Hypercalcemic Disorders in Children

Abstract

Hypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)‐dependent or PTH‐independent, and may be congenital or acquired. PTH‐independent hypercalcemia, ie, hypercalcemia associated with a suppressed PTH, is commoner in children than PTH‐dependent hypercalcemia. Acquired causes of PTH‐independent hypercalcemia in children include hypervitaminosis; granulomatous disorders, and endocrinopathies. Congenital syndromes associated with PTH‐independent hypercalcemia include idiopathic infantile hypercalcemia (IIH), William's syndrome, and inborn errors of metabolism. PTH‐dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH‐dependent hypercalcemia in neonates include maternal hypocalcemia and extracorporeal membrane oxygenation. PHPT usually occurs as an isolated nonsyndromic and nonhereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis. The management of symptomatic hypercalcemia includes interventions such as fluids, antiresorptive medications, and parathyroid surgery. This article presents a clinical, biochemical, and genetic approach to investigating the causes of pediatric hypercalcemia. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

A case of primary hyperparathyroidism due to an intrathymic ectopic parathyroid adenoma in a 15-year-old boy

“…However, genetic testing should be carried out in PHPT patients who meet the following criteria: young age (<45 years of age); multigland disease; carcinoma or atypical adenoma; a firstdegree relative who is a known mutation carrier; an index case with 2 or more MEN syndrome-associated tumors. 2) In cases where MEN affects multiple glands, subtotal or total parathyroidectomy is recommended. 19) If ectopic parathyroid adenoma is well localized and ioPTH level decreases sharply after resection, minimally invasive parathyroidectomy without bilateral neck exploration could be a better option to avoid unnecessary morbidity in children.…”

“…1) The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)-dependent or PTH-independent and may be either congenital or acquired. 2) Primary hyperparathyroidism (PHPT) accounts for > 90% of hypercalcemia in adults, and most patients with PHPT present with a single adenoma (80%) or hyperplasia (15%-20%) of the parathyroid gland. Parathyroid carcinoma occurs rarely, accounting for <1% of all cases of PHPT.…”

“…2) Pediatric PHPT may occur due to genetic causes, such as familial hypocalciuric hypercalcemia (FHH), familial isolated hyperparathyroidism, and multiple endocrine neoplasia (MEN). 2,4) PHPT is caused by a solitary parathyroid adenoma in 80% of diagnosed adults 5) and 65%-70% of children. 6,7) In a previous study, the authors reported that ectopic parathyroid adenoma accounts for 6%-16% of total parathyroid adenomas, and the most common ectopic location is the thymus, which accounts for 38% of ectopic parathyroid adenomas.…”

“…Hypercalcemia is uncommon in children; patients typically present with characteristic signs/symptoms or may be diagnosed incidentally following investigations for a variety of nonspecific conditions [ 1 ]. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)-dependent or PTH-independent and may be either congenital or acquired [ 2 ]. Primary hyperparathyroidism (PHPT) accounts for > 90% of hypercalcemia in adults, and most patients with PHPT present with a single adenoma (80%) or hyperplasia (15%–20%) of the parathyroid gland.…”

Electrolytes Profile of Critically Ill Patients Admitted To Pediatric Intensive Care Unit (PICU) Dr. Soetomo General Hospital

“…8 Pediatric patients with hypercalcemia were far fewer cases than the incidence rate in adult patients and one of the causes of hypercalcemia was impaired of parathyroid hormone production and kidney disorders. 16 And this applied also in this study because we only found three hypercalcemia patients.…”