PO:20:011 | Suspected tumor-induced osteomalacia in a patient with polymyalgia rheumatica and persistent hyperphosphaturic hypophosphatemia

Andrea Faggiano^1|2, Francesco Goatelli^1|2, Lucia Dardani², Carlo Salvarani³ | ¹Unit of Rheumathology, Department of Precision and Regenerative Medicina, Area Jonica, University of Bari; ²Scuola di Specializzaione in Reumatologia, Università degli Studi di Modena e Reggio Emilia, Modena, Italy; ³Direttore SOC Reumatologia, IRCCS Arcispedale Santa Maria Nuova, AUSL REGGIO EMILIA, Italy  

Background. To describe the case of a patient with polymyalgia rheumatica (PMR) and suboptimal response to steroid therapy with the incidental finding of hyperphosphaturic hypophosphatemia, suspected for tumor-induced osteomalacia (TIO), to highlight the importance of a multidisciplinary approach and targeted diagnostic laboratory and instrumental workup.

Materials and Methods. Male patient, 76 years old, with a functionally single kidney following nephrectomy of an ectopic kidney at age 33, medical history of arterial hypertension, dyslipidemia, OSAS, subcritical stenosis of the supraaortic trunks, and polyglobulia (JAK2 mutation negative, endogenous EPO within normal limits); on chronic therapy with NSAIDs as needed, antihypertensives, ASA 100 mg/day, statins, and benzodiazepines for anxiety-depressive syndrome. Symptom onset approximately 3 months prior with arthralgias of the shoulder and pelvic girdles, prolonged morning stiffness >2 h, functional limitation, and elevation of inflammatory markers. Underwent initial treatment with prednisone 37.5 mg/day with tapering as indicated by the general practitioner. Subsequent relapse upon discontinuation and therefore referred for urgent rheumatology evaluation with reintroduction of PDN 18.75 mg/day and slow tapering and initiation of antiresorptive therapy with risedronate, calcium, and vitamin D supplementation.

Results. At 3-month rheumatology follow-up visit, reported recurrence of arthralgias and morning stiffness upon reduction of prednisone below 7.5 mg/day. Laboratory tests revealed CRP 2.1 mg/dL; serum calcium 9.9 mg/dL; serum phosphorus 2.0 mg/dL (normal range 2.7-5.1); serum magnesium 2.1 mg/dL; spot urine phosphorus 49.9 mg/dL; plasma creatinine 1.01 mg/dL; TmPO4/GFR 1.42 mg/dL (normal range >2.7). Given suspicion of TIO, intact and C-terminal FGF23 assays were requested, with values resulting inappropriately normal in relation to serum phosphorus levels. Systematic monitoring of serum phosphorus was concurrently initiated, with IV supplementation of fructose-1,6-diphosphate and oral potassium phosphate as needed, and introduction of calcitriol up to 0.5 µg/day. Gallium-DOTAPEPTIDE PET/CT extended to the appendicular skeleton was also requested, with results not yet available at the time of publication.

Conclusions. Tumor-induced osteomalacia represents a rare cause of renal hyperphosphaturia and severe hypophosphatemia, frequently masked by nonspecific musculoskeletal symptoms in elderly patients; this case highlights the need to integrate clinical suspicion of PMR with complete biochemical investigations, including serum phosphate and TmPO4/GFR calculation, and to employ advanced imaging techniques for localization of FGF23-secreting neoplasms, in order to promptly direct the patient toward specific surgical or medical therapy and improve functional and metabolic outcome. Currently, burosumab, a recombinant human monoclonal antibody (IgG1) directed against FGF23, is approved in both children and adults for the treatment of FGF23-related hypophosphatemia secondary to phosphaturic mesenchymal tumors that cannot be curatively resected or localized.