Tumor-induced Osteomalacia Research Articles

A clinical case of phosphopenic osteomalacia due to paraneoplastic secretion of metastatic prostate cance

Phosphaturic mesenchymal tumor can cause osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23), which disrupts the metabolism of phosphate and vitamin D. These tumors are predominantly benign, but less than 5% of them are malignant forms. This article presents the first clinical case in the Russian Federation of a 69-year-old patient with severe hypophosphatemia due to metastatic prostate cancer. Increased secretion of FGF23 are described in the androgen-resistent prostate cancer, which led to pronounced disorders of mineral metabolism, accompanied by a clinical symptom of weakness, pain in the bones, immobilization of the patient. The condition was regarded as worsening against the background of the progression of the disease. However, symptomatic therapy aimed at increasing the level of phosphate significantly improved the patient’s general condition. The medical community should be aware of the possibility of developing hypophosphatemia in patients with weakness and bone pain, which are not always associated with the progression of metastatic prostate cancer.

Delayed diagnosis of plasma cell disorder-related Fanconi syndrome in young adults presenting as osteomalacia: report of two cases with normokalemia and normal haematological parameters at the time of presentation.

Adult-onset hypophosphatemic osteomalacia is rare and diagnosis is frequently delayed. Fanconi syndrome (FS) due to monoclonal gammopathy is a well-recognized, but rare cause of hypophosphatemia. The relatively young age of patients and normal routine hematological parameters often results in late recognition of this treatable disease entity. Low phosphorus, elevated alkaline phosphatase, mildly impaired renal function and hypokalemia are often the only abnormalities on routine evaluation. We summarize the clinico-pathological features of two cases who initially presented with fractures and proximal myopathy and were subsequently found to have FS secondary to light chain proximal tubulopathy. Atypical features like absence of hypokalemia at presentation and elevated Fibroblast Growth Factor 23(FGF 23), a marker of oncogenic osteomalacia were noted. Marked clinical improvement and recovery of renal parameters were evident with phosphate supplements and chemotherapy for the plasma cell disorder. FS due to monoclonal gammopathy may present with atypical features and diagnosis may be challenging

Delayed diagnosis of plasma cell disorder-related Fanconi syndrome in young adults presenting as osteomalacia: report of two cases with normokalemia and normal haematological parameters at the time of presentation

Adult-onset hypophosphatemic osteomalacia is rare and diagnosis is frequently delayed. Fanconi syndrome (FS) due to monoclonal gammopathy is a well-recognized, but rare cause of hypophosphatemia. The relatively young age of patients and normal routine hematological parameters often results in late recognition of this treatable disease entity. Low phosphorus, elevated alkaline phosphatase, mildly impaired renal function and hypokalemia are often the only abnormalities on routine evaluation. We summarize the clinico-pathological features of two cases who initially presented with fractures and proximal myopathy and were subsequently found to have FS secondary to light chain proximal tubulopathy. Atypical features like absence of hypokalemia at presentation and elevated Fibroblast Growth Factor 23(FGF 23), a marker of oncogenic osteomalacia were noted. Marked clinical improvement and recovery of renal parameters were evident with phosphate supplements and chemotherapy for the plasma cell disorder. FS due to monoclonal gammopathy may present with atypical features and diagnosis may be challenging

"Non-phosphaturic" Variant of Phosphaturic Mesenchymal Tumor of the Middle Ear Expressing Multiple Phosphatonins.

"Non-phosphaturic" Variant of Phosphaturic Mesenchymal Tumor of the Middle Ear Expressing Multiple Phosphatonins.

Tumour-induced osteomalacia: 18 months of 2-weekly burosumab treatment.

Tumour-induced osteomalacia (TIO) is due to an overproduction of fibroblast growth factor 23 (FGF23) by mesenchymal tumours, causing hypophosphatemia, osteomalacia and muscle weakness. TIO is usually cured by tumour resection, but neoplasms may be unidentifiable and unresectable or the patient may refuse surgery. In these cases, medical treatment with oral phosphate and calcitriol is mandatory, but it is not fully effective and it is associated with low compliance. Burosumab, a human MAB against FGF23 employed to treat X-linked hypophosphatemia (XLH), has recently been approved for TIO in the USA. Maximum burosumab dose in XLH is 90 mg administered for 2 weeks; there are no data on clinical efficacy and safety of this dose in TIO. We reported the case of a 73 years old male with multiple non-traumatic fractures, low bone mineral density, pain and reduced independence of activities of daily living. Biochemical evaluation showed hypophosphatemia, high alkaline phosphatase (ALP) and C-terminal telopeptide (CTX) and normal albumin-corrected total calcium and parathyroid hormone. Tubular phosphate reabsorption was low (80%), whereas C-terminal tail of FGF23 (cFGF23) was elevated. A 68Ga-DOTATOC PET was performed, identifying a lesion in the first left rib. The patient refused surgery; therefore, burosumab therapy was started. After 18 months of treatment (maximum dose: 60 mg administered for 2 weeks), plasma phosphate normalized and ALP levels improved (138 U/L). Patient clinical symptoms as well as pain severity and fatigue improved. Neither adverse events nor tumour progression was reported during follow-up except for a painless fracture of the second right rib. Our case shows efficacy and safety of burosumab treatment administered every 2 weeks in a tumour-induced osteomalacia (TIO) patient. After 18 months of treatment at a maximum dose of 60 mg every 2 weeks, we found plasma phosphate normalization and ALP reduction as well as improvement in clinical symptoms and fatigue. Neither adverse events nor tumour progression was reported during follow-up, except for a painless fracture of the second right rib.

Tumour-Induced Osteomalacia in Metastatic Prostate Carcinoma.

Tumour-Induced Osteomalacia in Metastatic Prostate Carcinoma.

Rare causes of Hypophosphatemia: diagnostic approach

Hypophosphatemia is common and may be overlooked due to its asymptomatic nature or non-specific symptoms. Two main mechanisms are at its origin: a shift towards the intracellular sector and an increase in urinary phosphate excretion. A measurement of the urinary phosphate reabsorption threshold allows a diagnostic orientation. Alongside common forms of parathyroid hormone-dependent hypophosphatemia, one should not ignore rare FGF23-mediated forms, in particular X-linked hypophosphatemic rickets. The treatment, above all etiological, also includes the administration of phosphate and, in the event of an excess of FGF23, supplementation with calcitriol. In cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets, the use of burosumab, an anti-FGF23 antibody, must be considered.

Phosphaturic Mesenchymal Tumors: Rethinking the Clinical Diagnosis and Surgical Treatment

The diagnosis of phosphaturic mesenchymal tumors (PMT) is easily delayed clinically, and their surgical treatment is unstandardized. This study aimed to evaluate our experience in the diagnosis and treatment of PMT and provide a research basis for the accurate and standardized treatment of PMT. Twelve patients diagnosed with PMT in our department and who underwent surgical treatment were included in this study. Preoperative demographic and clinical information were recorded. CT, MRI, and technetium-99m (Tc99m)-octreotide PET/CT imaging techniques were used to evaluate the general conditions and lesion boundaries of the tumors. Surgical treatment was performed using radical resection and microwave ablation-assisted extended curettage according to the lesion location and size. Patients were strictly followed up with and evaluated for oncological prognosis, radiological results, bone healing, serum ion levels, limb function, and pain level; the occurrence of complications was also recorded. Three patients underwent radical resection, and nine underwent microwave ablation-assisted extended curettage. The average duration of symptoms in this group was 1.5 years (9-35 months) before diagnosis. Serum phosphate and AKP levels returned to normal one and two weeks postoperatively, respectively. There was no apparent specificity in the pathological findings; however, the immunohistochemistry of FGF-23 was positive, and the original fracture sites were effectively healed during the follow-up. The limb function and pain scores were significantly improved. The MSTS score increased from 15.3 to 29.0, and the VAS score decreased from 5.3 to 0.4. All patients recovered, and 90% resumed their original jobs. Accurate diagnosis and standardized surgical treatment are crucial to achieving a clinical cure for PMT. Combining clinical manifestations, biochemical examinations, imaging characteristics, and pathological findings is an effective way to diagnose PMT accurately. Radical resection and microwave ablation-assisted extended curettage are reliable surgical treatment methods for PMT.

Misdiagnosis and Mistreatment of a Rare Case of Intracranial Oncogenic Osteomalacia with an Altered Amino Acid Profile

Background. Oncogenic osteomalacia (OO), also known as tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome caused by mesechymal tumors secreting fibroblast growth factor 23 (FGF23). Common in middle age, these tumors are often disclosed by progressive generalized bone pain and muscle weakness, along with an altered biochemical profile. Despite its characteristic presentation, the disease is often underrecognized with delayed onset of surgical or pharmacological intervention that can have serious repercussions on the patients' health and quality of life. Case presentation. We describe the case of a 65-year-old Caucasian man presenting TIO with intracranial and spinal localizations and Fanconi-like aminoaciduria. The condition was misdiagnosed and mistreated for three years, leading to loss of self-sufficiency and depression. Following proper identification, the spinal mass was excised with complete remission of the functional symptoms. As it was not possible to remove the intracranial lesion, the patient was treated conservatively with calcitriol and phosphorous supplements that granted good metabolic control up to the time of a recent follow-up visit (at 5 years). Conclusions. The finding of an altered amino acid profile, not usually reported in these cases, should prompt clinicians to a wider usage of these molecules as suitable candidates for metabolic diseases. In addition to providing central information, they are easy to obtain and inexpensive to analyze. Such determination could help to speed up the diagnostic process, as a long-lasting history of misdiagnosis and mistreatments can lead primarily to clinical worsening, but also to the use of expensive, useless medications with side effects that contribute to poor patient health.

Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with progressive bone pain, muscle weakness, and fragility fractures. TIO is characterized by hypophosphatemia, excess renal phosphate excretion, and low/inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2 D) levels. Rarity and enigmatic clinical presentation of TIO contribute to limited awareness among the medical community. Accordingly, appropriate diagnostic tests may not be requested, leading to delayed diagnosis and poorer patient outcomes. We have developed a global guidance document to improve the knowledge of TIO in the medical community, enabling the recognition of patients with TIO and appropriate referral. We provide recommendations aiding diagnosis, referral, and treatment, helping promote a global standard of patient management. We reviewed the literature and conducted a three-round Delphi survey of TIO experts. Statements were drafted based on published evidence and expert opinions (≥70% consensus required for final recommendations). Serum phosphate should be measured in patients presenting with chronic muscle pain or weakness, fragility fractures, or bone pain. Physical examination should establish features of myopathy and identify masses that could be causative tumors. Priority laboratory evaluations should include urine/serum phosphate and creatinine to assess renal tubular reabsorption of phosphate and TmP/GFR, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25(OH)2 D, and FGF23. Patients with the clinical/biochemical suspicion of TIO should be referred to a specialist for diagnosis confirmation, and functional imaging should be used to localize causative tumor(s). Recommended treatment is tumor resection or, with unresectable/unidentifiable tumors, phosphate salts plus active vitamin D, or burosumab.

A case of tumor-induced osteomalacia masked by acute kidney injury

Introduction: Hypophosphatemia in patients with tumor-induced osteomalacia (TIO) is due to abnormal excess production of fibroblast growth factor 23 (FGF-23) causing urinary phosphate wasting. However, in patients with coexisting acute kidney injury (AKI), hypophosphatemia may not be apparent as AKI reduces filtration and excretion of phosphate. Case report: We describe a case of 36-year-old woman who presented with right-sided abdominal pain. Initial laboratory testing revealed non oliguric AKI with creatinine (Cr) of 2.0 mg/dL (baseline 1.2 mg/dL), low phosphate (1.8 mg/dL), and normal parathyroid (PTH) levels. Hypophosphatemia in the setting of AKI and normal PTH raised suspicion for renal phosphate wasting disorder independent of PTH, triggering an order for FGF-23 level. Further into hospital stay, the AKI worsened (Cr rose to 7.2 mg/dL) and phosphate levels increased to 6.7 mg/dL casting doubt on the initial suspicion. However, FGF-23 level resulted at 12,715 RU/mL, strongly suggesting TIO. Random liver biopsy was obtained as part of TIO work up due to liver ultrasound findings of hepatomegaly, diffuse parenchymal heterogenicity mimicking steatosis and potential ill-defined mass. Liver specimen showed tumor cells positive for CD56 and Ki-67, indicating high-grade metastatic neuro endocrine tumor which was the likely source of FGF-23. Patient rapidly deteriorated and opted for comfort measures. Conclusion: TIO typically manifests with overt hypophosphatemia. This case highlights the fact that decreased glomerular filtration rate may mask the degree of urinary phosphate wasting resulting in normal to high serum phosphate level. This warrants high index of suspicion to diagnose an underlying phosphate wasting disorder in the setting of normal to high serum phosphate levels and reduced kidney function.

Tumor-induced osteomalacia treated with T12 tumor resection

Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia caused by fibroblast growth factor-23 (FGF23)-secreting tumors. Most of these tumors are phosphaturic mesenchymal tumors (PMTs) typically involving soft tissue in the extremities and bone of the appendicular skeleton and cranium. We report the case of a 60-year-old woman with about 3 years of persistent bone pain and multiple fractures, initially diagnosed as osteoporosis, who was found to have hypophosphatemia with low 1,25-dihydroxyvitamin D and elevated alkaline phosphatase and inappropriately normal FGF23 consistent with TIO. Her symptoms improved with phosphate supplementation, vitamin D and calcitriol. 68Ga-DOTATATE imaging revealed a T12 vertebral body lesion confirmed on biopsy to be a PMT. She underwent resection of the PMT with resolution of TIO and increased bone density. This rare case of TIO secondary to a PMT of the thoracic spine highlights some of the common features of PMT-associated TIO and draws attention to PMT-associated TIO as a possible cause of unexplained persistent bone pain, a disease entity that often goes undiagnosed and untreated for years. Tumor-induced osteomalacia (TIO) is typically caused by phosphaturic mesenchymal tumors (PMTs) that are usually found in the soft tissue of the extremities and bone of the appendicular skeleton/cranium and rarely in the spine. TIO may be misdiagnosed as osteoporosis or spondyloarthritis, and the correct diagnosis is often delayed for years. However, osteoporosis, in the absence of fracture, is not associated with bone pain. The hallmark of TIO is hypophosphatemia with inappropriately normal or low 1,25-dihydroxyvitamin D and elevated or inappropriately normal fibroblast growth factor-23 (FGF23) levels. In patients with unexplained persistent bone pain, a serum phosphate should be measured. Consider PMT-associated TIO as a potential cause of unexplained persistent bone pain and hypophosphatemia. PMTs express somatostatin receptors and may be identified with 68Ga-DOTATATE imaging. Complete surgical resection is the preferred treatment for spinal PMTs associated with TIO.

Utility of Multimodality Approach Including Systemic FGF23 Venous Sampling in Localizing Phosphaturic Mesenchymal Tumors.

Tumor-induced osteomalacia (TIO) is one of the most common forms of acquired fibroblast growth factor 23 (FGF23)-related hypophosphatemia and is usually caused by phosphaturic mesenchymal tumors (PMTs). Although the complete resection of PMTs can cure TIO, preoperative localization of tumors by standard imaging modalities is often challenging. In addition to 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG-PET) and 111In-pentetreotide scintigraphy (SRS), systemic FGF23 venous sampling (FGF23VS) has been used to help localize PMTs in specialized institutions. This study aimed to evaluate the diagnostic performance of each imaging test and their combinations in localizing PMTs. In an observational retrospective study of patients with adult-onset FGF23-related osteomalacia who underwent all 3 imaging studies (FDG-PET, SRS, and FGF23VS), the rate of successful preoperative localization of the tumors was evaluated only in the patients with pathological diagnoses of PMTs, considering the possibility that pathogenesis of patients without identified tumors might be due to other causes such as late-onset hereditary FGF23-related hypophosphatemia. A total of 30 Japanese patients with TIO (median age, 60 years [range, 28-87 years]; 10 women [33.3%]) were included in the study. The success rate of preoperative localization for each test and combinations of 2 or 3 tests among 18 patients with PMTs was as follows: 72% (FDG-PET), 72% (SRS), 94% (FGF23VS), 89% (FDG-PET, SRS), 100% (FDG-PET, FGF23VS), 94% (SRS, FGF23VS), and 100% (FDG-PET, SRS, and FGF23VS). We observed the highest localization rate of PMTs in patients with identified PMTs with the combination of FDG-PET and FGF23VS.

#1324100: A Suspected Case of Phosphaturic Mesenchymal Tumor

Phosphaturic mesenchymal tumor is a rare disease that usually affects middle-aged adults and can lead to a wide range of symptoms such as weight loss, bone pain, muscle weakness, sensorimotor disturbances, heart failure etc. It causes renal phosphate wasting through the secretion of FGF23 (fibroblast growth factor 23), which acts on sodium-phosphate co-transporter at the renal tubule and inhibits phosphate reabsorption. It also inhibits 1α-hydroxylation of 25-hydroxyvitamin D, leading to decreased bone mineralization and Tumor-induced osteomalacia (TIO).

New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia.

Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases.

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. This retrospective study enrolled 202 patients with TIO. Occurrence of HPT in patients with TIO. HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

Tumor-induced Osteomalacia: A Comprehensive Review.

Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to overproduction of fibroblast growth factor 23 (FGF23), with profound effects on patient morbidity. TIO is an underdiagnosed disease, whose awareness should be increased among physicians for timely and proper management of patients. Symptoms reported by patients with TIO are usually nonspecific, thus rendering the diagnosis elusive, with an initial misdiagnosis rate of more than 95%. Biochemical features of TIO are represented by hypophosphatemia, increased or inappropriately normal levels of FGF23, and low to low normal circulating 1,25-dihydroxyvitamin D (1,25(OH)2D). Phosphaturic mesenchymal tumors are the pathological entities underlying TIO in most affected patients. There is now evidence that FN1-FGFR1 and FN1-FGF1 fusion genes are present in about half of tumors causing this paraneoplastic syndrome. Tumors causing TIO are small and grow slowly. They can occur in all parts of the body from head to toe with similar prevalence in soft tissue and bone. There are a number of functional and anatomical imaging techniques used for tumor localization; 68Ga DOTA-based technologies have better sensitivity. Surgery is the treatment of choice; several medical treatments are now available in case of inability to locate the tumor or in case of incomplete excision.

PSAT218 Technetium 99m-Methyl Diphosphonate (99mTc MDP) Radioguided Surgery in Patient With Tumor-Induced Osteomalacia (TIO)

Abstract Introduction TIO is a rare paraneoplastic syndrome of excess FGF23 secretion by mesenchymal tumors that results in myopathy, pain, weakness and osteomalacic fractures. Tumors are small and often difficult to locate, frequently delaying diagnosis. Surgery is considered definitive therapy, but recurrences remain common due to incomplete tumor resection. We present a novel approach of using Gallium (Ga) 68 DOTATATE PET/CT to identify the culprit tumor preoperatively followed by intraoperative 99mTc MDP radioguided surgical resection. Case Report A 41-year-old female presented with a four-year history of progressive weakness, fatigue, muscle and bone pain, and multiple subacute rib fractures and bilateral hip fractures with minimal trauma. On exam, she had proximal muscle weakness and walked with an antalgic gait aided by crutches. Laboratory evaluation revealed serum phosphorus of 2.1 mg/dL (2.5-4.5), tubular reabsorption of phosphate (TRP) of 78.9% (>85%), elevated alkaline phosphatase of 209 IU/L (31-125), 1,25 dihydroxy vitamin D [1,25 (OH)2 D] of 17 pg/ml (18-72) and serum FGF23 610 RU/ml (<180). Serum calcium, parathyroid hormone (PTH), estimated GFR and 25 hydroxy vitamin D were normal. Testing for genetic causes of hypophosphatemia was negative. With biochemical and genetic testing consistent with TIO, functional imaging was performed. Ga 68 DOTATATE PET/CT identified a single, 1.8 cm non-expansile sclerotic focus along the anterior left sixth rib with moderate uptake. She denied any recent trauma to the site. She was referred to thoracic surgery for a left sixth rib resection. Intraoperatively, she received 8.1 mCi Tc99m-MDP intravenously and the margin of the tumor was localized using a gamma probe allowing complete resection. Surgical pathology confirmed a 2.0 cm phosphaturic mesenchymal tumor (PMT)with widely negative margins. Postoperatively, her muscle strength, fatigue and ambulation improved significantly within six weeks and her serum phosphorus, TRP, 1,25 (OH)2 D normalized. Discussion Localization of PMTs is difficult because tumors are small and can be located anywhere in the body. Functional imaging using somatostatin analogs such Ga 68 DOTATATE PET/CT exploits the presence of somatostatin receptors expressed by many PMTs. Complete resection of PMTs can be challenging because they tend to be locally infiltrative along bone trabeculae. 99mTc MDP is a radiotracer localized to bone in proportion to osteoblastic activity as seen at sites of bony remodeling or bone metastasis. Accurate tumor localization and complete resection with widely negative margins are imperative for definitive treatment and cure. This case is unique in utilizing Ga 68 DOTATATE PET/CT for localization of the PMT paired with intraoperative 99mTc MDP in conjunction with a gamma camera for identifying tumor margins facilitating complete tumor resection and cure of the patient. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP125 Soft Bones in Crohn's: Tumor-induced osteomalacia and inflammatory bowel disease

Abstract Introduction Bone loss is common in patients with inflammatory bowel disease (IBD) and is usually attributed to Vitamin D malabsorption, treatment with glucocorticoids or chronic inflammation. We report a case of bone loss, hypophosphatemia, and atypical fractures in a patient with IBD who was ultimately diagnosed with tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome of chronic hypophosphatemia and impaired vitamin D metabolism. Clinical Case A 39-year-old male presented for evaluation of low bone density, hypophosphatemia, and multiple stress fractures. His medical history includes Crohn's disease in biochemical remission on adalimumab and bilateral hip avascular necrosis. There was no history of significant steroid use or known family history of metabolic bone disease. He was previously highly active as a modern dancer. Over the course of 3 years, he developed progressive diffuse bony pain and he became wheelchair-bound. A whole body bone scan visualized multiple age-indeterminate atraumatic fractures, including bilateral metatarsal fractures and numerous rib fractures. Dual energy x-ray absorptiometry showed significantly low bone mass for age (Z-scores –3.4, -3.1, -3.7 at the L1-L4 spine, total right femur and right femoral neck, respectively). Physical exam was notable for a soft, subcutaneous 8 cm mass posterior to the left paraspinal muscle at the level of T12, which had previously been diagnosed as a lipoma. Laboratory evaluation revealed phosphorus 1 mg/dL (2.5-4.5 mg/dL), calcium 9.1 mg/dL (8.6-10.2 mg/dL), PTH 35 pg/mL (15-65 pg/mL), c-telopeptide 592 pg/mL (38-724 pg/mL), bone specific alkaline phosphatase 114.5 mcg/L (4-27 mcg/L), vitamin D-1,25 8.9 pg/mL (19.9-79.3 pg/mL), and vitamin D-25 34 ng/mL (normal >30 ng/mL). Fibroblast growth factor-23 (FGF-23) level was 1200 RU/mL (44-215 RU/mL), consistent with TIO. Thyroid function, dexamethasone suppression test, testosterone and IGF-1 were normal. Ga-DOTATATE PET scan demonstrated that the paraspinal soft tissue mass was strongly somatostatin avid. The patient was treated with oral calcitriol and phosphate replacement. He underwent a biopsy of the left paraspinal mass, which was consistent with a bland epithelioid and spindle cell neoplasm, most suggestive of a phosphaturic mesenchymal tumor. He is scheduled for a radical resection of the soft tissue mass. Conclusion To date, there are no published case reports of TIO with coexisting IBD. Inflammatory cytokines, such as tumor necrosis factor alpha, have been shown to positively correlate with FGF-23 levels, and FGF-23 has been documented to be elevated during IBD flares. Given this, the presence of IBD may portend a worsened metabolic bone prognosis in patients who simultaneously develop FGF-23 secreting tumors. Presentation: No date and time listed

PSAT223 A Delayed Diagnosis of Oncogenic Osteomalacia Presenting with Bone Pain, Muscle Weakness and Elevated Alkaline Phosphatase

Abstract Background Tumor-induced osteomalacia (TIO) is a rare bone disease caused by excess production of FGF23 by a phosphaturic mesenchymal tumor, resulting in severe hypophosphatemia, bone demineralization, insufficiency fractures, bone pain and muscle weakness. The Fibroblast Growth Factor-23 (FGF23) is a phosphaturic hormone produced by osteocytes, whose primary effect is to decrease serum phosphate by suppressing proximal tubular phosphate reabsorption and intestinal phosphate absorption (via diminished 1,25D production). Clinical case A 65-year-old male was referred to endocrinology clinic for a second opinion due to severe rib pain and elevated alkaline phosphatase levels. His first endocrinologist diagnosed Paget's disease of the bone based on symptoms of rib pain, an elevated alkaline phosphatase level, and abnormal Tc99 bone scintigraphy demonstrating uptake in multiple areas, including bilateral humeri, ribs, knees, ankles, and L4 vertebral body. He received 5 mg IV zoledronate for treatment of Paget's disease, and immediately post-infusion reported worsening of severe rib pain. Upon presentation to our institution, he reported ongoing severe rib pain and bilateral knee pain. On exam, he had extreme difficulty rising from a seated position. Laboratories revealed calcium 9.0 mg/dL, albumin 5.0 g/dL, alkaline phosphatase 116 U/L, 25D 43 ng/dL, PTH 66 pg/mL and serum phosphorous 1.5 mg/dL. Tubular Reabsorption of Phosphate (TRP) was 59%, based on a spot second morning void with corresponding fasting morning blood draw. 1,25D was 13 pg/mL (19-79 pg/mL). Intact FGF23 was 346 pg/mL (<59 pg/nL). CT revealed bilateral tibial plateau insufficiency fractures. When asked if he noticed any "lumps or bumps", the patient reported a lump under his left second toe. MRI showed a 1.8 cm soft tissue mass. A GA68-DOTA-TATE PET CT revealed a 2.3 cm soft tissue mass plantar to the 2nd left proximal phalanx with intense activity mass (SUVmax 39.8). This mass was surgically excised. Post-operative FGF23 levels were as follows: 38 pg/mL → 15 pg/mL → <14 pg/mL. Within 14 days, the patient's ability to rise from a seated position was markedly improved. His severe rib pain persisted for three weeks but was significantly improved by six weeks post-op. Despite treatment with 1 mcg calcitriol daily and 5000 IU vitamin D daily, he developed evidence of post-operative hungry bone syndrome with calcium 8.3 mg/dL, PTH 64 pg/mL, and alk phos 157 U/L. Conclusion Tumor-induced osteomalacia is a rare but treatable condition, presenting with severe hypophosphatemia, bone pain, bone demineralization, insufficiency fractures, and muscle weakness. Due to the nonspecific nature of the presenting symptoms, delays in diagnosis are common. Serum phosphorous should be obtained in all patients presenting with unexplained elevations in alkaline phosphatase. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.