RESTING ENERGY-EXPENDITURE IS SENSITIVE TO SMALL DOSE CHANGES IN PATIENTS ON CHRONIC THYROID-HORMONE REPLACEMENT

We have investigated the effects of modifying the dose of thyroxine on resting energy expenditure (REE) and on the thermic effect of glucose (TEG) in 9 randomly recruited patients on chronic treatment with this hormone. The initial dose was changed twice in each patient at 6-8 wk intervals, aiming to have a normal, a slightly reduced, and a slightl y elevated serum TSH concentration. A total of 27 dose points for each measured variable (3 per patient) were gathered. Dose changes were mo nitored with serum free T-4, T-3, and TSH. At the end of each dose per iod, low density lipoprotein and high density lipoprotein cholesterol, triglycerides, angiotensin converting enzyme, and sex hormone binding globulin were also measured, along with a systematic assessment of sy mptoms and signs. The investigators involved in the measurements were blinded to the dose of T-4. Serum free T-4 and TSH significantly corre lated to the dose in each patient and in the whole group, whereas seru m T-3 levels were minimally affected by the dose and did not correlate with it, with free T-4 or with TSH. This latter was below normal on 9 occasions, normal in 12, and above normal in 6. Serum free T-4 and T- 3 remained within the normal range on all except 2 occasions. REE and TEG were normalized to fat-free mass (FFM). In each patient there was a significant negative correlation between REE and TSH. This correlati on was maintained when all data were pooled (r(2) = 0.64; P < 0.001). Also, initial REE and its change between the highest and the lowest th yroxine dose were significantly correlated with, respectively, initial serum TSH (r(2) = 0.85; P < 0.001) and the change in serum TSH betwee n the highest and the lowest dose of T-4 (r(2) = 0.67; P < 0.0065). RE E decreased approximately 15% when TSH increased between 0.1 and 10 mU /L. In 6 of the 9 patients, TEG increased with the reduction of the do se, and higher values were associated with higher TSH levels but witho ut reaching statistical significance (F = 2.852, P = 0.077). None of t he other indices were significantly affected by the changes in dose. T hese results indicate that, in patients on chronic treatment with thyr oxine, REE is significantly influenced by the dose of this hormone in a dose range encompassing serum TSH concentrations that are considered acceptable in the management of hypothyroid patients. In the absence of physiological or behavioral compensations, these changes in REE may be clinically relevant.