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.


OBJECTIVE
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.


METHODS
This was a placebo-controlled trial (double-blind, crossover).


METHODS
A total of 29 patients (age 52 +/- 2 yr; females/males, 8/21) with hypopituitarism, including TSH deficiency, participated in the study.


METHODS
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.


CONCLUSIONS
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.
Slawik
Marc
M
Division of Endocrinology and Diabetes, University Hospital Freiburg, 79104 Freiburg, Germany.
Klawitter
Björn
B
Meiser
Edith
E
Schories
Marcus
M
Zwermann
Oliver
O
Borm
Katrin
K
Peper
Martin
M
Lubrich
Beate
B
Hug
Martin J
MJ
Nauck
Markus
M
Olschewski
Manfred
M
Beuschlein
Felix
F
Reincke
Martin
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects; D013963:Thyroid Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D013974:Thyroxine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D004338:Drug Combinations; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013974:Thyroxine