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Introduction The secretion of copeptin, an easily measurable surrogate of arginine vasopressin (AVP), is mainly regulated by osmotic and volume stimuli, but also increases in situations of physical stress. Venipuncture has been found to be a stressful procedure, due to physical pain and anxiety, particularly in children. Falsely elevated copeptin concentrations can substantially affect establishment of reference intervals and interpretation of results in conditions such as syndrome of inappropriate antidiuresis, sepsis, infections. We thus tested the hypothesis that venipuncture, as a stressful stimulus, could stimulate copeptin secretion in children. Subjects & Methods We evaluated 92 children (75% males, 5-19 years) enrolled in a study assessing fasting and stimulated serum copeptin concentrations in response to arginine-hydrochloride (500 mg/kg IV in 30 minutes, ArgST) or insulin (0.1 U/Kg IV, insulin tolerance test/ITT) during GH stimulation tests in healthy short children. Subjects underwent phlebotomy for placement of an IV cannula (angiocath) by trained nurses, without percutaneous anesthesia. Copeptin was measured at 0 min. and at sampling times of the expected copeptin peak (60 min post arginine; 45, 60 min post-insulin) by the immunometric B.R.A.H.M.S. Kryptor assay (Quest laboratories) Results Two distinct groups of fasting copeptin values were identified. The majority of subjects, 86/92 (93.5%, "controls") had serum copeptin concentrations in the expected range for overnight fasting (median 9, IQR 6-12, range 2-29 pM/L). Six subjects (6.5%) were outliers with very elevated copeptin values (>50 in one, >100 pM/L in five of them). In 50 controls who underwent ArgST, copeptin increased from a median of 9 (IQR 6-13, range 2-25) to 11 (IQR 8-15, range 2-28) pM/L at 60 min; In the 5 outliers who underwent ArgST, it paradoxically decreased, but remained elevated, from 272 (IQR 154-406, range 62-1361) to 95.5 (IQR58-128, range 42-282) pM/L at 60 min. Similarly, in 8 controls who underwent ITT, copeptin increased minimally from a median of 8 (IQR 7-11, range 5-12) to 10 (IQR10-14, range 6-17) at 45 min, and 9(IQR 2-13, range 8-12) pM/L at 60 min. In the outlier who underwent ITT, copeptin decreased from 202 (0 min) to 63 (45 min) and 51(60 min) pM/L. None of these children had abnormalities of fluid regulation (polydipsia, polyuria, abnormal serum Na+ levels). The highest copeptin level (>1000 pM/L) occurred in a subject who had 3 successive attempts at phlebotomy. Conclusions Very elevated serum concentrations of copeptin occur in a minority of pediatric subjects undergoing phlebotomy, suggesting that pain of venipuncture can be a potent stimulus of copeptin secretion. Unexplained high values were observed in another pediatric study (Bonnet, Clin Endocrinol 2022;96: 47-53). This information is relevant to clinicians measuring copeptin for diagnostic or prognostic purposes or to establish reference values. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m. |
