Studies on the nature of plasma thyroid stimulating activity in hyperthyroidism.

Abstract

SummaryPrevious reports from this and other laboratories indicate the importance of the activity of abnormal plasma long‐acting thyroid stimulator (LATS) characteristic of thyrotoxicosis in relation to the various clinical features of the disease.Studies on the nature of this agent have now been carried out by comparison of its thyroid stimulating activity in the 131I‐labelled mouse with that of bovine pituitary thyrotropic stimulating hormone (TSH) and plasma from hypothyroid patients in which an excess of pituitary TSH has been demonstrated, as well as by chemical studies.A short‐acting response with a maximum at three hours is characteristic of pituitary TSH. A long‐acting response with maximum at eight hours or longer is characteristic of LATS. However, in the present study a long‐acting response with a maximum at eight hours has been demonstrated after multiple injections of bovine TSH. A long‐acting response can also be produced by injecting bovine TSH after it has been mixed with an appropriate concentration of rabbit antiserum to bovine TSH. These findings indicate that the pattern of response is not necessarily a distinguishing feature differentiating LATS and TSH.In contrast to the activity of TSH, LATS activity is unaffected by an antiserum to bovine TSH prepared in the rabbit. However, LATS activity is diminished by mixing it with an antiserum to human 7S gamma globulin prepared in the sheep, which in turn fails to affect the thyroid stimulating activity of bovine TSH on plasma from hypothyroid patients. These findings indicate that there is a distinct immunological difference between LATS and TSH.Large plasma samples from three thyrotoxic patients have been subjected to gel filtration (with the use of a “Sephadex” G‐200 apparatus). LATS activity was mainly confined to the 7S gamma globulin peak; although there was a degree of overlap into the macroglobulin and albumin peaks, starch gel electrophoresis revealed 7S gamma globulin was invariably a component of these fractions. Further purification was achieved by DEAE‐ “Sephadex” chromatography. This produced three fractions—the first two were found to have LATS activity and to contain 7S gamma globulins on starch gel electrophoresis, while the third contained beta globulins and albumin but was devoid of 7S gamma globulin and was inactive in the mouse assay.These findings are consistent with the findings of other laboratories, in that they clearly indicate that LATS belongs to the 7S gamma globulins and is therefore probably an antibody. These data strongly support clinical evidence indicating the importance of immunological mechanisms in the pathogenesis of hyperthyroidism. The possibility of hyperthyroidism being an autoimmune disorder is discussed.