scholarly journals The case of oncogenic hypophosphatemic osteomalacia

2020 ◽  
Vol 17 (2) ◽  
pp. 220-227
Author(s):  
Anna K. Eremkina ◽  
Svetlana S. Mirnaya ◽  
Anna M. Gorbacheva ◽  
Taras S. Panevin ◽  
Iya A. Voronkova ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Fibroblast Growth Factor 23 ◽  
Organic Matrix ◽  
Complete Removal ◽  
Oncogenic Osteomalacia ◽  
Mesenchymal Tumors ◽  
Renal Tubular Reabsorption ◽  
Hypophosphatemic Osteomalacia ◽  
Renal Tubular ◽  
Excessive Accumulation

Osteomalacia is a systemic bone disease, characterized by an excessive accumulation of non-mineralized osteoid and an imbalance in the organic matrix formation and mineralization. A rare cause of disease is tumor-induced osteomalacia, most often due to phosphaturic mesenchymal tumors (PMT). Usually there are benign small tumors, affecting the soft tissues and bones of any location. The basic pathogenesis of underlying oncogenic osteomalacia is a decreased renal tubular reabsorption of phosphate consequent to hyperproduction of fibroblast growth factor 23 in PMT. Clinical features are nonspecific, the average period from the symptoms onset to diagnosis reaches 3 years and at least 5 years before surgical treatment. Finding the tumour is crucial, as complete removal is curative. We present a clinical case of tumor-induced osteomalacia due to PMT required the complex differential diagnosis with other rare diseases.

Disorders of phosphate metabolism

2019 ◽  
Vol 72 (11) ◽  
pp. 741-747 ◽  
Author(s):  
Jenny Leung ◽  
Martin Crook
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
The Body ◽  
Plasma Phosphate ◽  
Phosphate Homeostasis ◽  
Organic Form ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular ◽  
Storage Pools

Phosphate in both inorganic and organic form is essential for several functions in the body. Plasma phosphate level is maintained by a complex interaction between intestinal absorption, renal tubular reabsorption, and the transcellular movement of phosphate between intracellular fluid and bone storage pools. This homeostasis is regulated by several hormones, principally the parathyroid hormone, 1,25-dihydroxyvitamin D and fibroblast growth factor 23. Abnormalities in phosphate regulation can lead to serious and fatal complications. In this review phosphate homeostasis and the aetiology, pathophysiology, clinical features, investigation and management of hypophosphataemia and hyperphosphataemia will be discussed.

scholarly journals Phosphaturic mesenchymal tumors: radiological aspects and suggested imaging pathway

2021 ◽  
Author(s):  
Mohsin A. M. Hussein ◽  
Francesco Pio Cafarelli ◽  
Maria Teresa Paparella ◽  
Winston J. Rennie ◽  
Giuseppe Guglielmi
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Accurate Diagnosis ◽  
Serum Phosphate Level ◽  
Fibroblast Growth ◽  
Oncogenic Osteomalacia ◽  
Radiological Findings ◽  
Mesenchymal Tumors ◽  
Mesenchymal Neoplasms ◽  
Ectopic Secretion

AbstractPhosphaturic mesenchymal tumors (PMTs) are rare mesenchymal neoplasms of soft tissue or bone origin that can give rise to a challenge in diagnostic imaging. These tumors are frequently associated with tumor-induced osteomalacia, also called oncogenic osteomalacia, which is a rare paraneoplastic syndrome characterized by ectopic secretion of fibroblast growth factor 23, a hormone that regulates serum phosphate level. PMTs show polymorphic features on both radiological findings and histological examination, causing problems in diagnosis owing to their similarity with other mesenchymal tumors. Thus, this paper aims to describe radiological aspects of PMTs and suggest an imaging pathway for accurate diagnosis throughout the evidence from the literature review.

Calcium and phosphorus metabolism and nutrition of poultry: are current diets formulated in excess?

2017 ◽  
Vol 57 (11) ◽  
pp. 2304 ◽  
Author(s):  
X. Li ◽  
D. Zhang ◽  
W. L. Bryden
Keyword(s):  
Parathyroid Hormone ◽  
Vitamin D3 ◽  
Fibroblast Growth Factor 23 ◽  
Limited Data ◽  
Endocrine Control ◽  
Evaluation Systems ◽  
Renal Tubular Reabsorption ◽  
Poultry Diets ◽  
Renal Tubular ◽  
P Bioavailability

Calcium (Ca) and phosphorus (P) are important nutrients in poultry diet formulations. In the present review, we discuss recent advances in our understanding of the metabolism of Ca and P in poultry. Recent data are provided in support of the proposition that current poultry diets are formulated in excess for Ca and P. The quantities of Ca and P available for metabolism reflect rates of intestinal absorption, bone accretion and resorption, glomerular filtration, renal tubular reabsorption, and intestinal endogenous losses. Ca and P homeostasis is largely under endocrine control. Parathyroid hormone and the hormonal form of vitamin D3 are the two hormones credited with this role. However, a novel hormonal axis involving Fibroblast Growth Factor 23 and Klotho has been recently delineated, which, in conjunction with parathyroid hormone and vitamin D3, tightly regulates Ca and P homeostasis. Recent studies have suggested that current commercial diets for both broilers and layers contain excess Ca and P, the content of which could be reduced without affecting production or bird welfare. The challenge in reducing Ca and P concentrations in poultry diets is the uncertainty about what concentrations of Ca and P can be fed without compromising bird welfare. This is because there are limited data on the available P and Ca concentrations in poultry feedstuffs determined biologically. This is further complicated by the need for agreement on evaluation systems for evaluation of Ca and P bioavailability. We conclude that direct ileal or pre-caecal digestible Ca and P values are preferred.

Utility of 18F-AlF-NOTA-octreotide PET/CT in the localization of Tumor-Induced Osteomalacia

2021 ◽  
Author(s):  
Tingting Long ◽  
Jiale Hou ◽  
Nengan Yang ◽  
Ming Zhou ◽  
Yulai Li ◽  
...  
Keyword(s):  
Patient Management ◽  
Fibroblast Growth Factor 23 ◽  
Pathological Examination ◽  
Mesenchymal Tumors ◽  
Curative Therapy ◽  
Pet Ct ◽  
Hypophosphatemic Osteomalacia ◽  
Sensitivity Specificity ◽  
Paraneoplastic Disorder ◽  
Pet Ct Scan

Abstract Purpose Tumor-induced osteomalacia (TIO) is a paraneoplastic disorder, usually caused by benign mesenchymal tumors that produce high levels of the hormone fibroblast-growth-factor 23 (FGF23). The only curative therapy of the disease is resection of the causative tumors. This research was conducted to evaluate the efficacy of 18F-AlF-NOTA-octreotide ( 18F-OC) PET/CT in detecting TIO and its impact on patient management. Methods Retrospective analysis of 17 patients with hypophosphatemic osteomalacia suspected of TIO was performed. 18F-OC PET/CT study was performed in all 17 patients to localize the tumor. 68Ga-DOTATATE PET/CT was performed in 4 out of 17 patients. 18F-OC and 68Ga-DOTATATE PET/CT studies were performed within 1 week of each other. Both studies were interpreted blindly without the knowledge of other imaging findings. The image findings were compared with the results of histopathological examinations and clinical follow-ups. Results 18F-OC PET/CT scans were positive in 14 patients. Moreover, 4 out of 14 patients were performed with both 18F-OC and 68Ga-DOTATATE PET/CT. Both studies were able to localize the tumor in all the 4 patients. In total, 14 patients had surgery to remove the lesions. Postsurgical pathological examination confirmed causative tumors in these patients whose symptoms diminished promptly. The serum phosphate levels became normal confirming the diagnosis of TIO. 18F-OC PET/CT sensitivity, specificity and accuracy were 87.5%, 100% and 88.2% respectively. 18F-OC PET/CT findings affected patient management in 88.2% of cases. Conclusion 18F-OC PET/CT scan is useful in the detection of tumors causing TIO. Further studies with larger patient population are needed to validate the result.

IMMUNOREACTIVE GROWTH HORMONE IN PLASMA AND URINE IN JUVENILE DIABETICS BEFORE AND DURING INITIAL INSULIN TREATMENT

1974 ◽  
Vol 75 (1) ◽  
pp. 50-63 ◽  
Author(s):  
Kristian F. Hanssen
Keyword(s):  
Growth Hormone ◽  
Insulin Treatment ◽  
Juvenile Diabetes ◽  
Control Group ◽  
List Type ◽  
Newly Diagnosed ◽  
Renal Tubular Reabsorption ◽  
Juvenile Diabetics ◽  
The Mean ◽  
Renal Tubular

ABSTRACT Twenty newly diagnosed, but as yet untreated patients of both sexes with classical juvenile diabetes were investigated by determining the mean plasma immunoreactive growth hormone (IRHGH) and urinary IRHGH for a 24 hour period before and during initial insulin treatment. The plasma IRHGH was significantly higher (0.05 > P > 0.01) before than during initial insulin treatment. During initial insulin treatment, the mean plasma IRHGH was significantly higher (0.01 > P > 0.001) than in a control group. The urinary IRHGH was significantly higher (0.01 > P > 0.001) before than during insulin treatment. The increased urinary IRHGH observed before insulin treatment is thought to be partly due to a defective renal tubular reabsorption of growth hormone. No significant correlation was found between the mean blood sugar and plasma or urinary IRHGH either before or during insulin treatment.

scholarly journals Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Egli-Spichtig ◽  
Martin Y. H. Zhang ◽  
Alfred Li ◽  
Eva Maria Pastor Arroyo ◽  
Nati Hernando ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Actin Polymerization ◽  
Fibroblast Growth Factor 23 ◽  
Wild Type ◽  
Vitamin D Metabolism ◽  
Endocrine Hormone ◽  
Dnase 1 ◽  
Sodium Dependent ◽  
Renal Tubular ◽  
High Phosphate

AbstractFibroblast growth factor 23 (FGF23) is a bone-derived endocrine hormone that regulates phosphate and vitamin D metabolism. In models of FGF23 excess, renal deoxyribonuclease 1 (Dnase1) mRNA expression is downregulated. Dnase-1 is an endonuclease which binds monomeric actin. We investigated whether FGF23 suppresses renal Dnase-1 expression to facilitate endocytic retrieval of renal sodium dependent phosphate co-transporters (NaPi-IIa/c) from the brush border membrane by promoting actin polymerization. We showed that wild type mice on low phosphate diet and Fgf23−/− mice with hyperphosphatemia have increased renal Dnase1 mRNA expression while in Hyp mice with FGF23 excess and hypophosphatemia, Dnase1 mRNA expression is decreased. Administration of FGF23 in wild type and Fgf23−/− mice lowered Dnase1 expression. Taken together, our data shows that Dnase1 is regulated by FGF23. In 6-week-old Dnase1−/− mice, plasma phosphate and renal NaPi-IIa protein were significantly lower compared to wild-type mice. However, these changes were transient, normalized by 12 weeks of age and had no impact on bone morphology. Adaptation to low and high phosphate diet were similar in Dnase1−/− and Dnase1+/+ mice, and loss of Dnase1 gene expression did not rescue hyperphosphatemia in Fgf23−/− mice. We conclude that Dnase-1 does not mediate FGF23-induced inhibition of renal tubular phosphate reabsorption.

scholarly journals Early post-transplantation hypophosphatemia is associated with elevated FGF-23 levels

2011 ◽  
Vol 164 (5) ◽  
pp. 839-847 ◽  
Author(s):  
Andrea Trombetti ◽  
Laura Richert ◽  
Karine Hadaya ◽  
Jean-Daniel Graf ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Tubular Reabsorption ◽  
Phosphate Metabolism ◽  
Multivariate Models ◽  
Intact Pth ◽  
Post Transplantation ◽  
Estimated Gfr ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular ◽  
Fgf 23

BackgroundWe examined the hypothesis that high FGF-23 levels early after transplantation contribute to the onset of hypophosphatemia, independently of parathyroid hormone (PTH) and other factors regulating phosphate metabolism.MethodsWe measured serum phosphate levels (sPi), renal tubular reabsorption of Pi (TmPi/GFR), estimated GFR (eGFR), intact PTH (iPTH), calcitriol, intact (int) and C-terminal (Cter) FGF-23, dietary Pi intake and cumulative doses of glucocorticoids in 69 patients 12 days (95% confidence interval, 10–13) after renal transplantation.ResultsHypophosphatemia was observed in 43 (62%) of the patients 12 days after transplantation. Compared with non-hypophosphatemic subjects, their post-transplantation levels of intact and CterFGF-23 were higher (195 (108–288) vs 48 (40–64) ng/l, P<0.002 for intFGF-23; 205 (116–384) vs 81 (55–124) U/ml, P<0.002, for CterFGF-23). In all subjects, Cter and intFGF-23 correlated inversely with sPi (r=−0.35, P<0.003; −0.35, P<0.003, respectively), and TmPi/GFR (r=−0.50, P<0.001; −0.54, P<0.001, respectively). In multivariate models, sPi and TmPi/GFR were independently associated with FGF-23, iPTH and eGFR. Pre-transplant iPTH levels were significantly higher in patients developing hypophosphatemia after renal transplantation. Pre-transplant levels of FGF-23 were not associated with sPi at the time of transplantation.ConclusionIn addition to PTH, elevated FGF-23 may contribute to hypophosphatemia during the early post-renal transplant period.

scholarly journals Pleiotropic Actions of FGF23

2017 ◽  
Vol 45 (7) ◽  
pp. 904-910 ◽  
Author(s):  
Reinhold G. Erben
Keyword(s):  
Vitamin D ◽  
Fibroblast Growth Factor 23 ◽  
Renal Tubules ◽  
Hormone Production ◽  
Membrane Expression ◽  
Fgf Receptor ◽  
Local Inhibition ◽  
Organ Systems ◽  
Key Enzyme ◽  
Renal Tubular

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor α-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium–phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate. In addition, FGF23 suppresses proximal tubular expression of 1α-hydroxylase, the key enzyme responsible for vitamin D hormone production. In distal renal tubules, FGF23 signaling activates with-no-lysine kinase 4, leading to increased renal tubular reabsorption of calcium and sodium. Therefore, FGF23 is not only a phosphaturic but also a calcium- and sodium-conserving hormone, a finding that may have important implications for the pathophysiology of chronic kidney disease. Besides these endocrine, Klotho-dependent functions of FGF23, FGF23 is also an auto-/paracrine suppressor of tissue-nonspecific alkaline phosphatase transcription via Klotho-independent FGFR3 signaling, leading to local inhibition of mineralization through accumulation of pyrophosphate. In addition, FGF23 may target the heart via an FGFR4-mediated Klotho-independent signaling cascade. Taken together, there is emerging evidence that FGF23 is a pleiotropic hormone, linking bone with several other organ systems.

Renal tubular reabsorption of trace alkaline earths compared with calcium

1965 ◽  
Vol 208 (6) ◽  
pp. 1165-1170 ◽  
Author(s):  
W. Joseph Rahill ◽  
Mackenzie Walser
Keyword(s):  
Protein Binding ◽  
Transport Mechanism ◽  
Tubular Reabsorption ◽  
Constant Infusion ◽  
Constant Power ◽  
Calcium Clearance ◽  
Renal Tubular Reabsorption ◽  
Order Of Magnitude ◽  
Alkaline Earths ◽  
Renal Tubular

Simultaneous clearances of inulin, calcium, and either Be7, Ba140, or Ra226, given by constant infusion, were measured in salt-depleted dogs or dogs undergoing mild saline, mannitol, or sulfate diuresis. Urine-to-plasma ratios of all three cations less than 0.5 were noted, suggesting that all can be actively reabsorbed. Clearances of barium and radium were correlated with calcium clearance, but the clearance of beryllium was unpredictable. Protein binding of beryllium was shown to be of the same order of magnitude as other alkaline earths when errors due to adsorption of Be7 onto containers were minimized. Protein binding of barium averaged 54%. The excreted-to-filtered ratio for barium was a constant power (.54) of the ratio for calcium. The data do not exclude the possibility that these cations are reabsorbed by a common transport mechanism with calcium.

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