Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.
In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.
Bengtsson
B A
BA
Department of Medicine, Sahlgrenska Hospital, Medical Faculty, University of Goteborg, Sweden.
Edén
S
S
Lönn
L
L
Kvist
H
H
Stokland
A
A
Lindstedt
G
G
Bosaeus
I
I
Tölli
J
J
Sjöström
L
L
Isaksson
O G
OG
D000273:Adipose Tissue; D000328:Adult; D001823:Body Composition; D001834:Body Water; D002118:Calcium / Q000097:blood; D004311:Double-Blind Method; D017097:Electric Impedance; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009132:Muscles; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D010919:Placebos; D011188:Potassium / Q000378:metabolism; D011347:Procollagen / Q000097:blood; D011581:Psychological Tests; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D010281:Parathyroid Hormone; D010710:Phosphates; D010919:Placebos; D011347:Procollagen; D011994:Recombinant Proteins; D014284:Triiodothyronine; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013974:Thyroxine; D011188:Potassium; D002118:Calcium