Euthyroid Sick Syndrome

Guillermo E. Umpierrez, MD, FACP, FACE


South Med J. 2002;95(5) 

In This Article

Diagnosis of Thyroid Disease in Euthyroid Sick Syndrome

During starvation and mild illness, a low T3 concentration, or low T3 and low T4 levels in a patient with a low-normal TSH level, is the hallmark of euthyroid sick syndrome. As previously discussed, however, nonthyroidal illness may present with a spectrum of abnormalities in thyroid function that may complicate the diagnosis of euthyroid sick syndrome. Low T3 levels with normal T4 and TSH levels is the most common abnormality seen in euthyroid sick syndrome. Serum TSH levels are typically normal or reduced.[7,8,48] The TSH levels are normal/subnormal in approximately 80% of patients, and are markedly suppressed (<0.1 µU/mL) in <10% of patients. Thus, in a patient with a systemic illness, low T4 and T3 levels and a normal or low-normal TSH level most likely indicate euthyroid sick syndrome. In the recovery phase of illness, mild elevation of TSH levels can be observed[39,41,48]; however, serum level of TSH >30 µU/mL is rarely seen in euthyroid sick syndrome and strongly suggests the diagnosis of primary hypothyroidism. Levels of TSH above 20 µU/mL are found in <3% of patients with nonthyroidal illness.[49]

Differentiation between secondary hypothyroidism (pituitary or hypothalamic) and euthyroid sick syndrome may be difficult. Both conditions present with decreased levels of total T4, T3, and TSH. Many chronically ill patients are edematous, have associated infections, or have cardiopulmonary disorders that could easily mask evidence of thyroid disorders. Additional tests, including obtaining basal and/or stimulated cortisol, serum gonadotropin, and prolactin levels may be of help in such cases. If the serum cortisol level is normal or elevated, as would be expected in stressful situations, euthyroid sick syndrome is probably the cause, rather than pituitary dysfunction. If serum cortisol and gonadotropin levels are low, pituitary dysfunction should be suspected, and treatment with corticosteroids and thyroid hormone supplementation is indicated. In some instances, it may be difficult to exclude hyperthyroid patients, who may present with suppressed TSH levels and normal T4 and T3 levels in the presence of infection or other catabolic illness. Hyperthyroid patients who are chronically ill or malnourished may have hypoproteinemia and low levels of TBG that lower their T4 and T3 levels. In such patients, an elevated free-T4 level and a low or undetectable TSH level will confirm the diagnosis of hyperthyroidism. A previous history of thyroid illness, a history of external radiation, or the presence of goiter and/or a midline neck scar may indicate a primary thyroid condition.

As mentioned before, certain pharmacologic agents may alter the serum concentration of thyroid hormones and should be taken into account in the evaluation of patients with nonthyroidal illness. The concentrations of total T3, free-T4, and TSH are reduced in patients treated with dopamine or corticosteroids,[21,45] due to suppression of pituitary TSH release[62] and/or inhibition of conversion of T4 to T3.[63] Levels of total and free-T4 may be increased in patients treated with amiodarone[64] or iodinated radiocontrast agents.[15,65] Intravenous or subcutaneous heparin therapy may result in increased free-T4 levels,[66] due to in vitro interference with the laboratory assay; however, most such patients remain clinically euthyroid and have normal total T4 and TSH levels.

As a general rule, it is not prudent to rely solely on a single thyroid test in the evaluation of thyroid function of patients with critical illness. In such patients, a careful assessment of multiple tests may be needed to distinguish patients with euthyroid sick syndrome.[1] In many instances, it is reasonable to delay the final diagnosis for several days to weeks, or after recovery from the acute illness, to determine the correct thyroid status.