Combined arginine and insulin stimulation elicits a robust and consistent copeptin response in short children

Abstract

Introduction: Copeptin, co-secreted with arginine-vasopressin, is regulated by osmotic and volume stimuli but also responds to intravenous arginine and insulin-induced hypoglycemia. The serum copeptin response to the latter agents has been studied in adults, but only to a limited extent in children. The objective of this study was to describe the copeptin response to combined arginine and insulin in children with normal posterior pituitary function. Methods: We conducted a prospective, single-arm assessment of serum copeptin concentrations in children (age 7-16 years, n=38) undergoing growth hormone stimulation testing with an arginine-insulin tolerance test (AITT) for short stature or growth deceleration in a tertiary referral center. After overnight fasting, arginine (500 mg/kg) was administered between 0-30 minutes intravenously (IV) followed by insulin (0.1 units/kg IV) at 60 minutes. Copeptin serum concentrations were measured at baseline (0 minutes), at the post-arginine peak (60 minutes), and at the post-insulin peak (90 minutes; 30 minutes post-insulin), respectively. The main outcome was the peak copeptin concentration. Results: Mean±SD copeptin concentrations increased from 9.9±5.0 pmol/L at 0 minutes to 13.2±5.8 pmol/L at 60 minutes (p<0.0001 vs. 0 minutes) and 27.7±14.2 pmol/L at 90 minutes (p<0.0001 vs 0 and 60 minutes). There was no significant correlation between copeptin concentrations and age, BMI, pubertal status, cortisol, growth hormone, or glucose concentrations. Discussion/Conclusion: Arginine and insulin appear to have an additive and consistent effect resulting in significant stimulation of copeptin secretion in children. The AITT may be a useful tool to evaluate for normal posterior pituitary function in this age group, with potential implications for the evaluation of polyuria-polydipsia syndrome.