Journal of Clinical Endocrinology & Metabolism, Vol 49, 292-299, Copyright © 1979 by Endocrine Society

ARTICLES

Inherited abnormal thyroid hormone-binding protein causing selective increase of total serum thyroxine

WN Lee, MP Golden, AJ Van Herle, BM Lippe and SA Kaplan

A 9-yr-old boy is described in whom increased serum T4 concentration, increased T3 uptake, and increased free T4 index were associated with a euthyroid clinical state with normal total serum T3. T4-binding globulin (TBG), measured by RIA, was decreased. Reverse flow paper electrophoresis of serum proteins after reaction with radioactively labeled T4 demonstrated increased binding of T4 to a protein with electrophoretic mobility corresponding to albumin. Displacement of serum protein-bo-nd [125I]T4 activity by increasing concentrations of T4 revealed the presence of a low affinity, high binding capacity system with an association constant similar to that of T4-binding prealbumin. This low affinity binding protein cochromatographed with TBG on a DEAE-Sephadex column which normally separates TBG from T4- binding prealbumin. At free T4 concentrations equivalent to those present in the plasma of normal individuals, the T4 bound to free ratio is higher in the patient than in normals and the total serum T4 level is increased in the presence of normal free T4 concentrations. The relative affinity of this abnormal T4-binding protein for T3 is low compared to that of TBG. The patient's father had the same abnormal binding protein, which was not found in his mother or fraternal twin brother. These data suggest an autosomal dominant mode of inheritance of an aberration leading to synthesis of a new protein instead of normal TBG. The new protein is different from TBG in electrophoretic mobility, T4 and T3 binding, and antigenic properties.

This article has been cited by other articles:

				P R Desai, A P Lipscomb, and J Slater Familial dysalbuminaemic hyperthyroxinaemia, a thyroid trap Arch. Dis. Child., December 1, 2004; 89(12): 1161 - 1162. [Full Text] [PDF]

				R. M. Ortiz, C. E. Wade, and C. L. Ortiz Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2001; 280(3): R790 - R795. [Abstract] [Full Text] [PDF]

				S. Pannain, M. Feldman, U. Eiholzer, R. E. Weiss, N. H. Scherberg, and S. Refetoff Familial Dysalbuminemic Hyperthyroxinemia in a Swiss Family Caused by a Mutant Albumin (R218P) Shows an Apparent Discrepancy between Serum Concentration and Affinity for Thyroxine J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2786 - 2792. [Abstract] [Full Text]

				C. E. Petersen, C.-E. Ha, K. Harohalli, D. S. Park, J. B. Feix, O. Isozaki, and N. V. Bhagavan Structural Investigations of a New Familial Dysalbuminemic Hyperthyroxinemia Genotype Clin. Chem., August 1, 1999; 45(8): 1248 - 1254. [Abstract] [Full Text] [PDF]

				T. Sunthornthepvarakul, S. Likitmaskul, S. Ngowngarmratana, K. Angsusingha, S. Kitvitayasak, N. H. Scherberg, and S. Refetoff Familial Dysalbuminemic Hypertriiodothyroninemia: A New, Dominantly Inherited Albumin Defect J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1448 - 1454. [Abstract] [Full Text]

				N. Wada, H. Chiba, C. Shimizu, H. Kijima, M. Kubo, and T. Koike A Novel Missense Mutation in Codon 218 of the Albumin Gene in a Distinct Phenotype of Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Kindred J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3246 - 3250. [Abstract] [Full Text] [PDF]

				C. E. Petersen, C.-E. Ha, D. M. Jameson, and N. V. Bhagavan Mutations in a Specific Human Serum Albumin Thyroxine Binding Site Define the Structural Basis of Familial Dysalbuminemic Hyperthyroxinemia J. Biol. Chem., August 9, 1996; 271(32): 19110 - 19117. [Abstract] [Full Text] [PDF]