Euthyroid Hyperthyroxinemia

Updated: Dec 12, 2014
  • Author: Justyna Kotus, MD; Chief Editor: George T Griffing, MD  more...
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Overview

Background

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.

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Pathophysiology

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

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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) 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]

Mortality/Morbidity

Most of the conditions resulting in euthyroid hyperthyroxinemia do not have any adverse clinical outcomes.

Race

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.

Sex

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

Age

Most of the causes may be observed in any age group. Older men who are frail may manifest higher free thyroxine levels. [4, 5]

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