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Euthyroid hyperthyroxinemia and hypothyroxinemia

Douglas S Ross, MD
Section Editor
David S Cooper, MD
Deputy Editor
Jean E Mulder, MD


Many conditions result in increases or decreases in serum total thyroxine (T4) and triiodothyronine (T3) concentrations, associated with normal thyroid-stimulating hormone (TSH) concentrations and no symptoms or signs of thyroid dysfunction. This constellation of laboratory values has been referred to as euthyroid hyperthyroxinemia and hypothyroxinemia, respectively. The free T4 should be normal, but many assays will report slightly abnormal values, for example the free T4 index and many direct free T4 assays report high values in familial dysalbuminemic hyperthyroxinemia.

In the past, these conditions presented a diagnostic challenge, and many of the patients with them were inappropriately treated for thyroid disease. Today, when most clinicians measure serum TSH as a screening test for thyroid function, a normal serum TSH value is usually not followed by measurement of a total serum T4. With the use of sensitive serum TSH assays and automated “direct” free T4 assays, euthyroid hyper- or hypothyroxinemia frequently remains undetected, with no harm to the patient.

However, the detection of a normal serum TSH concentration associated with a high or low serum T4 concentration, and sometimes free T4 concentration, should immediately alert the clinician to search for one of the causes of euthyroid hyperthyroxinemia or hypothyroxinemia, especially if the patient has no symptoms or signs of either hyper- or hypothyroidism.

This topic will review these conditions. Individual thyroid function tests are discussed in detail separately. (See "Laboratory assessment of thyroid function".)


Both thyroxine (T4) and triiodothyronine (T3) circulate in blood bound to one of three binding proteins:

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Literature review current through: Nov 2017. | This topic last updated: Feb 26, 2016.
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