Familial Resistance to Thyroid Hormone Associated with Decreased Transport Across the Plasma Membrane

doi:10.1059/0003-4819-98-6-904

Familial Resistance to Thyroid Hormone Associated with Decreased Transport Across the Plasma Membrane

JACOBO WORTSMAN, M.D.;
BHARTUR N. PREMACHANDRA, Ph.D.;
KELLEY WILLIAMS, B.S.;
KENNETH D. BURMAN, M.D.;
IAN D. HAY, M.B., Ph.D.; and
PAUL J. DAVIS, M.D.

Springfield, Illinois; St. Louis, Missouri; Washington, D.C.; Rochester, Minnesota; and Buffalo, New York

Abstract

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 thyrotrophinreleasing hormore (TRH) after the administration of L-thyroxine, 600 µg 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.

Article and Author Information

▸From the Department of Medicine, Southern Illinois University School of Medicine, Springfield, Illinois; the Veterans Administration Medical Center, Jefferson Barracks and Washington University, St. Louis, Missouri; the Walter Reed Army Medical Center, Washington, D.C.; the Mayo Clinic, Rochester, Minnesota; and the State University of New York, Buffalo, New York.
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
▸Requests for reprints should be addressed to Jacobo Wortsman, M.D.; Department of Medicine, Southern Illinois University School of Medicine, P.O. Box 3926; Springfield, IL 62708.