Hypercalcemia Etiologies in Pediatric Patients: An Informative Narrative Review

Abstract

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.