Congenital Hypothyroidism Associated with Thyrotropin Unresponsiveness and Thyroid Cell Membrane Alterations

Abstract
TSH stimulates thyroid functions via the TSH receptor-adenylate cyclase (AC) system. Congenital alterations of this system might be expected to result in thyroid dysfunction. This report concerns a 17-yr-old boy in whom congenital hypothyroidism was noted at the age of 18 months. The thyroid gland was not enlarged and was in a normal position, as confirmed by scintiscan. Treatment with dessicated thyroid allowed satisfactory development. The following investigations were performed 1 month after the treatment was stopped. Serum levels were: T3≤5 ng/dl; T4 ≤1 μg/dl;thyroglobulin,≤l ng/ml; and TSH, 385 μU/ml by RIA and 400 μU/ml by the McKenzie bioassay. 131I thyroidal uptake studies showed that the increase over the basal uptake was higher after dibutyryl cAMP administration (0.1 mg/kg-min for 1 h) than after TSH stimulation, which gave essentially noresponse. Light microscopy of a biopsy specimen of the isthmus obtained under local anesthesia showed a heterogeneous cellular activity; the follicles were of small and medium sizes, with follicular lumina generally devoid of colloid. Electron microscopy showed extensive increases of the surface and width of the basal plasma membrane and basal lamina. The characteristics of the membranes from the thyroid specimen were compared with standard values obtained with normal thyroid membranes. The TSH receptor as well as the basal and NaF-stimulated TSH receptor-adenylate cyclase system activity were normal. However, TSH stimulation of the TSH receptoradenylate cyclase system was markedly decreased, suggesting a coupling abnormality between the TSH receptor and the TSH receptor-adenylate cyclase system.