Neonatal Hyperparathyroidism and Pamidronate Therapy in an Extremely Premature Infant

Fox, Lisa M; Sadowsky, Joel; Pringle, Kevin P.; Kidd, Alexa; Murdoch, J. R.; Cole, David E. C.; Wiltshire, Esko

doi:10.1542/peds.2006-3209

Cited by 46 publications

(42 citation statements)

References 28 publications

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“…In some cases, bisphosphonates (pamidronate) have been used to maintain the calcemia and prevent bone demineralization, even in premature babies [11,24]. However, because of the risk of hypocalcemia and the exacerbation of secondary hyperparathyroidism, other authors caution that bisphosphonates must be used carefully [10].…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

Soblechero¹,

Castillo

Crespo

et al. 2013

Neonatology

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A neonate affected by a novel inactivating mutation in the calcium-sensing receptor (CASR) gene is presented. This mutation is homozygously inherited and has not been previously described. A deletion in exon 5 (c.1392_1404del13) of the gene causes a loss of function of the receptor, which results in neonatal severe hyperparathyroidism and an ensuing extreme hypercalcemia. In a case of homozygosis of the CASR gene, the use of cinacalcet is the second reported calcimimetic treatment attempt and the first treatment attempt prior to surgery. However, because of the type of mutation, parathyroid surgery was necessary at 4 months of age after therapeutic failure. Because there are multiple mutations that affect the CASR gene in different ways, treatment with cinacalcet as an alternative to surgery may be valuable in homozygous cases that are caused by different mutations than the reported case.

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Section: Discussionmentioning

confidence: 99%

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

Soblechero¹,

Castillo

Crespo

et al. 2013

Neonatology

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“…General measures, however, like hydration or forced diuresis and calcitonin do not yield clinically sufficient responses in both variants of neonatal hyperparathyroidism (15,66,67,68,69). Restriction of calcium intake is also mostly ineffective and further aggravates total body calcium deficiency in NSHPT and NHPT patients (70,71,72,73).…”

Section: Casr As a Drug Target For Allosteric Modulatorsmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Mayr¹,

Schnabel²,

Dörr³

et al. 2016

European Journal of Endocrinology

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The calcium-sensing receptor (CASR) is the main calcium sensor in the maintenance of calcium metabolism. Mutations of the CASR, the G protein alpha 11 (GNA11) and the adaptor-related protein complex 2 sigma 1 subunit (AP2S1) genes can shift the set point for calcium sensing causing hyper-or hypo-calcemic disorders. Therapeutic concepts for these rare diseases range from general therapies of hyper-and hypo-calcemic conditions to more pathophysiology oriented approaches such as parathyroid hormone (PTH) substitution and allosteric CASR modulators. Cinacalcet is a calcimimetic that enhances receptor function and has gained approval for the treatment of hyperparathyroidism. Calcilytics in turn attenuate CASR activity and are currently under investigation for the treatment of various diseases. We conducted a literature search for reports about treatment of patients harboring inactivating or activating CASR, GNA11 or AP2S1 mutants and about in vitro effects of allosteric CASR modulators on mutated CASR. The therapeutic concepts for patients with familial hypocalciuric hypercalcemia (FHH), neonatal hyperparathyroidism (NHPT), neonatal severe hyperparathyroidism (NSHPT) and autosomal dominant hypocalcemia (ADH) are reviewed. FHH is usually benign, but symptomatic patients benefit from cinacalcet. In NSHPT patients pamidronate effectively lowers serum calcium, but most patients require parathyroidectomy. In some patients cinacalcet can obviate the need for surgery, particularly in heterozygous NHPT. Symptomatic ADH patients respond to vitamin D and calcium supplementation but this may increase calciuria and renal complications. PTH treatment can reduce relative hypercalciuria. None of the currently available therapies for ADH, however, prevent tissue calcifications and complications, which may become possible with calcilytics that correct the underlying pathophysiologic defect.

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“…Total parathyroidectomy produces hypoparathyroidism; thus hypercalcemia in NSHPT is PTH dependent, and loss of Ca 2ϩ receptors in tissues other than the parathyroid (e.g., kidney, C cell) is insufficient to sustain hypercalcemia. A potentially useful temporizing measure in a severely ill neonate with NSHPT is the use of a bisphosphonate such as pamidronate, which can lower serum Ca 2ϩ concentration substantially and allow stabilization before surgery, if the latter is indicated (46,162). Remission of hyperparathyroidism after parathyroidectomy produces rapid clinical improvement and healing of bony lesions within weeks to months; the prognosis thereafter is usually excellent (31, 61, 67, 148).…”

Section: Inherited and Acquired Disorders Impacting Function Of Casr mentioning

confidence: 99%

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

Riccardi

Brown

2010

American Journal of Physiology-Renal Physiology

298

239

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Neonatal Hyperparathyroidism and Pamidronate Therapy in an Extremely Premature Infant

Cited by 46 publications

References 28 publications

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

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