Resident Atrium Health Carolinas Medical Center Charlotte, North Carolina, United States
Introduction : Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23 (FGF23) from an underlying mesenchymal tumor. FGF23 acts on the proximal renal tubule to decrease phosphate reabsorption and 1alpha-hydroxylation of 25-hydroxyvitamin D leading to impaired bone metabolism. TIO classically presents with muscle weakness, bone pain, and multiple fractures. However, these nonspecific symptoms can pose several challenges in initialidentification of TIO and can delay diagnosis and appropriate treatment.
Case(s) Description : A 50-year-oldmarathon runnerpresented with twoyears of proximal lower extremity muscle cramping, followed by oneyear of right hip pain, requiring a cane to walk. He was diagnosed with a femoral stress fracture. Initial workup revealed low serum phosphorus of 1.5 mg/dL (normal 2.5-5), normal parathyroid hormone, and mildly elevated alkaline phosphatase. Bone scan was done showing subacute bilateral femoral stress fractures and multiple rib fractures. Bone density scan revealed severe osteoporosis and patient was referred to endocrinology.Work-up for hypophosphatemiawas significant for alow 25-hyroxyvitamin D of 25 ng/mL (normal 30-59.9), very low 1,25-dihydroxyvitamin D of5.8 pg/mL (normal 24.8-81.5), andelevated FGF23of285 pg/mL (normal < 59). Basic metabolic panel waswithout electrolyte abnormalities to suggest Fanconi syndrome. Genetic testing was negative for autosomal dominant hypophosphatemic rickets. DOTATATE positron emission tomography (PET) was performed to look for TIO and a somatostatin avid right flank mass was found consistent with neuroendocrine tumor (NET). Patient was referred to surgical oncology for consideration of surgical resection. For treatment, he was placed on phosphorus and calcitriol replacement with normalization of levels. Once approved, he received one dose of burosumab as well.Patient then underwent excision of the right flank mass. Two weeks post-operatively, patient’s low phosphorous and symptoms of lower extremity weakness and pain had resolved.
Discussion : This case featuresthe classic, but nonspecific symptoms of a rare disease.Ithighlights the importance of working up hypophosphatemia, especially in rapid onset symptoms in a previously healthy individual. Once TIO is diagnosed, finding the FGF23-producing tumor can pose a great challenge as well. The DOTATATE PET scan is becoming the imaging of choice for finding these small NETs.Delay in tumor diagnosis and localization can lead to significant long-term morbidity. Therefore, it isimportant to keep a broad differential in patients presenting with these nonspecific symptoms.
