Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia.
BACKGROUND
Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors that cause TIO and is, at least partly, responsible for the manifestations of TIO.


OBJECTIVE
The objective of this study was to determine the sensitivity of FGF23 measurements in TIO.


METHODS
FGF23 concentrations were measured on stored samples with three ELISAs.


METHODS
This study was conducted at subspecialty referral centers.


METHODS
Twenty-two patients with suspected TIO, 13 with confirmed tumors, were studied.


METHODS
There were no interventions in this study.


METHODS
FGF23 concentration was the main outcome measure of this study.


RESULTS
Elevated FGF23 concentrations were detected using the Immunotopics C-terminal assay in 16 of 22 TIO patients (for a sensitivity of 73%), the Immunotopics Intact assay in five of 22 patients (sensitivity, 23%), and the Kainos Intact assay in 19 of 22 patients (sensitivity, 86%). In the 13 patients with confirmed tumors, the sensitivity was higher with all assays: 92% for the Immunotopics C-terminal assay, 38% for the Immunotopics Intact assay, and 100% for the Kainos assay.


CONCLUSIONS
The Kainos Intact assay was the most sensitive, followed by the Immunotopics C-terminal assay. The findings of normal FGF23 concentrations in some patients with TIO may indicate that FGF 23 is not responsible for the hypophosphatemia in these patients or that FGF23 secretion by some tumors is partially responsive to serum phosphate. Normal FGF23 concentrations should be interpreted in relation to the serum phosphate and 1,25-dihydryxyvitamin-D concentrations.
Indiana University School of Medicine, 541 North Clinical Drive, Clinical Building 459, Indianapolis, Indianapolis 46202, USA.
Erik A
EA
Imel
Munro
M
Peacock
Pisit
P
Pitukcheewanont
Howard J
HJ
Heller
Leanne M
LM
Ward
Dorothy
D
Shulman
Moustapha
M
Kassem
Paula
P
Rackoff
Mark
M
Zimering
Alan
A
Dalkin
Elaine
E
Drobny
Giacomo
G
Colussi
Joseph L
JL
Shaker
Elizabeth H
EH
Hoogendoorn
Siu L
SL
Hui
Michael J
MJ
Econs
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D017674:Hypophosphatemia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010018:Osteomalacia / Q000097:blood*; D010257:Paraneoplastic Syndromes / Q000097:blood*; D012680:Sensitivity and Specificity
C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23