Thyroid dysfunction in pseudohypoparathyroidism: evidence for a coupling failure of the thyrotropin receptor adenylate cyclase system associated with morphological abnormalities of the thyroid follicles

Abstract

A case of pseudohypoparathyroīdism type I in a 17 years old female coexisting with thyroid dysfunction meeting all the criteria for thyrotropin (TSH) insensitivity is studied.Thyroid gland was not enlarged as confirmed by scintiscan. Laboratory findings included : high basal concentration of TSH (17-19.2 μU/ml), normal values of circulating thyroīd hormones (T4 : 6.3 μg/ml, T3 : 98 ng/ml) exagerated response of TSH to thyrotropin releasing hormone (TRH) (200 μg) and low 131 I thyroīd uptake with impaired response to exogenous TSH (bovine TSH 10 UI daily for 6 days). After T3 therapy (50 μg per day for 2 months), serum TSH decreased to the normal range and its response to TRH almost normalize. Tests for circulating thyroid antibodies were negative. Light microscopy of a biopsy specimen showed a heterogenous cellular activity with large follicles with abundant colloid and flattened lining cells. The electron microscopy showed deep infoldings of the basal membrane. The TSH receptor as well as the basal and NaF stimulated adenylate cyclase (AC) of thyroid membranes were found to be normal, but the ability of TSH to stimulate AC was markedly decreased suggesting a coupling abnormality between the TSH receptor and AC. This abnormality could cause the resistance of target organs in pseudohypoparathyroīdism to parathyroid hormone.