In a prospective randomized placebo-controlled study, we assessed potential physiological effects of nonthyroidal illness syndrome (NTIS) in acute illness. Coronary artery bypass graft surgery was employed as a prospective model of acute illness and NTIS. Triiodothyronine (T(3)) or placebo was infused for 24 h after surgery, with a T(3) dose selected to maintain postoperative serum T(3) concentrations at preoperative levels. Patients were evaluated before coronary artery bypass graft and during the postoperative period. Cardiovascular function was monitored with Swan-Ganz catheter measurements and ECG. Urinary nitrogen excretion and L-[1-(13)C]leucine flux were used to evaluate protein metabolism. Serum measurements of relevant hormones, iron, and total iron-binding capacity were used to assess effects on sex steroid, growth hormone axis, and iron responses to illness. Cardiovascular function was not affected by T(3) infusion, except for a transient higher cardiac index in the T(3) group 6 h after surgery (3.04 +/- 0.12 for T(3) and 2.53 +/- 0.08 for placebo, P = 0.0016). Protein metabolism was not affected; changes in urinary nitrogen excretion and L-[1-(13)C]leucine flux were equivalent in the two groups (P = 0.35 and P = 0.95, respectively). No differences were observed in changes in testosterone, estrogens, growth hormone, insulin-like growth hormone I, iron, or total iron-binding capacity between T(3) and placebo groups. We conclude that, in the early stages of major illness, the decrease in circulating T(3) concentrations in NTIS has only a minimal transient physiological impact on cardiac function and plays no significant role in protecting against protein catabolism or modulating other endocrine responses or iron responses to illness.