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Dose-response study of biosynthetic human growth hormone (GH) in GH-deficient children: effects on auxological and
S M de Muinck Keizer-Schrama1, B Rikken, H J Wynne
1Department of Pediatrics, Medical School, Erasmus University, Rotterdam, The Netherlands.
Insights
Higher doses of growth hormone (GH) significantly improved growth in children with GH deficiency (GHD). The 4 IU/m2/day dose showed greater efficacy than 2 IU/m2/day, with comparable bone maturation and no observed adverse effects.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Therapy
- Metabolic Research
Background:
- Growth hormone deficiency (GHD) affects auxological parameters in children.
- Previous studies indicate dose-dependent responses to biosynthetic human growth hormone (GH).
- Understanding optimal dosing is crucial for effective GHD management.
Purpose of the Study:
- To evaluate the dose-response relationship of biosynthetic GH in prepubertal children with GHD.
- To compare auxological and biochemical outcomes between 2 IU and 4 IU GH/m2/day treatment.
- To assess the impact of GH dosing on growth velocity, height, bone maturation, and metabolic markers.
Main Methods:
- A multicenter, dose-response study involving 38 prepubertal children with GHD (21 new, 17 transfer patients).
- Patients received either 2 or 4 IU GH/m2/day subcutaneously for 1-2 years.
- Key parameters measured included height velocity (HV), height standard deviation score (SDS), bone maturation, plasma insulin-like growth factor-I (IGF-I), and lipid profiles.
Main Results:
- Both GH doses significantly increased HV and height SDS in new patients; the 4 IU dose showed a significantly greater increase in HV SDS after GHD severity correction.
- Transfer patients showed significant improvements in HV, height SDS, and predicted adult height only with the 4 IU dose.
- Plasma IGF-I levels increased significantly in new patients, correlating positively with growth response; elevated IGF-I was noted, particularly with the 4 IU dose.
- Lipid profiles showed a trend towards decreased cholesterol and LDL levels; no adverse effects were observed with the higher GH dose.
Conclusions:
- Treatment with 4 IU GH/m2/day resulted in a greater growth response compared to 2 IU/m2/day in both newly diagnosed and previously treated GHD patients.
- Bone maturation remained comparable between the two doses.
- While effective, long-term monitoring of IGF-I levels and lipid metabolism is warranted with higher GH doses.
Abstract:
A multicenter dose-response study evaluated the effect of two different doses of biosynthetic GH on auxological and biochemical parameters in 38 prepubertal children with GH deficiency (GHD). Twenty-one were newly diagnosed, while 17 transfer patients had been on GH treatment for at least 1 yr before the study. New and transfer patients alike were treated with either 2 or 4 IU GH/m2.day sc. At evaluation all new patients had completed 1 yr of treatment, while transfers had completed 2 yr of treatment under study. In the new patients both doses resulted in a significant increase in height velocity (HV) and height SD score (SDS), with comparable bone maturation. After correction for the severity of GHD, the increase in HV SDS was significantly greater with 4 IU than with 2 IU (P less than 0.01). In the transfer patients HV, height SDS, and predicted adult height only increased significantly with 4 IU (P less than 0.05). Bone maturation was comparable for the two doses. There was a significant correlation between first year growth response and GH dose. In the new patients, the plasma insulin-like growth factor-I (IGF-I) concentration increased significantly without a significant difference between dosage groups. There was a positive correlation between growth response and increment of plasma IGF-I SDS. In new and transfer patients alike, above normal plasma IGF-I levels were observed, particularly with 4 IU. Hemoglobin-A1 remained constant with both GH doses in both groups, while cholesterol and LDL levels tended to decrease. In the new patients, the mean apolipoprotein-A1 level was lower than the control value after 1 yr on 4 IU GH. Treatment with 4 IU GH/m2.day led to a greater growth response than a dose of 2 IU in newly diagnosed as well as previously treated GHD patients. Bone maturation was comparable for both doses. No adverse effects were observed with the higher GH dose, but the long term effects on IGF-I and lipid metabolism need further attention.