Tumor localization and biochemical response to cure in tumor-induced osteomalacia

Authors

  • William H Chong,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Panagiota Andreopoulou,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
    2. Division of Endocrinology, Department of Medicine, Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
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  • Clara C Chen,

    1. Nuclear Medicine, Radiology and Imaging Sciences, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD, USA
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  • James Reynolds,

    1. Nuclear Medicine, Radiology and Imaging Sciences, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD, USA
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  • Lori Guthrie,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Marilyn Kelly,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Rachel I Gafni,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Nisan Bhattacharyya,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Alison M Boyce,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
    2. Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Medical Center, Washington, DC, USA
    3. Division of Endocrinology and Diabetes, Children's National Medical Center, Washington, DC, USA
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  • Diala El-Maouche,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Diana Ovejero Crespo,

    1. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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  • Richard Sherry,

    1. Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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  • Richard Chang,

    1. Nuclear Medicine, Radiology and Imaging Sciences, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD, USA
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  • Felasfa M Wodajo,

    1. Musculoskeletal Oncology, Virginia Hospital Center, Arlington, VA, USA
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  • Gad B Kletter,

    1. Pediatric Endocrinology, Swedish Pediatric Specialty Clinics, Swedish Hospital, Seattle, WA, USA
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  • Andrew Dwyer,

    1. Nuclear Medicine, Radiology and Imaging Sciences, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD, USA
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  • Michael T Collins

    Corresponding author
    • Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
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Address correspondence to: Michael Collins, MD, Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 218, Bethesda, MD 20892. E-mail: mc247k@nih.gov

ABSTRACT

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.

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