Primary Hyperparathyroidism in Children and Adolescents

Primary hyperparathyroidism (PHPT) is common in adults, and usually presents as incidentally discovered asymptomatic hypercalcemia. By contrast, PHPT is much less common in children and adolescents, but in this age group the disorder has greater urgency as most young patients with PHPT will have symptomatic hypercalcemia or manifest complications such as kidney stones, abdominal pain, and skeletal fragility. A distinguishing feature of PHPT in younger patients is frequent occurrence of germline inactivating mutations of the CASR gene, which encodes the calcium-sensing receptor. Loss-of-function mutations that affect both CASR alleles cause neonatal severe hyperparathyroidism, a life-threatening condition that presents within days of life with marked hypercalcemia, respiratory distress, failure to thrive, and skeletal demineralization. When mutations affect only one CASR, allele patients develop a more benign variant of PHPT termed familial (FHH) hypercalcemia. Due to the relatively common presentation of FHH as hypercalcemia in children and adolescents, it is critically important to distinguish between FHH, which generally requires no specific treatment, and other forms of PHPT that are best treated by parathyroidectomy.