title: Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine.
abstract: 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.
authors: Division of Endocrinology and Diabetes, University Hospital Freiburg, 79104 Freiburg, Germany.
authors: Marc
authors: M
authors: Slawik
authors: Björn
authors: B
authors: Klawitter
authors: Edith
authors: E
authors: Meiser
authors: Marcus
authors: M
authors: Schories
authors: Oliver
authors: O
authors: Zwermann
authors: Katrin
authors: K
authors: Borm
authors: Martin
authors: M
authors: Peper
authors: Beate
authors: B
authors: Lubrich
authors: Martin J
authors: MJ
authors: Hug
authors: Markus
authors: M
authors: Nauck
authors: Manfred
authors: M
authors: Olschewski
authors: Felix
authors: F
authors: Beuschlein
authors: Martin
authors: M
authors: Reincke
mesh_terms: 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*
chemical_list: D004338:Drug Combinations; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013974:Thyroxine