Thyroxine-binding Globulin (TBG), Serum

Distinguish between high T4 levels due to hyperthyroidism and due to increased binding by TBG in euthyroid individuals who have normal levels of free hormones; document cases of hereditary deficiency or increase of TBG; work-up of thyroid disease. In patients with low T4, high T3 (uptake) or the reverse, who clinically seem eumetabolic and have normal FTI, measurement of TBG is only occasionally needed. Some such patients may have hereditary anomalies of TBG. TBG is increased by estrogens, tamoxifen, pregnancy, perphenazine, and in some cases of liver disease, including hepatitis. Decreased TBG is found with some instances of chronic liver disease, nephrosis and systemic disease, and with large amounts of glucocorticoids, androgens/anabolic steroids, and acromegaly. Although alterations of TBG are usually resolved by the thyroid profile, TBG must occasionally be directly measured.

Kindreds are described with elevated TBG and hyperthyroxinemia as a harmless genetic abnormality. They have normal levels of TSH and free T4 and decreased T3 uptake.2 Structural variants of TBG are inherited as X-chromosome-linked traits, most inherited structural abnormalities in TBG cause decreased affinity for thyroid hormone.3

TBG is normal in familial dysalbuminemic hyperthyroxinemia, an entity which can be incorrectly identified as thyrotoxicosis.4 Triiodothyronine uptake was described as having produced information equivalent to TBG in a study of 372 subjects.5

1. Hicks JM, Godwin ID, Beatey J, Bailey J, Bjorn S, Soldin SJ. Pediatric reference ranges for thyroid binding globulin. Clin Chem. 1993; 39:1172. Poster 248

2. Viscardi RM, Shea M, Sriwantanakul K, McCormick K. Hyperthyroxinemia in newborns due to excess thyroxine-binding globulin. N Engl J Med. 1983 Oct 13; 309(15):897-899. PubMed 6412142

3. Sarne DH, Refetoff S, Nelson JC, Linarelli LG. A new inherited abnormality of thyroxine-binding globulin (TBG-San Diego) with decreased affinity for thyroxine and tri-iodothyronine. J Clin Endocrinol Metab. 1989 Jan; 68(1):114-119. PubMed 2491856

4. Ruiz M, Rajatanavin R, Young RA, et al. Familial dysalbuminemic hyperthyroxinemia: A syndrome that can be confused with thyrotoxicosis. N Engl J Med. 1982 Mar 18; 306(11):635-639. PubMed 6173750

5. Wilke TJ. Free thyroid hormone index, thyroid hormone/thyroxine-binding globulin ratio, tri-iodothyronine uptake, and thyroxine-binding globulin compared for diagnostic value regarding thyroid function. Clin Chem. 1983 Jan; 29(1):74-79. PubMed 6401235

Borst GC, Eil C, Burman KD. Euthyroid hyperthyroxinemia. Ann Intern Med. 1983 Mar; 98(3):366-378 (review). PubMed 6187257

Ingbar SH. Diseases of the thyroid. In: Braunwald E, Isselbacher KJ, Petersdorf RG, et al, eds. Harrison's Principles of Internal Medicine. 11th ed. New York, NY: McGraw-Hill;1987: 1732-1752.

Nelson JC, Tomei RT. Dependence of the thyroxine/thyroxine-binding globulin (TBG) ratio and the free thyroxine index on TBG concentrations. Clin Chem. 1989 Apr; 35(4):541-544. PubMed 2495196

Oberkotter LV, Farber M. Thyroxine-binding globulin in serum and milk specimens from puerperal lactating women. Obstet Gynecol. 1984; 64(2):244-247. PubMed 6429594

Refetoff S. Inherited thyroxine-binding globulin abnormalities in man. Endocr Rev. 1989 Aug; 10(3):275-293. PubMed 2506004