Phosphaturic mesenchymal tumors: what an endocrinologist should know

AbstractTumor-induced osteomalacia (TIO), also known as “oncogenic osteomalacia”, is a rare cause of osteomalacia. TIO often has an insidious onset characterized clinically by progressive muscle weakness and bone pain with fractures. The hallmark biochemical finding is a persistent low serum phosphorus concentration due to renal phosphate wasting. Th e vast majority of cases of TIO result from production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) by a histologically distinctive mesenchymal tumor, termed “phosphaturic mesenchymal tumor” (PMT). Circulating FGF23 induces internalization of renal sodium/phosphate co-transpor ters resulting in reduced proximal tubular phosphate reabsorption. FGF23 also inhibits production of 1α,25-dihydroxyvitamin D which is inappropriately low or normal in the context of hypophosphatemia. Diagnosis is often delayed owing to the rarity of the condition and an underappreciation for the r ole of phosphorus as a cause for the constellation of symptoms. Primary treatment for TIO is identification of the offending tumor and surgical removal. However, these tumors are notoriously difficult to find, precluding the opportunity for a curative surgery in many. In such cases, phosphate and ca lcitriol therapy is used to improve symptoms and heal the osteomalacia. Recently, molecular genetic studies have shown recurrent genetic events in PMT, including the novel fusionsFN1–FGFR1 and less commonlyFN1–FGF1. These fusion events ...

Source: Journal of Endocrinological Investigation - February 14, 2018 Category: Endocrinology Source Type: research