T3 releasing activity by Graves' sera from Graves' thyroid in vitro

Abstract

Abstract. The insensitivity of Graves' thyroid to stimulation of cAMP formation by TSH as well as Graves' immunoglobulins in vitro is well known. The present study was performed to find out Graves' sera which may induce a final activation i.e. stimulation of T3 release in Graves' thyroid slices despite this insensitivity of tissue and to characterize determinants responsible for the efficiency of those sera. Out of 20 sera from patients with active untreated Graves' disease 6 were found to stimulate T3 release from Graves' thyroid in vitro. These 6 sera were effective in stimulating different Graves' glands, irrespective of pretreatment with propranolol, thiamazole (methimazole) or thiamazole plus iodine. In contrast, a significant response to bTSH was not observed in any Graves' gland. For comparison, 17/20 of the same sera were able to stimulate T3 release when tested on human goitrous thyroid. Sera which stimulated Graves' slices revealed no higher stimulating activities in goitrous tissue than serum samples which did not. All sera were additionally assessed for TSH binding inhibiting immunoglobulins in a radioreceptor assay. Remarkably, Graves' thyroid stimulating sera had a low or absent TSH binding inhibiting activity. Thus, hormone release from Graves' thyroid in vitro – in contrast to that from goitrous tissue – could only be activated by a minority of Graves' sera. These Graves' thyroid stimulating sera could be characterized to contain a selected spectrum of biologically active antibodies with a high TSH agonistic potency stimulating in the presence of a negligible TSH binding inhibiting activity. We conclude the qualitative composition of the antibody spectrum in the individual sera, such as the occurrence of so-called 'TSH superagonists', rather than the height of antibody titre as determined by various methods seems to be relevant for their Graves' thyroid stimulating potency.