Euthyroid Hyperthyroxinemia
No Results
No Results
processing….
Euthyroid hyperthyroxinemia is defined as a condition in which the serum total thyroxine (T4) and triiodothyronine (T3) concentrations are increased, but the thyroid-stimulating hormone (TSH) concentration is normal and there are no clinical signs or symptoms of thyroid dysfunction. These changes may be transient or persistent. [1]
In the past, euthyroid hyperthyroxinemia was a diagnostic challenge and many patients were inappropriately treated for thyroid disease. Today, serum TSH is a screening test for thyroid function, and a normal TSH value should not be followed by measurement of total T4. In these circumstances, euthyroid hyperthyroxinemia frequently remains undetected with no harm to the patients.
Related Medscape topics include Hypothyroidism, Pediatric Hypothyroidism, Neurological Manifestations of Thyroid Disease, and Thyroid Dysfunction Induced by Amiodarone Therapy.
Both thyroxine (T4) and triiodothyronine (T3) circulate in the blood bound to the following three different binding proteins:
Thyroxine-binding globulin (TBG)
Thyroxine-binding prealbumin (TBPA), or transthyretin (TTR)
Albumin
Approximately 99.97% of circulating T4 and 99.7% of circulating T3 are bound to these proteins. TBG carries 75% of the circulating T4 and T3, owing to its high affinity. TBPA binds to only approximately 15% of the hormones (mostly T4), and albumin binds to the remaining 10%. In comparison, T3 is less avidly bound to TBG and TBPA.
Serum total T4 and T3 assays measure both bound and free (unbound) hormone. As a result, factors that alter binding protein concentrations have profound effects on serum total T4 and T3 concentrations even though serum free T4 and T3 do not change and the patient is euthyroid.
The various causes of hyperthyroxinemia in patients who are euthyroid are listed in Causes. Among them, the most common cause is an increase in the levels of serum binding proteins
United States
Because this condition is characterized by a number of different disorders, its true prevalence is unknown. However, among the hereditary conditions, familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited elevation of serum T4 in white populations and its prevalence rate is 0.08-0.17%. Rare occurrences of FDH have also been reported in a Japanese and Chinese families. [2, 3]
Most of the conditions resulting in euthyroid hyperthyroxinemia do not have any adverse clinical outcomes.
No race predilection exists in nonhereditary euthyroid hyperthyroxinemia. Familial dysalbuminemic hyperthyroxinemia (FDH) is a genetic disorder, most often occurring in patients of Latino and Portuguese background. Rare cases of FDH in Japanese and Chinese families have been reported [2, 3] ; no cases of FDH have been reported in the African American population.
No sex predilection exists for any of the conditions (except those associated with pregnancy).
Most of the causes may be observed in any age group. Older men who are frail may manifest higher free thyroxine levels. [4, 5]
Borst GC, Eil C, Burman KD. Euthyroid hyperthyroxinemia. Ann Intern Med. 1983 Mar. 98(3):366-78. [Medline].
Tang KT, Yang HJ, Choo KB, et al. A point mutation in the albumin gene in a Chinese patient with familial dysalbuminemic hyperthyroxinemia. Eur J Endocrinol. 1999 Oct. 141(4):374-8. [Medline]. [Full Text].
Wada N, Chiba H, Shimizu C, et al. 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. 1997 Oct. 82(10):3246-50. [Medline]. [Full Text].
Yeap BB, Alfonso H, Chubb SA, Walsh JP, Hankey GJ, Almeida OP, et al. Higher free thyroxine levels are associated with frailty in older men. The Health In Men Study. Clin Endocrinol (Oxf). 2011 Nov 11. [Medline].
Yeap BB, Alfonso H, Hankey G, Flicker L, Golledge J, Norman PE, et al. Higher free thyroxine levels are associated with all-cause mortality in euthyroid older men. The Health In Men Study. Eur J Endocrinol. 2013 Jul 12. [Medline].
Molashenko NV, Sviridenko NIu, Platonova NM, et al. [The specific features of thyrotoxicosis and euthyroid hyperthyroxinemia developed due to the use of cordarone]. Klin Med (Mosk). 2004. 82(12):35-9. [Medline].
Sänger N, Stahlberg S, Manthey T, et al. Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use. Contraception. 2008 Jun. 77(6):420-5. [Medline].
Mooradian A, Morley JE, Simon G, et al. Propranolol-induced hyperthyroxinemia. Arch Intern Med. 1983 Nov. 143(11):2193-5. [Medline].
McKerron CG, Scott RL, Asper SP, Levy RI. Effects of clofibrate (Atromid S) on the thyroxine-binding capacity of thyroxine-binding globulin and free thyroxine. J Clin Endocrinol Metab. 1969 Jul. 29(7):957-61. [Medline].
Beex LV, Ross A, Smals AG, Kloppenborg PW. Letter: 5-fluorouracil and the thyroid. Lancet. 1976 Apr 17. 1(7964):866-7. [Medline].
Chekuri L, Lange JR, Thapa PB. Lithium-induced transient euthyroid hyperthyroxinemia: a case report. Prim Care Companion CNS Disord. 2014. 16(2):[Medline]. [Full Text].
Azizi F, Vagenakis AG, Portnay GI, Braverman LE, Ingbar SH. Thyroxine transport and metabolism in methadone and heroin addicts. Ann Intern Med. 1974 Feb. 80(2):194-9. [Medline].
Wiener M, Lo Y, Klein R. Abnormal thyroid function in older men with or at risk for HIV infection. HIV Med. 2008 Jun 11. [Medline].
Vaidya B, Hubalewska-Dydejczyk A, Laurberg P, Negro R, Vermiglio F, Poppe KG. Treatment and Screening of Hypothyroidism in Pregnancy: Results of a European Survey. Eur J Endocrinol. 2011 Oct 24. [Medline].
Kvetny J, Poulsen H. Transient hyperthyroxinemia in newborns from women with autoimmune thyroid disease and raised levels of thyroid peroxidase antibodies. J Matern Fetal Neonatal Med. 2006 Dec. 19(12):817-22. [Medline].
Moses AC, Rosen HN, Moller DE, et al. A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia. J Clin Invest. 1990 Dec. 86(6):2025-33. [Medline]. [Full Text].
Hishinuma A, Mochizuki Y, Kasai K, et al. [Thyroxine-binding proteins–familial euthyroid hyperthyroxinemia due to point mutations of transthyretin]. Nippon Rinsho. 1994 Apr. 52(4):886-9. [Medline].
Magalhães PK, Rodrigues Dare GL, Rodrigues Dos Santos S, et al. Clinical features and genetic analysis of four Brazilian kindreds with resistance to thyroid hormone. Clin Endocrinol (Oxf). 2007 Nov. 67(5):748-53. [Medline].
Tucker WS Jr. Euthyroid hyperthyroxinemia due to familial excess of thyroxine-binding globulin. South Med J. 1989 Mar. 82(3):368-71. [Medline].
Maye P, Bisetti A, Burger A, et al. Hyperprealbuminemia, euthyroid hyperthyroxinemia, Zollinger-Ellison-like syndrome and hypercorticism in a pancreatic endocrine tumour. Acta Endocrinol (Copenh). 1989 Jan. 120(1):87-91. [Medline].
Refetoff S, Marinov VS, Tunca H, Byrne MM, Sunthornthepvarakul T, Weiss RE. A new family with hyperthyroxinemia caused by transthyretin Val109 misdiagnosed as thyrotoxicosis and resistance to thyroid hormone–a clinical research center study. J Clin Endocrinol Metab. 1996 Sep. 81(9):3335-40. [Medline].
Moses AC, Rosen HN, Moller DE, Tsuzaki S, Haddow JE, Lawlor J, et al. A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia. J Clin Invest. 1990 Dec. 86(6):2025-33. [Medline]. [Full Text].
Gharib H, Klee GG. Familial euthyroid hyperthyroxinemia secondary to pituitary and peripheral resistance to thyroid hormones. Mayo Clin Proc. 1985 Jan. 60(1):9-15. [Medline].
Rushbrook JI, Becker E, Schussler GC, et al. Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb. 80(2):461-7. [Medline]. [Full Text].
Schoenmakers N, Moran C, Campi I, et al. A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 2014 Jul. 99(7):E1381-6. [Medline]. [Full Text].
Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T. 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. 1997 Oct. 82(10):3246-50. [Medline].
Pannain S, Feldman M, Eiholzer U, Weiss RE, Scherberg NH, Refetoff S. 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. 2000 Aug. 85(8):2786-92. [Medline].
Greenberg SM, Ferrara AM, Nicholas ES, Dumitrescu AM, Cody V, Weiss RE, et al. A novel mutation in the Albumin gene (R218S) causing familial dysalbuminemic hyperthyroxinemia in a family of Bangladeshi extraction. Thyroid. 2014 Jun. 24(6):945-50. [Medline]. [Full Text].
Eber O, Langsteger W, Florian W, et al. [Evaluating thyroid gland function in patients with protein anomalies]. Acta Med Austriaca. 1991. 18(1):11-9. [Medline].
George PM, Sheat JM, Palmer BN. Detection of protein binding abnormalities in euthyroid hyperthyroxinemia. Clin Chem. 1988 Sep. 34(9):1745-8. [Medline]. [Full Text].
Jackson JA, Verdonk CA, Spiekerman AM. Euthyroid hyperthyroxinemia and inappropriate secretion of thyrotropin. Recognition and diagnosis. Arch Intern Med. 1987 Jul. 147(7):1311-3. [Medline].
Loh TP, Leong SM, Loke KY, Deepak DS. Spuriously elevated free thyroxine associated with autoantibodies, a result of laboratory methodology: case report and literature review. Endocr Pract. 2014 Aug 1. 20(8):e134-9. [Medline].
Cogan E, Abramow M. Transient hyperthyroxinemia in symptomatic hyponatremic patients. Arch Intern Med. 1986 Mar. 146(3):545-7. [Medline].
Stockigt JR, Barlow JW. The diagnostic challenge of euthyroid hyperthyroxinemia. Aust N Z J Med. 1985 Apr. 15(2):277-84. [Medline].
Justyna Kotus, MD Resident Physician, Department of Internal Medicine, Albert Einstein Medical Center
Disclosure: Nothing to disclose.
Jane V Mayrin, MD, FACE Staff Attending Physician, Einstein Endocrine Associates, Albert Einstein Medical Center; Staff Endocrinologist, Kindred Hospital
Jane V Mayrin, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Medical Association, American Thyroid Association, Endocrine Society
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School
Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society
Disclosure: Nothing to disclose.
George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society
Disclosure: Nothing to disclose.
Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R Adams Cowley Shock Trauma Center
Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American College of Physicians, American Geriatrics Society, Endocrine Society, Gerontological Society of America, Association of Professors of Medicine
Disclosure: Nothing to disclose.
Serge A Jabbour, MD, FACP, FACE Professor of Medicine, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University
Serge A Jabbour, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Thyroid Association, Pennsylvania Medical Society, and The Endocrine Society
Disclosure: Nothing to disclose.
Reetu Singh, MD Fellow, Department of Internal Medicine, Beebe Medical Center
Reetu Singh, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Thyroid Association, and The Endocrine Society
Disclosure: Nothing to disclose.
Euthyroid Hyperthyroxinemia
Research & References of Euthyroid Hyperthyroxinemia|A&C Accounting And Tax Services
Source
0 Comments