Prolonged Hypophosphatemia and Intensive Care After Curative Surgery of Tumor Induced Osteomalacia: A Case Report.

Introduction: Rare FGF23-producing mesenchymal tumors lead to paraneoplastic tumor-induced osteomalacia (TIO) presenting with phosphate wasting, hypophosphatemia, chronic hypomineralization of the bone, fragility fractures and muscle weakness. Diagnosis of TIO requires exclusion of other etiologies and careful search for a mesenchymal tumor that often is very small and can appear anywhere in the body. Surgical removal of the tumor is the only definitive treatment of TIO. Surgical complications due to chronic hypophosphatemia are not well recognized. Case Description: The current case describes severe fragility fractures in a 58-year-old woman, who lost her ability to walk and was bedridden for two years. First, the initial diagnostic laboratory work-up did not include serum phosphorus measurements, second, the suspicion of adverse effects of pioglitazone as an underlying cause delayed correct diagnosis for at least two years. After biochemical discovery of hyperphosphaturic hypophosphatemia at a tertiary referral centre, a FGF23-producing tumor of the mandible was discovered on physical examination, and then surgically removed. Postoperatively, severe hypophosphatemia and muscle weakness prolonged the need for ventilation support, intensive care and phosphate supplementation. After two years of rehabilitation, the patient was able to walk short distances. The tumor has not recurred, and serum phosphate concentration has remained within normal limits during 3.5 years of follow-up. Conclusions: The case report illustrates knowledge gaps in the diagnostic work-up of rare causes of low bone mass and fragility fractures. Compared to other low phosphate conditions, surgical recovery from TIO-induced hypophosphatemia warrants special attention. Increased alkaline phosphatase concentration may indicate impaired postsurgical recovery due to prolonged hypophosphatemia, underlining the need for proactive perioperative correction of hypophosphatemia.

Recurrent Metastasized Parathyroid Carcinoma-Long-Term Remission After Combined Treatments With Surgery, Radiotherapy, Cinacalcet, Zoledronic Acid, and Temozolomide.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism with rather poor prognosis. Apart from surgery, no evidence-based treatments exist. A 48-year-old woman presented with weight loss, nausea, constipation, hypercalcemic crisis, and a recurrent neck tumor 5 years after primary surgery of a parathyroid tumor that primarily was classified as an adenoma. Histopathological reevaluation of the original tumor revealed the correct diagnosis to be parathyroid carcinoma (PC). The patient underwent surgery of the recurrent tumor, which was locally invasive with metastatic spread to the mediastinum and neck lymph nodes. Computed tomography demonstrated large lytic bone lesions in both iliac bones including, on the right, a soft tissue mass compatible with bone metastasis. The patient was treated with cinacalcet, repeated zoledronic acid infusions, and temozolomide cycles for 1 year. She underwent two additional neck surgeries for PC and sternotomy for resection of mediastinal metastases. Massive osteolytic lesions in both femoral necks caused imminent fracture risk and therefore both femurs were prophylactically stabilized by intramedullary nail. Serum calcium normalized after the third neck surgery, cinacalcet was discontinued, and parathyroid hormone gradually normalized during continued treatments with temozolomide, adjuvant radiotherapy, and zoledronic acid, with no signs of active disease on imaging and normal biochemistry. The patient remains in remission 17 years after successful combined treatments for recurrent, metastasized PC. The parathyroid tumor tissue demonstrated high O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, a known predictor of positive temozolomide treatment response in other tumors. In addition, synergistic effects of multiple treatments may have accounted for the favorable response. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.