SUN-755 Tumor Induced Osteomalacia Caused by Metastatic Thyroid Cancer

Abstract Disclosure: C.R. Lichtenfeld: None. L. Rehm: None. L.T. Drake: None. S.S. Dahir: None. K.M. Dahir: Alexion Pharmaceuticals, Inc., Ultragenyx. Background: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization due to fibroblast growth factor 23 (FGF23) production by mesenchymal tumors. We present a case of cancer-associated FGF23-mediated hypophosphatemia following diagnosis and treatment of metastatic papillary thyroid cancer (PTC). Case Description: A 52-year-old female was referred for evaluation of low serum phosphorus. Four years earlier, she underwent thyroidectomy, central neck dissection and RAI for PTC. This was complicated by recurrence when a T7 vertebral fracture and left zygoma bone lesion proved to be metastatic disease with immunophenotype and immunohistochemical pattern consistent with poorly differentiated thyroid cancer which was not radioiodine avid. Cabozantinib, a tyrosine kinase inhibitor, and palliative radiation therapy were initiated along with zoledronate. She ultimately had progressive muscle weakness, decline in mobility, pain and developed multiple atraumatic fractures including the left femur, scapula and humerus and multiple ribs. She was referred to endocrinology due an elevated PTH level of 372 pg/ml (16-77). Further evaluation was remarkable for a low serum phosphorus of 1.2 mg/dl (2.3-4.7), urine phosphorus 157 (20-150), urine creatinine 157 mg/dl (40-200), 1,25 vitamin D of 15.5 pg/ml (19-79) and an elevated intact FGF23 of 261 pg/ml (<59) with a calculated TMP GFR of 0.6 mg/dl (2.60 - 3.8). DOTATATE PET imaging showed widespread skeletal lesions without obvious evidence of a secondary mesenchymal tumor. Conventional therapy with calcitriol and phosphorus were started without symptomatic relief and poor compliance. Burosumab was then initiated at 20mg every 2 weeks with improvement in pain, mobility and fatigue and no further fracture occurrence for the subsequent two years. Conclusions: TIO is a rare paraneoplastic disorder often associated with phosphaturic mesenchymal tumors. The patient's clinical presentation of severe FGF23 mediated hypophosphatemia and diffuse skeletal fragility was initially misattributed to metastatic poorly differentiated thyroid cancer. Despite extensive evaluation, no secondary mesenchymal tumor was identified on imaging. This case underscores the diagnostic challenge of TIO in the context of malignancy and the need to consider FGF23-mediated hypophosphatemia in patients with skeletal fragility and low serum phosphorus. Initiation of burosumab, an FGF23 inhibitor, resulted in significant clinical improvement, including pain reduction, enhanced mobility, and cessation of fractures over a two-year follow-up. This case emphasizes the importance of recognizing and addressing paraneoplastic endocrine etiologies to optimize patient outcomes, even in complex oncologic settings. Presentation: Sunday, July 13, 2025