Dissociation of the early decline in serum T-3 concentration and serum IL-6 rise and TNF alpha in nonthyroidal illness syndrome induced by abdominal surgery

The etiology of the prompt decline in serum T-3, in patients with nonthyroi dal illness syndrome has not been adequately explained. It has been attribu ted to various parameters, including test artifacts, inhibitors of T-4 and T-3 binding to proteins, decreased 5'-deiodinase activity, and circulating cytokines. Currently, much attention is centered on the role of IL-6 and TN F alpha in developing the nonthyroidal illness syndrome through an effect o n the hypothalamus, pituitary, and possibly 5'-deiodinase activity. We therefore studied the relation of the endogenous serum IL-6 and TNF alph a rise early in the course of nonthyroidal illness syndrome to the early de cline in serum T-3 in 19 apparently healthy individuals, aged 43 +/- 16 yr, who underwent elective abdominal surgery for cholelithiasis or gastroplast y. Serum T-3, free T-3, T-4, free T-4, rT(3), TSH, IL-6, and TNF alpha were measured before and at various time intervals up to 42 h after skin incisi on. We observed a prompt decline in serum T-3 30 min before skin incision, which continued to decline throughout the observational period. The magnitu de of the decline reached 20% from the baseline value at 2 h. The early dec line of T-3 was attenuated and lasted from the 2-8 h, probably due to the s harp increase in serum TSH that started immediately after the entrance to t he operating room and lasted for 2 h. In contrast, serum T-4 and free T-4 c oncentrations were increased soon after skin incision and remained elevated during the first postoperative day. Serum rT(3) increased approximately 6 h after the initiation of surgery and remained elevated thereafter. Serum I L-6 remained essentially undetectable for 2 h after skin incision, whereas serum T-3 was low. Two hours after skin incision, serum IL-6 increased shar ply and remained elevated throughout the observational period. Serum TNF al pha remained essentially undetectable throughout the postoperative period. Serum cortisol increased rapidly upon entrance to the operating room and re mained elevated throughout the postoperative period. We conclude that the decline in serum T-3 early in the course of nonthyroid al illness syndrome is not due to increased serum IL-6 or TNF alpha levels. The brisk TSH secretion soon after the onset of the syndrome attenuates th e decline in serum T-3 due to T-3 secretion from the thyroid. The early and brisk cortisol response to surgery may at least in part explain the early decrease in serum T-3 in nonthyroidal illness syndrome.