Very elevated serum copeptin concentrations occur in a subset of healthy children in the minutes after phlebotomy

Shruti Sastry; Christine A. March; Michael J. McPhaul; Luigi R. Garibaldi

doi:10.1515/jpem-2023-0390

Article

Very elevated serum copeptin concentrations occur in a subset of healthy children in the minutes after phlebotomy

Shruti Sastry , Christine A. March , Michael J. McPhaul and Luigi R. Garibaldi

Published/Copyright: November 23, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 1

Abstract

Objectives

Although AVP and its surrogate, copeptin, are mainly regulated by osmotic and volume stimuli, their secretion is also elicited by stress and growth hormone (GH) stimulating agents. The aim of this report is to describe unusual patterns of copeptin response in a subset of children undergoing GH stimulation tests (GH-ST).

Methods

We conducted a secondary analysis of a cohort of 93 healthy short children with no polydipsia, polyuria or fluid/electrolyte abnormalities, undergoing GH-ST with intravenous arginine, insulin, oral clonidine, or L-Dopa/carbidopa in various combinations. Serum copeptin concentrations were measured 1–3 min after phlebotomy (0 min) and at 60, 90, 120 min during GH-ST.

Results

In 85 subjects (normal response group, NRG) serum copeptin concentrations increased from a 0 min median of 9 pmol/L (IQR 6, 11.5) (all values ≤21) to a median peak between 60 and 120 min of 22 (IQR15, 38) pmol/L, which varied depending on the stimulating agent. Conversely, in the eight outliers, copeptin concentrations decreased gradually from a median of 154 (IQR 61, 439) pmol/L (all ≥40 pmol/L) to values as low as 14 % of the basal value, by 120 min. Test-associated anxiety was described in 17 subjects in the NRG (20 %) and five of the outliers (63 %).

Conclusions

A distinctive pattern of very elevated serum copeptin concentrations occurred in 9 % of children undergoing GH-ST, similar to reports in previous pediatric studies. Etiology may include pain or stress of phlebotomy. This phenomenon should be recognized for proper interpretation of copeptin values in children.

Keywords: polyuria; polydipsia; copeptin; stress; phlebotomy

Corresponding author: Christine A. March, MD, MS, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; and Division of Pediatric Endocrinology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA, E-mail: christine.eklund@chp.edu

Acknowledgments

We wish to thank our study participants and all the personnel at both the Children’s Hospital of Pittsburgh and Quest Diagnostics for assisting with specimen handling and laboratory Assays.

Research ethics: This study protocol was reviewed and approved by the University of Pittsburgh Institutional Review Board, approval number 19120068. The study was conducted in accordance with the Declaration of Helsinki.
Informed consent: Written informed consent was obtained from the participants’ parent/legal guardian/next of kin to participate in the study.
Author contributions: Dr. Luigi Garibaldi conceptualized the study. Study activities were completed by Dr. Luigi Garibaldi and Dr. Shruti Sastry, laboratory measurements supervised by Dr. Michael J McPhaul, and analysis by Dr. Christine March. Dr. Luigi Garibaldi drafted the initial manuscript, which was edited by all authors. All authors reviewed and approved the final version of the manuscript.
Competing interests: Dr. Michael J. McPhaul is a consultant for Quest Diagnostics and owns stock in the company. The other authors have no significant conflicts to disclose.
Research funding: Dr. Christine A. March is funded by the University of Pittsburgh Clinical and Translational Science Institute Clinical and Translational Science Scholars Program (NIH/NCATS 1 KL2 TR001856, PI: Rubio).
Data availability: All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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Received: 2023-08-23

Accepted: 2023-11-08

Published Online: 2023-11-23

Published in Print: 2024-01-29

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0390

Keywords for this article

polyuria; polydipsia; copeptin; stress; phlebotomy