Effects of nonthyroidal illness on thyroid function

J. M. Tibaldi, M. I. Surks

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32 Scopus citations


Despite the absence of thyroid disease, patients with nonthyroidal illness frequently have changes in serum thyroid hormone measurements that may suggest either hypothyroidism or hyperthyroidism. Serum T3 levels are frequently decreased mainly because of a decrease in the rate of T3 production from T4. The free T3 concentration may be either normal or reduced as well. The binding of T4 and T3 by the serum-binding proteins is almost always impaired, resulting in an increase in the dialyzable fraction (free) fraction. This is due to a decrease in the concentration of thyroxine-binding proteins and the presence of circulating inhibitors of binding. If serum T4 concentration remains within the normal range, the free T4 concentration can be increased. However, serum T4 is frequently decreased in patients with chronic and/or severe illness. The decrease in serum T4 in these patients, combined with an increase in the dialyzable fraction, results in normal free T4. In patients who are critically ill, none of the available methods for measurement of free T4 may give results that accurately reflect the euthyroid state. Since T3 is the major active thyroid hormone, it is surprising that patients with decreased serum T3 do not appear hypothyroid. The decrease in serum T3 is probably an adaptive change to nonthyroidal illness, which at least enables the sick patient to conserve protein. The clinical impression of euthyroidism is supported by the finding of a normal serum TSH level in most patients. Although TSH regulation may not be entirely normal in patients with nonthyroidal disease, it is likely that serum TSH will be increased in most sick patients who also have significant thyroid failure. The normal clinical findings in patients with decreased serum T3 may result from an augmentation of those biologic responses associated with the clinical manifestations of the euthyroid state. Several animal models of nonthyroidal disease or starvation show that cells have the ability to modulate some biologic responses to thyroid hormone. Further study should elucidate the mechanisms underlying these changes. This article has emphasized that no single laboratory measurement may reliably predict the thyroid state in patients with nonthyroidal disease. This fact emphasizes the need for careful clinical evaluation of these patients and judicious use of laboratory tests. Because the changes in thyroid hormone metabolism that occur in nonthyroidal disease probably represent adaptive changes to the illness, treatment with L-thyroxine to restore serum thyroid concentrations to the normal range is not indicated.

Original languageEnglish (US)
Pages (from-to)899-911
Number of pages13
JournalMedical Clinics of North America
Issue number5
StatePublished - 1985

ASJC Scopus subject areas

  • Medicine(all)


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