Thyrotropin and Long-Acting Thyroid Stimulator Assays in Thyroid Disease

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Abstract
Assays for thyrotropin (TSH) and long-acting thyroid stimulator (LATS) have been carried out on sera and other biological material from subjects with and without thyroid disease. Circulating TSH has been detected only in hypothyroid patients and LATS has been found virtually only in treated or untreated patients with toxic diffuse goiter, a minority of those without exophthalmos, and the majority of those with exophthalmos. All of these with pretibial myxedema had positive assays. Correlation of LATS with exophthalmos was qualitative rather than quantitative, its level being best correlated with the presence of pretibial myxedema. Furthermore, only one of 7 subjects with exophthalmic ophthalmoplegia without history of thyrotoxicosis had detectable LATS activity in the serum. The incidence of positive LATS assays in patients treated with radioiodine (I131) was higher than in those untreated or treated with other therapeutic maneuvers. Serial assays disclosed that in some instances the administration of 1131 was followed by a transient rise in the level of LATS. Concentration of plasma proteins fractionated by gel-filtration allowed the detection of LATS in pooled plasma from 2 subjects with negative direct assays. No significant thyroid-stimulating activity has been detected in extracts of pretibila myxedema, retro-orbital, liver and thyroid tissue from patients with moderate or high serum LATS activity. Similarly, negative results have been obtained with specimens of saliva and urine concentrates. Recovery studies showed no evidence of urinary inhibitors to TSH and LATS. Chromatography showed that the release of hormoneal iodine produced in the mouse by the injection of LATS (and TSH as well) is accompanied by the release of inorganic iodide. LATS and TSH did not stimulate significantly in vitro the oxygen consumption and the glucose metabolism in slices of human thyroid tissue obtained from a treated thyrotoxic patient. The biological activity of sera containing TSH and LATS was neither inactivated nor altered by incubation with slices and cell membranes of the toxic gland.