(20.04) Tumor-Induced Osteomalacia Due to Paraneoplastic Production of FGF23 in Metastatic Prostate Cancer

Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results due to excessive production of fibroblast growth factor 23 (FGF23). Given its rare nature, misdiagnosis or delayed diagnosis is common. Here we present a case of TIO in metastatic prostate cancer.

Case(s) Description : A 71-year-old man with history of prostate cancer presented for evaluation of hypophosphatemia. Eight years prior to presentation, he was treated with bicalutamide, leuprorelin, and docetaxel for prostate cancer with metastasis to the bone. There was initially a good treatment response with PSA < 1 and decreased bone metastases on imaging. Seven years later, imaging showed worsening bone metastases. Shortly thereafter, he was noted to have phosphorous 1.2 mg/dL (2.4-5) and calcium 7.8 mg/dL (8.5-10.5). He was started on Neutra-Phos 500 mg 4 times a day and elemental calcium 2000 mg daily. Despite this, repeat calcium was 8.1 and phosphorous 1.0. Given this, he was referred to Endocrinology. During this time, patient had bilateral foot drop and lower extremity weakness. He was diagnosed with TIO after labs revealed FGF23 424 RU/mL (< 180), parathyroid hormone 399 pg/mL (15-65), and 1,25 (OH) Vitamin D3 40 pg/mL (18-64). Cabazitaxel was started for prostate cancer treatment: he received 5 cycles and FGF23 decreased from 424 to 202. His phosphorous and calcium levels initially improved after this treatment and supplementation was able to be decreased.  One month later, he was admitted to the hospital due to cognitive slowing and diffuse weakness. Calcium was 12.4, PTH 24, phosphorous 4.1, 1,25 (OH) Vitamin D3 17, and FGF23 7301.  His cognitive slowing improved with normalization of calcium. He received glucocorticoids and cyclophosphamide for suspected paraneoplastic neuropathy. At discharge, FGF23 decreased to 1123 and to 140 about 1 month later. His neurologic symptoms improved and he was continued on cyclophosphamide for 13 cycles followed by rituximab maintenance therapy. FGF23 continued to improve to 50s, but later increased to 80. MRI scan revealed worsening bone metastases for which he was started on enzalutamide. FGF23 level again decreased to 47. With reduction in FGF23 levels, phosphorous supplementation was able to be stopped.

Discussion :

Patients with hormone resistant metastatic prostate cancer who present with hypophosphatemia should have paraneoplastic TIO considered in the differential diagnosis. Definitive treatment is treatment of metastatic disease along with immunosuppressive therapy. This case illustrates the value of FGF23 as a marker of disease status closely corresponding with improvement in hypophosphatemia and neurological symptoms.