Thyroid Research Thyroid Research Archive Nonthyroidal Illness

Critical illness alters the activity of enzymes that metabolize thyroid hormones

(November 2003)

The background of the study. Patients with severe nonthyroidal illness have many abnormalities in thyroid function, most often low serum triiodothyronine (T3) concentrations and high serum reverse triiodothyronine (rT3) concentrations. (T3 is an active hormone and rT3 is inactive.) These changes are caused by changes in the activity of one or more of the three deiodinase enzymes that remove iodine atoms from thyroxine (T4), T3, or rT3. Serum T4, T3, and rT3 and the activity of the deiodinases in liver and muscle were measured in patients who died during an acute illness.

How the study was done. Serum or biopsies of liver or skeletal muscle were obtained from 80 patients who died of cardiovascular collapse, sepsis, multiple organ failure, or severe brain damage. Serum T4, T3, rT3, and thyrotropin (TSH) were measured, and the activity of the deiodinases was determined by measuring the formation of iodine-125 in tissue homogenates incubated with iodine-125-labeled T4, T3, or rT3.

The results of the study. The patients had low serum T4 and T3 values, high serum rT3 values, and low serum TSH values. Liver deiodination of T4 to T3 was decreased, and liver and muscle deiodination of T4 to rT3 was increased. Hepatic T4 to T3 deiodinating activity was lowest in the patients who died from cardiovascular collapse, and highest (and normal) in the patients who died from severe brain damage. This activity was low in patients with acute renal failure, and was negatively correlated with serum creatinine concentrations in all patients.

The conclusions of the study. Critically ill patients have alterations in the activity of the deiodinating enzymes that activate and inactivate T4. Whether these changes are beneficial or harmful is not known.

The original article. Peeters RP, Wouters PJ, Kaptein E, van Toor H, Visser TJ, Van den Berghe G. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab 2003;88:3202-11.