scholarly journals Sternal Phosphaturic Mesenchymal Tumor-Induced Osteomalacia, Diagnosis and Management: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A224-A225
Author(s):  
Mopelola Adetola Adeyemo ◽  
Aili Guo
Keyword(s):  
Ct Scan ◽  
Functional Status ◽  
Muscle Weakness ◽  
Bone Pain ◽  
Mesenchymal Tumor ◽  
Phosphaturic Mesenchymal Tumor ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
History Of ◽  
Fgf 23

Abstract Background: Tumor induced osteomalacia (TIO) is a rare paraneoplastic disorder in which overproduction of fibroblast growth factor-23 (FGF-23) by mesenchymal tumor results in decreased renal phosphorus reabsorption and low to inappropriately normal 1,25-dihydroxyvitamin D, leading to hypophosphatemia and osteomalacia. Patients often present with bone pain, fractures, muscle weakness, and progressive decline in mobility. Due to the nonspecific nature of presenting symptoms of TIO diagnosis is often delayed. Clinical Case: A 55-year-old male presented with complaints of chest pain, shortness of breath, and generalized weakness following a ground level fall. Patient also reported a 10-year history of osteoarthritis with chronic back pain and 1-year history of generalized weakness, resulting in significant decline in functional status. On work-up, the initial CT scan of chest revealed multiple fractures including ribs, manubrium, scapula, and pubic rami. Subsequent biochemical evaluation was remarkable for hypophosphatemia to low of 1.3 mg/dL (2.4 - 5.0 mg/dL), low of 1,25-dihydroxyvitamin D of 13.1 pg/ml (19.9 - 79.3 pg/mL), reduced tubular phosphate reabsorption rate of 28% (normal > 80%) ratifying for renal phosphate wasting, normal iPTH level, and elevated serum FGF-23 level of 460 (normal < 180). Then, localization imaging for TIO was performed. After PET/CT scan showing increased uptake at the sternal area suggestive of lytic metastasis, subsequent CT angiogram of the chest identified mottled, irregular, mildly expansile appearance of the sternal manubrium. Sternal biopsy revealed phosphaturic mesenchymal tumor with positive FGF 23 mRNA expression. Surgical resection was delayed due to poor functional status and concurrent discovery of an EBV-positive nasopharyngeal carcinoma. Prior to surgery patient was treated with phosphorus and calcitriol supplements. Post-operatively serum phosphorus and FGF-23 levels were normalized. Patient also improved clinically. Patients treatment course was complicated by secondary hyperparathyroidism; however, this improved following surgery. Conclusion: Diagnosis of TIO can be delayed due to its nonspecific symptoms. Thus, in patients with chronic bone pain, muscle weakness, and atraumatic fractures, TIO should be kept on the differential and these patients should undergo thorough biochemical and imaging evaluation. Tumor localization could be challenging. Patients should be managed with supplements of active vitamin D and phosphorus with goal to normalize phosphorus level to prevent further bone demineralization prior to surgery. However, surgical intervention remains the mainstay of management as this is curative of TIO.

Oncogenic osteomalacia associated with a meningeal phosphaturic mesenchymal tumor

1996 ◽  
Vol 84 (2) ◽  
pp. 288-292 ◽  
Author(s):  
Karoly David ◽  
Tamas Revesz ◽  
George Kratimenos ◽  
Thomas Krausz ◽  
H. Alan Crockard
Keyword(s):  
Ct Scan ◽  
Symptomatic Relief ◽  
Symptomatic Improvement ◽  
Mesenchymal Tumor ◽  
Phosphaturic Mesenchymal Tumor ◽  
Oncogenic Osteomalacia ◽  
Content Type ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

✓ A 60-year-old woman suffered from hypophosphatemic osteomalacia secondary to a frontal intracranial tumor. Oral administration of phosphate and 1-α-hydroxyvitamin D3 provided only temporary symptomatic relief. A computerized tomography (CT) scan of the patient's head revealed a large subfrontal tumor attached to the dura. Following removal of the tumor, the patient's hypophosphatemia subsided; her level of 1,25-dihydroxyvitamin D3, which was undetectable preoperatively, returned to normal, and she had symptomatic improvement. Three years later, decreasing levels of phosphate and 1,25-dihydroxyvitamin D3 indicated tumor recurrence, before it was detected by CT scan. Histological examination of the tumor provided the diagnosis of “mixed connective tissue variant of phosphaturic mesenchymal tumor.” The characteristic histological features of this relatively rare entity are discussed. This is the first report of a surgically treated intracranial phosphaturic mesenchymal tumor that caused oncogenic osteomalacia.

scholarly journals Tumor-induced osteomalacia: a case report

2009 ◽  
Vol 53 (3) ◽  
pp. 378-382 ◽  
Author(s):  
Daniel Dutra Romualdo-Silva ◽  
Bárbara Campolina Carvalho Silva ◽  
Cristiane Vasconcelos Caetano ◽  
Angélica Maria França Paiva Tibúrcio ◽  
Maurício Buzelin Nunes ◽  
...  
Keyword(s):  
Case Report ◽  
Bone Pain ◽  
Fibroblast Growth Factor 23 ◽  
Blood Chemistry ◽  
Tissue Type ◽  
Surgical Removal ◽  
Phosphaturic Mesenchymal Tumor ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Low Levels

Tumor-induced osteomalacia (TIO) is a rare paraneoplasic syndrome with overproduction of fibroblast growth factor 23 as a phosphaturic agent, leading to chronic hyperphosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of 1,25-dihydroxyvitamin D. Diagnosis of this disease is often challenging. The following case report described a middle-aged man with symptoms of bone pain and severe muscle weakness, who was found to have TIO. The tumor responsible for the symptoms was localized on his thigh and its resection resulted in normalization of blood chemistry and complaints. Subsequent microscopic examination revealed a phosphaturic mesenchymal tumor, mixed connective tissue type. The authors reinforce the importance of recognition of this disease, as severe disability and even death can be avoided with the surgical removal of the causative tumor.

scholarly journals Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chih-Huang Li ◽  
Xiaolei Tang ◽  
Samiksha Wasnik ◽  
Xiaohua Wang ◽  
Jintao Zhang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Vitamin D ◽  
Growth Factor ◽  
Kidney Failure ◽  
Mechanistic Study ◽  
Blood Levels ◽  
Biological Functions ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Fgf 23

Abstract Background Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. Methods We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. Results We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. Conclusions Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

scholarly journals Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 34
Author(s):  
Cornelia Then ◽  
Evelyn Asbach ◽  
Harald Bartsch ◽  
Niklas Thon ◽  
Christian Betz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Olfactory Neuroblastoma ◽  
Mesenchymal Tumor ◽  
Fibroblast Growth ◽  
Phosphaturic Mesenchymal Tumor ◽  
Oncogenic Osteomalacia ◽  
Pet Ct ◽  
Fgf 23

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

scholarly journals Clinical Significance of FGF-23 in Patients with CKD

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Domenico Russo ◽  
Yuri Battaglia
Keyword(s):  
Ventricular Hypertrophy ◽  
Vascular Dysfunction ◽  
Left Ventricular ◽  
Vitamin D Metabolism ◽  
Fgf Receptor ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Phosphate Retention ◽  
Fgf 23

FGF23 is a bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 principally acts in the kidney to induce urinary phosphate excretion and suppress 1,25-dihydroxyvitamin D synthesis in the presence of FGF receptor 1 (FGFR1) and its coreceptor Klotho. In patients with chronic kidney disease (CKD), circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to hypersecretion of parathyroid hormone. Furthermore, FGF23 is associated with vascular dysfunction, atherosclerosis, and left ventricular hypertrophy. This paper summarizes the role of FGF23 in the pathogenesis of mineral, bone, and cadiovascular disorders in CKD.

scholarly journals Peptide Receptor Radionuclide Therapy for a Phosphaturic Mesenchymal Tumor

2020 ◽  
Vol 13 (3) ◽  
pp. 1373-1380
Author(s):  
Simon Häfliger ◽  
Ann-Katrin Seidel ◽  
Eric Schoch ◽  
Jan Reichmann ◽  
Damian Wild ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Fibroblast Growth Factor 23 ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Mesenchymal Tumor ◽  
Surgical Removal ◽  
Phosphaturic Mesenchymal Tumor ◽  
Peptide Receptor ◽  
Wasting Syndrome ◽  
Fgf 23

Tumor-induced osteomalacia is a very rare paraneoplastic syndrome. It can be caused by phosphaturic mesenchymal tumor (PMT), a generally benign tumor that produces fibroblast growth factor 23 (FGF-23), which can cause a severe renal phosphate wasting syndrome. Upon complete surgical removal of the tumor, FGF-23 normalizes and the osteomalacia is cured. In cases in which surgery is not feasible, radiofrequency ablation (RFA) is the treatment of choice. We describe a case with a PMT situated in the sacrum, in close proximity to the sacral plexus. Both surgery and RFA were considered potentially nerve damaging. Since the tumor showed expression of somatostatin receptors, we opted for a peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTATOC. However, the therapy did not show the expected success, since the FGF-23 level had even temporarily increased. The patient was then successfully treated with RFA. A partial remission of the tumor was achieved and FGF-23 levels nearly normalized. Despite some severe neurological side effects, the patient showed a remarkable clinical improvement, with no symptoms of osteomalacia within a few weeks.

scholarly journals Tumor-Induced Osteomalacia: Increased Level of FGF-23 in a Patient with a Phosphaturic Mesenchymal Tumor at the Tibia Expressing Periostin

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Anke H. Hautmann ◽  
Josef Schroeder ◽  
Peter Wild ◽  
Matthias G. Hautmann ◽  
Elisabeth Huber ◽  
...  
Keyword(s):  
Postoperative Radiotherapy ◽  
Somatostatin Receptor ◽  
Tumor Resection ◽  
Distal Tibia ◽  
Immunohistochemical Analysis ◽  
Mesenchymal Tumor ◽  
Phosphaturic Mesenchymal Tumor ◽  
Multiple Fractures ◽  
Magnetic Resonance Imaging Mri ◽  
Fgf 23

In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. Electron microscopy demonstrated a poorly differentiated mesenchymal tumor with a multifocal giant cell component and evidence of neurosecretory-granules. However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. The patient is still in complete remission after 34 months. Tumor resection of PMTMCTs is the therapy of choice. Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. The prognostic value of expression of Periostin has to be evaluated more precisely in a larger series of patients with TIO.

scholarly journals MON-352 When Osteoporosis Does Not Make Sense: Tumor-Induced Osteomalacia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pawarid Techathaveewat ◽  
Ghada Elshimy ◽  
Kelvin Tran ◽  
Karyne L Vinales ◽  
Ricardo R Correa
Keyword(s):  
The Body ◽  
Mesenchymal Tumor ◽  
Renal Tubules ◽  
Mineral Density ◽  
Multiple Fractures ◽  
Post Surgery ◽  
Surgery Patient ◽  
Multiple Imaging ◽  
History Of ◽  
Fgf 23

Abstract Background: Tumor-induced Osteomalacia (TIO) is a rare paraneoplastic disorder that relates to excess FGF-23 secretion from mesenchymal tumors. Typical presentations include weakness, severe bone pain, but more importantly; multiple false or true fractures. Severe Hypophosphatemia with hyperphosphaturia is one of the pathognomonic findings due to FGF-23 action on renal tubules as phosphaturic agent. Multiple imaging modalities usually required as tumor can be in any size and anywhere in the body. Case: 58 yo male with past medical history of multiple fractures: bilateral rib cage, and metatarsal, dextroscoliosis who present to endocrine clinic due to low bone mineral density (BMD). On initial visit, screening bloodwork done was unremarkable except for mild elevation of Alkaline Phosphatase and extremely low phosphorus (1.2). 24 Urine phosphorus ordered which was elevated but it was thought to be nutrition related thus phosphorus replacement was prescribed (4 times per day). On follow up, repeat labs noted again with severe hypophosphatemia with elevated FePhos. DEXA was also performed which noted with T score -4.0 of lumbar spine. During that appointment, he informed also that currently in the process of evaluating right lung mass with biopsy resulted with benign mesenchymal tumor which he was happy to hear. TIO was then suspicious to be the cause of decrease BMD along with history of multiple fractures and height loss. Subsequently, FGF-23 staining was then made to the biopsy sample which was positive thus confirming the diagnosis. Patient then underwent surgical resection of the tumor which post-surgery, patient experienced overall symptoms improvement, resolution of phosphatemia, as well as significant improvement of BMD without additional therapy besides calcium and vitamin D. Discussion: Osteomalacia is a pathological bone disease involving poor mineralization of existing bone during remodeling phrase. It is commonly involved with chronic hypophosphatemia and/or hypocalcemia. Persistent decrease in calcium-phosphate product leads to reduction in bone mineralization activity and bone stiffness with Bowing deformities of the long bone being one of the common findings as well as false fracture.In TIO, FGF-23 is excessively secreted by mesenchymal tumor that is usually difficult to locate due to its small size. When FGF-Receptor is activated, NaPi-2a transcription is reduced in proximal tubule cells which leads to Phosphate excretion and wasting.TIO is a curable disease once tumor is located and surgically removed thus it is important for providers to be aware of it and pursue diagnostic work up when high suspicious. One of the most common reason for misdiagnosis is due to standard metabolic panel on its own does not include phosphorus level which is crucial. TIO has to be distinguish from osteoporosis as Bisphosphonates is not indicated as treatment which is first line for the latter.

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