Details

Autor(en) / Beteiligte

• Berg, C. A.
• Pokrajac, A.
• Bidlingmaier, M.
• Strasburger, C. J.
• Shalet, S. M.
• Trainer, P. J.

Titel

Use of a GH receptor antagonist (GHRA) to explore the relationship between GH and IGF-I in adults with severe GH deficiency (GHD)

Ist Teil von

• Clinical endocrinology (Oxford), 2009-03, Vol.70 (3), p.439-445

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2009

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Summary Objective  At diagnosis, approximately 50% of adults with severe GH deficiency (GHD) have an IGF‐I within the reference range. It is unclear whether in such patients serum IGF‐I levels are regulated by factors other than GH. Design and patients  We performed a double‐blind, randomized, placebo‐controlled, cross‐over study to investigate the effect of the GH receptor antagonist – pegvisomant (20 mg daily for 14 days) on GH and IGF‐I levels in three cohorts: patients with GHD and a normal IGF‐I (NORMS); patients with GHD and a low IGF‐I (LOWS) and healthy volunteers (CONS). Results  Pegvisomant decreased IGF‐I in CONS and NORMS [158·5 (101–206) vs. 103 (77–125) µg/l, P < 0·01; 124 (81–136) vs. 95 (51–113) µg/l, P < 0·01 respectively], but not in LOWS [31 (< 31–32) vs. 34·5 (< 31–38) µg/l], and this was associated with an increase in mean 24 h GH in CONS [0·49 (0·12–0·89) to 1·38 (0·22–2·45) µg/l (P = 0·03)] and in NORMS [69 (0–320)% from 0·1 (< 0·1–0·13) to 0·17 (0·11–0·42) µg/l (P = 0·03)], but not in the LOWS. The peak GH response to arginine was increased by pegvisomant in CONS and NORMS [6·1 (0·8–9) vs. 20·4 (13·1–28·8) µg/l, P = 0·03; 0·4 (0·1–0·5) vs. 0·5 (0·3–0·6) µg/l, respectively], but not in LOWS. Conclusions  These data indicate that patients with severe GHD with a normal IGF‐I are able to increase GH secretion in response to a pegvisomant‐induced fall in IGF‐I, whereas those with low IGF‐I levels are unable to increase GH secretion. Therefore circulating IGF‐I appears to be GH‐independent in GHD patients with a low IGF‐I, but remains partially GH‐dependant in GHD patients with a normal IGF‐I.