Euthyroid Hyperthyroxinemia 

  • Author: Reetu Singh, MD; Chief Editor: George T Griffing, MD   more...
 
Updated: Nov 28, 2011
 

Background

Euthyroid hyperthyroxinemia is defined as a condition in which the serum total or, rarely, the free thyroxine (T4) concentrations are abnormal without evidence of clinical thyroid disease. These changes may be transient or persistent and may be associated with normal, low, or high triiodothyronine (T3) levels.[1]

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Pathophysiology

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.

T4 and T3 circulate in the blood bound to 3 different binding proteins, ie, thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA, or transthyretin (TTR), and albumin.

Approximately 99.97% of circulating T4 and 99.7% of circulating T3 are bound to these proteins. TBG carries 70% of the circulating T4 and T3 due to its high affinity. TBPA binds to only approximately 10-15% of the hormones (mostly T4), and albumin binds to the remaining 10-15%.

In comparison, T3 is less avidly bound to TBG and TBPA.

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Epidemiology

Frequency

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) has a prevalence rate of 0.08-0.17% in white persons.

International

FDH is the most common cause of inherited elevation of serum T4 in white persons. Rare occurrences of FDH also have been reported in a Japanese family and in China.[2, 3]

Mortality/Morbidity

  • Most of the conditions resulting in euthyroid hyperthyroxinemia do not have any adverse clinical outcomes.
  • An exception to this is the syndrome of thyroid hormone resistance; children with this disorder may have learning difficulties because of hypothyroidism. The mortality associated with this condition is unknown.

Race

  • No race predilection exists in nonhereditary euthyroid hyperthyroxinemia.
  • FDH is observed most frequently in Hispanic and Portuguese people. Rare cases of FDH in Japanese and Chinese persons have been reported[2, 3] ; no cases of FDH have been reported in black persons.

Sex

  • No sex predilection exists for any of the conditions (except, of course, those associated with pregnancy).

Age

  • Most of the causes may be observed in any age group. However, thyroid hormone resistance may present in infancy or early childhood.
  • Older men who are frail may manifest higher free thyroxine levels.[4]
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Contributor Information and Disclosures
Author

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 Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Serge A Jabbour, MD  Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University

Serge A Jabbour, MD 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, Endocrine Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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 College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America

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: Medscape Salary Employment

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, and Endocrine Society

Disclosure: Nothing to disclose.

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.

References

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  2. 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. Oct 1999;141(4):374-8. [Medline]. [Full Text].

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