Oncogenic osteomalacia due to FGF23-expressing colon adenocarcinoma

J Clin Endocrinol Metab. 2013 Mar;98(3):887-91. doi: 10.1210/jc.2012-3473. Epub 2013 Feb 7.


Context: Oncogenic osteomalacia, a paraneoplastic syndrome associated with hypophosphatemia due to increased urinary phosphate excretion, is caused by excessive synthesis and secretion of fibroblast growth factor 23 (FGF23), a phosphaturic hormone that is normally produced by osteocytes. Most cases of oncogenic osteomalacia have been associated with benign tumors of bone or soft tissue; however, whether malignant neoplasms can also produce and secrete FGF23 is currently unknown.

Objective: The aim was to determine whether a malignant neoplasm could cause oncogenic osteomalacia through excessive production and secretion of FGF23.

Setting: We describe an 80-year-old woman with stage IV colon adenocarcinoma who presented with severe hypophosphatemia (0.4 mg/dL; reference, 2.6-4.5 mg/dL).

Results: Fractional excretion of phosphate was 34% (reference, <5% in the setting of hypophosphatemia), and plasma levels of FGF23 were highly elevated at 674 RU/mL (reference, <180 RU/mL). Immunohistochemical analysis of the patient's tumor showed strong staining for FGF23. Genetic analyses revealed a point mutation in the KRAS gene.

Conclusions: We present the first case in which a malignant neoplasm is documented to produce and secrete FGF23, leading to renal phosphate-wasting. Oncogenic osteomalacia should be considered in the differential diagnosis for patients with a malignant tumor who present with hypophosphatemia.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / complications*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Aged, 80 and over
  • Colonic Neoplasms / complications*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Hypophosphatemia / etiology
  • Hypophosphatemia / metabolism
  • Osteomalacia / etiology*
  • Osteomalacia / metabolism
  • Paraneoplastic Syndromes / etiology
  • Paraneoplastic Syndromes / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics


  • FGF23 protein, human
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins