), modified NOSPECS score (R = 0.173 and 0.316, respectively; p < 0.05), and proptosis (R = 0.136 and 0.167, respectively; p < 0.05). Both assays demonstrated significant differences in the level of TRAb between patients with and without compressive optic neuropathy or corneal epithelial defects.Conclusions: The levels of TRAbs according to both TBII and TSI assays showed significant correlations with clinical signs of corneal involvement, optic neuropathy, and TED activity and severity.

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Premachandra, B. N., A. Radparvar, and I. K. Williams. "Reciprocal Relation of Thyroid-Stimulating Hormone and Thyroid-Stimulating Immunoglobulin in a Patient with Endogenous Subclinical Hyperthyroidism." American Journal of the Medical Sciences 333, no. 5 (2007): 296–99. http://dx.doi.org/10.1097/maj.0b013e318053e17c.

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Endo, Toyoshi, Kazutaka Haraguchi, Masayuki Ohmori, Masato Ikeda, Kazuyasu Ohta, and Toshimasa Onaya. "Thyrotropin receptor non-mediated thyroid stimulating immunoglobulin in Graves' disease." Biochemical and Biophysical Research Communications 179, no. 3 (1991): 1543–47. http://dx.doi.org/10.1016/0006-291x(91)91748-2.

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Larsson, Anders, Mats Gåfvels, and Torbjörn Karlsson. "Falsely Elevated Thyroid-Stimulating Hormone Results due to Interference by M-Component of IgG-Lambda Type." Case Reports in Oncology 13, no. 2 (2020): 680–82. http://dx.doi.org/10.1159/000507754.

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Heterophilic antibodies but also M-components can interfere with laboratory tests causing erroneous results. We report the case of a 75-year-old man with myeloma and a monoclonal immunoglobulin component (M-component) that caused elevated thyroid-stimulating hormone (TSH) results. The M-component was of the IgG-lambda type. Thyroid markers were analyzed repeatedly, and there was a clear association between IgG concentrations and TSH values (R2 = 0.724). The highest TSH value was 75 mIU/L. Polyethylene glycol (PEG) precipitation of intact immunoglobulins was used to investigate if there was an antibody-related interference problem. The PEG treatment normalized the TSH value, showing that the cause of the elevated TSH result was due to interference caused by the M-component. In conclusion, it is important to remember that both heterophilic antibodies and M-components may cause erroneous results.

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Li, Jonathan C., Deepika Nandiraju, Serge Jabbour, and Alan A. Kubey. "PANCYTOPENIA AND LYMPHOID ORGAN HYPERPLASIA IN A PATIENT WITH GRAVES DISEASE: RESPONSE TO ANTITHYROID DRUG THERAPY." AACE Clinical Case Reports 5, no. 6 (2019): e388-e392. http://dx.doi.org/10.4158/accr-2019-0170.

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Objective: In rare instances, cytopenias manifest as a complication of thyrotoxicosis. Here, we report a case of Graves disease (GD) thyrotoxicosis presenting as pancytopenia that resolved with antithyroid therapy. Methods: A 35-year-old male presented with fever and chills following an outpatient colonoscopy. Initial blood work revealed pancytopenia. Workup included viral antigen titers, blood cultures, rheumatologic antibodies, inflammatory markers, immunocompetency, nutrient deficiency, metal toxicity, and malignancy. Bone marrow aspirate was analyzed by microscope, flow cytometry, fluorescence in situ hybridization, and genetic analysis. Computed tomography scan of the chest, abdomen, and pelvis was obtained. Thyroid labs included thyroid-stimulating hormone, total triiodothyronine, free thyroxine, thyroid-stimulating immunoglobulin, anti-thyroid peroxidase antibody, and radioiodine uptake scan. Results: All workup above was non-revelatory except as follows. Imaging revealed thymic hyperplasia and splenomegaly. Thyroid labs revealed thyroid-stimulating hormone <0.02 μIU/mL (reference range is 0.30 to 5.00 μIU/mL), free thyroxine of 4.7 ng/dL (reference range is 0.7 to 1.7 ng/dL), total triiodothyronine of 191 pg/mL (reference range is 90 to 180 pg/mL), thyroid-stimulating immunoglobulin of 522% (reference range is <140%). Bone marrow biopsy was consistent with a reactive process suggesting an infectious or autoimmune process. Radioiodine uptake scan confirmed GD. He was discharged on antithyroid medication. Two-month follow-up labs revealed improved cell counts; his absolute neutrophil count was 1.94 × 109 cells/L (reference range is 1.50 to 8.00 × 109 cells/L), hemoglobin was 12.9 g/dL (reference range is 14.0 to 17.0 g/dL), and platelets were 153 × 109 cells/L (reference range is 140 to 400 × 109 cells/L). Definitive treatment was obtained with 12 mCi of 131-iodine. Conclusion: Pancytopenia and lymphoid organ hyperplasia (splenomegaly, thymic hyperplasia, and lymphadenopathy) have been previously reported to be associated with thyrotoxicosis secondary to GD, rarely simultaneously, and manifest from both thyrotoxic and immunologic mechanisms. After excluding alternative life-threatening pathologies, in such presentations, GD should be considered and treated if confirmed.

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Ko, JaeSang, Koung Hoon Kook, Jin Sook Yoon, Kyung In Woo, and Jae Wook Yang. "Longitudinal association of thyroid-stimulating immunoglobulin levels with clinical characteristics in thyroid eye disease." BMJ Open 12, no. 6 (2022): e050337. http://dx.doi.org/10.1136/bmjopen-2021-050337.

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ObjectivesThe clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the longitudinal association between changes in serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb) levels and course of disease activity and severity over time.DesignThis was a multicentre, prospective, observational study.SettingFifteen tertiary care oculoplastic service centres in Korea.ParticipantsSeventy-six patients with newly diagnosed TED were included and followed up for 12 months.MethodsWe evaluated clinical characteristics and serum TRAb levels at baseline, 6 and 12 months of TED diagnosis. Additionally, we analysed longitudinal associations between the serum TRAb levels and clinical activity score (CAS), no signs or symptoms, only signs, soft tissue involvement, proptosis, extraocular muscle involvement, corneal involvement, sight loss (NOSPECS) score and proptosis.ResultsThyroid-stimulating immunoglobulin (TSI) and TSH-binding inhibitory immunoglobulin (TBII) levels decreased during the 1-year follow-up, whereas disease activity measured using CAS decreased mainly in the first 6 months. Disease severity measured using NOSPECS score and proptosis remained unchanged. Moreover, inter-person differences in TBII levels were associated with CAS, NOSPECS score and proptosis over time, whereas inter-person differences in TSI levels were associated with NOSPECS score. Subgroup analysis of patients with a baseline CAS≥4 demonstrated that within-person changes in TSI levels affected the CAS and NOSPECS score.ConclusionsFollow-up measurement of serum TSI and TBII levels may help evaluate TED prognosis and enable accurate clinical decision-making.

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Cui, Yiwen, and Asha Rijhsinghani. "Role of Maternal Thyroid-Stimulating Immunoglobulin in Graves' Disease for Predicting Perinatal Thyroid Dysfunction." American Journal of Perinatology Reports 09, no. 04 (2019): e341-e345. http://dx.doi.org/10.1055/s-0039-1694035.

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Objective To assess maternal thyroid-stimulating immunoglobulin (TSI) as a predictor of neonatal thyroid hyperthyroidism in pregnancies complicated by Graves' disease. Methods This is a 10-year retrospective study of patients with a history of Graves' disease and elevated TSI activity level defined as 1.3 times the normal. All subjects underwent cordocentesis for ultrasound findings of suspected fetal thyrotoxicosis (fetal tachycardia, oligohydramnios, hydrops, and thyromegaly). Neonatal diagnosis was made based on neonatal thyroid function testing or symptoms. Results Fourteen patients were included in the study, seven with active Graves' disease requiring antithyroid drug (“ATD group”) and seven with iatrogenic hypothyroidism on levothyroxine (“levothyroxine group”). Four cases (57%) of neonatal thyrotoxicosis were diagnosed in the levothyroxine group compared with two cases (28%) in the ATD group. The lowest maternal TSI level at which a neonate did not develop hyperthyroidism was 2.6 for the levothyroxine group and 2.5 for the ATD group. The odds ratio of a neonate from the levothyroxine group developing hyperthyroidism compared with one from the ATD group is 3.3 (95% confidence interval: 0.4–30.7). Conclusion For patients with Graves' disease, those with iatrogenic hypothyroidism and TSI > 2.5 times the basal level are at the highest risk for neonatal thyrotoxicosis.

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Kraiem, Z., B. Glaser, J. Pauker, O. Sadeh, and M. Sheinfeld. "Bioassay of thyroid-stimulating immunoglobulin in cryopreserved human thyroid cells: optimization and clinical evaluation." Clinical Chemistry 34, no. 2 (1988): 244–49. http://dx.doi.org/10.1093/clinchem/34.2.240.

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Abstract We have explored the method of Rapoport et al. (J Clin Endocrinol Metab 1984;58:332-8) for the bioassay of thyroid-stimulating immunoglobulin (TSI) in cultured human thyroid cells, to optimize the assay and to evaluate its utility in clinical diagnosis and management of patients with autoimmune thyroid disease. Here we describe the procedure ultimately adopted, its major properties, and the results it has yielded in various clinical states. Clinical sensitivity of the assay was established by demonstrating TSI activity in all of 60 cases of active Graves' disease. We observed in these patients a nonlinear correlation between concentrations of TSI and of triiodothyronine, as well as between TSI concentration and the clinical severity of the thyrotoxicosis. Specificity of the assay was demonstrated by finding no TSI bioactivity in 13 patients with toxic adenoma, five with cold nodule, and 18 of 19 with nontoxic goiter. Remission of Graves' disease in 25 patients was invariably accompanied by undetectable concentrations of TSI; evidently this assay may be useful in identifying patients who are likely to go into remission. TSI activity was present in eight of 11 patients with euthyroid ophthalmopathy (unilateral and bilateral) associated with a normal response to the thyrotropin-releasing hormone test and absence of increased titers of antithyroid antibodies, suggesting that this assay may provide a powerful tool in the clinical diagnosis of this disorder.

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Damante, Giuseppe, Daniela Foti, Rosaria Catalfamo, and Sebastiano Filetti. "Desensitization of the thyroid cyclic AMP response to thyroid stimulating immunoglobulin: Comparison with TSH." Metabolism 36, no. 8 (1987): 768–73. http://dx.doi.org/10.1016/0026-0495(87)90114-4.

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Kangelaris, Gerald T., and Lisa A. Orloff. "Role of Thyroid Stimulating Immunoglobulin in Rapidly Progressive Metastatic Thyroid Cancer Following Total Thyroidectomy." Laryngoscope 121, S4 (2011): S131. http://dx.doi.org/10.1002/lary.22008.

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Ning Purwani, Ni Putu Ayu Elistya, and Anak Agung Made Sucipta. "Penyakit Graves pada Anak Perempuan Usia 10 Tahun." Cermin Dunia Kedokteran 49, no. 5 (2022): 280. http://dx.doi.org/10.55175/cdk.v49i5.1853.

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Penyakit Graves (PG) adalah penyakit autoimun akibat pembentukan antibodi TSH receptor-stimulating immunoglobulin (TSI) yang menyebabkan produksi hormon tiroid meningkat. Seorang anak perempuan, usia 10 tahun, dengan benjolan pada leher bagian kanan dan kiri depan yang baru disadari sejak 3 hari, tidak nyeri. Prestasi belajar seperti biasa. Tangannya bergetar ringan saat menulis. Penyakit Graves didiagnosis berdasarkan pemeriksaan fisik dan ultrasonografi tiroid, fungsi tiroid, dan pemeriksaan antibodi tiroid. Terapi dengan methimazole tablet 5 mg setiap 12 jam dan kontrol FT4 dan TSH setelah 1 bulan. Graves’ disease is an autoimmune disease with formation of TSH receptor-stimulating immunoglobulin (TSI) antibodies resulting in increased thyroid hormone production. A 10 year-old girl with a painless lump in the right and left side of her anterior neck, noticed since 3 days ago. Learning achievement is still good. Her hands were slightly trembling while writing. Graves’ disease was diagnosed based on physical examination and thyroid ultrasound, thyroid function, and thyroid antibody tests. The treatment was methimazole 5 mg tablets every 12 hours and laboratory check for FT4 and TSH after 1 month.

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Cho, B. Y., Y. K. Shong, H. K. Lee, C. S. Koh, and H. K. Min. "Graves' hyperthyroidism following primary hypothyroidism: sequential changes in various activities of thyrotropin receptor antibodies." Acta Endocrinologica 120, no. 4 (1989): 447–50. http://dx.doi.org/10.1530/acta.0.1200447.

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Abstract. 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 <38%) and [3H]thymidine incorporation (99.5%, normal<40%) into rat thyroid cells, FRTL-5 cells, with very high activity (80.2%, normal <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.

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Wadeleux, P. A., and R. J. Winand. "Thyroid growth modulating factors in the sera of patients with simple non-toxic goitre." Acta Endocrinologica 112, no. 4 (1986): 502–8. http://dx.doi.org/10.1530/acta.0.1120502.

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Abstract. Since 'Thyroid-Growth-Immunoglobulins' are implicated in the pathogenesis of some goitrous thyroid diseases, we have investigated the presence of thyroid growth modulators in the sera from patients with simple non-toxic goitre (diffuse non-toxic goitre and colloid nodular goitre). To detect growth effect, two procedures were employed, both using [3H]thymidine incorporation into DNA. In one procedure, porcine thyroid follicles in suspension were employed. Gamma-globulin (2 mg/ml) from 10/26 of patients with diffuse non-toxic goitre and 8/27 of patients with colloid nodular goitre were found to increase [3H]thymidine incorporation when compared to gamma-globulins from control group. The other procedure used sparsely plated thyroid cells isolated from normal or porcine thyroid gland and from human simple non-toxic goitre. No serum from patients with simple goitre showed greater growth stimulating activity than that of normal individuals. Moreover, using simple goitre cells as target, a lower serum activity was observed in 7/28 of patients with diffuse non-toxic goitre and in 9/30 of patients with colloid nodular goitre. Analogous results were obtained with normal porcine thyroid cells. The lower serum activity of these patients was observed in a wide range of serum concentrations (1 to 15%) and was associated with and inhibitory effect recovered in the gamma globulin fraction. By the two different procedures, we have therefore evidenced the presence of thyroid growth modulators in the sera of several patients with simple non-toxic goitre. The stimulatory effect observed with the thyroid follicles strengthens the implication of thyroid growth stimulating immunoglobulin in the pathogenesis of some simple sporadic non-toxic goitre. The negative effect detected with monolayers of sparsely plated thyroid cells needs further characterization but, at least, it points out the importance of the culture conditions in the interpretation of the results.

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Fröhlich, Eleonore, and Richard Wahl. "Pars Distalis and Pars Tuberalis Thyroid-Stimulating Hormones and Their Roles in Macro-Thyroid-Stimulating Hormone Formation." International Journal of Molecular Sciences 24, no. 14 (2023): 11699. http://dx.doi.org/10.3390/ijms241411699.

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Thyroid-stimulating hormone (TSH) and thyroid hormone levels are standard parameters in blood analysis. However, the immunoassays employed may lead to false-positive or false-negative results when the sample contains certain materials that interfere with the assay. Macro-TSH, a complex of TSH with immunoglobulin or albumin, may cause apparently increased TSH concentrations. TSH is produced in the pars tuberalis (PT) of the pituitary gland and by thyrotrophs of the pars distalis (PD). It was found that variable glycosylation can render the molecule more strongly bound to antibodies or albumin in the blood, leading to the hypothesis that macro-TSH consists mainly of PT-TSH. Although less known than PD-TSH, PT-TSH plays an important role in the central regulation of thyroid metabolism. The present review summarizes the physiological function of human PT-TSH and its role in macro-TSH formation. The prevalence of macro-hyperthyrotropinemia, the structure of PT-TSH and macro-TSH, problems in the measurement of TSH, and the action of PT-TSH in animals with seasonal breeding are discussed. Despite the absence of a specific function of macro-TSH in the organism, the identification of macro-TSH is important for avoiding unnecessary treatment based on a falsified readout of increased TSH concentrations as numerous individual case reports describe.

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Padmanaban, Preethi, Eric Nylen, Kenneth Burman, and Sabyasachi Sen. "Resolution of hyperthyroidism and thyroid antibodies following struma ovarii resection: an uncommon entity." BMJ Case Reports 14, no. 4 (2021): e240924. http://dx.doi.org/10.1136/bcr-2020-240924.

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We report a case of 34-year-old clinically asymptomatic woman who had been followed for 6 years for hyperthyroidism with thyroid stimulating hormone <0.006 uIU/mL, free T4 1.98 ng/mL, free T3 5.3 pg/mL, elevated thyroid stimulating immunoglobulin 1.70 IU/L, thyroid peroxidase antibody 38 IU/mL and thyroglobulin antibody 9.3 IU/mL. Radioiodine thyroid scan showed minimal uptake in both thyroid lobes (24-hour uptake was 0.3%). She subsequently underwent evaluation for lower abdominal pain and menstrual irregularities, which revealed a large left ovarian cyst measuring 15.9 cm × 10.8 cm × 13.2 cm and right-sided ovarian cyst measuring 2.7 cm × 3.3 cm × 3.5 cm. Laparoscopic bilateral ovarian cystectomy was performed and the final pathology revealed struma ovarii of the left ovarian cyst with the entire ovarian tumour made up of benign thyroid tissue. Thyroid function tests performed 3 months after surgical removal of struma ovarii showed euthyroidism. We present a rare case with detailed laboratory and immunological data before and after ovarian extirpation with resolution of hyperthyroidism associated with functional struma ovarii.

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MORRIS, JOHN C., NAI-SIANG JIANG, IAN D. HAY, M. CRISTINE CHARLESWORTH, DANIEL J. McCORMICK та ROBERT J. RYAN. "The Effects of Syntheticα-Subunit Peptides on Thyroid-Stimulating Immunoglobulin Activity*". Journal of Clinical Endocrinology & Metabolism 67, № 4 (1988): 707–12. http://dx.doi.org/10.1210/jcem-67-4-707.

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Kahaly, George J., Tanja Diana, and Paul D. Olivo. "TSH RECEPTOR ANTIBODIES: RELEVANCE & UTILITY." Endocrine Practice 26, no. 1 (2020): 97–106. http://dx.doi.org/10.4158/ep-2019-0363.

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Objective: Antibodies (Abs) to the thyrotropin (TSH) receptor (TSH-R) play an important role in the pathogenesis of autoimmune thyroid disease (AITD). We define the complex terminology that has arisen to describe TSH-R-Abs, review the mechanisms of action of the various types of TSH-R-Abs, and discuss significant advances that have been made in the development of clinically useful TSH-RAb assays. Methods: Literature review and discussion. Results: TSH-R-Abs may mimic or block the action of TSH or be functionally neutral. Stimulating TSH-R-Abs are specific biomarkers for Graves disease (GD) and responsible for many of its clinical manifestations. TSH-R-Abs may also be found in patients with Hashimoto thyroiditis in whom they may contribute to the hypothyroidism of the disease. Measurement of TSH-R-Abs in general, and functional Abs in particular, is recommended for the rapid diagnosis of GD, differential diagnosis and management of patients with AITD, especially during pregnancy, and in AITD patients with extrathyroidal manifestations such as orbitopathy. Measurement of TSH-R-Abs can be done with either immunoassays that detect specific binding of Abs to the TSH-R or cell-based bioassays that also provide information on their functional activity and potency. Application of molecular cloning techniques has led to significant advances in methodology that have enabled the development of clinically useful bioassays. When ordering TSH-R-Ab, clinicians should be aware of the different tests available and how to interpret results based on which assay is performed. The availability of an international standard and continued improvement in bioassays will help promote their routine performance by clinical laboratories and provide the most clinically useful TSH-R-Ab results. Conclusion: Measurement of TSH-R-Abs in general, and functional (especially stimulating) Abs in particular, is recommended for the rapid diagnosis, differential diagnosis, and management of patients with Graves hyperthyroidism, related thyroid eye disease, during pregnancy, as well as in Hashimoto thyroiditis patients with extra-thyroidal manifestations and/or thyroid-binding inhibiting immunoglobulin positivity. Abbreviations: Ab = antibody; AITD = autoimmune thyroid disease; ATD = antithyroid drug; cAMP = cyclic adenosine 3′,5′-monophosphate; ELISA = enzyme-linked immunosorbent assay; GD = Graves disease; GO = Graves orbitopathy; HT = Hashimoto thyroiditis; MAb = monoclonal antibody; TBAb = thyrotropin receptor blocking antibody; TBII = thyroid-binding inhibiting immunoglobulin; TSAb = thyrotropin receptor–stimulating antibody; TSB-Ab or TRBAb = thyrotropin receptor–stimulating blocking antibody; TSH = thyrotropin; TSH-R = thyrotropin receptor

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Lee, Jaekyoung, and Dong Cheol Lee. "Correlation between Changes in Thyroid Stimulating Immunoglobulin Levels and Chorioretinal Vessels in Thyroid Eye Disease." Journal of the Korean Ophthalmological Society 62, no. 5 (2021): 595–604. http://dx.doi.org/10.3341/jkos.2021.62.5.595.

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Penne, R. B. "Longitudinal Correlation of Thyroid-Stimulating Immunoglobulin With Clinical Activity of Disease in Thyroid-Associated Orbitopathy." Yearbook of Ophthalmology 2007 (January 2007): 177–78. http://dx.doi.org/10.1016/s0084-392x(08)70138-2.

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Dragan, Laryssa R., Stuart R. Seiff, and David Chung Lee. "Longitudinal Correlation of Thyroid-Stimulating Immunoglobulin With Clinical Activity of Disease in Thyroid-Associated Orbitopathy." Ophthalmic Plastic & Reconstructive Surgery 22, no. 1 (2006): 13–19. http://dx.doi.org/10.1097/01.iop.0000192649.23508.f7.

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Kraiem, Z., O. Sadeh, and E. Sobel. "Triiodothyronine and 3′,5′-cyclic AMP secretion by cultured human thyroid cells in response to thyrotropin and thyroid-stimulating immunoglobulin." Acta Endocrinologica 119, no. 4 (1988): 493–500. http://dx.doi.org/10.1530/acta.0.1190493.

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Abstract. We have established a relatively simple and sensitive system for measuring T3 as well as cAMP secretion using cryopreserved human thyroid cells in culture. We defined optimal culture conditions and characterized the system. T3 secretion from human thyrocytes (only 1 × 105 cells/well) could be stimulated in a time- and dose-dependent fashion by both TSH (doses as low as 10 mU/l) and thyroid-stimulating immunoglobulin to levels 5- to 10-fold above baseline. The response to the thyroid stimulating agents was preserved for at least 3 weeks. Experiments with inhibitors of iodothyronine synthesis (propylthiouracil and methimazole) indicated that the bulk of the TSH-stimulated T3 secretion measured apparently derives from de novo iodothyronine biosynthesis rather than preformed T3. We utilized the system to investigate some aspects in the regulation of human thyrocyte T3 and cAMP secretion. Maximum stimulation of the thyroid hormone was achieved at TSH doses capable of evoking a further rise in levels of cAMP. A rise in cAMP accumulation was observed as early as 15 min following exposure to TSH, whereas it took 1–4 days to detect a significant increase in T3 secretion. Within 6 h of incubation, the bulk of TSH-stimulated intracellular cAMP was found released into the medium. l-methyl-3-isobutylxanthine (MIX) caused a dose-related decrease (beyond 0.1 mmol/l MIX) in TSH-stimulated T3 secretion which contrasted with a concomitant expected increase in cAMP accumulation. Hence, as also observed in adrenal and testicular tissue, xanthines at high concentration seem to exhibit a dual action: potentiation of cAMP accumulation by inhibiting phosphodiesterase activity and a concomitant reduction of hormone formation.

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Rakover, Y., O. Sadeh, E. Sobel, A. Shneyour, and Z. Kraiem. "A case of transient hypothyroidism: Sequential serum measurements of autoantibodies inhibiting thyrotropin-stimulated thyroid cAMP production in a neonate." Acta Endocrinologica 123, no. 1 (1990): 118–22. http://dx.doi.org/10.1530/acta.0.1230118.

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Abstract. Transient neonatal hypothyroidism has been observed in three successive offspring of a mother with autoimmune thyroiditis. Thyroxine replacement therapy was initiated in a 23-year-old woman with overt clinical and laboratory findings of non-goitrous primary hypothyroidism. While on such treatment, she gave birth to three infants manifesting hypothyroidism immediately after birth. The neonates were treated with thyroxine replacement therapy which was discontinued in the three siblings at ages 2½ years, 3½ years, and 13 months. Continuous observation following cessation of therapy revealed clinical and biochemical euthyroidism in the children. Thyroid scanning during the neonatal period in the first child failed to identify functional thyroid tissue, suggesting thyroid agenesis, whereas thyroid scan performed on subsequent follow-up revealed a normal gland. Sequential serum measurements of autoantibodies directed towards the thyrotropin receptor were made in the mother and third child by a cAMP bioassay. High titres (five-six fold above normal) of blocking antibodies (tested by measuring the inhibition of TSH-stimulated cAMP production of cultured human thyroid cells by serum immunoglobulin preparations) were present in the mother and newborn 10 days after birth. The levels remained persistently high in the mother, whereas they declined and were undetectable in the child at four months. Thyroid-stimulating immunoglobulin was absent in both mother and child. The data are compatible with transient neonatal hypothyroidism caused by transplacental transfer of antibodies which block thyroid response to TSH. The half-life of the maternally-derived blocking antibody in the infant was estimated as 1-2 months. This is the first report on sequential serum measurements and estimate of half-life of the blocking antibodies performed by a cAMP bioassay (using thyroid cells of human origin). Unlike the radioreceptor assay employed so far in such cases, this assay can distinguish between stimulating and blocking TSH receptor antibodies.

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Gafny, Mira, Chava Ben-David, Nava Sirkis, Amirav Gordon, and Jack Gross. "The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes." Acta Endocrinologica 127, no. 2 (1992): 161–67. http://dx.doi.org/10.1530/acta.0.1270161.

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The purpose of these studies was to examine whether thyroid stimulating antibodies in Graves' patients could arise as auto-antiidiotypic antibodies to endogenous anti-TSH antibodies. The model system chosen was the thyroidectomized mouse, exhibiting an elevated level of endogenous, circulating TSH. Mice were thyroidectomized by 131I administration. Sera samples were drawn 1 to 14 months later. The following activities were measured in the immunoglobulin (Ig) fractions prepared: (a) TSH binding by elisa techniques, (b) iodide pump activity (as measured by 99mTcO4 uptake) and (c) increased [3H]thymidine incorporation into the DNA of FRTL-5 cells. TSH binding Igs were detected in 29/98 mice thyroidectomized for 7–14 months. Stimulation of technetium uptake was observed in 59/110 mice and stimulated labeled thymidine uptake in 37/102 mice, beginning eight and nine months after thyroidectomy, respectively. Of the positive animals, 51 showed a single stimulating activity. The incidence and the serum titers of Igs that stimulate technetium uptake increased significantly with time. Indeed, in the group tested 14 months post-thyroidectomy, 75% of the sera were positive for this antibody with a mean titer eightfold higher than the controls. Hybridomas were prepared from the spleen lymphocytes of thyroidectomized mice. Of these, 18 produced 99mTcO4 uptake stimulating Igs, 12 [3H]thymidine-uptake stimulating Igs and 18 TSH binding Igs. Most of the hybridomas secreted Igs with a single bioactivity. One monoclonal antibody was isolated which neutralized the bioactivity of bTSH on FRTL-5 cells. 99mTcO4 uptake was decreased by 50% and [3H]thymidine uptake was virtually abolished. These results suggest that the hypothyroid mouse can develop anti-TSH antibodies and thyroid-stimulating antiidiotypic antibodies by an autoimmune process.

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Ortiz, Yineli, Alegyari Figueroa Cruz, Luis Norberto Madera Marin, Gabriel Mora, Angela Torres, and Jose M. Garcia-Mateo. "Hyperthyroidism Times 2: Dual Cause of Thyroid Hormone Excess." Journal of the Endocrine Society 5, Supplement_1 (2021): A935. http://dx.doi.org/10.1210/jendso/bvab048.1911.

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Abstract The most common etiology of Hyperthyroidism is due to circulating antibodies that are directed against the thyroid-stimulating hormone (TSH) receptor, known as Grave’s Disease (GD). Another cause is an autonomously functioning thyroid nodule over-producing hormones or Toxic Adenoma. The mechanism of these two pathologies are very distinct, but the question that arises is, can they coexist? This is a case of 44-year-old female who comes to the clinic referred by her ophthalmologist after been diagnosed with severe thyroid-associated orbitopathy currently on steroid therapy. Thyroid ultrasound has done previously showed enlarged homogenous thyroid gland with a single isoechoic nodule of 2.2x1.6x1.9cm with faint peripheral calcifications and vascularity. The patient was presenting with palpitations, heat intolerance, sweating, and discriminatory features such as double vision and left eye exophthalmos. On physical examination, there was no goiter or palpable thyroid nodules, but it was remarkable for left eyelid lag retraction and mild proptosis. Evaluation showed clinical and biochemical hyperthyroidism with TSH: 0.068 mU/ml (n:0.5-5.0mU/ml), FT4: 1.39ng/dl (n:0.87-1.85ng/dl), TSH receptor antibody: &lt;1.10IU/L and thyroid-stimulating immunoglobulin: 0.54IU/L (borderline high). The patient was placed in antithyroid drugs and B-blockers for disease control. Afterward, the patient underwent a thyroid uptake scan reporting toxic adenoma on the left lobe, however even when the biochemical workup of GD is inconclusive, patient clinical findings are highly suggestive of it. Due to the risk of worsening orbitopathy with radioactive iodine therapy, patient was referred for surgical excision of toxic adenoma and total thyroidectomy was decided since residual thyroid tissue may expose the patient to circulating thyroid-stimulating immunoglobulin leading to hyperthyroidism recurrence and put her at risk of associated thyroid excess detrimental complications. Surgical specimen gross pathology biopsy reported the thyroid gland with hyperplastic changes of Grave’s Disease. Severe thyroid-associated orbitopathy was managed with decompression surgery but did not improve, for which an alternative therapeutic approach is decided with novel immunomodulatory agent and recent approved therapy, Teprotumumab. A monoclonal antibody that works on TSHR/IGF-1R signaling complex involved in Thyroid Eye Disease. Is unusual to see two different superimposing thyroid pathologies, but disease presentations can be atypical and can be present concomitantly. In this scenario, several factors must be taken into consideration when choosing an adequate therapy approach. Our case is an example that we need to individualize management options based on guidelines recommendations, patient’s clinical settings and decreased risks of future complications.

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