Role of Blocking TSH Receptor Antibodies on the Development of Hypothyroidism and Thyroid Atrophy in Primary Myxedema

Abstract

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<0.01) and TGBAb (r=0.618; p<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.

Thyrotropin Receptor Blocking Antibodies

“…Potent blocking type anti-TSHR-Ab was observed in the majority of patients with primary myxedema using a FRTL-5 cell-based bioassay in which the prevalence of TBAb in primary myxedema was 75% versus 0% in goitrous HT 66 67 . In line with this, inhibition of TSH-stimulated RAI uptake in FRTL-5 cells by crude Ig fractions was reported for patients with goitrous and atrophic HT as well as from patients with overt hypothyroidism 16 68 .…”

Severe Ascites with Hypothyroidism and Elevated CA125 Concentration: A Case Report

“…Cho et al evaluated blocking TSH receptor antibody levels in primary myxedema and goitrous Hashimoto's thyroiditis [16]. In their report, the incidence of TSH-binding inhibitor immunoglobulins (TBII), thyroid stimulation blocking antibody (TSBAb) and thyroid growth blocking antibody (TGBAb) in primary myxedema were high (53.6%, 75.0% and 65.2%, respectively).…”

Can Hashimoto's thyroiditis cause vertigo? [Czy choroba Hashimoto może być przyczyną zawrotów głowy?]

“…In the first stage of the disease, transient subclinical hyperthyroidism may occur due to the release of excess thyroid hormones from the damaged thyroid cells. The risk factors for HT include genetic and environmental factors such as impaired intake of iodine, iron, and selenium, chronic inflammation, and adverse effects of chemotherapeutic agents [20][21][22][23].…”

“…W pierwszym etapie choroby, na skutek uwalniania z uszkodzonych komórek tarczycy nad-REVIEW miernej ilości hormonów tarczycowych, może dojść do przemijającej, subklinicznej nadczynności tarczycy. Do czynników ryzyka choroby Hashimoto zalicza się uwarunkowanie genetyczne, czynniki środowiskowe, w tym zaburzenia spożywania jodu, żelaza i selenu, czy przewlekły stan zapalny jak również działania niepożądane leków (cytostatyków) [20][21][22][23].…”