L-Tri-iodothyronine is a major determinant of resting energy expenditure in underweight patients with anorexia nervosa and during weight gain

Abstract

We aimed to define the effect of L-3,5,3'-tri-iodothyronine (T(3)) on metabolic adaptation in underweight patients with anorexia nervosa (AN) as well as during weight gain. This involved clinical investigation of 28 underweight patients with AN, who were compared with 49 normal-weight controls. A subgroup of 17 patients was followed during weight gain. Resting energy expenditure was measured by indirect calorimetry. Body composition was measured by anthropometry as well as bioelectrical impedance analysis. Energy intake (EI) was assessed by a 3-day dietary record. Plasma concentrations of thyroid hormones (thyroxine (T(4)), T(3) and thyrotropin (TSH)) were analyzed by enzyme immunoassays. When compared with normal-weight women, underweight patients with AN had reduced fat mass (FM) (-71.3%), fat-free mass (FFM) (-13.1%), resting energy expenditure (REE) (-21.8%), T(3)- (-33.4%) and T(4)-concentrations (-19.8%) at unchanged TSH. REE remained reduced after adjustment for FFM (-24.6%). T(3) showed a close association with REE. This association remained after adjustment of REE for FFM. Treatment of underweight AN patients resulted in a mean weight gain of 8.3 kg. This was mainly explained by an increase in FM with small or no changes in FFM. REE and T(3) also increased (+9.3% and +33.3% respectively) at unchanged TSH and T(4). There was a highly significant association between weight gain-induced changes in T(3) and changes in adjusted REE (r = 0.78, P < 0.001, based on Pearson's correlation). An increase in plasma T(3) concentrations of 1.8 pmol/l could explain an increase in REE of 0.6 MJ/day (that is, a 32% increase in T(3) was associated with a 13% increase in REE). Our data provide evidence that the low T(3) concentrations add to metabolic adaptation in underweight patients with AN. During weight gain, increases in T(3) are associated with increases in REE, which is independent of FFM. Both results are evidence for a physiologic role of T(3) in modulation of energy expenditure in humans.