Endocrine Abstracts

JOINT3601

Introduction: It has become increasingly evident that many effects on hormone secretion—most notably for insulin—previously attributed to glucose per se, are partially mediated by hormones released from the gastro-intestinal tract. It is unknown if gastrointestinal tract deviated hormones are involved in the suppression of growth hormone (GH) during oral glucose intake. Interestingly, about 30% of patients with acromegaly show a paradoxical GH increase during an oral glucose tolerance test (OGTT). This phenomenon has been attributed to the presence of GIP receptors on a subset of GH-secreting adenomas, thereby linking GH secretion to gut-hormones.

Materials and Methods: 12 healthy controls (6 women, mean age 48 years) underwent a 2-hour OGTT and an isoglycemic intravenous glucose infusion on a separate day, with sequential GH, insulin, glucagon, GLP1 and GIP measurement. The effect of oral vs. intravenous (IV) glucose on plasma GH, insulin, glucagon, GLP1 and GIP was assessed by a mixed-effect model and by area under the curve (AUC).

Results: GH levels were significantly influenced by the route of glucose administration (P = 0. 005, mixed effect model). During iv glucose, 9/12 participants showed a paradoxical increase in GH within the first 20 minutes post-exposition. The AUC (median (range)) during OGTT was 70 (6-178) vs. 56 (6-474) mg/lxmin during IV glucose (P = 0. 20). During OGTT, one participant did not reach the threshold (<0. 4 mg/l) for excluding acromegaly (nadir GH 0. 66 mg/l), whereas two did not meet the criteria during iv glucose (nadir 0. 72 and 2. 68 mg/l). AUC was significantly reduced during IV vs. oral glucoseload for insulin (P < 0. 001), glucagon (P = 0. 018), GLP1 (P = 0. 002) and GIP (P < 0. 001) Similar results were obtained using mixed effect models with all P-values < 0. 001

Conclusion: Our findings suggest that gastrointestinal-derived hormones may play a physiological role in suppressing GH secretion. As one hypothesis, reduced ghrelin during oral administration may contribute to GH suppression. However, previous studies have reported conflicting results regarding the impact of oral vs. IV glucose on plasma ghrelin levels. We observed significant differences in insulin, glucagon, GIP and GLP-1 levels between the two conditions, which might also influence GH secretion. Further investigations are needed to elucidate the precise mechanisms underlying these observations.