Comparison of continuation or cessation of growth hormone HGH therapy on body composition and metabolic status in adolescents with severe HGH deficiency at completion of linear growth.

Carroll PV - J Clin Endocrinol Metab - 01-AUG-2004; 89(8): 3890-5
NLM Citation ID:
15292323 (PubMed)
Full Source Title:
Journal of Clinical Endocrinology and Metabolism
Publication Type:
Clinical Trial; Journal Article; Multicenter Study
Author Affiliation:
Department of Endocrinology, St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom.
Carroll PV; Drake WM; Maher KT; Metcalfe K; Shaw NJ; Dunger DB; Cheetham TD; Camacho-Hübner C; Savage MO; Monson JP
Although HGH replacement improves the features of HGH deficiency (GHD) in adults, it has yet to be established whether cessation of HGH at completion of childhood growth results in adverse consequences for the adolescent with GHD. Effects of continuation or cessation of GH on body composition, insulin sensitivity, and lipid levels were studied in 24 adolescents (13 males, 11 females, aged 17.0 +/- 0.3, yr, mean +/- se, puberty stage 4 or 5) in whom height velocity was less than 2 cm/yr. Provocative testing confirmed severe GHD [peak GH < 9 mU/liter (3 microg/liter)] in all cases and was followed by a lead-in period of 3 months during which the pediatric dose of HGH continued unchanged. Baseline investigations were then performed using dual-energy x-ray absorptiometry (body composition), lipid measurements, and assessment of insulin sensitivity by both homeostasis model assessment and a short insulin tolerance test. Twelve patients remained on HGH (0.35 U/kg.wk), and 12 patients ceased GH treatment. The groups were followed up in parallel with repeat observations made after 6 and 12 months.No endocrine differences were evident between the groups at baseline. GH cessation resulted in a reduction of serum IGF-I Z score [-1.62 +/- 0.29, baseline vs. -2.52 +/- 0.12, 6 months (P < 0.05) vs. -2.52 +/- 0.10, 12 months (P < 0.01)] but values remained unchanged in those continuing GH replacement. Lean body mass increased by 2.5 +/- 0.5 kg ( approximately 6%) over 12 months in those receiving HGH but was unchanged after HGH discontinuation. Cessation of HGH resulted in increased insulin sensitivity [short insulin tolerance test, 153 +/- 22 micromol/liter.min, baseline vs. 187 +/- 20, 6 months (P < 0.05) vs. 204 +/- 14, 12 months (P = 0.05)], but no significant change was seen during 12 months of HGH continuation. Lipid levels remained unaltered in both groups. Continuation of HGH at completion of linear growth resulted in ongoing accrual of lean body mass (LBM), whereas skeletal muscle mass remained static after HGH cessation in these adolescents with GHD. This divergence of gain in LBM is of potential importance because increases in LBM occur as a feature of healthy late adolescent development. HGH is a major mediator of insulin sensitivity, independent of body composition in adolescents. Further studies are required to determine whether discontinuation of HGH in the adolescent with severe GHD once linear growth is complete results in long-term irreversible adverse physical and metabolic consequences and to determine conclusively the benefits of continuing HGH therapy.
Major Subjects:

Additional Subjects:

Chemical Compound Name:
(Lipids); 12629-01-5(Human Growth Hormone); 67763-96-6(Insulin-Like Growth Factor I); 9002-72-6(Human Growth Hormone)

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