Objective: To investigate the diagnosis and surgical treatment of sinonasal phosphaturic mesenchymal tumor (PMT). Methods: The medical records of nine patients who had been diagnosed as sinonasal PMT in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai JiaoTong University Affiliated Sixth People's Hospital between January 2015 and May 2020 were collected, including 4 males and 5 females, ranging from 36 to 59 years. The patient's previous history, clinical manifestations, imaging findings, laboratory results, surgical procedure, pathological results and postoperative follow-up data were analyzed by descriptive statistical analysis. Results: All patients presented hypophosphatemia and tumor-induced osteomalacia (TIO) with a disease course of 1 to 19 years. The imaging examination and intraoperative findings identified two cases with peripheral tissue infiltration, two cases with contralateral nasal cavity invasion, and one case with intracranial invasion. Five patients underwent unilateral endoscopic resection while two patients underwent bilateral endoscopic resection, and the remaining two patients underwent unilateral transorbital ethmoid artery ligation plus endoscopic tumor resection and endoscopic combined with transfrontal tumor resection (n=1 each). Expect for one case developed recurrence and intracranial involvement, the other patients achieved clinical remission and no recurrence was observed during the six-month follow-up. Conclusions: The diagnosis of sinonasal PMT needs combination of clinical manifestation, imaging, and pathological findings. Complete surgical excision and long-term postoperative follow-up are imperative.
China ; Female ; Humans ; Hypophosphatemia ; Male ; Mesenchymoma/surgery* ; Neoplasm Recurrence, Local ; Neoplasms, Connective Tissue/surgery* ; Retrospective Studies

Hypophosphatemic osteomalacia is a rare form of metabolic bone disorder in neurofibromatosis type 1 (NF1). The exact disease mechanism of this disorder in NF1 is yet to be established. We present a 44-year-old female known to have NF1, who presents with debilitating bone pain, weakness and multiple fractures. Laboratory investigations showed persistent hypophosphatemia with renal phosphate wasting suggestive of hypophosphatemic osteomalacia. She also had concomitant vitamin D deficiency which contributed to the disease severity. Medical therapy with oral phosphate and vitamin D improved her symptoms without significant changes in fracture healing or phosphate levels.
Hypophosphatemia ; Osteomalacia ; FGF23 ; Vitamin D Deficiency

Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments.
Absorption ; Alkaline Phosphatase ; Calcium ; Chondrocytes ; Collagen ; Diagnosis ; Durapatite ; Enzyme Replacement Therapy ; Extracellular Matrix ; Extracellular Vesicles ; Familial Hypophosphatemic Rickets ; Fibroblast Growth Factors ; Gene Expression ; Humans ; Hypophosphatasia ; Hypophosphatemia ; Metabolism ; Miners ; Osteoblasts ; Osteocytes ; Prognosis ; Quality of Life ; Receptors, Fibroblast Growth Factor ; Rickets ; Signal Transduction ; Vitamin D ; Vitamin D Deficiency

PURPOSE: This study was aimed to investigate the effect of early phosphorus intake on respiratory distress in extremely low-birth-weight infants (ELBWIs) with a high incidence of hypophosphatemia. METHODS: We performed a retrospective study to target 164 ELBWIs admitted to the neonatal intensive care unit in Seoul National University Children's Hospital. Birth characteristics, nutritional intake, and electrolyte levels during the first week were investigated as predictors that would affect the clinical outcomes. The correlations among invasive ventilation at postnatal age of 2 weeks, moderate-to-severe bronchopulmonary dysplasia (BPD), and phosphorous intake were analyzed. RESULTS: Hypophosphatemia (phosphorus level <4 mg/dL) was observed in 72.0% of the subjects. The rates of invasive ventilation (P=0.001) and moderate-to-severe BPD (P=0.005) were significantly lower in the high phosphorus intake group (≥0.7 mM/kg/day) than in the low phosphorus intake group (<0.7 mM/kg/day). Phosphorus intake during the first week was a significant factor affecting invasive ventilation at 2 weeks of age (adjusted odds ratio [OR], 8.212; 95% confidence interval [CI], 2.256 to 28.896; P=0.001) and moderate-to-severe BPD (adjusted OR, 3.402; 95% CI, 1.274 to 9.084; P=0.015). CONCLUSION: Early insufficient phosphorus intake confers a significantly higher risk with invasive ventilation at 2 weeks of age and moderate-to-severe BPD. Therefore, early sufficient phosphorus supply may improve respiratory outcomes in ELBWIs.
Bronchopulmonary Dysplasia ; Humans ; Hypophosphatemia ; Incidence ; Infant, Extremely Low Birth Weight ; Infant, Low Birth Weight ; Infant, Newborn ; Intensive Care, Neonatal ; Odds Ratio ; Parturition ; Phosphorus ; Retrospective Studies ; Seoul ; Ventilation

Idiopathic infantile hypercalcemia is characterized by hypercalcemia, dehydration, vomiting, and failure to thrive, and it is due to mutations in 24-hydroxylase (CYP24A1). Recently, mutations in sodium-phosphate cotransporter (SLC34A1) expressed in the kidney were discovered as an additional cause of idiopathic infantile hypercalcemia. This report describes a female infant admitted for evaluation of nephrocalcinosis. She presented with hypercalcemia, hypercalciuria, low intact parathyroid hormone level, and high 1,25-dihydroxyvitamin D3 level. Exome sequencing identified novel compound heterozygous mutations in SLC34A1 (c.1337G>A, c.1483C>T). The patient was treated with fluids for hydration, furosemide, a corticosteroid, and restriction of calcium/vitamin D intake. At the age of 7 months, the patient's calcium level was within the normal range, and hypercalciuria waxed and waned. Renal echogenicity improved on the follow-up ultrasonogram, and developmental delay was not noted. In cases of hypercalcemia with subsequent hypercalciuria, DNA analysis for SLC34A1 gene mutations and CYP24A1 gene mutations should be performed. Further studies are required to obtain long-term data on hypercalciuria and nephrocalcinosis.
Calcitriol ; Calcium ; Dehydration ; DNA ; Exome ; Failure to Thrive ; Female ; Follow-Up Studies ; Furosemide ; Humans ; Hypercalcemia ; Hypercalciuria ; Hypophosphatemia ; Infant ; Kidney ; Nephrocalcinosis ; Parathyroid Hormone ; Reference Values ; Sodium-Phosphate Cotransporter Proteins ; Ultrasonography ; Vitamin D ; Vitamin D3 24-Hydroxylase ; Vomiting

BACKGROUND/AIMS: Refeeding syndrome (RFS) is a fatal clinical complication that can occur as a result of fluid and electrolyte shifts during early nutritional rehabilitation for malnourished patients. This study was conducted to determine the clinical implications of RFS in patients with acute pancreatitis (AP). METHODS: Between 2006 and 2016, AP patients with very early mortality were retrospectively enrolled from three university hospitals. RESULTS: Among 3,206 patients with AP, 44 patients died within 3 days after diagnosis. The median age was 52.5 years (range, 27 to 92 years), male-to-female ratio was 3:1, and median duration from admission to death was 33 hours (range, 5 to 72 hours). The etiology of AP was alcohol abuse in 32 patients, gallstones in five patients, and hypertriglyceridemia in two patients. Ranson score, bedside index for severity of AP, and acute physiology and chronic health evaluation-II were valuable for predicting very early mortality (median, [range]; 5 [1 to 8], 3 [0 to 5], and 19 [4 to 45]). RFS was diagnosed in nine patients who died of septic shock (n=5), cardiogenic shock (n=2), or cardiac arrhythmia (n=2). In addition, patients with RFS had significant hypophosphatemia compared to non-RFS patients (2.6 mg/dL [1.3 to 5.1] vs 5.8 mg/dL [0.8 to 15.5]; p=0.001). The early AP-related mortality rate within 3 days was approximately 1.4%, and RFS occurred in 20.5% of these patients following sudden nutritional support. CONCLUSIONS: The findings of current study emphasize that clinicians should be aware of the possibility of RFS in malnourished AP patients with electrolyte imbalances.
Alcoholism ; Arrhythmias, Cardiac ; Diagnosis ; Gallstones ; Hospitals, University ; Humans ; Hypertriglyceridemia ; Hypophosphatemia ; Mortality ; Nutritional Support ; Pancreatitis ; Physiology ; Prognosis ; Refeeding Syndrome ; Rehabilitation ; Retrospective Studies ; Shock, Cardiogenic ; Shock, Septic

This case report concerns a 34-year-old woman who had been diagnosed with ankylosing spondylitis (AS), fibromyalgia syndrome (FMS), osteoarthritis (OA), lumbar disc herniation and the like in different hospitals during the past 18 months. She had progressive osteoarthrosis, significant muscle weakness, gait abnormalities in weightbearing areas, however without typical inflammatory low back pain, while the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was invalid, with normal inflammation index, negative results for rheumatic factor (RF) and human leukocyte antigen (HLA)-B27, and normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She had hyphosphatemia, normal serum calcium, 1,25-(OH)2-D3 reduction, elevated alkaline phosphatase (ALP) and normal parathyroid hormone (PTH), however with elevated urinary phosphorus. Finally, the medial thigh nodule was found in the subcutaneous of her inner leg by careful examination and imaging scans including B-ultrasound and PET/CT. The final pathology confirmed that the nodule was phosphate urinary mesenchymal tumors. After the tumor was removed, the patient was treated with anti-osteoporosis and phosphorus supplementation. The symptoms of bone pain and muscle weakness were alleviated, and hypophosphatemia was corrected. It was confirmed that the patient had low-phosphorus osteomalacia due to tumor. Tumor-induced hypophosphatemia osteomalacia (TIO) was a rare paraneoplastic syndrome which was caused by excessive phosphorus excretion induced by the tumor, and was thus categorized as an acquired hypophosphatemic osteomalacia. TIO had an occult onset and was associated with a high rate of misdiagnosis, although TIO has some typical clinical features. Early diagnosis, correctly positioning of the tumor, and surgical resection can achieve good outcomes.
Adult ; Endocrine System Diseases ; Female ; Humans ; Hypophosphatemia ; Neoplasms, Connective Tissue ; Osteomalacia ; Positron Emission Tomography Computed Tomography

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m²). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.
Acidosis, Renal Tubular ; Adult ; Biopsy ; Blood Urea Nitrogen ; Bone Density ; Creatinine ; Drug-Related Side Effects and Adverse Reactions ; Fanconi Syndrome ; Female ; Glomerular Filtration Rate ; Glycosuria, Renal ; Humans ; Hypophosphatemia, Familial ; Middle Aged ; Molecular Biology ; Osteoporosis ; Parathyroid Hormone ; Pathology ; Proteinuria ; Vitamin D

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.
Calcification, Physiologic ; Diagnosis ; Fibroblast Growth Factors ; Humans ; Hypophosphatemia ; Metabolism ; Neoplasm Metastasis ; Osteomalacia ; Paraneoplastic Syndromes ; Physical Examination ; Prognosis ; Radionuclide Imaging ; Radiotherapy ; Recurrence ; Rickets ; Vitamin D ; Vitamin D Deficiency

Phosphate is essential in regulating human metabolic processes, and severe hypophosphatemia can induce neurologic and hematological complications and result in respiratory failure and cardiac dysfunction. Therefore, correction of severe hypophosphatemia can be pivotal in the management of diabetic ketoacidosis (DKA). We report the case of a 14-year-old female who was diagnosed with type 1 diabetes and referred to our institute for treatment of DKA. Although the patient received fluid and continuous insulin administration according to the current DKA treatment protocol, generalized tonic seizures and cardiac arrest developed. After cardiopulmonary resuscitation, the patient recovered and was stable. Within 16 hours after DKA treatment, the patient developed respiratory failure with severe hypophosphatemia that required mechanical ventilation. Concurrent neurologic evaluation revealed no specific abnormalities. The patient recovered without any complications after correcting the hypophosphatemia. We suggest vigilant monitoring of the phosphate level in DKA patients and active replacement when required.
Adolescent ; Cardiopulmonary Resuscitation ; Clinical Protocols ; Diabetic Ketoacidosis* ; Female ; Heart Arrest ; Humans ; Hypophosphatemia* ; Insulin ; Metabolism ; Respiration, Artificial ; Respiratory Insufficiency* ; Seizures