Tumor localization and biochemical response to cure in tumor-induced osteomalacia.
Tumor-induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor-23 (FGF23)-secreting tumors that are often difficult to locate. We present a systematic approach to tumor localization and postoperative biochemical changes in 31 subjects with TIO. All had failed either initial localization, or relocalization (in case of recurrence or metastases) at outside institutions. Functional imaging with ¹¹¹Indium-octreotide with single photon emission computed tomography (octreo-SPECT or SPECT/CT), and ¹⁸fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) were performed, followed by anatomic imaging (CT, MRI). Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern. Tumors were localized in 20 of 31 subjects (64.5%). Nineteen of 20 subjects underwent octreo-SPECT imaging, and 16 of 20 FDG-PET/CT imaging. Eighteen of 19 (95%) were positive on octreo-SPECT, and 14 of 16 (88%) on FDG-PET/CT. Twelve of 20 subjects underwent VS; 10 of 12 (83%) were positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were as follows: sensitivity = 0.95, specificity = 0.64, PPV = 0.82, and NPV = 0.88 for octreo-SPECT; sensitivity = 0.88, specificity = 0.36, PPV = 0.62, and NPV = 0.50 for FDG-PET/CT. Fifteen subjects had their tumor resected at our institution, and were disease-free at last follow-up. Serum phosphorus returned to normal in all subjects within 1 to 5 days. In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days. C-terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio. Serum 1,25-dihydroxyvitamin D₃ (1,25D) rose and exceeded the normal range. In this systematic approach to tumor localization in TIO, octreo-SPECT was more sensitive and specific, but in many cases FDG-PET/CT was complementary. VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery. Sustained elevations in cFGF23 and 1,25D were observed, suggesting novel regulation of FGF23 processing and 1,25D generation.
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
William H
WH
Chong
Panagiota
P
Andreopoulou
Clara C
CC
Chen
James
J
Reynolds
Lori
L
Guthrie
Marilyn
M
Kelly
Rachel I
RI
Gafni
Nisan
N
Bhattacharyya
Alison M
AM
Boyce
Diala
D
El-Maouche
Diana Ovejero
DO
Crespo
Richard
R
Sherry
Richard
R
Chang
Felasfa M
FM
Wodajo
Gad B
GB
Kletter
Andrew
A
Dwyer
Michael T
MT
Collins
D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000601:surgery; D002117:Calcitriol / Q000097:blood*; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D015282:Octreotide / Q000031:analogs & derivatives; D010018:Osteomalacia / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000601:surgery; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D012189:Retrospective Studies; D015899:Tomography, Emission-Computed, Single-Photon
C000717427:FGF23 protein, human; D009363:Neoplasm Proteins; D019275:Radiopharmaceuticals; C094279:indium-111-octreotide; D019788:Fluorodeoxyglucose F18; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D015282:Octreotide