Adult GH deficiency in Japanese patients: effects of GH treatment in a randomised, placebo-controlled trial

Abstract

Objective: To evaluate the influence of factors intrinsic to the Japanese population on consequences of growth hormone deficiency (GHD) and effects of GH treatment in adult Japanese hypopituitary patients with GHD. Study design: A 24-week, randomised, placebo-controlled, double-blind study in 64 patients in Japan, with GHD onset during adulthood (AO; n ¼ 27) or childhood (CO; n ¼ 37). Body composition measured by dual-energy X-ray absorptiometry (DXA) was evaluated centrally. Serum IGF-I, IGF binding protein-3 (IGFBP-3) and lipid levels were determined centrally. Results: In contrast to Caucasian patients, there were no significant differences before treatment between AO and CO patients for body mass index (BMI), lean body mass (LBM) and fat mass (FM). Baseline BMI was $ 25 kg/m 2 for 32.8% of patients. For all patients combined, a significant increase in LBM and decrease in FM (P , 0.001 for each) was seen with GH treatment. Serum IGF-I and IGFBP-3 were significantly lower at baseline in CO compared with AO patients, similar to Caucasian patients, and were increased in both onsets following GH treatment. Serum total and low-density lipoprotein (LDL)-cholesterol concentrations did not differ between AO and CO patients at baseline and were elevated compared with normal ranges. GH-induced decreases were significant compared with placebo for both total (P ¼ 0.036) and LDL-cholesterol (P ¼ 0.040). Glycosylated haemoglobin was increased with GH compared with placebo treatment (P ¼ 0.016) but remained within the upper limit of normal for all patients at endpoint. Conclusions: Adult Japanese hypopituitary patients with GHD demonstrated obesity relative to healthy Japanese subjects but the clinical presentation differed from that of Caucasian patients. GH treatment improved body composition and serum cholesterol profiles of adult Japanese hypopituitary patients with GHD. European Journal of Endocrinology 151 343-350

Growth Hormone (GH) Effects on Central Fat Accumulation in Adult Japanese GH Deficient Patients: 6-month Fixed-dose Effects Persist during Second 6-month Individualized-dose Phase

“…This was less pronounced in CO subjects, who exhibited the same pattern of IGF-I changes but at significantly lower levels. These results confirm a variety of studies in Caucasians [16][17][18] and also in Japanese [19], showing that adult CO GHD patients have lower baseline as well as GH-stimulated IGF-I levels than AO patients.…”

Heterogeneity in responsiveness of perceived quality of life to body composition changes between adult- and childhood-onset Japanese hypopituitary adults with GH deficiency during GH replacement

“…Despite various psychological and cognitive deficits, as well as an abnormal lipid profile and central adiposity, young patients with CO GHD who discontinue pediatric GH replacement exhibit only mild impairment of QoL when compared with GH-sufficient peers (14,15). Our CO patients have also consistently shown findings adverse to those characteristic of adult GHD, such as abnormal body composition and lipid profile at baseline (8). These findings may suggest another possibility, namely CO patients have adapted to the chronic effects of GHD during development and do not perceive their QoL as impaired (5,14,16) Responsiveness, defined as the ability to detect a change due to a treatment, is an important characteristic of a QoL instrument (17).…”

“…In previous reports on Japanese hypopituitary adults with GHD (8,9), it was demonstrated that the effects of GH replacement on body composition were comparable to those seen in Caucasian patients. QoL before and after GH replacement was assessed with the SF-36 in these studies, whose results have not been reported thus far.…”

“…The studies were performed with appropriate local ethical approval according to the Declaration of Helsinki and all enrolled patients gave informed consent to participate in both the studies. Details of diagnosis, exclusion criteria, concomitant therapy including other hormone replacement, dose regimen, and clinical observations for both studies have been reported previously (8,9).…”

“…To obviate physician influence, the patient completed the questionnaire and returned it in a sealed envelope to hospital staff before interview with the attending physician. Body composition was determined at 24-week intervals throughout the studies by dual-energy X-ray absorptiometry (DXA), as previously described (8,9). Blood sampling for measurement of serum IGF-I levels and other laboratory parameters was also performed at the scheduled visits, with the assays performed centrally (8,9).…”