Dehydroepiandrosterone (DHEA) replacement reduces growth hormone (GH) dose requirement in female hypopituitary patients on GH replacement.

GH dose requirement is lower in ACTH replete compared with ACTH deficient hypopituitary patients suggesting that adrenal androgens may augment IGF-I generation for a given GH dose. This study aimed to determine the effect of dehydroepiandrosterone (DHEA) administration on GH dose requirements in hypopituitary adults. A double blind placebo controlled trial was conducted adding 50 mg DHEA to the standard replacement of hypopituitary patients, including GH, over an initial 6 months, followed by an open phase study of 6 months DHEA replacement and a final 2 month washout phase after DHEA withdrawal. The dose of GH was adjusted to achieve a constant serum IGF-I. Thirty female and 21 male hypopituitary patients were enrolled. Data from 26 women and 18 men were analysed after patient withdrawal. The primary outcome objective was the GH dose required to achieve a stable serum IGF-I. Secondary outcome measures were lipoprotein profiles, insulin, insulin sensitivity, IGFBP-3, waist/hip ratio and indices of bone remodelling. DHEA replacement in female patients lead to a 14.6 +/- 20% reduction in the dose of GH for a constant serum IGF-I (P < 0.05, 95% CI: 1.8, 32.7). This was maintained for 12 months and there was a significant fall in serum IGF-I two months after withdrawal of DHEA. There was no change in the male group. DHEA replacement may reduce GH dose requirements in female hypopituitary patients.

Brooke AM ，Kalingag LA ，Miraki-Moud F ，Camacho-Hübner C ，Maher KT ，Walker DM ，Hinson JP ，Monson JP ... -  《CLINICAL ENDOCRINOLOGY》

Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement.

Brooke AM ，Kalingag LA ，Miraki-Moud F ，Camacho-Hübner C ，Maher KT ，Walker DM ，Hinson JP ，Monson JP ... -  《JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM》

Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD).

To assess the effects of a growth hormone (GH) replacement therapy using a GH dose regimen based on serum insulin-like growth factor (IGF-I) concentrations in Japanese adults with GH deficiency (GHD). In this multicentre, uncontrolled, open-label study, Japanese adults with GHD who had received either GH replacement therapy (GH-GH group, n=35) or placebo (Placebo-GH group, n=36) in a previous randomised, double-blind, placebo-controlled trial were treated with GH replacement therapy for 48 weeks. GH treatment was started at a dose of 0.003 mg/kg/day administered by subcutaneous injection for the first 8 weeks, after which the dose was adjusted to maintain patients' serum IGF-I levels within the reference range adjusted for age and gender. Body composition, serum lipids, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured throughout study. Symptom and quality of life scores were also determined. Lean body mass (LBM) was increased compared with baseline (the end of the preceding double-blind trial) at 24 and 48 weeks, with a mean (+/-SD) increase of 1.3% (+/-4.2%) at week 48 in the GH-GH group (an increase of 6.6% [+/-6.0%] from the start of the preceding double-blind trial) and a larger increase of 4.7% (+/-5.9%) in the Placebo-GH group. Body fat mass (BFM) increased slightly from baseline in the GH-GH group with a mean increase of 2.9+/-10.6% at week 48 (a decrease from the start of the preceding double-blind trial at 48 weeks of 7.8% [+/-15.0%]) but decreased by 6.5% (+/-11.7%) at week 48 in the Placebo-GH group. Serum lipids were unchanged or slightly increased from baseline in the GH-GH group but patients' lipid profiles improved in the Placebo-GH group. In patients who received placebo during the double-blind study, individualised GH therapy in this open-label study increased mean LBM at 48 weeks by 6.2+/-6.8% in patients with CO GHD and by 3.0+/-4.4% in patients with AO GHD. Changes in mean LBM and mean BFM at week 48 were +4.1+/-4.5% and -2.4+/-10.5%, respectively, in females and +5.0+/-6.7% and -8.9+/-11.8%, respectively, in males. In patients who received GH treatment during the double-blind study, overall changes in LBM, BFM and IGF-I SD score after 24 weeks and 48 weeks were small, with no significant differences between subgroups. While the overall incidence of adverse events was broadly similar in the GH-GH and Placebo-GH groups (97% and 89%, respectively), the incidence of treatment-related events was higher in the GH-GH group (83% vs 42% in the Placebo-GH group). Most adverse events in both treatment groups were of mild or moderate severity and not clinically significant. The incidences of oedema and cases of high IGF-I during the IGF-I level-adjusted treatment regimen were lower than those during the preceding fixed dose titration. Long-term GH replacement therapy was well tolerated in Japanese adults with GHD. GH treatment maintained the improvements in body composition and lipid profiles in the patients previously treated in the double-blind study (GH-GH group) and improved these parameters in previously untreated patients (Placebo-GH group). Individualised GH administration based on IGF-I levels was well-tolerated and effective.

Chihara K ，Kato Y ，Kohno H ，Takano K ，Tanaka T ，Teramoto A ，Shimatsu A ... -  《GROWTH HORMONE & IGF RESEARCH》

Dehydroepiandrosterone supplementation in women with adrenal failure: impact on twenty-four hour GH secretion and IGF-related parameters.

In women, GH secretion is strongly influenced by oestrogen status, whereas the role of androgens is unclear. We, therefore, examined GH secretory dynamics during low vs. normalized androgen levels in women with adrenal failure. Ten females with adrenal failure (AF), mean age of 42 years (range 22-54 years). The effects of 8 days of oral dehydroepiandrosterone (DHEA; 50 mg/day) were studied in a double-blind placebo-controlled, cross-over design. A control group of healthy women was studied once without any treatment. Before and after each treatment period, blood was sampled for measurement of androgens, IGF-I, IGFBP-3 and GHBP. A 24-h GH profile with measurements every 20 min was performed at the end of each period. DHEA supplementation normalized the mean circulating levels of testosterone and androgen precursors. The secretory pattern of GH was unaltered during DHEA [placebo vs. DHEA; half-life 22.83 +/- 1.24 vs. 21.45 +/- 1.19 (min), P = 0.429; pulse frequency 9.9 +/- 0.7 vs. 10.5 +/- 0.5 (/24 h), P = 0.502; total production rate 62.27 +/- 13.44 vs. 52.61 +/- 7.06 (microg/l/day), P = 0.317]. Subgroup analysis, however, indicated that DHEA treatment increased GH secretion in patients not receiving oestrogen (n = 5), whereas the opposite was observed among patients receiving exogenous oestrogen derivatives (n = 5). Compared to the control group (CON), GH half-life was longer in AF (half-life CON: 16.48 +/- 0.91, P = 0.001). The additional features of GH secretion were similar. Unexpectedly, the levels of IGF-I, IGFBP-3 and GHBP were elevated in the patients as compared to controls, without significant effects of DHEA [AF vs. CON. IGF-I: 186 +/- 20 vs. 144 +/- 7 (microg/l), P = 0.04; IGFBP-3: 5196 +/- 224 vs. 3687 +/- 212 (microg/l), P = 0.001; GHBP: 2.27 +/- 0.25 vs. 1.41 +/- 0.13 (nmol/l), P = 0.002]. (1) Short-term DHEA administration in women with adrenal failure normalizes the circulating levels of androgens without uniformly affecting the GH-IGF axis; (2) The observation that exogenous oestradiol may mask a stimulatory effect of DHEA on GH secretion merits future investigation.

Christiansen JJ ，Gravholt CH ，Fisker S ，Svenstrup B ，Bennett P ，Veldhuis J ，Andersen M ，Christiansen JS ，Jørgensen JO ... -  《CLINICAL ENDOCRINOLOGY》

The effect of growth hormone substitution on cognitive performance in adult patients with hypopituitarism.

Oertel H ，Schneider HJ ，Stalla GK ，Holsboer F ，Zihl J ... -  《PSYCHONEUROENDOCRINOLOGY》