Low T3 syndrome

Low T3 syndrome (Euthyroid Sick Syndrome) is characterized by low serum thyroid hormone levels in clinically euthyroid patients with systemic diseases of nonthyroid etiology. The diagnosis is made after excluding hypothyroidism. Therapy includes treatment of the associated disease; thyroid hormone replacement therapy is not indicated.

Causes of low-T3 syndrome

Patients with various acute and chronic nonthyroidal pathologies may have altered laboratory parameters characterizing thyroid function. This pathology includes acute and chronic diseases such as exhaustion, starvation, protein-calorie malnutrition, severe trauma, myocardial infarction, chronic renal failure, diabetic ketoacidosis, nervous anorexia, liver cirrhosis, burn wounds, and sepsis.

Most commonly, euthyroid low T3 syndrome is characterized by decreased T3 levels. Patients with more severe manifestations of the underlying disease or with long-standing chronic diseases also have decreased T3 levels. Serum reverse T (rT3) is elevated. Patients are clinically euthyroid and do not have elevated TSH.

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Pathogenesis

The pathogenesis of the syndrome is still unknown, but it is thought to involve decreased peripheral conversion of T to T3, decreased clearance of rT3 derived from T3, and decreased ability of thyroid hormones to bind to thyroxine-binding globulin (TBG). Proinflammatory cytokines (tumor necrosis factor a, IL-1) may be responsible for some of the changes.

Interpretation of thyroid function laboratory abnormalities is complicated by the influence of various drugs, including iodine contrast agents and amiodarone, which worsen the impairment of peripheral conversion of T to T3, and by the influence of other drugs, such as dopamine and glucocorticoids, which decrease pituitary secretion of TSH, resulting in low serum TSH levels and subsequent decreased T3 secretion.

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Diagnostics of low-T3 syndrome

There is a diagnostic dilemma: does the patient have hypothyroidism or low T3 syndrome? The best laboratory test to resolve the dilemma is the TSH level, which in the case of low T syndrome is low, normal, or moderately elevated, but not as high as it would be in hypothyroidism. Serum pT is elevated, although this test is rarely performed in clinical practice. Serum cortisol is often elevated in low T3 syndrome and decreased (or normally low) in secondary and tertiary hypothyroidism (pituitary-hypothalamic pathology).

Because laboratory tests are nonspecific, clinical judgment is needed to interpret changes in thyroid function tests. Thyroid function tests should not be performed in patients in intensive care units unless thyroid disease is clearly present.

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Treatment of low-T3 syndrome

Treatment with hormone replacement therapy is not used; laboratory parameters normalize with successful treatment of the underlying disease.