IMPAIRED CYCLIC-AMP RESPONSE TO THYROTROPIN IN CONGENITAL HYPO-THYROIDISM WITH THYROGLOBULIN DEFICIENCY

A 19 yr old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (thyroxine, 2.8 .mu.g/100 ml) and T3 (triiodothyronine, 16 ng/100 ml) with a high level of TSH (thyrotropin, 52 .mu.U[units]/ml) that rose to 192 .mu.U/ml after TRH [thyroliberin]. 131I uptake by the thyroid was normal (41.5% at 24 h) and did not show a normal increase after exogenous TSH administration (49.5% at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low I- trapping by the thyroid slices and no formation of cyclic[c]AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cAMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. The fundamental defect in this gland is apparently an impaired generation of cAMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate T4 and T3 synthesis.