Review Explores Evolving Diagnostic Strategies for Hypotonic Polyuria in Children
November 4, 2025
A team from the Division of Pediatric Endocrinology at UPMC Children’s Hospital of Pittsburgh recently published a review article in the Journal of Pediatric Endocrinology and Metabolism that gives a detailed overview of emerging diagnostic approaches for evaluating polyuria-polydipsia syndrome in pediatric populations.
Luigi R. Garibaldi, MD, professor emeritus of pediatrics, was the first author of the review. Also collaborating on the paper were Shruti Sastry, MD, (former division fellow); Michael McPhaul (Quest Diagnostics); and Christine A. March, MD, MS, assistant professor of pediatrics in the Division.
About the Review - Summary of Learnings for Physicians
Hypotonic polyuria in children, which may be caused by primary polydipsia, central diabetes insipidus, or arginine vasopressin resistance, continues to present clinicians with diagnostic challenges because of the overlapping nature of symptoms with the disorders and the limitations and complexity of traditional testing approaches.
The review from Dr. Garibaldi and colleagues discusses the limitations of traditional arginine vasopressin assays and explains the advantages of using copeptin stimulation as a more stable and easier measurable biomarker for vasopressin activity. The review evaluates a range of osmotic and nonosmotic stimulation tests and provides detailed comparisons of arginine, insulin, glucagon, levodopa, and combination strategies, including the arginine–insulin tolerance test (AITT) and the arginine–levodopa/carbidopa stimulation test (ALD-ST).
Explaining the Division’s Testing Procedures
In the discussion section of Dr. Garibaldi and colleague’s review, they present the division’s institutional experience and diagnostic framework that reflects how the clinical team at UPMC Children’s evaluates children with suspected polyuria-polydipsia syndrome. Based on prior research and clinical testing validation by the team, the division has adopted the arginine–levodopa/carbidopa stimulation test (ALD-ST) as a practical and effective early step in the process, following initial laboratory screening and analysis of fasting serum sodium, copeptin levels, and urine osmolality.
In this approach, ALD-ST is used routinely in the outpatient setting to differentiate primary polydipsia from central diabetes insipidus. Additional testing, including the water deprivation test or pituitary magnetic resonance imaging, is reserved for cases with borderline copeptin responses or persistently unclear clinical findings.
The team also highlights factors that may affect test interpretation, including variability in copeptin thresholds for partial vasopressin deficiency and the impact of procedural stress or nausea on stimulated copeptin levels.
Reference
Read the complete open access review using the following link.
Further Reading on Copeptin Stimulation Testing Research From the Division
- Sastry S, Tas E, Filingeri D, McCann E, Amruthapuri R, McPhaul MJ, Garibaldi L. The Effect of Phlebotomy and Placement of an Intravenous Catheter on Plasma Catecholamine and Serum Copeptin Concentrations. J Pediatr Endocrinol Metab. 2024 Dec 18;38(2):110-115.
- March CA, Sastry S, McPhaul MJ, Wheeler SE, Garibaldi L. Copeptin Stimulation by Combined Intravenous Arginine and Oral LevoDopa/Carbidopa in Healthy Short Children and Children with the Polyuria-Polydipsia Syndrome. Horm Res Paediatr. 2025; 98(3): 316-326.
- Sastry S, March CA, McPhaul MJ, Garibaldi LR. Very Elevated Serum Copeptin Concentrations Occur in a Subset of Healthy Children in the Minutes After Phlebotomy. J Pediatr Endocrinol Metab. 2023 Nov 23; 37(1): 8-14.
- March CA, Sastry S, McPhaul MJ, Wheeler SE, Garibaldi L. Combined Arginine and Insulin Stimulation Elicits a Robust and Consistent Copeptin Response in Short Children. Horm Res Paediatr. 2023; 96(4): 395-403.
