eMedicine Specialties > Endocrinology > Thyroid

Thyroxine-Binding Globulin Deficiency: Treatment & Medication

Author: Nicholas J Sarlis, MBBS, MD, PhD, FACP, Medical Director, Department of Oncology-US Medical Affairs Department, Sanofi-Aventis Pharmaceuticals
Coauthor(s): Boaz Hirshberg, MD, Associate Director, CVMD, Pfizer
Contributor Information and Disclosures

Updated: Dec 18, 2008

Treatment

Medical Care

  • The most important aspect of dealing with thyroxine-binding globulin (TBG) deficiency is to recognize and correctly diagnose this condition in order to avoid unnecessary treatment for a mistaken diagnosis of hypothyroidism.26
  • A firm diagnosis of secondary TBG deficiency may be important when it indicates the coexistence of a previously unrecognized or underestimated serious general medical disease. Prompt evaluation of the possible causative conditions (see Thyroid binding protein deficiency states) is mandatory.

Surgical Care

No surgical care is indicated or necessary for patients with thyroxine-binding globulin deficiency.

Consultations

In cases of secondary thyroxine-binding globulin (TBG) deficiency, referral to consultants should be made as appropriate for the evaluation and treatment of the primary disorder.

A geneticist may be of value for selected cases of inherited TBG deficiency. Occasionally, referral to an endocrinologist is necessary because concomitant disease (eg, euthyroid sick syndrome, glucocorticoid therapy, concurrent thyroidopathy) may complicate the laboratory test picture in TBG deficiency, rendering the establishment of the diagnosis almost impossible without expert subspecialty input. Follow-up evaluations with the endocrinologist may be necessary until the concurrent illness subsides.

Diet

Dietary modification or other types of restrictions are not necessary for patients with thyroxine-binding globulin deficiency. In cases of malnutrition/malabsorption, protein supplementation may be necessary.

Activity

No changes in the intensity or frequency of physical activity or exercise patterns are recommended or necessary for patients with thyroxine-binding globulin deficiency.

Medication

Medications are not needed for patients with thyroxine-binding globulin (TBG) deficiency. The condition does not necessitate specific therapy, with the exception of cases of secondary TBG deficiency, in which treatment of the primary disorder is indicated.

More on Thyroxine-Binding Globulin Deficiency

Overview: Thyroxine-Binding Globulin Deficiency
Differential Diagnoses & Workup: Thyroxine-Binding Globulin Deficiency
Treatment & Medication: Thyroxine-Binding Globulin Deficiency
Follow-up: Thyroxine-Binding Globulin Deficiency
References
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References

  1. Chandurkar V, Shik J, Randell E. Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation. Endocr Pract. Jan-Feb 2008;14(1):97-103. [Medline].

  2. Lambert M. Thyroid dysfunction in HIV infection. Baillieres Clin Endocrinol Metab. Oct 1994;8(4):825-35. [Medline].

  3. Corrigan DF, Wartofsky L, Dimond RC, et al. Parameters of thyroid function in patients with active acromegaly. Metabolism. Feb 1978;27(2):209-16. [Medline].

  4. Inada M, Sterling K. Thyroxine turnover and transport in active acromegaly. J Clin Endocrinol Metab. Jul 1967;27(7):1019-27. [Medline].

  5. Flink IL, Bailey TJ, Gustafson TA, et al. Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases. Proc Natl Acad Sci U S A. Oct 1986;83(20):7708-12. [Medline]. [Full Text].

  6. Mori Y, Miura Y, Oiso Y, et al. Precise localization of the human thyroxine-binding globulin gene to chromosome Xq22.2 by fluorescence in situ hybridization. Hum Genet. Oct 1995;96(4):481-2. [Medline].

  7. Trent JM, Flink IL, Morkin E. Localization of the human thyroxine-binding globulin gene to the long arm of the X chromosome (Xq21-22). Am J Hum Genet. Sep 1987;41(3):428-35. [Medline]. [Full Text].

  8. Gershengorn MC, Lippoldt RE, Edelhoch H, et al. Structure and stability of human thyroxine-binding globulin. J Biol Chem. Dec 10 1977;252(23):8719-23. [Medline].

  9. Janssen OE, Chen B, Buttner C, et al. Molecular and structural characterization of the heat-resistant thyroxine-binding globulin-Chicago. J Biol Chem. Nov 24 1995;270(47):28234-8. [Medline]. [Full Text].

  10. Lacka K, Nizankowska T, Ogrodowicz A, et al. A novel mutation (del 1711 G) in the TBG gene as a cause of complete TBG deficiency. Thyroid. Nov 2007;17(11):1143-6. [Medline].

  11. Carvalho GA, Weiss RE, Vladutiu AO, et al. Complete deficiency of thyroxine-binding globulin (TBG-CD Buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene. Thyroid. Feb 1998;8(2):161-5. [Medline].

  12. Miura Y, Hershkovitz E, Inagaki A, et al. A novel mutation causing complete thyroxine-binding globulin deficiency (TBG-CD-Negev) among the Bedouins in southern Israel. J Clin Endocrinol Metab. Oct 2000;85(10):3687-9. [Medline]. [Full Text].

  13. Ueta Y, Mitani Y, Yoshida A, et al. A novel mutation causing complete deficiency of thyroxine binding globulin. Clin Endocrinol (Oxf). Jul 1997;47(1):1-5. [Medline].

  14. Carvalho GA, Weiss RE, Refetoff S. Complete thyroxine-binding globulin (TBG) deficiency produced by a mutation in acceptor splice site causing frameshift and early termination of translation (TBG-Kankakee). J Clin Endocrinol Metab. Oct 1998;83(10):3604-8. [Medline]. [Full Text].

  15. Fingerhut A, Reutrakul S, Knuedeler SD, et al. Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide. J Clin Endocrinol Metab. May 2004;89(5):2477-83. [Medline]. [Full Text].

  16. Reutrakul S, Dumitrescu A, Macchia PE, et al. Complete thyroxine-binding globulin (TBG) deficiency in two families without mutations in coding or promoter regions of the TBG genes: in vitro demonstration of exon skipping. J Clin Endocrinol Metab. Mar 2002;87(3):1045-51. [Medline]. [Full Text].

  17. Bigazzi M, Ronga R, Olivotti AL, et al. Inherited X chromosome linked thyroxine-binding globulin (TBG) deficiency in a homozygous female. J Endocrinol Invest. Oct-Dec 1980;3(4):349-52. [Medline].

  18. Vermeer S, Kremer HP, Leijten QH, et al. Cerebellar ataxia and congenital disorder of glycosylation Ia (CDG-Ia) with normal routine CDG screening. J Neurol. Oct 2007;254(10):1356-8. [Medline].

  19. Quelhas D, Quental R, Vilarinho L, et al. Congenital disorder of glycosylation type Ia: searching for the origin of common mutations in PMM2. Ann Hum Genet. May 2007;71:348-53. [Medline].

  20. Bhatkar SV, Rajan MG, Velumani A, et al. Thyroid hormone binding protein abnormalities in patients referred for thyroid disorders. Indian J Med Res. Sep 2004;120(3):160-5. [Medline]. [Full Text].

  21. Watson F, Dick M. Distribution and inheritance of low serum thyroxine-binding globulin levels in Australian Aborigines: a new genetic variation. Med J Aust. Oct 4 1980;2(7):385-7. [Medline].

  22. Waltz MR, Pullman TN, Takeda K, et al. Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks. J Endocrinol Invest. Apr 1990;13(4):343-9. [Medline].

  23. Alen M, Rahkila P, Reinila M, et al. Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes. Am J Sports Med. Jul-Aug 1987;15(4):357-61. [Medline].

  24. Oppenheimer JH, Werner SC. Effect of prednisone on thyroxine-binding proteins. J Clin Endocrinol Metab. Jul 1966;26(7):715-21. [Medline].

  25. Refetoff S, Selenkow HA. Familial thyroxine-binding globulin deficiency in a patient with Turner's syndrome (XO). Genetic study of a kindred. N Engl J Med. May 16 1968;278(20):1081-7. [Medline].

  26. Gruters A, Krude H. Update on the management of congenital hypothyroidism. Horm Res. 2007;68 Suppl 5:107-11. [Medline].

  27. Bartalena L, Robbins J. Thyroid hormone transport proteins. Clin Lab Med. Sep 1993;13(3):583-98. [Medline].

  28. Bartalena L, Robbins J. Variations in thyroid hormone transport proteins and their clinical implications. Thyroid. Fall 1992;2(3):237-45. [Medline].

  29. Benvenga S, Robbins J. Lipoprotein-thyroid hormone interactions. Trends Endocrinol Metab. Aug 1993;4(6):194-8. [Medline].

  30. Benvenga S, Trimarchi F, Robbins J. Circulating thyroid hormone autoantibodies. J Endocrinol Invest. Dec 1987;10(6):605-19. [Medline].

  31. Bernstein RS, Robbins J, Rall JE. Polymorphism of monkey thyroxin-binding prealbumin (TBPA): mode of inheritance and hybridization. Endocrinology. Feb 1970;86(2):383-90. [Medline].

  32. Bertenshaw R, Takeda K, Refetoff S. Sequencing of the variant thyroxine-binding globulin (TBG)-Quebec reveals two nucleotide substitutions. Am J Hum Genet. Apr 1991;48(4):741-4. [Medline].

  33. Blomstedt B, Einhorn J. Effect of cortisone on the PBI and the resin uptake I-131- triiodothyronine. Metabolism. Apr 1967;16(4):319-23. [Medline].

  34. Burr WA, Ramsden DB, Hoffenberg R. Hereditary abnormalities of thyroxine-binding globulin concentration. A study of 19 kindreds with inherited increase or decrease of thyroxine-binding globulin. Q J Med. 1980;49(195):295-313. [Medline].

  35. Charbonneau M, Dussault JH, Refetoff S. A study on the inheritance of thyroxine-binding globulin (TBG) deficiency from data obtained in 13 families detected by a neonatal screening program. Clin Invest Med. Feb 1988;11(1):34-9. [Medline].

  36. Domingues R, Bugalho MJ, Garrao A, et al. Two novel variants in the thyroxine-binding globulin (TBG) gene behind the diagnosis of TBG deficiency. Eur J Endocrinol. Apr 2002;146(4):485-90. [Medline]. [Full Text].

  37. Ekins RP, Sinha AK, Pickard MR, et al. Transport of thyroid hormones to target tissues. Acta Med Austriaca. 1994;21(2):26-34. [Medline].

  38. Emerson CH, Seiler CM, Alex S, et al. Gene expression and serum thyroxine-binding globulin are regulated by adrenal status and corticosterone in the rat. Endocrinology. Sep 1993;133(3):1192-6. [Medline]. [Full Text].

  39. Gamstedt A, Jarnerot G, Kagedal B, et al. Effects of betamethasone on serum iodothyronines and thyroid hormone-binding proteins in Graves' disease. Acta Med Scand. 1986;220(3):237-40. [Medline].

  40. Gershengorn MC, Larsen PR, Robbins J. Radioimmunoassay for serum thyroxine-binding globulin: results in normal subjects and in patients with hepatocellular carcinoma. J Clin Endocrinol Metab. May 1976;42(5):907-11. [Medline].

  41. Golden MH. Transport proteins as indices of protein status. Am J Clin Nutr. May 1982;35(5 Suppl):1159-65. [Medline].

  42. Grimaldi S, Bartalena L, Ramacciotti C, et al. Polymorphism of human thyroxine-binding globulin. J Clin Endocrinol Metab. Dec 1983;57(6):1186-92. [Medline].

  43. Hayashi Y, Mori Y, Janssen OE, et al. Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation. Mol Endocrinol. Aug 1993;7(8):1049-60. [Medline].

  44. Heidemann PH, Stubbe P, Beck W. Transient secondary hypothyroidism and thyroxine binding globulin deficiency in leukemic children during polychemotherapy: an effect of L- asparaginase. Eur J Pediatr. Jul 1981;136(3):291-5. [Medline].

  45. Herrick AL, McColl KE, Wallace AM, Moore MR, Goldberg A. Elevation of hormone-binding globulins in acute intermittent porphyria. Clin Chim Acta. Feb 28 1990;187(2):141-8. [Medline].

  46. Janssen OE, Astner ST, Grasberger H, et al. 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. Jan 2000;85(1):368-72. [Medline]. [Full Text].

  47. Janssen OE, Takeda K, Refetoff S. Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency. Hum Genet. Jun 1991;87(2):119-22. [Medline].

  48. Kobayashi H, Sakurai A, Katai M, et al. Autosomally transmitted low concentration of thyroxine-binding globulin. Thyroid. Feb 1999;9(2):159-63. [Medline].

  49. Korcek L, Tabachnick M. Thyroxine-protein interactions. Interaction of thyroxine and triiodothyronine with human thyroxine-binding globulin. J Biol Chem. Jun 25 1976;251(12):3558-62. [Medline]. [Full Text].

  50. Langsteger W. Clinical aspects and diagnosis of thyroid hormone transport protein anomalies. Curr Top Pathol. 1997;91:129-61. [Medline].

  51. Li P, Janssen OE, Takeda K, et al. Complete thyroxine-binding globulin (TBG) deficiency caused by a single nucleotide deletion in the TBG gene. Metabolism. Nov 1991;40(11):1231-4. [Medline].

  52. Macchia PE, Harrison HH, Scherberg NH, et al. Thyroid function tests and characterization of thyroxine-binding globulin in the carbohydrate-deficient glycoprotein syndrome type I. J Clin Endocrinol Metab. Dec 1995;80(12):3744-9. [Medline]. [Full Text].

  53. Mandel S, Hanna C, Boston B, et al. Thyroxine-binding globulin deficiency detected by newborn screening. J Pediatr. Feb 1993;122(2):227-30. [Medline].

  54. Miura Y, Kambe F, Yamamori I, et al. A truncated thyroxine-binding globulin due to a frameshift mutation is retained within the rough endoplasmic reticulum: a possible mechanism of complete thyroxine-binding globulin deficiency in Japanese. J Clin Endocrinol Metab. Feb 1994;78(2):283-7. [Medline]. [Full Text].

  55. Mori Y, Refetoff S, Flink IL, et al. Detection of the thyroxine-binding globulin (TBG) gene in six unrelated families with complete TBG deficiency. J Clin Endocrinol Metab. Oct 1988;67(4):727-33. [Medline].

  56. Mulaisho C, Utiger RD. Serum thyroxine-binding globulin: determination by competitive ligand- binding assay in thyroid disease and pregnancy. Acta Endocrinol (Copenh). Jun 1977;85(2):314-24. [Medline].

  57. Munro SL, Lim CF, Hall JG. Drug competition for thyroxine binding to transthyretin (prealbumin): comparison with effects on thyroxine-binding globulin. J Clin Endocrinol Metab. Jun 1989;68(6):1141-7. [Medline].

  58. Murata Y, Magner JA, Refetoff S. The role of glycosylation in the molecular conformation and secretion of thyroxine-binding globulin. Endocrinology. Apr 1986;118(4):1614-21. [Medline].

  59. Murata Y, Takamatsu J, Refetoff S. Inherited abnormality of thyroxine-binding globulin with no demonstrable thyroxine-binding activity and high serum levels of denatured thyroxine-binding globulin. N Engl J Med. Mar 13 1986;314(11):694-9. [Medline].

  60. Narendran P, Lado-Abeal J, Moeller LC, et al. Partial thyroxine-binding globulin (TBG) deficiency in a family with no detectable mutation of the TBG gene. Clin Endocrinol (Oxf). Dec 2003;59(6):824-5. [Medline].

  61. Okamoto H, Mori Y, Tani Y, et al. Molecular analysis of females manifesting thyroxine-binding globulin (TBG) deficiency: selective X-chromosome inactivation responsible for the difference between phenotype and genotype in TBG-deficient females. J Clin Endocrinol Metab. Jun 1996;81(6):2204-8. [Medline].

  62. Peters T Jr. Serum albumin. Adv Protein Chem. 1985;37:161-245. [Medline].

  63. Refetoff S. Thyroid hormone transport proteins: thyroxine-binding globulin, transthyretin, and albumin. In: Henry HL, Norman AW, eds. Encyclopedia of Hormones. 3rd ed. New York, NY: Academic Press; 2003:483-90.

  64. Refetoff S, Fang VS, Marshall JS. Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess. J Clin Invest. Feb 1976;57(2):485-95. [Medline]. [Full Text].

  65. Refetoff S, Murata Y, Mori Y. Thyroxine-binding globulin: organization of the gene and variants [published erratum appears in Horm Res 1996 Jul;46(1):37]. Horm Res. 1996;45(3-5):128-38. [Medline].

  66. Refetoff S, Robin NI, Alper CA. Study of four new kindreds with inherited thyroxine-binding globulin abnormalities. Possible mutations of a single gene locus. J Clin Invest. Apr 1972;51(4):848-67. [Medline]. [Full Text].

  67. Reutrakul S, Janssen OE, Refetoff S. Three novel mutations causing complete T(4)-binding globulin deficiency. J Clin Endocrinol Metab. Oct 2001;86(10):5039-44. [Medline]. [Full Text].

  68. Robbins J. Inherited variations in thyroxine transport. Mt Sinai J Med. May-Jun 1973;40(3):511-9. [Medline].

  69. Sarne D, Barokas K, Scherberg NH. Elevated serum thyroglobulin level in congenital thyroxine-binding globulin deficiency. J Clin Endocrinol Metab. Sep 1983;57(3):665-7. [Medline].

  70. Schollen E, Pardon E, Heykants L. Comparative analysis of the phosphomannomutase genes PMM1, PMM2 and PMM2psi: the sequence variation in the processed pseudogene is a reflection of the mutations found in the functional gene. Hum Mol Genet. Feb 1998;7(2):157-64. [Medline]. [Full Text].

  71. Schussler GC. The thyroxine-binding proteins. Thyroid. Feb 2000;10(2):141-9. [Medline].

  72. Seo H. Mutations of the thyroxine-binding globulin gene in Japanese. Intern Med. Apr 1996;35(4):237. [Medline]. [Full Text].

  73. Snyder SM, Cavalieri RR, Goldfine ID. Binding of thyroid hormones and their analogues to thyroxine-binding globulin in human serum. J Biol Chem. Nov 10 1976;251(21):6489-94. [Medline]. [Full Text].

  74. Snyder SM, Cavalieri RR, Goldfine ID. The binding of thyroid hormone analogues to thyroxine binding globulin (TBG). In: Robbins J, Braverman LE, eds. Thyroid Research: Proceedings of the Seventh International Thyroid Conference, Boston, Massachusetts, June 9-13, 1975. New York, NY: Elsevier; 1976:297-9.

  75. Su CC, Wu YC, Chiu CY, et al. Two novel mutations in the gene encoding thyroxine-binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan. Clin Endocrinol (Oxf). Apr 2003;58(4):409-14. [Medline]. [Full Text].

  76. Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med. Dec 21 1995;333(25):1688-94. [Medline].

  77. Takamatsu J, Refetoff S, Charbonneau M. Two new inherited defects of the thyroxine-binding globulin (TBG) molecule presenting as partial TBG deficiency. J Clin Invest. Mar 1987;79(3):833-40. [Medline]. [Full Text].

  78. Tojo K, Miura Y, Mori Y, et al. Familial thyroxine-binding globulin deficiency associated with hyperthyroidism. Intern Med. May 1995;34(5):413-7. [Medline]. [Full Text].

  79. Vassart G, Dumont JE, Refetoff S. Thyroid disorders. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995:2908-11.

  80. Zinn AB, Marshall JS, Carlson DM. Carbohydrate structures of thyroxine-binding globulin and their effects on hepatocyte membrane binding. J Biol Chem. Oct 10 1978;253(19):6768-73. [Medline]. [Full Text].

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Further Reading

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Keywords

thyroxine-binding globulin deficiency, thyroid, thyroid disease, thyroid gland, thyroid hormone, thyroxine, albumin, protein binding, thyroid levels, prealbumin, triiodothyronine, thyroid hormones, TH, T4, T3, thyroxine binding globulin, thyroxine-binding globulin, TBG, transthyretin, TTR, prealbumin, serum lipoproteins

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Contributor Information and Disclosures

Author

Nicholas J Sarlis, MBBS, MD, PhD, FACP, Medical Director, Department of Oncology-US Medical Affairs Department, Sanofi-Aventis Pharmaceuticals
Nicholas J Sarlis, MBBS, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American Federation for Medical Research, American Head and Neck Society, American Medical Association, American Society for Therapeutic Radiology and Oncology, American Society of Clinical Oncology, American Thyroid Association, Association for Psychological Science, Endocrine Society, European Society for Medical Oncology, New York Academy of Sciences, and Royal Society of Medicine
Disclosure: Sanofi-Aventis Salary Employment

Coauthor(s)

Boaz Hirshberg, MD, Associate Director, CVMD, Pfizer
Boaz Hirshberg, MD is a member of the following medical societies: American Dietetic Association
Disclosure: Nothing to disclose.

Medical Editor

Harris C Taylor, MD, Clinical Professor of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University School of Medicine
Harris C Taylor, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Thyroid Association, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kent Wehmeier, MD, Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine
Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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