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 and 30 min intravenously (IV) followed by insulin (0.1 units/kg IV) at 60 min. Copeptin serum concentrations were measured at baseline (0 min), at the post-arginine peak (60 min), and at the post-insulin peak (90 min; 30 min 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 min to 13.2 ± 5.8 pmol/L at 60 min (p < 0.0001 vs. 0 min) and 27.7 ± 14.2 pmol/L at 90 min (p < 0.0001 vs. 0 and 60 min). 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.