PTHrP-Related Hypercalcaemia in Infancy and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

Kodous, Nardeen; Filler, Guido; Sharma, Ajay; Hooren, Tamara A Van

doi:10.1186/s40697-015-0052-y

Cited by 11 publications

(4 citation statements)

References 19 publications

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“…Elevated PTH levels were observed in 3/10 patients and increased 25OHD levels was observed in only 1 patient. To date, there are two case reports of hypercalcemia associated with increased PTHrP levels in children with CAKUT who are not on dialysis ( Grob et al, 2013 ; Kodous et al, 2015 ). Mechanisms by which PTHrP production is increased in CKD associated with CAKUT are unknown.…”

Section: Case Reportmentioning

confidence: 99%

Vitamin D and kidney disease

Keung¹,

Perwad²

2018

Bone Reports

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Calcium and phosphorus are essential minerals required for many critical biologic functions including cell signaling, energy metabolism, skeletal growth and integrity. Calcium and phosphate homeostasis are maintained primarily by regulation of epithelial calcium and phosphate cotransport in the kidney and intestine, processes that are tightly regulated by hormones including 1,25 dihydroxyvitamin D (1,25(OH)2D), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). In patients with chronic kidney disease (CKD), as renal function declines, disruption of feedback loops between these hormones have adverse consequences on several organ systems, including the skeleton, heart and vascular system. CKD-associated mineral and bone disorder (CKD-MBD) is defined as a systemic disorder of mineral and bone metabolism due to CKD manifested by abnormalities of calcium, phosphorus, PTH or vitamin D metabolism, abnormalities of bone turnover, mineralization and volume, and ectopic soft tissue calcification. Complications of CKD-MBD include vascular calcification, stroke, skeletal fracture and increased risk of death. Increased FGF23 and PTH concentrations, and 1,25(OH)2D deficiency contribute to the pathogenesis of CKD-MBD. Therefore, treatment of patients with CKD-MBD is focused on restoring the feedback loops to maintain normal calcium and phosphate balance to prevent skeletal and cardiovascular complications.

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Section: Case Reportmentioning

confidence: 99%

Vitamin D and kidney disease

Keung¹,

Perwad²

2018

Bone Reports

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“…(46)(47)(48)(49)(50) Hypercalcemia is associated with malignancy in <1% of children, (4) and may be caused by: osteolysis due to metastases or leukemias; or osteoclastic bone resorption stimulated by hormones (eg, PTHrP) that are produced by the tumor. PTHrP acts as a paracrine and intracrine hormone to regulate bone development, but some tumors (eg, renal cell carcinomas, squamous cell carcinomas, dysgerminomas, ovarian and breast carcinomas, pheochromocytoma, (51,52) benign congenital mesoblastic nephroma, (53) multicystic dysplastic kidney disease, (54) and renal dysplasia (55,56) ) may secrete PTHrP systemically, and the actions of circulating PTHrP on the type 1 PTH/PTHrP receptor cause hypercalcemia.…”

Section: Malignancy and Pthrpmentioning

confidence: 99%

Hypercalcemic Disorders in Children

Stokes

Nielsen

Hannan

et al. 2017

Journal of Bone and Mineral Research

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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.

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“…This is no different from what has been reported in the literature with other dosing methods. In fact, although the production of PTHrP is widespread in many normal tissues of healthy individuals, its concentration is often low or not detectable with normal analytical methods [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…PTHrP produced by malignant tumors is responsible for severe hypercalcemia (HHM), a rare but clinically significant condition in infancy and childhood. Benign tumors, sarcomas and hematolymphatic neoplasms can also produce PTHrP [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. The hypercalcemia associated with pheochromocytoma may be due to secretion of PTHrP [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Parathyroid Hormone-Related Peptide (PTHrP): Evaluation of Pediatric, Covariate-Stratified Reference Intervals

et al. 2022

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Parathyroid hormone-related peptide (PTHrP) is expressed at a wide range of sites in the body and performs different functions including vasodilation, relaxation of smooth muscle cells, and regulation of bone development. PTHrP also mediates hypercalcemia related to neoplastic diseases. However, reference ranges specific method and age were not evaluated. We establish PTHrP reference ranges in apparently healthy, normocalcemic, normophosphatemic pediatric individuals. In this observational prospective, study we measured PTHrP in serum from 178 samples (55.06% 44.94% female) from apparently healthy pediatric subjects [median age 10 years (range 1–18)] subunit ELISA method The statistical analysis performed provided for the calculation of the 95% reference interval, right-sided, with a non-parametric percentile method (CLSI C28-A3). Upper reference limits (URL) for PTHrP was 2.89 ng/mL (2.60 to 3.18; 90% CI). No significant differences were found between the median PTHrP concentrations in males vs females and in the age range categories selected. Comprehensive normal values for PTHrP are indispensable to the assessment of calcium phosphorus dysfunction in children. Severe hypercalcemia is a rare, but clinically significant condition, in infancy and childhood. PTHrP values higher than the reference value may help to distinguish the hypercalcemic product of a malignancy, paraneoplastic syndromes mediated by PTHrP, from other causes.

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PTHrP-Related Hypercalcaemia in Infancy and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

Cited by 11 publications

References 19 publications

Vitamin D and kidney disease

Vitamin D and kidney disease

Hypercalcemic Disorders in Children

Parathyroid Hormone-Related Peptide (PTHrP): Evaluation of Pediatric, Covariate-Stratified Reference Intervals

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