The diagnosis of growth hormone deficiency (GHD) in successfully treated acromegalic patients

OBJECTIVE Due to persistent qualitative abnormalities in GH secretion follo wing treatment, and lack of a sensitive marker of GHD in mid-adult life it is extremely difficult to diagnose GHD in treated acromegalic patients. The diagnosis of GHD in patients with pituitary disease relies on provocative tests of GH reserve. Arginine releases GH by reducing somatostatin inhibiti on of GH release, whereas GH secretagogues (GHS) affect GH release by direc t stimulation of the GHS receptor, though an intact GH releasing hormone (G HRH) axis is a prerequisite. The peak GH response to insulin-induced hypogl ycaemia and arginine in acromegalic patients, in whom basal serum GH levels of less than 5 mU/l have been achieved, is greatly diminished in those tre ated by hypothalamo-pituitary irradiation. We aimed to study the response o f successfully treated acromegalic patients to the growth hormone secretago gue hexarelin in view of its different putative mechanism of action, and in addition, to determine whether it has any value in the diagnosis of GH def iciency in this subset of patients. PATIENTS Nineteen acromegalic patients, in whom mean serum GH levels below 5 mU/l have been achieved through treatment, were recruited. Eight of the p atients had been treated by surgery alone (Group A) and 11 had received pri mary or postoperative irradiation (Group B). MEASUREMENTS All patients underwent 20 min blood sampling to provide a 24-h GH profile. Serum IGF-I was measured from a sample drawn between 0900 h an d 1000 h. On a second visit arginine 20 g/m(2) was infused over 30 min, blo od samples were taken before commencing the infusion and at 30-min interval s thereafter for 180 min. At the final visit hexarelin 1.5 mcg/kg was admin istered as an intravenous bolus at t = 0. Blood was drawn at 15-min interva ls from - 30 to 180 min. RESULTS All patients in group A showed an increment in serum GH following h exarelin (Delta GH(HEX)) > 20 mU/l, a normal response to arginine, and a me an 24-h GH > 0.5 mU/l. In group B only 4/11 achieved a Delta GH(HEX) > 20 m U/l, 5/11 producing a response of < 2 mU/l. Four of the five patients with a Delta GH(HEX) < 2 mU/l were also demonstrated to have a mean 24-h GH of < 0.5 mU/l and serum IGF-I SDS < + 0.5. All four patients in Group B who ach ieved a Delta GH(HEX) > 20 mU/l, were observed to show an absent or minimal GH response to arginine. CONCLUSIONS Despite loss of the GH response to arginine, the Delta GH(HEX) is retained in a proportion of those patients in whom 'safe' GH levels were achieved following irradiation. From the putative mechanisms of action of these provocative agents a plausible explanation would be that the GHRH axi s is more resilient than endogenous somatostatin-secreting neurones to radi ation-induced damage. Furthermore, GH secretagogues may have a role, in com bination with serum IGF-I levels, in the diagnosis of GH deficiency in trea ted acromegaly.