A Low Starting Dose of Genotropin in Growth Hormone-Deficient Adults

Abstract

We investigated the effect of 12 weeks of recombinant human GH therapy given in three different doses on serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) in patients with GH deficiency (GHD). We used low doses of recombinant human GH (Genotropin), as we and others recently found a strong decrease in physiological GH production with age in healthy controls, especially in those older than 30 yr. Sixty patients with GHD (aged 20-70 yr) were randomized to one of the three dose groups. Group 1 used a dose of 0.6 IU/day for 12 weeks. Group 2 started at a dose of 0.6 IU for 4 weeks followed by 1.2 IU/day for 8 weeks. Group 3 used 0.6 IU for 4 weeks, followed by 1.2 IU/day for 4 weeks and 1.8 IU/day thereafter. IGF-I concentrations (nanomoles per L) were determined by RIA after extraction and purification on ODS-silica columns. The measurement of IGFBP-3 (milligrams per L) was performed by RIA. The three groups were equal with regard to age, sex and body mass index. At the start of the study, we found lower levels of both serum IGF-I and IGFBP-3 in childhood-onset GHD than in adult-onset GHD. Moreover, there was a gender difference; female GHD patients had lower serum IGF-I levels than male patients. Serum IGF-I levels were low in both childhood-onset and adult-onset GHD. Serum IGFBP-3 levels, however, were low in patients with childhood-onset GHD, but normal in patients with adult-onset GHD. After 12 weeks of treatment, IGF-I levels were low normal in the low dose group and normal in groups 2 and 3 of both adult-onset and childhood-onset GHD. In adult-onset GHD, serum IGFBP-3 increased to high normal levels in all groups, whereas it increased to low normal levels in childhood-onset GHD. This study demonstrates differences in the biochemical characteristics of childhood-onset and adult-onset GHD. In patients with adult-onset GHD, serum IGFBP-3 levels are not significantly decreased and, therefore, cannot be used as a screening method for GHD or as a dose-finding parameter. GH therapy at doses of 0.6 and 1.2 IU/day in male and female patients, respectively, is, in general, able to increase serum IGF-I into the normal range after 12 weeks of treatment, without reaching supranormal levels of serum IGF-I. This dose could, therefore, be a starting dose in GH-deficient adults.

High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly

“…IGF1 is expressed as SDS for age-and gender-related normal levels determined in the same laboratory (20). From 2005 onwards, serum IGF1 concentration (ng/ml) was measured using an immunometric technique on an Immulite 2500 system (Diagnostic Products Corporation, Los Angeles, CA, USA).…”

The prevalence of the metabolic syndrome is increased in patients with GH deficiency, irrespective of long-term substitution with recombinant human GH

“…The detection limit of this assay is 1.5 nmol/l, and the intra-and inter-assay coefficients of variation were below 11%. Age-and gender-adjusted IGF-I data were determined in the same laboratory (13,14). IGF-I was expressed as SDS for age-and gender-related normal levels.…”

Long-term maintenance of the anabolic effects of GH on the skeleton in successfully treated patients with acromegaly

“…Normal values were expressed as age-related S.D. scores derived from normal values in 137 healthy controls (5). Serum GH concentrations were measured before 1992 by RIA (Biolab, Serona, Coissins, Switzerland) calibrated against WHO International Reference Preparations (IRP) 66/21 (detection limit 0.5 mU/l; interassay CV of , 5%).…”