Hypophosphatemia Associated with Tumor-Induced Osteomalacia Caused by A Third Primary Tumor: A Case Report

Abstract

Tumor-induced osteomalacia (TIO) is a paraneoplastic condition in which a tumor, usually of mesenchymal origin, causes osteomalacia often by producing Fibroblast Growth Factor-23 (FGF-23). FGF-23 induces hypophosphatemia through its phosphaturic action. Case Presentation: A 65-year-old male patient presented with complaints of muscle weakness, difficulty walking and severe bone pain. His medical history included distal gastrectomy for a moderate-risk gastrointestinal stromal tumor (GIST) of 4 cm in diameter, Billroth II antecholic gastroenterostomy and subsequently total thyroidectomy for Stage 1 multicentric micropapillary carcinoma (CA). Widespread lesions detected on bone scintigraphy were considered as bone metastases of GIST. Laboratory investigations revealed the following results: calcium (Ca): 8.3 mg/dL; phosphate (P): 1.5 mg/dL; Parathormone (PTH): 75 pg/mL; 25-OH vit D3: 31 ng/mL; 1-25-(OH)2 vit D3: 36 pg/mL; creatinine: 0.75 mg/dL; alkaline phosphatase (ALP): 109 IU/L, urine phosphate: 2.54 g/day. His hypophosphatemia was considered to be most probably due to TIO induced by bone metastases of GIST. Since it was not possible to remove the metastases, the patient was started on oral phosphate and calcitriol therapy. However, despite an improvement in Ca levels after the initiation of the treatment, P levels persisted around 2 mg/dL. After one year of treatment, an ulcer developed on his right first toe, which was excised and identified as “extraskeletal myxoid chondrosarcoma” on pathological examination. Following excision of the tumor, the patient’s Ca and P values returned to normal range. The development of TIO in the presence of a GIST and thyroid CA is an unusual occurrence. As a matter of fact, the cause of hypophosphatemia was TIO which induced by a third primary tumor in this patient. To the best of our knowledge, TIO due to a third primary tumor is the first and only case in the literature. Another primary tumor focus should be suspected and carefully investigated if the patient already has a primary tumor and that tumor is not among those frequently inducing TIO.