Thyroid-stimulating hormone (TSH) receptor antibodies and antibodies stimulating adenyl cyclase in relatives from two families with a high prevalence of Graves' hyperthyroidism: A ten-year follow-up study

ABSTRACT Previous studies have shown that freezing and thawing of human thyroid homogenates releases a water-soluble substance which reversibly binds to TSH-receptor antibodies. This substance has been designated long-acting thyroid stimulator absorbing activity (LAA). We now describe a new method for measuring LAA based on the TSH-receptor assay and application of the technique to the study of LAA. Our results indicate that LAA is a heat-labile glycoprotein which co-elutes with haemoglobin on gel filtration. Furthermore, LAA is retarded by columns of Sepharose–TSH but not by Sepharose coupled to human chorionic gonadotrophin, normal immunoglobulin G or bovine serum albumin, suggesting that LAA contains a binding site for TSH as well as for TSH-receptor antibodies. It would seem therefore that LAA is a water-soluble fragment of the TSH receptor possibly resulting from proteolytic cleavage of the receptor at a site close to the cell surface. J. Endocr. (1984) 100, 113–118

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Anti-thyroid stimulating hormone (TSH) receptor antibodies (anti-TBII)

10.1007/springerreference_37541 ◽

2011 ◽

Keyword(s):

Thyroid Stimulating Hormone ◽

Tsh Receptor ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies ◽

Stimulating Hormone

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Transient high thyroid stimulating hormone and hypothyroidism incidence during follow up of subclinical hypothyroidism

Endocrine Regulations ◽

10.2478/enr-2021-0022 ◽

2021 ◽

Vol 55 (4) ◽

pp. 204-214

Author(s):

Munir Abu-Helalah ◽

Hussam Ahmad Alshraideh ◽

Sameeh Abdulkareem Al-Sarayreh ◽

AbdelFattah Al-Hader

Keyword(s):

Subclinical Hypothyroidism ◽

Screening Program ◽

Thyroid Stimulating Hormone ◽

Overt Hypothyroidism ◽

Thyroid Peroxidase ◽

Free Triiodothyronine ◽

High Prevalence ◽

Levothyroxine Replacement ◽

Stimulating Hormone

Abstract Objectives. Given the high prevalence of subclinical hypothyroidism (SCH), defined as high thyroid stimulating hormone (TSH) and normal free thyroxine (FT4), and uncertainty on treatment, one of the major challenges in clinical practice is whether to initiate the treatment for SCH or to keep the patients under surveillance. There is no published study that has identified predictors of short-term changes in thyroid status amongst patients with mild elevation of TSH (4.5–10 mIU/L). Subjects and Results. A cohort study was conducted on patients with SCH detected through a general population screening program, who were followed for six months. This project identified factors predicting progression to hypothyroid status, persistent SCH and transient cases. A total of 656 participants joined the study (431 controls and 225 were patients with SCH). A part of participants (12.2%) developed biochemical hypothyroidism during the follow-up, while 73.8% of the subjects became euthyroid and the remained ones (13.4%) stayed in the SCH status. The incidence of overt hypothyroidism for participants with TSH above 6.9 mIU/L was 36.7%, with incidence of 42.3% for females. Anti-thyroid peroxidase antibodies (TPO) positivity is an important predictor of development of hypothyroidism; however, it could be also positive due to transient thyroiditis. Conclusions. It can be concluded that females with TSH above 6.9 mIU/L, particularly those with free triiodothyronine (FT3) and FT4 in the lower half of the reference range, are more likely to develop biochemical hypothyroidism. Therefore, it is recommended to give them a trial of levothyroxine replacement. It is also recommended to repeat TSH after six months for male subjects and participants with baseline TSH equal or less than 6.9 mIU/L.

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OR18-03 Functional TSH Receptor Antibodies Are a Biomarker for Graves’ Disease - a Prospective Trial

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.140 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

George Jean Kahaly ◽

Tanja Diana ◽

Michael Kanitz ◽

Paul D Olivo

Keyword(s):

Predictive Value ◽

Prospective Trial ◽

Tsh Receptor ◽

Luciferase Expression ◽

Graves Disease ◽

Free T4 ◽

Baseline Serum ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies

Abstract Objective We aimed to evaluate the clinical utility and predictive value of stimulatory (TSAb) and blocking (TBAb) TSH receptor antibodies in the management of Graves’ disease (GD). Methods Hundred well-defined, consecutive, unselected, untreated hyperthyroid patients with GD were enrolled in a prospective two-year trial. Methimazole (MMI) was administered for 24 weeks according to baseline serum concentrations of free T3/free T4. Starting dose was 5–30 mg/day. Through a titration regimen, this dose was respectively tapered or increased at each subsequent study visit as the patient became euthyroid or remained hyperthyroid. Goals of therapy were to maintain normal fT4 and TSH levels. MMI therapy was stopped at week 24. The main outcome measure was clinical response versus non-response to a 24-week MMI treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96. TSAb was reported as percentage of specimen-to-reference ratio (cut-off SRR% <140). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off >40% inhibition). Results Forty-four patients responded to MMI of whom 43% had Graves’ orbitopathy (GO) while 56 were non-responders (66% with GO, p<0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibiting immunoglobulins (TBII) differentiated between thyroidal GD only versus GD+GO (p<0.001). Further, at baseline responders demonstrated marked differences in diluted TSAb titers compared with non-responders (p<0.001). All patients with a TSAb dilution titer above three did not respond to MMI treatment. In contrast, TBII dilution titers did not differentiate between responders and non-responders to MMI and serum samples became TBII negative already at low dilutions. During treatment, serum TSAb levels decreased markedly in responders (p<0.001) but increased in non-responders (p<0.01). In contrast, TBII strongly decreased in non-responders (p=0.002). All non-responders at week 24 and/or those who relapsed during the 72-week follow-up were TSAb positive at week 24. A shift from TSAb to TBAb was noted in eight patients during treatment and/or follow-up and led to remission. Conclusions Serum TSAb levels are a biomarker for and mirror severity of GD. Their increase during MMI treatment is a marker for on-going disease activity. TSAb dilution analysis had additional predictive value.

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SAT-410 Long Term Evaluation of TSH Receptor Antibodies and Thyroid Stimulating Immunoglobulin After Radioiodine Therapy for Thyrotoxicosis

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1301 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Suemi Marui ◽

Bruna Irigoitia ◽

Aline Lenczuk ◽

Nelisa Helena Rocha ◽

Luciana Pinto Brito ◽

...

Keyword(s):

Tsh Receptor ◽

Subclinical Hyperthyroidism ◽

Degree Correlation ◽

Analytical Range ◽

One Year ◽

Roche Diagnostics ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies

Abstract Background Radioioactive iodine therapy (RAI) is an excellent choice to treat thyrotoxicosis, particularly Graves′ disease (GD) patients. After RAI therapy, it is well known that TSH receptor antibodies (TRAb) rise in GD patients and autoimmunity can eventually surge in patients with toxic multinodular or uninodular goiter (TNG). Recently, biological assay distinguishes stimulating TRAb, called thyroid stimulating immunoglobulin (TSI) bringing a new perspective on follow-up, as TSI is involved in Graves′ pathogenesis of persistent thyrotoxicosis and ophthalmopathy after RAI therapy. Objective Analyze TRAb and TSI levels after 6 and 12 months of RAI therapy for thyrotoxicosis. Patients and Methods Patients were evaluated prospectively immediately before and 6 to 12 months after RAI therapy for thyrotoxicosis. Thyroid hormones were all measured using immunoassays (Roche Diagnostics Ltd). TRAb was analyzed by Elecsys Anti-TSHR assay (Roche Diagnostics, Germany) and was considered negative if < 1.75 IU/L (analytical range: 0.3 to 40 IU/L). TSI was measured by Immulite TSI assay (Siemens Healthcare, UK) and was considered negative if < 0.55 IU/L (analytical range: 0.1 to 40 IU/L). Clinical data and comparison of assays were analyzed by SPSS and MedCalc softwares. Results From 2017 to 2019, 54 patients (44 females) were prospectively evaluated after 6 months of RAI therapy, mostly because of GD (40 patients). A high degree correlation was observed between TRAb and TSI (Spearman correlation coefficient =0.875; p < 0.0001, 95% CI 0.784 to 0.929). After 6 months, among patients with GD, 5/40 patients had negative TRAb levels and 2/40 had negative TSI levels, whereas all TNG patients had both negative TRAb and TSI levels. In GD group, 4 patients showed subclinical hyperthyroidism and relapse occurred in 1 case. All patients with TNG showed euthyroidism status with or without thyroid medications. One year after RAI therapy, we evaluated 32 patients (23 GD) and 4/23 of GD had negative TRAb levels and only 1/23 had negative TSI level. All patients with TNG had negative TRAb and TSI levels after one year fo treatment. Subclinical hyperthyroidism was diagnosed in 5 patients with GD but none with TNG. Along follow-up, 4 patients with clinical diagnosis of GD with TRAb negative before RAI therapy became positive after RAI therapy and 3 patients became TSI positive. Conclusions Long term after RAI therapy for thyrotoxicosis treatment, TRAb and TSI are still positive in most GD patients and few cases can even turned to positive levels. Nevertheless, in TNG patients, RAI therapy is safe as TRAb and TSI maintained at negative concentrations and thyrotoxicosis is properly resolved.

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