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International Journal of Molecular... Mar 2024X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset...
X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, = 0.01). A total of 106 metabolites were identified. Acetylcarnitine ( = 0.03), pyruvate = (0.04), ethanolamine ( = 0.03), and butyric acid ( = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.
Topics: Adult; Humans; Familial Hypophosphatemic Rickets; Cross-Sectional Studies; Hypertension; Fibroblast Growth Factors
PubMed: 38542517
DOI: 10.3390/ijms25063545 -
Journal of Clinical Medicine Mar 2024Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study...
Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study assesses the efficacy of [Ga]Ga-DOTATATE PET/CT in identifying the primary tumour. Six patients with suspected TIO underwent [Ga]Ga-DOTATATE PET/CT. The patients' clinical history and biochemical parameters were analysed. [Ga]Ga-DOTATATE PET/CT successfully identified primary tumours in four patients (femoral bones for two, iliac bone for one, subcutaneous tissue of pubic region for one). Tumour removal led to clinical and laboratory improvement. In one patient, PET/CT showed rib uptake, but the biopsy was negative. One patient showed no tumour lesions on PET/CT despite clinical evidence. Two patients had focal recurrence at the primary tumour site, detected by follow-up PET/CT. [Ga]Ga-DOTATATE PET/CT is a valuable tool for detecting primary tumours in TIO, aiding in accurate diagnosis and guiding surgery, leading to improved outcomes. Further research is needed to validate these findings and explore [Ga]Ga-DOTATATE PET/CT in other paraneoplastic syndromes.
PubMed: 38542041
DOI: 10.3390/jcm13061817 -
The Journal of Biological Chemistry Apr 2024O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the...
O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D-binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system.
Topics: Animals; Male; Mice; Bone and Bones; Calcium; Glycosylation; Homeostasis; Parathyroid Hormone; Polypeptide N-acetylgalactosaminyltransferase; Vitamin D; Vitamin D-Binding Protein
PubMed: 38484798
DOI: 10.1016/j.jbc.2024.107164 -
Endocrinology and Metabolism (Seoul,... Apr 2024Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant... (Review)
Review
Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning-Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.
Topics: Humans; Fibroblast Growth Factor-23; Osteomalacia; Fibroblast Growth Factors; Paraneoplastic Syndromes; Hypophosphatemia; Rickets, Hypophosphatemic; Neoplasms, Connective Tissue
PubMed: 38467164
DOI: 10.3803/EnM.2023.1908 -
Therapeutic Advances in Medical Oncology 2024Phosphaturic mesenchymal tumors (PMTs) are rare tumors that can cause tumor-induced osteomalacia (TIO) through overproduction of FGF23, a peptide hormone that causes...
Phosphaturic mesenchymal tumors (PMTs) are rare tumors that can cause tumor-induced osteomalacia (TIO) through overproduction of FGF23, a peptide hormone that causes renal phosphate wasting and reduced osteoblastic activity. The diagnosis of PMTs can be difficult to make as the presenting symptoms are non-specific. Although PMT is a rare entity, most cases are benign in nature, not requiring further intervention after surgery, as resection is typically curative. Here, we present a unique case of malignant PMT with liver metastasis in a female patient who presented with TIO and underwent surgical resection of her primary lesion with subsequent regression of her liver metastasis. Moreover, we analyze a review of literature and discuss the importance of a timely diagnosis of this rare phenomenon. It is encouraged that providers strongly consider a diagnosis of PMT in patients with otherwise unexplained bone pain, fatigue, weakness, especially if accompanied with hypophosphatemia. Further studies are also warranted to identify prognostic factors that predict a PMT's malignant potential as they may help identify possible therapeutic targets.
PubMed: 38455709
DOI: 10.1177/17588359241232092 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Dec 2023Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion...
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23 (FGF23) by tumor tissue. We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism. The patient's symptoms did not improve after removal of the tumor from the hyoid body, and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland. TIO derived from the tongue tumor is very rare, and also subsequent tertiary hyperparathyroidism is even rarer. This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.
Topics: Humans; Paraneoplastic Syndromes; Hyperparathyroidism; Osteomalacia; Parathyroid Glands
PubMed: 38448388
DOI: 10.11817/j.issn.1672-7347.2023.220547 -
Journal of Orthopaedic Case Reports Feb 2024An uncommon medical disorder known as tumor-induced osteomalacia (TIO) is characterized by severe hypophosphatemia, renal phosphate wasting, and osteomalacia due to a...
INTRODUCTION
An uncommon medical disorder known as tumor-induced osteomalacia (TIO) is characterized by severe hypophosphatemia, renal phosphate wasting, and osteomalacia due to a tumor. TIO has recently been linked to a particular kind of tumor known as phosphaturic mesenchymal tumor (PMT). PMTs release phosphatonins, such as fibroblast growth factor-23 (FGF23), which elevates serum levels of FGF23, leading to phosphate wasting and osteomalacia. However, due to their infrequent occurrence and vague symptoms, such as bone pain, myopathies, arthralgias, fractures, and weakness, the diagnosis of PMTs is often delayed or misdiagnosed. In this case report, a rare case of PMT in the proximal femur resulted in TIO, and it highlights the long and difficult journey from symptom onset to correct diagnosis and successful surgical management.
CASE REPORT
A 51-year-old woman endured persistent joint pain, muscle weakness, and fatigue for 2 years. Despite having no known health issues, she suffered from hip pain that spreads to her knees and ankles, and tingling and paresthesia in her legs, making it difficult to bear weight. She underwent surgery to remove a parathyroid adenoma, but unfortunately, her symptoms returned. Her magnetic resonance imaging revealed a lesion in her proximal femur, which was promptly removed. The tissue examination results verified the identity of the tumor as a PMT. The patient's phosphorus levels returned to normal and after a year of follow-up, she was able to resume normal daily activities, bear weight on the affected limb and showed no signs of the tumor recurrence.
CONCLUSION
Adult patients experiencing bone pain, progressive weakness, and multiple fractures with no family history of similar conditions should consider TIO as a potential cause. It is rare and often misdiagnosed and complete surgical removal of the tumor is the optimal treatment for TIO, resulting in the resolution of long-standing symptoms and biochemical abnormalities. Timely recognition, localization, and surgical removal of the tumor are crucial for symptom resolution and the restoration of normal bone mineralization.
PubMed: 38420233
DOI: 10.13107/jocr.2024.v14.i02.4204 -
Case Reports in Gastroenterology 2024Hypophosphatemia occurs commonly in inflammatory bowel disease (IBD) patients and can cause considerable morbidity. The differential diagnoses in IBD include nutritional...
INTRODUCTION
Hypophosphatemia occurs commonly in inflammatory bowel disease (IBD) patients and can cause considerable morbidity. The differential diagnoses in IBD include nutritional causes and hypophosphatemia induced by some formulations of intravenous iron infusions.
CASE PRESENTATION
We present the case of a 37-year-old man with active Crohn's disease, presenting with difficulty walking and fractures of the vertebrae and calcaneus. He had long-standing hypophosphatemia. Nutritional causes for hypophosphatemia were considered in the first instance given the presence of chronic diarrhea and vitamin D deficiency; however, there was minimal response to appropriate supplementation with oral phosphorous and vitamin D. Iron infusion-induced hypophosphatemia was then considered, but the nadir phosphate level preceded any iron infusion. Therefore, work-up was undertaken for less common causes. He was ultimately diagnosed with tumor-induced osteomalacia, caused by excess fibroblast growth factor 23 (FGF23) secretion from a phosphaturic mesenchymal tumor about the knee. He had complete resolution of symptoms and biochemical abnormalities following successful resection of the tumor.
CONCLUSION
This case illustrates the approach to investigation of hypophosphatemia in IBD patients. If the time course and response to phosphate supplementation are not as expected for nutritional or iron infusion-induced hypophosphatemia, less common causes should be considered.
PubMed: 38410687
DOI: 10.1159/000536136 -
Journal of Medical Economics 2024Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous iron is the preferred ID anemia (IDA) treatment where oral iron is contraindicated, ineffective or not tolerated, or where ID correction is urgent. The objective was to evaluate the cost-utility of ferric derisomaltose (FDI) versus ferric carboxymaltose (FCM) in patients with IBD and IDA in England, in whom IV iron treatment is preferred.
MATERIALS AND METHODS
A patient-level simulation model was developed, capturing quality of life (QoL) differences based on SF-36v2 data from the PHOSPHARE-IBD randomized controlled trial, monitoring and incidence of post-infusion hypophosphatemia, and number of iron infusions required. Analyses were conducted over a five-year time horizon from the Department of Health and Social Care (DHSC) perspective, with healthcare provider and societal perspectives adopted in separate analyses. Future costs and effects were discounted at 3.5% and one-way and probabilistic sensitivity analyses were performed.
RESULTS
FDI increased quality-adjusted life expectancy by 0.075 QALYs versus FCM from 2.57 QALYs to 2.65 QALYs per patient. Patients receiving FDI required 1.63 fewer iron infusions over the five-year time horizon, driving infusion-related cost savings of GBP 496 per patient (GBP 2,188 versus GBP 1,692) from the DHSC perspective. Costs of monitoring and treating hypophosphatemia after FCM were GBP 226, yielding total savings of GBP 722 per patient (GBP 2,414 versus GBP 1,692) over the five-year time horizon. FDI also led to reduced costs versus FCM in the societal and provider analyses and was therefore the dominant intervention across all three perspectives.
LIMITATIONS
The analysis did not capture patient adherence, hypophosphatemic osteomalacia, or fractures.
CONCLUSIONS
Results showed that FDI improved patient QoL and reduced direct healthcare expenditure versus FCM in patients with IBD and IDA in England.
Topics: Humans; Anemia, Iron-Deficiency; Quality of Life; Cost-Benefit Analysis; Ferric Compounds; Maltose; Iron; Anemia; England; Hypophosphatemia; Inflammatory Bowel Diseases; Disaccharides
PubMed: 38391240
DOI: 10.1080/13696998.2024.2313932 -
Cureus Feb 2024Tumor-induced osteomalacia (TIO) is a rare complication of certain tumors involving the skeletal bones, mainly in the lower extremities and rarely the spine, that can...
Tumor-induced osteomalacia (TIO) is a rare complication of certain tumors involving the skeletal bones, mainly in the lower extremities and rarely the spine, that can cause skeletal abnormalities, osteopenia, and osteoporosis. The etiology of these tumors is unknown, and they are considered benign tumors that usually localize in bone or soft tissue anywhere in the body. Symptoms are nonspecific and vague, which causes a delay in diagnosis. These tumors produce fibroblast growth factor-23, which causes hypophosphatemia due to renal wasting of phosphate and inhibits vitamin D3 activation, resulting in osteomalacia. The majority of these tumors are osteoblastic and rarely osteolytic. A PET scan can detect the location and diagnose these tumors. Surgical resection, when feasible, is the treatment of choice and can lead to improvement, resolution of symptoms, and correction of hypophosphatemia. Patients usually present with a wide variety of nonspecific complaints. This case report presents an unusual presentation of TIO from a phosphaturic mesenchymal tumor involving the left acetabulum.
PubMed: 38389570
DOI: 10.7759/cureus.54712