Tumor induced osteomalacia: Difference between revisions
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==Overview== | |||
'''Tumor induced osteomalacia''' (also known as oncogenic hypophosphatemic osteomalacia or oncogenic osteomalacia) is an uncommon disorder resulting in increased renal [[phosphate]] excretion, [[hypophosphatemia]] and [[osteomalacia]]. | '''Tumor induced osteomalacia''' (also known as oncogenic hypophosphatemic osteomalacia or oncogenic osteomalacia) is an uncommon disorder resulting in increased renal [[phosphate]] excretion, [[hypophosphatemia]] and [[osteomalacia]]. | ||
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==References== | ==References== | ||
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[[Category: Skeletal disorders]] | [[Category: Skeletal disorders]] | ||
Latest revision as of 15:39, 6 September 2012
| Tumor induced osteomalacia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Tumor induced osteomalacia (also known as oncogenic hypophosphatemic osteomalacia or oncogenic osteomalacia) is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia.
Signs and symptoms
Adult patients have worsening myalgias, bone pains and fatigue which are followed by recurrent fractures. Children present with difficulty in walking, stunted growth and deformities of the skeleton (features of rickets)[1].
Diagnosis
Biochemical studies reveal hypophosphatemia, elevated alkaline phosphatase and low serum calcitriol (1, 25 dihydroxyvitamin D) levels. Routine laboratory tests do not include serum phosphate levels and this can result in considerable delay in diagnosis.
Pathogenesis
FGF-23 (fibroblast growth factor-23) inhibits phosphate transport in the renal tubule and reduces calcitriol production by the kidney. Tumor production of FGF-23[2], frizzled-related protein 4 [3]and matrix extracellular phosphoglycoprotein (MEPE)[4] have all been identified as possible causative agents for the hypophosphatemia.
Causative tumors
Tumor induced osteomalacia is usually referred to as a paraneoplastic phenomenon, however, the tumors are usually benign and the symptomatology is due to osteomalacia or rickets[5]. Seen most often are benign mesenchymal or mixed connective tissue tumors (commonly hemangiopericytomas). Association with malignant tumors has also been reported. Locating the tumor can prove to be difficult and may require whole body magnetic resonance imaging (MRI). Some of the tumors express somatostatin receptors and may be located by octreotide scanning.
Differential diagnosis
Serum chemistries are identical in tumor induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopepetidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF-23 gene will identify patients with ADHR.
Treatment
Resection of the tumor is the ideal treatment and results in correction of hypophosphatemia (and low calcitriol levels) within hours of resection. Resolution of skeletal abnormalities may take many months.
If the tumor cannot be located, treatment with calcitriol (1-3 µg/day) and phosphorus (1-4 g/day in divided doses) is instituted. Tumors which secrete somatostatin receptors may respond to treatment with octreotide
References
- ↑ Jan de Beur SM Tumor-induced osteomalacia JAMA 2005 Sep 14;294(10):1260-7 PMID:16160135
- ↑ Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Shimada T; Mizutani S; Muto T; Yoneya T; Hino R; Takeda S; Takeuchi Y; Fujita T; Fukumoto S; Yamashita T Proc Natl Acad Sci U S A 2001 May 22;98(11):6500-5
- ↑ Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent.Berndt T; Craig TA; Bowe AE; Vassiliadis J; Reczek D; Finnegan R; Jan De Beur SM; Schiavi SC; Kumar R J Clin Invest 2003 Sep;112(5):785-94
- ↑ MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Rowe PS; de Zoysa PA; Dong R; Wang HR; White KE; Econs MJ; Oudet CL Genomics 2000 Jul 1;67(1):54-68
- ↑ Carpenter TO Oncogenic osteomalacia—a complex dance of factors N Engl J Med. 2003 April 24:348(17):175-8 PMID: 12711747