Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration

A randomized prospective study was done to assess the response of hypothyroxinemic patients with severe nonthyroidal illnesses to T4 therapy. Patients admitted to a medical intensive care unit who had a total serum T4 concentration less than 5 micrograms/dl were randomly assigned to a control (12 patients) or a T4 treatment group (11 patients). L-T4 in a dose of 1.5 micrograms/kg was given iv each day for 2 weeks. In the treatment group, serum T4 and free T4 concentrations significantly increased by day 3 and were normal on day 5. Serum TSH levels decreased significantly in the T4 treatment group, as did the TSH response to TRH. A significant rise in serum T3 occurred in the control group on day 7, but was delayed until day 10 in the treatment group. Mortality was equivalent in the 2 groups (75% control vs. 73% treatment). Regardless of group assignment, survivors and nonsurvivors were completely separable based on baseline T3 to T4 ratios [17.0 +/- 1.8 (+/- SE) ng/micrograms in survivors vs. 7.0 +/- 0.7 in nonsurvivors; P less than 0.001]. Angiotensin-converting enzyme was significantly reduced in the T4 treatment group, but did not rise significantly in response to treatment. T4 therapy was not beneficial in this population of intensive care unit patients, and by inhibiting TSH secretion, it may suppress an important mechanism for normalization of thyroid function during recovery.