Thyroid hormone replacement for central hypothyroidism:: A randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine

Background: Dosage of T-4 in central hypothyroidism is primarily guided by the free serum T-4 level ( fT4). However, the optimum fT4 range is ill defined, and subtle hypothyroidism might be missed using this approach. Objectives: Our aim was to investigate the effects of a body weight (bw)-adapted T-4 treatment, alone or in combination with T-3, on metabolism, well-being, and cognitive function in comparison to a regimen leading to normal fT4. Design: This was a placebo-controlled trial ( double-blind, crossover). Patients: A total of 29 patients ( age 52 +/- 2 yr; females/ males, 8/21) with hypopituitarism, including TSH deficiency, participated in the study. Interventions: Three regimens were compared ( 5 wk each): EMPIRICAL- T4, empirical T-4 dosage (1 +/- 0.05 mu g/ kg bw) leading to normal fT4; BW-ADAPTED- T4 (1.6 mu g/ kg bw T-4); and BW- ADAPT-ED-T3T4, bw-adapted combination of T-3 and T-4 ( ratio of 1:10). Results: BW-ADAPTED-T4 administration increased mean fT4 concentrations to the upper limit of the normal range ( peak levels). Compared with EMPIRICAL- T4, BW- ADAPTED-T4 treatment resulted in a lower body mass index (BMI) ( 29.0 +/- 0.7 vs. 29.5 +/- 0.7 kg/m(2); P < 0.03), lower total cholesterol ( 198 +/- 9 vs. 226 +/- 7 mg/dl; P < 0.01), and lower low-density lipoprotein (LDL) cholesterol ( 116 +/- 5 vs. 135 +/- 7 mg/dl; P < 0.01). BW-ADAPTED-T3T4 treatment was associated with additional beneficial effects on ankle reflex time and working memory but resulted in supraphysiological free serum T3 ( fT(3)) levels. Limitations: Long-term side effects may have been missed. Conclusions: Using a dose of 1.6 mu g/ kg bw improved markers commonly associated with central hypothyroidism. This suggests that T-4 dosage based on bw and aiming at fT4 in the upper reference range is superior to titration of T-4 aiming at middle normal fT4 concentrations in those patients.