Tumor-induced osteomalacia (TIO) is a rare paraneoplastic form of renal
phosphate wasting that results in severe hypophosphatemia, a defect in vitamin
D metabolism, and osteomalacia. This debilitating disorder is illustrated
by the clinical presentation of a 55-year-old woman with progressive fatigue,
weakness, and muscle and bone pain with fractures. After a protracted clinical
course and extensive laboratory evaluation, tumor-induced osteomalacia was
identified as the basis of her clinical presentation. In this article, the
distinctive clinical characteristics of this syndrome, the advances in diagnosis
of TIO, and new insights into the pathophysiology of this disorder are discussed.
A, Octreotide scan demonstrating small mesenchymal tumor in the head
of the humerus (arrowhead). B, Hemangiopericytoma with numerous pericytes
and vascular channels (hematoxylin and eosin stain). Original magnification
×100. C, Bone biopsy with Goldner stain. Excessive osteoid or unmineralized
bone matrix composed mainly of collagen stains pink. Mineralized bone stains
blue. Normal bone usually has a very thin, barely visible layer of osteoid.
The presence of excessive osteoid is indicative of osteomalacia. This bone
biopsy demonstrates severe osteomalacia. Original magnification ×20.
In tumor-induced osteomalacia, fibroblast growth factor 23 (FGF-23)
and other phosphatonins ectopically produced by a mesenchymal tumor lead to
excess circulating FGF-23 levels. In autosomal dominant hypophosphatemic rickets,
FGF-23 excess results from mutations in the FGF-23 gene
that render the protein resistant to cleavage and inactivation. In X-linked
hypophosphatemia, the mechanism of FGF-23 excess is more speculative; mutations
in the PHEX endopeptidase (presumably located on
osteoblasts or osteocytes), are thought to either directly or indirectly result
in FGF-23 excess by interfering with processing and inactivation of FGF-23.
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