Growth hormone and insulin signaling in acromegaly: Impact of surgery versus somatostatin analog treatment

Abstract

Context: Somatostatin analogs (SAs) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling. Objective: To compare GH and insulin signaling after iv GH exposure in acromegalic patients controlled by surgery (n = 9) or SA (n = 9). Design: Each patient was studied for 3 hours after an overnight fast (t =-60 to 120 minutes). GH was administered at t = 0 minutes; muscle and fat biopsies were obtained at t = 0 minutes and at t = 30 minutes (muscle) and t = 120 minutes (fat). Interstitial fluid was obtained from skin suction blisters (t = 0 minutes). Main Outcome Measures: GH and insulin signalling in muscle and fat. GH and IGF-1 in serum and interstitial fluid; insulin and free fatty acids in serum. Results: The groups were comparable as regards GH and IGF-1. The SA group exhibited higher free fatty acid and glucose levels; basal suppressor of cytokine signaling protein 1 (SOCS1) mRNA in fat was increased in the SA group and correlated positively with SA dose (r2 = 0.54; P =.04). GHinduced GH signalling (pSTAT5b) in muscle occurred in both groups together with increased expression of SOCS and CISH genes. GH-induced pAKTthr308 was observed in SA patients. In both groups, mRNA expression of phosphatase and tensin homolog, a suppressor of insulin signaling, increased in fat after GH. Conclusion: 1) Signatures of GH and insulin signaling differ as a function of acromegaly treatment modality. 2) Extra-pituitary effects of SA may account for this. 3) The clinical implications remain to be investigated.