title: Exercise capacity and hormonal response in adults with childhood onset growth hormone deficiency during long-term somatropin treatment.
abstract: Growth hormone (GH) deficiency in adults in associated with reduced muscular strength and peak oxygen uptake (peak Vo2). How these variables are influenced by long-term somatropin therapy in adults with childhood onset GH-deficiency has not been precisely defined. The effect of somatropin treatment in 20 childhood onset GH-deficient adults on muscular strength, maximal exercise capacity, and hormonal response to exercise were therefore examined in a double-blind placebo-controlled study with recombinant human GH (rhGH, 12 microg/kg/day) for 6 months, followed by 36 months of open-labeled uninterrupted therapy, after which treatment was stopped for 9 months. After 6 months of treatment, exercise capacity increased significantly, as assessed by time to exhaustion [mean change (95% CI) 0.8 (0.2, 1.4) min, P<0.05], total (accumulated) work [11.6 (0.8, 22.4) kJ, P<0.05] and peak Vo2 [2.6 (0.3, 4.9) ml/kg/min, P<0.01], whereas no significant changes were observed during placebo. This effect on exercise capacity remained unchanged during long-term somatropin treatment, mainly due to increased capacity among patients with isolated GH deficiency. Nine months after stopping treatment, peak Vo2 decreased by 11% from 32.8+/-2.5 to 29.1+/-2.1 ml/kg/min (P<0.05). Maximal muscular handgrip strength was not affected by treatment. Long-term GH therapy resulted in decreased respiratory exchange value (R value) at rest and during exercise (P<0.001), suggesting a metabolic role with increased fat combustion. Resting and submaximal noradrenaline levels decreased during somatropin treatment (P<0.05), while no effect was observed for other exercise-induced hormonal responses, including adrenaline, insulin, prolactin, renin, and ACTH. We conclude that somatropin therapy to childhood onset GH deficient adults has a favourable effect on exercise capacity and may have a potentially beneficial effect on plasma catecholamines.
authors.affiliation: Medical Department B, Rikshospitalet University Hospital, Oslo, Norway. lagulles@onlin.no
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
authors.forename: K
authors.initials: K
authors.lastname: Birkeland
authors.forename: R
authors.initials: R
authors.lastname: Bjønerheim
authors.forename: O
authors.initials: O
authors.lastname: Djøseland
authors.forename: O
authors.initials: O
authors.lastname: Trygstad
authors.forename: S
authors.initials: S
authors.lastname: Simonsen
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002395:Catecholamines / Q000097:blood; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000188:drug therapy*; D006439:Hemodynamics; D006728:Hormones / Q000097:blood*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D010100:Oxygen / Q000493:pharmacokinetics; D011388:Prolactin / Q000097:blood; D011659:Pulmonary Gas Exchange
chemical_list: D002395:Catecholamines; D006728:Hormones; D007328:Insulin; D007773:Lactates; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D010100:Oxygen