Primary Hyperparathyroidism in Children and Adolescents

Abstract

Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in whom the typical presentation is incidentally discovered as asymptomatic hypercalcemia. PHPT is much less common in children and adolescents, but has greater morbidity in this age group, as most young patients with PHPT will have symptomatic hypercalcemia or complications such as kidney stones, abdominal pain, and skeletal fragility. An important feature of PHPT in younger patients is the relatively high prevalence of germline inactivating mutations of the CASR gene, which encodes the calcium-sensing receptor. Biallelic CASR mutations 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. By contrast, more common heterozygous CASR mutations are generally associated with a benign variant of PHPT termed familial hypocalciuric hypercalcemia. Appropriate management of PHPT in children and adolescents requires distinction between familial hypocalciuric hypercalcemia, which generally requires no specific treatment, and other forms of PHPT that are best treated by parathyroidectomy.

Parathyroid Surgery in Children

“…In children and young adults with primary HPT, 60-92% have a single adenoma and 0-40% have four-gland hyperplasia (2)(3)(4). In both adults and children with primary HPT four gland hyperplasia is more common in patients with hereditary conditions such as Multiple Endocrine Neoplasia Type 1 (MEN1) (1,5) Patients with hyperparathyroidism can have a wide range of symptoms, or they can be asymptomatic (see Table 1) (2,4). Children are more likely to be symptomatic than adults.…”

“…Children are more likely to be symptomatic than adults. In most adult series 30-40% of patients are asymptomatic at presentation while in pediatric series only 0-20% of patients are asymptomatic at presentation (2,4,5). Children are also more likely to present with end organ damage, including pathologic bone fractures, osteitis fibrosa cystica, nephrolithiasis, and pancreatitis (4).…”

“…NSHPT is associated with inactivating mutations in the calcium-sensing receptor genes. Neonates with NSHPT have complete or near-complete absence of functioning calcium-sensing receptors with resulting parathyroid hyperplasia, unregulated PTH secretion, and severe hypercalcemia (5). This rare disease presents in the first few days of life with failure to thrive, hypotonia, and respiratory distress.…”

“…NSHPT must be distinguished from transient neonatal hyperparathyroidism due to maternal hypocalcemia. A milder form of NSHPT results from a monoallelic mutation in the calcium-sensing receptor genes and can result an asymptomatic form of primary HPT, know as familial hypocalciuric hypercalcemia (FHH) (5). In FHH reduced levels of calciumsensing receptors result in modest elevation of PTH and mild hypercalcemia that can be managed with medical intervention alone (5).…”

Intraoperative Parathyroid Hormone Monitoring in Neonatal Severe Primary Hyperparathyroidism

“…It is associated with an inactivating homozygous mutation of the calcium sensing receptor (CaSR) gene. [1][2][3] Total parathyroidectomy is the treatment of choice. Residual or ectopic parathyroid tissue explains persistence of hyperparathyroidism after surgery; any parathyroid remnant quickly becomes hyperplastic.…”