Defective thyroid hormone action in fibroblasts cultured from subjects with the syndrome of resistance to thyroid hormones.

Two preadolescent girls and their mother with the syndrome of central and peripheral resistance to thyroid hormones are reported. The sisters had goiters, high radioiodine uptakes, high plasma levels of thyroid hormones, normal TSH levels, and brisk increases in TSH after TRH administration, but had no clinical evidence of thyrotoxicosis. The mother, who had undergone partial thyroidectomy and radioiodine therapy, presented with mild hypothyroid symptoms, normal thyroid hormone levels, and a high TSH level. On T4 treatment, her TSH fell toward normal, and thyroid levels became elevated without thyrotoxic symptoms. Special studies were performed with cultured skin fibroblasts. T3 stimulated low density lipoprotein receptor activity in cells from normal subjects, but failed to do so in fibroblasts form the three patients, indicating that their fibroblasts had a defective response to T3. However, after incubation of fibroblasts with labeled T3, no abnormalities in the binding capacity or affinity of nuclei were observed. These findings suggest that in this family, the thyroid hormone resistance demonstrable in vivo and in vitro results from a cellular defect at a site other than at the nuclear binding site.