title: Oncogenic osteomalacia: evidence for a humoral phosphaturic factor.
abstract: Oncogenic osteomalacia is a syndrome characterized by phosphaturia, hypophosphatemia, reduced vitamin D levels, and osteomalacia. The cause is not known, but all patients have had a tumor; usually of mesenchymal origin. Removal of the tumor reverses the metabolic abnormalities. We report a patient with osteomalacia, severe hypophosphatemia, elevated alkaline phosphatase, low 1,25-dihydroxyvitamin D3, and phosphaturia. A tumor was identified in the infratemporal fossa. The tumor was removed, and all of the biochemical abnormalities resolved over the subsequent 8 months. The bone density returned to normal values. The tumor had the appearance of a paraganglioma and was used to establish a cell culture line called JH-55. Electron microscopy of the original tumor and the JH-55 cells demonstrated the presence of neurosecretory granules. A bioassay using opossum kidney cells was used to evaluate phosphate transport. Conditioned medium from the JH-55 cells inhibited phosphate reabsorption by the kidney tubular cells. Maximal inhibition required a 24-h incubation period and was not altered by the presence of an inhibitor of protein synthesis (10 micrograms/mL cycloheximide). Immunoassays revealed no detectable PTH-related peptide or intact PTH in the JH-55 medium. The cause of this paraneoplastic syndrome is not known, but all of the evidence is consistent with the action of a hormone that produces phosphaturia. This putative factor is distinct from other hormones that cause phosphaturia.
authors.affiliation: Department of Medicine, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: G E
authors.initials: GE
authors.lastname: Wilkins
authors.forename: S
authors.initials: S
authors.lastname: Granleese
authors.forename: R G
authors.initials: RG
authors.lastname: Hegele
authors.forename: J
authors.initials: J
authors.lastname: Holden
authors.forename: D W
authors.initials: DW
authors.lastname: Anderson
authors.forename: G P
authors.initials: GP
authors.lastname: Bondy
mesh_terms: D000818:Animals; D001681:Biological Assay; D001692:Biological Transport; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009893:Opossums; D010018:Osteomalacia / Q000209:etiology*; D010710:Phosphates / Q000378:metabolism / Q000652:urine*; D012888:Skull Neoplasms / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D010710:Phosphates