scholarly journals MON-353 Tumor-Induced Osteomalacia from a Hypervascular Thoracic Paraspinal Mass: Challenges in Diagnosis and Management

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Paola M Perez ◽  
Polly Fu ◽  
Andrew Folick ◽  
Gregory Michael Ku ◽  
Dolores M Shoback ◽  
...  
Keyword(s):  
Vitamin D ◽  
Surgical Resection ◽  
General Circulation ◽  
Fibroblast Growth Factor 23 ◽  
Femoral Shaft ◽  
Venous Sampling ◽  
Lower Extremity Weakness ◽  
Selective Venous Sampling ◽  
Pet Ct ◽  
Phosphate Salts

Abstract Background: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome driven by ectopic production of fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting, hypophosphatemia, and bone demineralization. Successful therapy requires complete resection of the tumor, which is often challenging to localize. Clinical Case: A bedridden 37-year-old woman presented to Endocrine Clinic after 9 years of progressive pain and weakness in her back, hips, and extremities. She had previously been diagnosed with a neurodegenerative disease, though an MRI from 5 years ago showed bilateral subacute sacral ala fractures. CT scan on presentation showed generalized osteopenia and numerous subacute to chronic atraumatic fractures (involving ribs, scapula, pubic rami, and right femoral shaft) concerning for osteomalacia. On exam, she had profound lower extremity weakness. Laboratory testing was notable for serum phosphorus 0.6 mg/dL (normal (nl) 2.5-4.9), calcium 8.4 mg/dL (nl 8.5-10.5), PTH 216 pg/mL (nl 13-85), 25-OH vitamin D 26 ng/mL (nl 30-100), alkaline phosphatase 345 U/L (nl 45-130), 1,25-(OH)2 vitamin D 28 pg/mL (nl 18-72), renal tubular phosphorus reabsorption TmP/GFR 0.53 mg/dL (nl 2.97-4.45), and inappropriately normal FGF23 level 170 RU/mL (nl<180). Phosphate salts, calcitriol, and cinacalcet were initiated. Octreotide scan was negative, but 18F-FDG PET/CT showed mild hypermetabolic activity in the lower thoracic paraspinal area correlating with a 3.4 cm hypervascular mass near the left 8th rib head and two adjacent nodules on MRI. Due to bleeding risk, biopsy was deferred and further confirmatory studies were pursued. Genetic testing for hereditary forms of hypophosphatemia (FGF23, CLCN5, DMP1, ENPP1, FGFR1, PHEX) was negative. 68Ga-DOTATATE PET/CT was not available, but selective venous sampling for FGF23 revealed a 3:1 ratio between venous drainage of the tumor bed and general circulation. Based on this localization, surgical resection was performed. Pathology was consistent with a phosphaturic mesenchymal tumor, but clear margins could not be confirmed due to intraoperative tumor fragmentation. Three months of medical management with phosphate salts and calcitriol normalized her phosphorus levels (2.5-3.3 mg/dL), and she underwent surgical repair of her femoral fracture. Although MRI revealed only postsurgical changes in the spine, her continued requirement for phosphate supplementation and persistently elevated FGF23 levels (258 RU/mL) are concerning for residual tumor. Conclusion: This case illustrates the challenges of TIO due to a hypervascular mass in a rare paraspinal site localized by selective venous sampling for the first time at our institution. The patient’s continued FGF23 elevation underscores the importance of advancing medical therapies, such as burosumab, in patients with TIO that are not amenable to complete surgical resection.

scholarly journals Effective localization in tumor-induced osteomalacia using 68Ga-DOTATOC-PET/CT, venous sampling and 3T-MRI

2017 ◽  
Vol 2017 ◽  
Author(s):  
Shintaro Kawai ◽  
Hiroyuki Ariyasu ◽  
Yasushi Furukawa ◽  
Reika Yamamoto ◽  
Shinsuke Uraki ◽  
...  
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
Somatostatin Receptor ◽  
List Type ◽  
Conventional Imaging ◽  
Imaging Studies ◽  
Venous Sampling ◽  
3T Mri ◽  
Positron Emission ◽  
Pet Ct ◽  
The Right

Summary Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting leading to hypophosphatemia due to excessive actions of fibroblast growth factor 23 (FGF23) produced by the tumors. Although the best way of curing TIO is complete resection, it is usually difficult to detect the culprit tumors by general radiological modalities owing to the size and location of the tumors. We report a case of TIO in which the identification of the tumor by conventional imaging studies was difficult. Nonetheless, a diagnosis was made possible by effective use of multiple modalities. We initially suspected that the tumor existed in the right dorsal aspect of the scapula by 68Ga-DOTATOC positron emission tomography/computed tomography (68Ga-DOTATOC-PET/CT) and supported the result by systemic venous sampling (SVS). The tumor could also be visualized by 3T-magnetic resonance imaging (MRI), although it was not detected by 1.5T-MRI, and eventually be resected completely. In cases of TIO, a stepwise approach of 68Ga-DOTATOC-PET/CT, SVS and 3T-MRI can be effective for confirmation of diagnosis. Learning points: TIO shows impaired bone metabolism due to excessive actions of FGF23 produced by the tumor. The causative tumors are seldom detected by physical examinations and conventional radiological modalities. In TIO cases, in which the localization of the culprit tumors is difficult, 68Ga-DOTATOC-PET/CT should be performed as a screening of localization and thereafter SVS should be conducted to support the result of the somatostatin receptor (SSTR) imaging leading to increased diagnosability. When the culprit tumors cannot be visualized by conventional imaging studies, using high-field MRI at 3T and comparing it to the opposite side are useful after the tumor site was determined.

scholarly journals AB0922 BUROSUMAB (ANTI-FGF23 MONOCLONAL ANTIBODY) IN THE TREATMENT OF A PATIENT WITH RECURRENT TUMOR INDUCED OSTEOMALACIA.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1762.3-1762
Author(s):  
C. Crotti ◽  
F. Zucchi ◽  
P. Messa ◽  
R. Caporali ◽  
M. Varenna
Keyword(s):  
Monoclonal Antibody ◽  
Vitamin D ◽  
Great Trochanter ◽  
Fibroblast Growth Factor 23 ◽  
Well Being ◽  
Hypophosphatemic Rickets ◽  
Imaging Evaluation ◽  
Left Femur ◽  
Pet Ct ◽  
Fgf 23

Background:Tumor-induced Osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia and osteomalacia. Surgery is the only curative treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location.Objectives:To describe a case of a 53-year-old woman affected by recurrent TIO after three surgical attempts of removal treated with Burosumab.Methods:We describe the case of a 53 years old woman with TIO treated with Burosumab, an anti-FGF-23 monoclonal antibody at present approved for X-linked hypophosphatemic rickets only.Results:A 46-year-old Caucasian female was referred to our Bone Unit after experiencing several fractures in different sites. She reported being in good health until three years prior consultation. At the time of symptoms onset, she experienced a progressive muscle pain, enabling her to stand for a long period. During imaging evaluation for atraumatic fracture of right great trochanter, the MRI abdomen and18FDG- PET-CT showed a metabolic pre-sacral lesion. She unsuccessfully underwent to an exploratory laparotomy of that lesion. Then, she suffered from atraumatic intertrochanteric fracture of right femur, surgically treated, and after 3 months, she had an insufficiency dyaphiseal fracture of the left femur, surgically treated. Furthermore, she experienced several ribs fractures. At the time of first evaluation, lab works showed: serum-Phosophate (PS) 1.2 mg/dL (reference range (RR) 2.5-4.5 mg/dL), urinary-phosphate of 24h (PU) 842 mg/24h, alkaline phosphatase (ALP) 565 UI (RR<300), 1,25(OH)2vitamin D327 ng/L (RR 25-86.5), PTH 24 (RR<75 pg/mL), intact-FGF-23 117 (RR 25-45 pg/mL), normal serum and 24h-urinary Calcium. Patient underwent to68Ga-DOTATATE-PET-CT that showed a pre-sacral lesion, who was studied with MRI and CT before surgery. In 2013 patient underwent surgical excision of the pre-sacral region. After 18 months of well-being, patient complained worsening of articular pain and muscle weakness, and further ribs fractures. Another68Ga-DOTATATE-PET-CT reported a relapse of the previous pre-sacral lesion (32x12x47 mm) with an increase of FGF-23levels (54.6 pg/mL). Even the subsequent surgery was not able to remove the tumor. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)2vitamin D3, but PS levels never normalized. We asked for compassionate use of Burosumab and, after ethical committee approval, in September 2019 she was started on Burosumab, at a dose of 30 mg per month (0.3 mg/kg). At baseline, she had PS 1.2 mg/dL, PU 1874 mg/24h, TRP 25.96%. After two months, she improved in pain symptom (VAS reduction from 65 to 12 mm), which allow her to walk and stand without crutches. She did not normalize her PS levels (1.3 mg/dL), while PU reduced to 1000 mg/24h. We titred Burosumab dose at 40 mg per month (0.6 mg/kg) and patient is still under therapy, waiting for next blood works.Conclusion:This is the first European patient affected by TIO treated with Burosumab. Burosumab could be a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery. Further data are needed to standardize the proper dose regimen.Disclosure of Interests:Chiara Crotti: None declared, Francesca Zucchi: None declared, Piergiorgio Messa: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Massimo Varenna: None declared

99mTc-MIBI-SPECT: Eine nicht invasive, sensitive Lokalisationsdiagnostik bei Verdacht auf Nebenschilddrüsenadenom

2018 ◽  
Vol 41 (02) ◽  
pp. 121-127
Author(s):  
Christina Schneider ◽  
Constanza Chiapponi ◽  
Monika Ortmann ◽  
Michael Faust ◽  
Markus Dietlein ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pet Ct ◽  
Ablative Verfahren ◽  
99Mtc Mibi ◽  
Met Pet ◽  
Mibi Spect

ZusammenfassungDie Aufgabe des Nuklearmediziners nach Diagnosestellung eines meist primären Hyperparathyreoidismus besteht in der erfolgreichen Lokalisation eines oder mehrerer Nebenschilddrüsenadenome. Die präoperative Lokalisation erlaubt die gezielte, heutzutage oft minimalinvasive Resektion. Hierzu ist 99 mTc-MIBI-SPECT eine klinisch fest etablierte Methode mit hoher Sensitivität. Wichtig ist die Kenntnis über Einflussfaktoren, die zu falsch-positiven oder falsch-negativen Ergebnissen führen. Eine wichtige Differenzialdiagnose für eine pathologische Anreicherung ist ein MIBI-positiver Schilddrüsenknoten. Häufigere Ursachen für negative Befunde sind kleinere hyperplastische Nebenschilddrüsen oder ein Vitamin-D-Mangel. In manchen Zentren ist als weiterführende Lokalisationsmethode C-11-MET PET/CT verfügbar. Ob sich neben der chirurgischen Therapie in Zukunft perkutan-ablative Verfahren etablieren können, was eine gezielte prätherapeutische Lokalisation voraussetzt, kann zum jetzigen Zeitpunkt noch nicht definitiv beantwortet werden.

scholarly journals Isolated thoracic intramedullary Erdheim-Chester disease presenting with paraplegia: a case report and literature review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ikchan Jeon ◽  
Joon Hyuk Choi
Keyword(s):  
Surgical Resection ◽  
Fdg Pet ◽  
Rare Case ◽  
Systemic Disease ◽  
Mass Lesion ◽  
Erdheim Chester Disease ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Background Erdheim-Chester disease (ECD) is a rare, idiopathic, systemic non-Langerhans cell histiocytosis involving long bone and visceral organs. Central nervous system (CNS) involvement is uncommon and most cases develop as a part of systemic disease. We present a rare case of variant ECD as an isolated intramedullary tumor. Case presentation A 75-year-old female patient with a medical history of diabetes and hypertension presented with sudden-onset flaccid paraparesis for 1 day. Neurological examination revealed grade 2–3 weakness in both legs, decreased deep tendon reflex, loss of anal tone, and numbness below T4. Leg weakness deteriorated to G1 before surgery. Preoperative magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed an intramedullary mass lesion at T2-T4 with no systemic lesion, which was heterogeneous enhancement pattern with cord swelling and edema from C7 to T6. Gross total removal was achieved for the white-gray-colored and soft-natured intramedullary mass lesion with an ill-defined boundary. Histological finding revealed benign histiocytic proliferation with foamy histiocytes and uniform nuclei. We concluded it as an isolated intramedullary ECD. The patient showed self-standing and walkable at 18-month with no evidence of recurrence and new lesion on spine MRI and whole-body FDG-PET/CT until sudden occurrence of unknown originated thoracic cord infarction. Conclusions We experienced an extremely rare case of isolated intramedullary ECD, which was controlled by surgical resection with no adjuvant therapy. Histological examination is the most important for final diagnosis, and careful serial follow-up after surgical resection is required to identify the recurrence and progression to systemic disease.

Fibroblast growth factor 23 and its role in phosphate homeostasis in growing children compared to adults

2020 ◽  
Vol 33 (8) ◽  
pp. 1065-1071
Author(s):  
Marjan Jeddi ◽  
Maryam Heidari ◽  
Neda Hatami ◽  
Gholam Hossein Ranjbar Omrani
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Fibroblast Growth Factor 23 ◽  
Fractional Excretion ◽  
Cross Sectional Study ◽  
Fibroblast Growth ◽  
Sectional Study ◽  
Phosphate Homeostasis ◽  
Cross Sectional ◽  
Fractional Excretion Of Phosphate

AbstractObjectivesPhosphate is essential for skeletal mineralization, which is regulated by parathyroid hormone, calcitriol and fibroblast growth factor 23 (FGF23). Serum phosphate is physiologically higher in younger children, but factors that contribute to this physiological state are poorly understood. This study aimed to evaluate phosphate and its regulators in children compared with adults.Materials and methodsThe participants were children aged 3–11 years and adults older than 20 years of age. Biochemical parameters including calcium, phosphorus, alkaline phosphatase, FGF23, and vitamin D were measured. Fractional excretion of phosphate was calculated, using serum and urine phosphate and creatinine.ResultsThis cross-sectional study was conducted on 45 children (mean age: 9.0 ± 2.1) and 44 adults (mean age: 38.9 ± 11.1). The children had higher serum calcium, phosphate, alkaline phosphatase, and FGF23 (p < 0.001), but fractional excretion of phosphate was greater in adults (14.1 ± 5.7, 11.4 ± 4.4, p = 0.019, 95% confidence interval [CI]: −0.7 to −0.2). Of all individuals, 61.8% had vitamin D deficiency. By multiple regression analysis, entering age, calcium, phosphate, and vitamin D level, the only independent predictor of FGF23 was 1, 25 dihydroxy-vitamin D3 (β: 0.78, p < 0.001, 95% CI: 0.5–1.1, R2: 0.59 for children, and β: 0.59, p < 0.001, 95% CI: 0.5–1.4, R2: 0.45 for adults).ConclusionAs far as we know, there is little information regarding the role of FGF23 in physiologic state. In this cross-sectional study no association was found between FGF23 and urinary phosphate excretion in growing children. Further studies with more detail are essential to evaluate phosphate homeostasis during childhood.

scholarly journals THU0421 TUMOR-INDUCED OSTEOMALACIA: DATA FROM A MONOCENTRIC EXPERIENCE ON 16 PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 448.2-449
Author(s):  
C. Crotti ◽  
F. Bartoli ◽  
M. Manara ◽  
P. A. Daolio ◽  
F. Zucchi ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Serum Alkaline Phosphatase ◽  
Fibroblast Growth Factor 23 ◽  
Diagnostic Delay ◽  
The Body ◽  
Definitive Treatment ◽  
Surgical Removal ◽  
Tumor Biopsy ◽  
Pet Ct ◽  
Fgf 23

Background:Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces fibroblast growth factor-23 (FGF-23), causing hyperphosphaturia, hypophosphoremia, low 1,25(OH)2VitD3and osteomalacia. Locating the tumor is critical, because lesions are typically small, benign mesenchymal tumors, anywhere in the body; the delay between onset of symptoms and diagnosis ranges from 2.5–28 years. Surgical removal is the only effective therapeutic approach.Objectives:To retrospectively evaluate patients affected by TIO, investigating clinical management and disease outcome.Methods:We retrospectively collected data of patients affected by TIO referred to a tertiary Rheumatology Center between Sep 2000 and Jan 2020.Results:We included 16 patients with a definite diagnosis of TIO, mean age±standard deviation 62.4±14.6 yrs, 56.2% females, mean age at symptoms onset 48.0±14.3 yrs (53.8±13.1 at diagnosis). Mean diagnostic delay between symptoms onset and tumor detection was 6.8±6.4 yrs. All patients complained bone pain, muscle weakness, and fractures before diagnosis of TIO. Biochemical findings were: mean serum Phosphorus (PS) 1.4±0.4 mg/dL (reference range (RR) 2.5-4.6), mean serum Calcium 9.4±0.7 mg/dL (RR 8.4-10.2), mean serum 1,25(OH)2VitD330.5±23.4 ng/L (RR 25-86). Intact-FGF-23 was dosed in 9 patients, always resulting elevated: mean 396.6±707.3 pg/mL (RR 25-45). PTH was increased in 30% of cases, while serum alkaline phosphatase was increased in 87.5%. 24h-Urine Phosphorus (PU) was increased in only 13% of patients, but, when renal phosphate wasting by tubular reabsorption of phosphate (TRP) was calculated, PU resulted increased in all.Tumor was localized in all cases (Fig.1) and were localized in bone and soft tissue, by using functional imaging, followed by anatomical techniques. Before the introduction in routinely practice of68Ga-DOTATATE-PET-CT in 2013, Octreoscan-SPECT/CT and18F FDG-PET were used as imaging modalities. Since 2013, diagnostic delay consistently reduced, from 8.6±8.3 yrs (7 patients) to 4.5±2.6 yrs (9 patients), confirming higher diagnostic accuracy of68Ga-DOTATATE-PET-CT.Figure 1.13 patients underwent surgery; in two cases surgery was not possible due to tumor location, so pharmacological support with phosphate supplements and calcitriol was started; a patient underwent to TC-guided radiofrequency ablation. After surgery, 7 patients experienced a complete remission, 3 had a persistence of the disease, and 3 an overtime relapse, even after a longstanding normalization of PS (6 years). After surgical tumor removal, PS significantly increased in few days (from 1.36±0.39 to 2.9±1.1, p=0.0001), while iFGF-23 levels tended to rapidly decreased (from 396.6±707.3 to 62.8±78.4). Before the introduction of68Ga-DOTATATE-PET-CT, 6 patients underwent to imaging-guided closed biopsy to confirm tumor localization; by using68Ga-DOTATATE-PET-CT only 2 subjects had closed biopsy. Furthermore, in our population only patients who had biopsy to detect the lesion (7 patients) had relapses compared to patients who did not.Conclusion:To our knowledge, this is the widest European cohort of patients affected by TIO reported in the last two decades. We confirm an important delay between symptoms onset and diagnosis. To locate tumor, a stepwise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging, preferring68Ga-DOTATATE-PET-CT. Tumor biopsy is not recommended due to the potential cell spilling. Surgery is considered the only definitive treatment, aiming to a wider excision. Active surveillance is always needed, due to the possible relapses, even after a long period of complete clinical and biochemical remission.Disclosure of Interests: :Chiara Crotti: None declared, Francesca Bartoli: None declared, Maria Manara Consultant of: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Speakers bureau: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Primo Andrea Daolio: None declared, Francesca Zucchi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Luigi Sinigaglia: None declared, Massimo Varenna: None declared

scholarly journals The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 563
Author(s):  
Jon Vincze ◽  
Brian W. Skinner ◽  
Katherine A. Tucker ◽  
Kory A. Conaway ◽  
Jonathan W. Lowery ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biological Effects ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Fractional Excretion ◽  
The United States ◽  
Vitamin D Supplementation ◽  
Loss Of Function ◽  
Case Presentation ◽  
Serum Inorganic Phosphate

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

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