PEDIATRIC SURGERY UPDATE ©

VOLUME 50 NO 06 JUNE 2018

Neonatal Hyperparathyroidism

Neonatal severe hyperparathyroidism (NSHPT) is a very rare autosomal recessive disease presenting in children during early infancy, usually within the first six months of life though the majority of cases occur in the first few weeks. Babies present with signs of hypercalcemia and hyperparathyroidism including poor feeding, polyuria, dehydration, lethargy, failure to thrive, hypotonia, gastrointestinal dysmotility, osteopenia and respiratory distress due to poorly developed chest cage. Early diagnosis and management of NSHPT is critical due to high morbidity, mortality and devastating effect to neurodevelopmental status. Calcium sensing receptors (CASR) are the major sensors of serum calcium level and have a critical role in maintaining calcium homeostasis. CARS are present in parathyroid chief cells and epithelial lining of renal tubules. The human CASR gene maps to 3q13.3. Through this receptor serum calcium higher than the set point inhibits the parathyroid hormone release from chief cells preventing renal tubular reabsorption of calcium. Mutation of the CASR causes loss or gain of function of the receptor. Heterozygous mutation of CASR results in familial hypocalciuric hypercalcemia and homozygous loss of function mutation results in NSHPT due to uncontrollable release of parathyroid hormone and severe hypercalcemia. Management of NSHPT hypercalcemia initiates with aggressive hydration and forced diuresis with furosemide and use of calcitonin which may provide some transient improvement in heterozygous cases. Homozygous cases do not respond well. Treatment could be escalated to the use of bisphosphonate therapy and calcimimetic such as Cinecalcet which is effective in heterozygous cases. If the child does not respond to medical therapy due to the homozygous state of the mutation then will require early parathyroidectomy. Total parathyroidectomy is performed without autotransplantation due to the high incidence of recurrence of the disease. Localization of parathyroid glands preoperative using Sestamibi nuclear scan and MRI influence the surgical approach.

References:
1- Reh CM, Hendy GN, Cole DE, Jeandron DD: Neonatal hyperparathyroidism with a heterozygous calcium-sensing receptor (CASR) R185Q mutation: clinical benefit from cinacalcet. J Clin Endocrinol Metab. 96(4):E707-12, 2011
2- Gannon AW, Monk HM, Levine MA: Cinacalcet monotherapy in neonatal severe hyperparathyroidism: a case study and review. J Clin Endocrinol Metab. 99(1):7-11, 2014
3- Fisher MM, Cabrera SM, Imel EA: Successful treatment of neonatal severe hyperparathyroidism with cinacalcet in two patients. Endocrinol Diabetes Metab Case Rep. 2015;2015:150040. doi: 10.1530/EDM-15-0040. Epub 2015 Jun 18.
4- Murphy H, Patrick J, Baez-Irizarry E, et al: Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia. Eur J Med Genet. 59(4):227-31, 2016
5- Hendy GN, D'Souza-Li L, Yang B, Canaff L, Cole DE: Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 16(4):281-96, 2000
6- Atay Z, Bereket A, Haliloglu B: Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet. Bone. 64:102-7, 2014

       Eccrine Spiradenoma

*Edited by: Humberto Lugo-Vicente, MD, FACS, FAAP
P.O. Box 10426, Caparra Heights Station, San Juan, Puerto Rico 00922-0426
Tel (787)-999-9450 Fax (787)-720-6103 E-mail: TITOLUGO@COQUI.NET
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Pediatric Surgery Update ISSN 1089-7739
Last updated: July 2017