INDIVIDUALIZED DOSE TITRATION OF GROWTH-HORMONE (GH) DURING GH REPLACEMENT IN HYPOPITUITARY ADULTS

OBJECTIVE Until now, GH treatment in GH-deficient adults has employed dose schedules of GH based on body weight or body surface area and has ignored individual responsiveness to GH. This trial has studied the e ffects of an individualized GH dose adjusted to match a combination of clinical response, normalization of serum IGF-I concentration and bod y composition. DESIGN AND PATIENTS Two closely-matched groups, each co mprising 30 GH-deficient adults, 38 men and 22 women aged 48 years, we re treated with GH for 12 months. The high dose (HD) group,received a target dose of 12 mu g/kg per day and the individualized dose (ID) gro up received an initial daily GH dose of 0.17 or 0.33 mg per day (0.5 a nd I IU, respectively), independent of body weight, with dose adjustme nts thereafter. MEASUREMENTS Serum concentrations of IGF-I, lipoprotei n(a), insulin, calcium, intact PTH, osteocalcin and blood glucose were measured. Body composition was determined according to a 4-compartmen t model using total body potassium and tritiated water as input variab les. Total body nitrogen was measured by in vivo neutron activation an d total body bone mineral content by dual energy X-ray absorptiometry. RESULTS At 12 months, the daily dose of GH was 0.55 +/- 0.03 mg and 0 .45 +/- 0.03 mg in the HD and ID groups, respectively (P < 0.05). In t he HD group, the mean serum IGF-I increased to levels well above the p redicted level, while in the ID group the mean serum IGF-I normalized. Side-effects were experienced by 70% of the subjects in the HD group and by 30% in the ID group (P < 0.001). A similar response to GH in te rms of body composition, glucose homeostasis, lipoprotein(a) and blood pressure was obtained in both treatment groups. However, the treatmen t response in terms of serum calcium, intact PTH and osteocalcin was m ore marked in the HD group. CONCLUSIONS Similar efficacy, with a lower dose of GH and fewer side-effects, was obtained by considering indivi dual responsiveness to GH as compared to higher doses of GH adjusted t o match body weight.