Hypercalcaemia and hyperparathyroidism

The single test that organises everything in paediatric hypercalcaemia is the parathyroid hormone level. When calcium is high, a normal parathyroid axis switches PTH off. So a PTH that has not switched off is the signature of a parathyroid-driven process, and a PTH that has switched off sends you looking elsewhere. Holding that fork in mind turns a long differential into two short lists and a clear plan. ^{[1] [6]}

This page covers the recognition and management of hypercalcaemia and hyperparathyroidism in children: the PTH-based classification that splits every high calcium, the urine calcium-to-creatinine clearance ratio that separates familial hypocalciuric hypercalcaemia from primary hyperparathyroidism, the saline-first resuscitation of hypercalcaemic crisis, the calcitonin-then-bisphosphonate drug sequence, the hereditary syndromes (MEN1, hyperparathyroid-jaw tumour, neonatal severe hyperparathyroidism), and the surgical pathway for parathyroidectomy. It links to the calcium-magnesium-phosphate leaf for broader electrolyte detail. ^{[1] [7]}

Overview & Definition

Hypercalcaemia is a serum calcium above the age-appropriate reference range, taken as an adjusted (albumin-corrected) calcium above 2.6 mmol/L or an ionised calcium above 1.3 mmol/L. The total calcium must be corrected for albumin, because nearly half of circulating calcium is protein-bound and a low albumin hides a high ionised fraction: add 0.02 mmol per litre for every gram per litre that the albumin sits below forty. ^[6]

What makes paediatric hypercalcaemia distinctive is that it is uncommon and that the causes cluster by age. Neonates present with inherited calcium-sensing receptor disorders, Williams syndrome, subcutaneous fat necrosis and iatrogenic causes. School-age children and adolescents more often have primary hyperparathyroidism or vitamin D intoxication. The threshold for action is the same regardless of cause: a symptomatic child or a calcium above 3.5 mmol per litre is an emergency, because the rising calcium poisons renal concentrating ability, depresses the central nervous system and shortens the cardiac QT interval. ^{[6] [10]}

References10ShowHide

1. [1]Bilezikian JP; Khan AA; Silverberg SJ; Fuleihan GE; et al Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop. J Bone Miner Res, 2022.PMID 36245251
2. [2]Bilezikian JP; Brandi ML; Eastell R; Silverberg SJ; et al Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab, 2014.PMID 25162665
3. [3]Khan AA; Hanley DA; Rizzoli R; Bollerslev J; et al Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int, 2017.PMID 27613721
4. [4]Marcocci C; Bollerslev J; Khan AA; Shoback DM Medical management of primary hyperparathyroidism: proceedings of the fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism. J Clin Endocrinol Metab, 2014.PMID 25162668
5. [5]Kollars J; Zarroug AE; van Heerden J; Lteif A; et al Primary hyperparathyroidism in pediatric patients. Pediatrics, 2005.PMID 15805373
6. [6]Gorvin CM Genetic causes of neonatal and infantile hypercalcaemia. Pediatr Nephrol, 2022.PMID 33990852
7. [7]Marx SJ; Goltzman D Evolution of Our Understanding of the Hyperparathyroid Syndromes: A Historical Perspective. J Bone Miner Res, 2019.PMID 30536424
8. [8]Marx SJ; Simonds WF; Agarwal SK; Burns AL; et al Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res, 2002.PMID 12412776
9. [9]Pidasheva S; Canaff L; Simonds WF; Marx SJ; et al Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia. Hum Mol Genet, 2005.PMID 15879434
10. [10]Hobbs A; Nair R; Ludwig K; Ambler GR; et al Denosumab as a treatment for pediatric hypercalcemia-a multicenter experience. JBMR Plus, 2026.PMID 41522662