Growth hormone (GH) responses to GH-releasing hormone alone or combined with arginine in patients with adrenal incidentaloma: Evidence for enhanced somatostatinergic tone

Spontaneous and stimulated GH secretion is blunted in hypercortisolemic sta tes due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incid entally discovered adrenal adenomas. They represent an interesting model fo r studying GH secretion, as a slight degree of cortisol excess may frequent ly be observed in such patients who do not present with any clear Cushingoi d sign. In the present study, 10 patients (3 men and 7 women, aged 48-63 yr ) with an adrenal mass discovered serendipitously underwent, on separate oc casions, a GHRH injection alone or combined with an infusion of the functio nal somatostatin antagonist, arginine. Thirteen age-matched healthy volunte ers served as controls. Briefly, arginine (30 g) was infused from -30 to 0 min, and GHRH (100 mu g) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Pla sma IGF-I (RIA after acid-ethanol extraction) was measured in a morning sam ple. The diagnosis of cortical adenoma was based on computed tomography fea tures and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary fre e cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h , morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the creased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexam ethasone in 1; the fifth patient displayed low ACTH and resistance to dexam ethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion an d lower ACTH concentrations than the controls. GH release after GHRH treatm ent was blunted in patients bearing adrenal incidentaloma compared with con trols (Gn peak, 5.7 +/- 5.2 vs. 18.0 +/- 7.0 mu g/L; P < 0.0001), whereas G HRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 +/- 20.3 vs. 33.7 +/- 17.5 mu g/L; P; NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significa ntly greater in patients than in controls (751 +/- 5318 us. 81 +/- 45%; P = 0.0001). Similar data were obtained when comparing GH are a under the curv e after GHRH plus saline or GHRH plus arginine between the 2 groups. In sum mary, the present data suggest that in patients with incidental adrenal ade nomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma.