Clinical description and evaluation Disease phenotypeTumor-induced osteomalacia (TIO) is a rare syndrome (about 350 such cases have been described), characterized by hypophosphatemia, increased urinary losses of phosphate as a result of reduced tubular phosphate reabsorption, reduced or inappropriately normal concentrations of 1,25-dihydroxyvitamin D, normal parathyroid hormone concentrations, rickets or osteomalacia which are caused by substances (generally, fibroblast growth factor-23, FGF-23, and more rarely other peptides) elaborated by mesenchymal tumors (1-8). Patients manifest symptoms of osteomalacia or rickets with bone pain and proximal muscle weakness. Sometimes the causal tumors are readily visible or palpable on physical examination, but more often the tumors are small and very difficult to detect. Removal of the tumor results in reversal of the biochemical abnormalities, thereby demonstrating that the tumors produce a substance which alters phosphate homeostasis.Key biochemical abnormalities seen in the syndrome of TIO are shown in Table 1. As shown, these include hypophosphatemia, normal or low serum calcium concentrations, normal parathyroid hormone concentrations, normal 25-hydroxyvitamin D concentrations, inappropriately low 1,25-dihydroxyvitamin D concentrations, normal renal function, elevated fractional excretion of phosphorus or a low TMP/GFR and generally elevated serum FGF-23 concentrations. Most, but not all, patients with TIO have elevations in serum FGF-23 concentrations (9, 10). Patients generally have osteomalacia or rickets noted on skeletal radiography ( Figure 1A) although the findings can often be quite subtle or absent.