Basal and stimulated GH secretion in Cushing's syndrome: effects of ghrelin and GHRH+arginine
Andreea Picu1, Elisa Marinazzo1, Flavia Prodam2, Fabio Broglio1, Sara Belcastro2, Gianluca Aimaretti2, Roberta Giordano3, Ezio Ghigo1 & Emanuela Arvat1
GH secretion is usually impaired in active Cushings syndrome (CS), due to concomitant mechanisms, including diminished GHRH and/or increased somatostatin release and impaired pituitary somatotrope responsiveness. Differently, IGF1 levels not parallel GH insufficiency in CS, being reported reduced, normal or increased. Both ghrelin and GHRH+arginine (ARG) are powerful GH secretagogues, influenced by age and/or BMI. In 27 CS (42.7±2.9 years, 28.8±0.9 kg/m2) we evaluated the GH response to both ghrelin (n=27) and GHRH+ARG (n=15), comparing them with those in 27 healthy controls (NS) (43.5±4.1 years, 26.0±1.3 kg/m2). Basal IGF1 levels were assayed in all the subjects. Both ghrelin and GHRH+ARG induced a lower (P<0.05) GH response in CS (28.2±4.0 and 13.5±2.6 μg/l, respectively) than in NS (64.4±6.1 and 39.4±5.2 μg/l, respectively). Similarly to NS, in CS GH levels after ghrelin were higher (P<0.05) than after GHRH+ARG. Differently to NS, in CS both ghrelin- and GHRH+ARG-induced GH levels were independent of age and BMI. A severe GHD was shown in six patients, based on standard and BMI-correlated GH cut-off levels for GHRH+ARG test. No association between GH peaks after both tests and HPA parameters (UFC, basal cortisol levels or peaks cortisol to ghrelin) were found, while IGF1 levels were positively correlated (P<0.01) with basal cortisol in CS. This study shows that: chronic hypercortisolism induces a dissociation between somatotrope and IGF1 secretion, probably due to an inhibitory effect at hypothalamic/pituitaric level associated with a stimulatory hepatic action; the GH-releasing effect of ghrelin in CS is higher than GHRH+ARG; chronic hypercortisolism is likely to override the influence of age and BMI on both basal and stimulated GH/IGF1 activity; testing with ghrelin, given appropriate hormonal cut-off levels, associated with basal IGF1, may be suggested for the assessment of somatotrope function in active phase and possibly during the follow up of treated CS patients.