Endocrine Abstracts

Introduction: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by the presence of phosphaturic hormone-secreting mesenchymal tumors - fibroblast growth factor 23 (FGF-23), which causes hypophosphatemia and osteomalacia. These tumors are small, frequently infiltrate the surrounding tissues and are located in the connective or bone tissue. Usually, these tumors are benign, but malignant tumors have also been reported.

Case report: We present the case of a 39-year-old female with persistent diffuse osteomuscular pain, progressive generalized muscle weakness and the impossibility of standing and walking for about five years. She underwent multiple medical examinations - neurologic, orthopedic and rheumatologic assessments, but did not identify any disorders to explain her symptoms. Laboratory testing showed severe hypophosphatemia (0.9 mg/dl), increased urinary phosphate excretion, increased alkaline phosphatase (320 U/l), normal renal function and elevated FGF-23 (551 kRU/l). Radiographic imaging revealed multiple, old, nontraumatic pelvic and rib fractures, evolved with vicious consolidation. SPECT CT with ^99mTc-Tektrotyde demonstrated increased uptake of the radiotracer in the right supraspinatus muscle. MRI of the right shoulder confirmed a 5 cm intramuscular tumor of the supraspinatus muscle. Surgery was performed with resection of the tumor. Postoperatively, we observed progressive normalization of phosphate levels within a few days and FGF23 decreased significantly, but without normalization 48 hours or 1 month after surgery, raising the suspicion of incomplete resection. Histopathological examination and immunohistochemical profile confirmed the presence of phosphaturic mesenchymal tumor (PMT) with a predominantly hemangiomatous component, showing positive expression of CD34, CD56, CD68, SMA, vimentin and Ki-67 < 5%. The resected margins showed tumor infiltration of the adipose tissue and skeletal muscle. The clinical outcome of the patient was favorable, with progressive and significant improvement of symptoms (regression of osteomuscular pain and gait abnormalities) and normalization of serum phosphate level and FGF-23 level at the upper limit of normal values. Given the histopathological result and failure of normalization of FGF-23 additional follow-up is necessary for detection of tumor recurrence.

Conclusion: Tumor-induced osteomalacia is a rare, frequently undiagnosed or misdiagnosed disease. The diagnosis is a real challenge because of the nonspecific symptoms that can delay detection of the disease. A stepwise approach, combining functional and anatomical imaging is necessary to identify the tumor. Surgery is the only curable option and should be performed whenever is possible.

Keywords: Tumor-induced osteomalacia, FGF-23, paraneoplastic syndrome, hypophosphatemia