Pre-treatment IGF-I level is the major determinant of GH dosage in adult GH deficiency.

Abstract

OBJECTIVE: Severe GH deficiency in adults is a definite clinical entity, the effects of which can be reversed by administration of subcutaneous recombinant GH. The ideal dosing regimen and determinants of the maintenance dose have, however, yet to be elucidated. PATIENTS: In an open study of GH replacement we treated 65 GH-deficient adults of mixed adult- and childhood-onset, of mean age 35.5 (range 17-72) years, and comprising 38 females and 27 males, using an individualized low-dose titration regimen aimed at normalization of the serum IGF-I and induction of clinical improvement. RESULTS: Before initiation of GH therapy, median IGF-I SD was significantly lower in female than male patients (- 3.3 vs. - 1.9, P = 0.007) and in childhood-onset compared with adult-onset patients (- 3.9 vs. - 2.0, P < 0.001). Once maintenance dosage had been achieved, the median GH requirement was significantly greater in female than male patients (1.6 vs. 0.8 IU/day, P = 0.013) and childhood-onset compared with adult-onset patients (1.6 vs. 0.8 IU/day, P = 0.019). The median maintenance GH dose for the cohort overall was 1.2 (range 0.4-2.4) IU/day. By univariate analysis a significant negative correlation was observed between the maintenance GH dose and baseline IGF-I SD (r = - 0.63, P < 0.001). No significant correlation was demonstrated between maintenance GH dose and either age or weight. Multiple linear regression analysis using age, gender, weight, time of onset of GH deficiency, peak GH to the insulin tolerance test (ITT) and baseline IGF-I SD as independent variables demonstrated baseline IGF-I SD to account for 51% of the variation in GH dose required to normalize the IGF-I SD (P < 0.001). Those patients with the lower IGF-I SD at initiation of GH therapy required the greater GH dose. None of the other variables studied significantly influenced the maintenance dose. CONCLUSION: We have demonstrated that the GH dose required in an individual is dependent on the serum IGF-I SD before commencement of replacement. In contrast, the severity of GH deficiency as judged by the peak GH response to an ITT was unrelated to the maintenance GH requirement. The effect of age, gender and age at onset of GH deficiency on the final GH dose are accounted for by the lower pretreatment IGF-I SD in young, female and childhood-onset patients relative to older, male and adult-onset patients, respectively.