Human thyroid stimulating activity and clinical state in antithyroid treatment of juvenile Graves' disease

Abstract

Human thyroid stimulating activity in 37 patients with juvenile hyperthyroidism was studied during the course of antithyroid drug treatment. Observation periods varied from 6 months to 6 years (average 3 years). The existence of human thyroid stimulator (HTS) in their sera was determined by triiodothyronine (T3) release from resected thyroid adenomas. A measurement of T3 above the control value of 140% was judged to be positive. Before treatment, 25 of the 28 patients with Graves' disease had HTS in their sera, one of the 7 patients with Hashimoto's thyroiditis had HTS, and none of the 19 normal children had HTS in their sera. During the therapy, 7 of 18 Graves' patients had HTS. After cessation of the therapy, 9 of 22 patients remained HTS-positive, and 8 of the 9 patients with positive HTS relapsed within 6 months, whereas in 13 HTS-negative patients, 3 escaped and 10 remained in remission. There was no significant correlation between human thyroid stimulating activity (HTSA) and the following: serum T3 concentration, 131I-thyroidal uptake, TSH responsiveness to TRH and antithyroid antibody titre. These results indicate that (1) almost all patients with Graves' disease have HTS when they are ina state of hyperthyroidism, (2) HTS tends to disappear with the clinicial remission, but its persistence seems to predict relapse in the future, and (3) routine laboratory tests cannot serve as alternative to HTS.

Immunological Parameters in Graves’ Disease: Are They Useful for Indication and Monitoring of Antithyroid Drug Treatment?

“…This led to the conclusion that only elevated end-treatment TSAb levels have predictive value. A similar conclusion was reached by others [6,7,10,11,15,16]. It should be remembered that the significance of low or undetectable levels of any parame ter is dependent on the sensitivity of the determination of this parameter.…”

The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

“…A similar mechanism may partially counter the effect of thyroid stimulating antibodies (TSAb) in Graves' disease, in which intrathyroidal TNF also occurs (Zheng et al 1992, Aust et al 1996. This would contribute to the lack of correlation between the level of TSAb and the severity of clinical hyperthyroidism (Takata et al 1980).…”

Regulation and tissue distribution of the human sodium iodide symporter gene

“…In the present study, IL-1, TNFa and IFNg all inhibited TSH-stimulated hNIS gene expression and iodide uptake in thyrocyte cultures. Furthermore, the lack of correlation between the level of TSAb and the severity of clinical hyperthyroidism in Graves' disease (Takata et al, 1980) could be attributable in part to the inhibitory effects of cytokines (commonly detected Graves' tissue) on hNIS mRNA expression. IL-1, TNFa and IFNg are produced by the inflammatory infiltrate and TFC in autoimmune thyroid disease (Del Prete et al, 1987;Zheng et al, 1992;Watson et al, 1995;Ajjan et al, 1996) and may therefore play a role in autoimmune hypothyroidism by downregulating hNIS mRNA expression.…”