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 microg/kg bw) leading to normal fT4; 
BW-ADAPTED-T4 (1.6 microg/kg bw T(4)); and "BW-ADAPTED-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 T(3) (fT(3)) levels.
LIMITATIONS: Long-term side effects may have been missed.
CONCLUSIONS: Using a dose of 1.6 microg/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.