Hypercalcemia Etiologies in Pediatric Patients: An Informative Narrative Review

Background: Hypercalcemia, although less prevalent, is a critical diagnosis in pediatric patients, consisting of numerous etiologies that differ significantly from those in adults. In children, congenital causes are more prevalent. The differential diagnosis of hypercalcemia encompasses a broad spectrum of etiologies; however, up to 90% of all cases are diagnosed with either primary hyperparathyroidism or malignancy. Primary hyperparathyroidism predominates in ambulatory patients, while malignancy is more common among critically ill hospitalized patients. Objectives: This review addresses several important issues related to calcium metabolism and hypercalcemia: (a) overview of Calcium Metabolism; (b) factors affecting serum total and ionized calcium concentration; (c) clinical manifestations and importance of Hypercalcemia in pediatric patients; (d) overview of the causes of Hypercalcemia in pediatric patients; (e) overview of Hypercalcemia management. Methods: A literature search was conducted for articles published from 2000 to 2024 using PubMed, Scopus, Web of Science, Cochrane, and Embase databases. The keywords used were: CALCIUM, Calcium metabolism disorders, hypercalcemia, Parathyroid hormone, Vitamin D, and acid-base imbalance. Results: This study provides a review of calcium metabolism and factors affecting total and ionized calcium concentrations, along with a definition of hypercalcemia, classification of its severity, its clinical manifestations, and a comprehensive overview of hypercalcemia etiologies categorized into parathyroid hormone (PTH)-related and unrelated causes. An overview of its management is also included. Conclusions: Hypercalcemia is an important disorder in both pediatric and adult patients. Before initiating a workup for hypercalcemia, it is crucial to understand the physiology of calcium and the factors affecting its serum concentrations. The etiologies of hypercalcemia in pediatric patients have a wide spectrum of differential diagnoses; primary hyperparathyroidism and malignancies account for 80-90% of all hypercalcemia cases found in clinical practice. Genetic and syndromic causes are usually more prevalent in pediatrics due to the nature of these conditions. Managing hypercalcemia requires two simultaneous approaches: First, measures aimed at lowering serum calcium concentrations and second, a workup for the underlying cause.