This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SARNE, D. H. Articles by LINARELLI, L. G. Search for Related Content PubMed PubMed Citation Articles by SARNE, D. H. Articles by LINARELLI, L. G.

A New Inherited Abnormality of Thyroxine-Binding Globulin (TBG-San Diego) With Decreased Affinity for Thyroxine and Triiodothyronine^*

Thyroid Study Unit, Departments of Medicine and Pediatrics, University of Chicago (D. H. S., S. R.) Chicago Illinois 60637
White Memorial Medical Center (J. C. N.) Los Angeles, California 90033
Children's Hospital (L. G. L.) San Diego, California 92123

Address all correspondence and requests for reprints to: David H. Same, M.D., Section of Endocrinology, Department of Medicine (M/ C 787), University of Illinois, 840 SouthWood, Chicago, Illinois 60612.

Evaluation of a family in which males were clinically euthyroid despite having low serum total T₄ (TT₄) and free T₄ index (FT₄I) values revealed the presence of a new inherited T₄-binding globulin (TBG) variant (TBG-San Diego). Two brothers had low TT₄ (39 and 49 nmol/L; normal range, 64–154 nmol/L) and FT₄I (4.0 and 4.4; normal range, 6.0–10.5) values, while their grandfather, despite treatment with T₄, had a low TT₄ (53 nmol/L) and normal FT₄I (7.2) in the presence of suppressed TSH (<0.1 mU/L). When measured by RIA, the mean TBG concentration (TBG-RIA) of the three affected males was low normal [160 ± 56 (±SD) nmol/L; normal range, 151– 253]. Their TBG-binding capacity measured by a T₄ binding assay at saturation (TBG-CAP) was similar, giving a mean TBGRIA/ TBG-CAP ratio not significantlydifferent from 1.0. In these males, the TBG affinity for T₄ (K_a = 0.48 ± 0.04 x 10¹⁰ mol^–1) was less than that in subjects with the common type TBG (TBG-C; K_a = 1.10 ± 0.14 x 10¹⁰ mol^–1; P< 0.0001) and similar to that in Aboriginal males from Australia with the variant TBG-A (0.52 ± 0.10 x 10¹⁰ mo^–1). TBG affinity for T₃ in the affected males (K_a = 0.68 ± 0.05 x 109 mol^–1) was less than that in subjects with TBG-C (1.39 ± 0.12 x 10⁹ mol^–1; P < 0.00001), but greater than that in males with TBG-A (0.44 ± 0.03 x 10⁹ mol^–1; P < 0.0005). The rate of TBG denaturation at 56 C was increased in the affected males (t = 28.4 and 26.9 min) compared to that in subjects with TBG-C (t = 54.1 ± 7.1 min), but was lower than that in males with TBG-A (t = 20.8 ± 1.9). A value intermediate between those in affected males and normal subjects was found in serum from an obligatory heterozygote.Microheterogeneity on isoelectric focusing was normal.

The exact nature of this structural TBG variant is not yet known. The presence of a TBG mutant should be considered in healthy, clinically euthyroid patients with low serum TT₄ and free T₄ index values, especially when such low values are found in several members of the same family.

^* This work was supported in part by USS Grants DK-15070 and DK-40181.

Received May 17, 1988.

This article has been cited by other articles:

				O. E. Janssen, S. T. Astner, H. Grasberger, S. K. Gunn, and S. Refetoff Identification of Thyroxine-Binding Globulin-San Diego in a Family from Houston and Its Characterization by in Vitro Expression Using Xenopus Oocytes J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 368 - 372. [Abstract] [Full Text]