Familial resistance to thyroid hormone associated with decreased transport across the plasma membrane.

Resistance to thyroid hormone associated with a defect in hormone transport across the plasma membrane occurred in a 74-year-old eumetabolic woman. She had marked elevations in the serum levels of total thyroxine (T4), free T4, and reverse triiodothyronine (rT3). Levels of T3 were only minimally increased. The hyperthyroxinemia was thyrotrophin (TSH) dependent, but was not due to an alteration in the binding of T4 to serum proteins. Refractoriness to thyroxine was only partial, as indicated by the increase in the basal metabolic rate and suppression of the response of TSH to thyrotrophin-releasing hormone (TRH) after the administration of L-thyroxine, 600 micrograms daily, for 3 weeks. The basic abnormality involved a selective decrease of T4 plasma membrane transport shown by in-vitro studies of erythrocytes. Screening of family members showed similar biochemical abnormalities in two other relatives. In this familial syndrome characterized by eumetabolic hyperthyroxinemia, the alteration of thyroid hormone metabolism seems to involve primarily the partition of T4 between the intra- and extracellular spaces.