THU154 The Effects Of Combined Arginine And Sinemet Stimulation On Copeptin Levels In The Pediatric Population

Abstract

Abstract Disclosure: S. Sastry: None. C. March: None. L. Garibaldi: None. M.J. McPhaul: None. S. Wheeler: None. Introduction: Most agents that stimulate the secretion of growth hormone (GH) also induce secretion of copeptin (COP), a stable surrogate of AVP. For the evaluation of the polyuria-polydipsia syndrome (PPS), COP stimulation by intravenous (IV) arginine (ARG) has been proposed as a less invasive test than those based on osmotic stimulation of the posterior pituitary, though it provides a weaker stimulus in children than in adults (∼30% vs. 50% increase). After having observed a robust COP response to combined ARG and insulin stimulation (March C, Horm Res Pediatr 2023, PMID: 36513057), we explored the effect of combined IV ARG and oral L-Dopa/carbidopa (LDc, 10:1 ratio), another known stimulus for GH secretion, on COP secretion in non-AVP deficient children. Subjects and Methods: We enrolled 30 healthy subjects with short stature (73% male, mean age ± SD 10.5±3.0 years) undergoing fasting GH stimulation testing in a prospective, single-arm study to assess their COP response. At 0 minutes (min), ARG (500 mg/kg) was infused over 30 min IV and LDc (200 mg/m2 BSA of L-Dopa) was given orally. Serum COP (B.R.A.H.M.S Kryptor assay, Quest Diagnostics) was measured at 0, 60, 90 and 120 min. Results: Median (interquartile range (IQR)) COP values (pmol/L) were 8 (5-10) at 0 min, 17 (13-44) at 60 min, 24 (13-41) at 90 min, and 30 (16-56) at 120 min. Peak COP concentrations at 60, 90, and 120 min all increased significantly from baseline (p<0.001, Wilcoxon sign rank test), but were highly variable in both value (range 10-449) and the timing of the peak (60 min in 33%, 90 min in 17%, 120 min in 50%). Except for 1 subject whose COP values did not change, all subjects had a robust COP peak, ranging from 1.6 to ∼90x the baseline value. The median (IQR) copeptin peak value [50 (41-129) pmol/L] was higher in subjects experiencing nausea/vomiting than in those who did not show this known side effect of LDc [25 (16-44), p=0.03 by Wilcoxon test]. Conclusions: Combined ARG and LDc appear to induce intense stimulation of COP secretion, with widely variable stimulated COP responses. The lowest COP peak value and the median response in this series were much greater than those previously reported to ARG alone in our previous study and the literature. Side effects were well tolerated. The data suggest that this test should be piloted for the differential diagnosis PPS as an alternative to ARG stimulation alone and/or the water deprivation test. Presentation: Thursday, June 15, 2023