The enigma of hyperparathyroidism in hypophosphatemic rickets

Schmitt, Claus Peter; Mehls, Otto

doi:10.1007/s00467-004-1443-y

Cited by 53 publications

(40 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Normal parathyroidectomized mice parabiosed to parathyroidectomized Hyp mice developed phosphaturia, indicating a primary role for a circulating factor other than PTH (11,60). Nonetheless, more recently, PTH levels were noted to be elevated in some untreated patients with XLH when intact PTH was measured (61,62). Similarly, PTH levels are high in Hyp mice and in some but not all mouse models of FGF23 overexpression (62)(63)(64)(65).…”

Section: Other Potential Phosphatonin/minhibins In Xlhmentioning

confidence: 99%

“…Nonetheless, more recently, PTH levels were noted to be elevated in some untreated patients with XLH when intact PTH was measured (61,62). Similarly, PTH levels are high in Hyp mice and in some but not all mouse models of FGF23 overexpression (62)(63)(64)(65). The reason for the variability in PTH levels in XLH is unclear but may depend on the overall balance among factors that regulate PTH levels (Table 3).…”

Section: Other Potential Phosphatonin/minhibins In Xlhmentioning

confidence: 99%

See 1 more Smart Citation

The Journey From Vitamin D–Resistant Rickets to the Regulation of Renal Phosphate Transport

Levine¹,

Felsenfeld²

2009

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

(6) discuss the genetic and acquired disorders of hypophosphatemia and hyperphosphatemia in which FGF23 plays a role. Although Albright could not measure parathyroid hormone, he concluded on the basis of his studies that showed calcemic resistance to parathyroid extract in W.M. that hyperparathyroidism was present. Using a conceptual approach, we suggest that a defect in the skeletal response to parathyroid hormone contributes to hyperparathyroidism in XLH. Finally, at the end of the review, abnormalities in renal phosphate transport that are sometimes found in patients with polyostotic fibrous dysplasia are discussed.

show abstract

Section: Other Potential Phosphatonin/minhibins In Xlhmentioning

confidence: 99%

Section: Other Potential Phosphatonin/minhibins In Xlhmentioning

confidence: 99%

The Journey From Vitamin D–Resistant Rickets to the Regulation of Renal Phosphate Transport

Levine¹,

Felsenfeld²

2009

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…However, patients who have XLH and have never been treated may have elevated PTH concentrations (74,75). Patients who are treated with phosphate and calcitriol will occasionally require parathyroidectomy (76), and hyperparathyroidism may play a role in hypertension in these patients (77).…”

Section: Pthmentioning

confidence: 99%

Fibroblast Growth Factor 23

Imel¹,

Econs²

2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

A lthough phosphate is important in skeletal mineralization, energy metabolism, and multiple enzymatic processes, little has been understood about the regulation of phosphate in health and disease until recently. Genetic and acquired disorders of phosphate homeostasis have begun to reveal important mechanisms for the regulation of phosphate metabolism. Candidate phosphate-regulating hormones ("phosphatonins") have been discovered, and their actions and interactions continue to be elucidated in an exciting area of ongoing clinical and basic research. Autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), tumor-induced osteomalacia (TIO), and fibrous dysplasia (FD) have similar phenotypes of hypophosphatemia, urinary phosphate wasting as measured by a low tubular maximum reabsorption of phosphate per deciliter of glomerular filtrate (TmP/GFR), osteomalacia, and rickets. The phenotypic similarities suggest a common metabolic pathophysiology. In addition, recent evidence concerning tumoral calcinosis, which results in hyperphosphatemia, inappropriately elevated calcitriol concentrations, and soft tissue calcifications and can be considered the phenotypic "converse" of the phosphate wasting disorders, indicates that this disorder may result from perturbations of some of the same metabolic pathways. Fibroblast growth factor 23 (FGF23) is a recently discovered, novel, secreted protein hormone involved in the pathogenesis of these disorders. This review focuses on the relationship of FGF23 to various disorders of phosphate homeostasis and its potential regulation and function in normal physiology. Hypophosphatemic DisordersADHR ADHR, initially described by Bianchine et al. (1), is characterized by renal phosphate wasting, hypophosphatemia, low or inappropriately normal calcitriol concentrations, and osteomalacia. Econs and McEnery (2) described a large ADHR kindred. Affected patients presented either in childhood with hypophosphatemia and rickets, which resulted in lower extremity deformities, or after puberty with hypophosphatemic osteomalacia, manifesting in weakness, fatigue, bone pain, and fractures. Patients with adult onset of symptoms clinically resemble TIO, but the disease is not a paraneoplastic process. To date, delayed onset of clinically evident disease has been observed only in female individuals. ADHR also exhibits incomplete penetrance, and, in some cases, the clinical and biochemical phenotype spontaneously resolved in patients who were previously documented to have hypophosphatemic rickets (2).The ADHR consortium used the positional cloning approach to identify the gene responsible for ADHR, FGF23 (3). ADHR results from mutations in either arginine 176 or arginine 179 in FGF23. These arginines make up an RXXR cleavage site, and mutations in either of these arginines protect the protein from degradation, potentially increasing the circulating concentration of FGF23 and, thereby, leading to the disease phenotype (4 -6). FGF23 is a 251-amino acid protein in the FGF fa...

show abstract

“…2 Established treatment of XLH includes high doses of oral phosphate and calcitriol. 3,4 Although treated patients demonstrate amelioration of rachitic symptoms and improved growth, 5 long-term administration of phosphate and vitamin D preparations is sometimes complicated with nephrocalcinosis, 6 secondary hyperparathyroidism, 5 hypertension 7 and cardiovascular abnormalities. 8 Hyperparathyroidism and hypercalcemia contribute to the development of hypertension and transient renal dysfunction in XLH patients.…”

Section: Introductionmentioning

confidence: 99%

Cinacalcet in hyperparathyroidism secondary to X-linked hypophosphatemic rickets: case report and brief literature review

Yavropoulou¹,

Kotsa²,

Ψαρράκου³

et al. 2010

View full text Add to dashboard Cite

X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic form of hypophosphatemic rickets. standard treatment of XLH patients includes long-term administration of phosphate and calcitriol. Treated patients usually respond well to the conventional therapy and demonstrate amelioration of rachitic symptoms and improved growth. However, long-term administration of phosphate and vitamin D preparations is sometimes complicated with nephrocalcinosis, secondary or tertiary hyperparathyroidism and arterial hypertension. We describe a patient with XLH, caused by a rare missense mutation of the PHEX gene. The patient, while under treatment with alphacalcidol and oral phosphate, developed hypercalciuria, nephrocalcinosis, secondary hyperparathyroidism and arterial hypertension. cinacalcet was added to the therapeutic regimen and the long-term effects on calciotropic parameters and FGF23 levels are herein reported.

show abstract

The enigma of hyperparathyroidism in hypophosphatemic rickets

Cited by 53 publications

References 60 publications

The Journey From Vitamin D–Resistant Rickets to the Regulation of Renal Phosphate Transport

The Journey From Vitamin D–Resistant Rickets to the Regulation of Renal Phosphate Transport

Fibroblast Growth Factor 23

Cinacalcet in hyperparathyroidism secondary to X-linked hypophosphatemic rickets: case report and brief literature review

Contact Info

Product

Resources

About