AlHamer Bassam, Singh Ajit, Patrascu Carmen, Al Mukaddam Mona
University of Pennsylvania Health System, Pennsylvania Hospital Department of Internal Medicine, Philadelphia, PA 19107, USA.
University of Pennsylvania Health System, Pennsylvania Hospital Nephrology, Philadelphia, PA 19107, USA.
JCEM Case Rep. 2024 May 30;2(6):luae101. doi: 10.1210/jcemcr/luae101. eCollection 2024 Jun.
Tumor-induced osteomalacia (TIO) is an exceedingly rare paraneoplastic condition characterized by hypophosphatemia, osteomalacia, fragility fractures, and fatigue. A 39-year-old man was assessed for hemoptysis, pathological rib fractures, and fatigue, and was found to have a chest mass with lung metastasis. Biopsy of the mass suggested high-grade epithelioid and spindle cell neoplasm. He was initially treated for soft tissue sarcoma with an ifosfamide-based regimen and developed Fanconi syndrome that resolved on cessation of ifosfamide. Serum phosphate remained low. A low tubular maximum reabsorption of phosphate to glomerular filtration rate ratio (TmP/GFR) indicated disproportionate phosphaturia, while a severely elevated fibroblast growth factor-23 (FGF23) level enabled a diagnosis of TIO. He was started on phosphate and calcitriol supplementation. Subsequent next-generation sequencing demonstrated a -fusion mutation, leading to reclassification of his malignancy to a sarcomatoid non-small cell lung carcinoma. He was switched to selpercatinib, a targeted -kinase inhibitor approved for locally advanced or metastatic -fusion-positive solid tumors. This induced tumor remission with subsequent normalization of his FGF23 levels and hypophosphatemia. Despite the presence of a confounding etiology like drug-induced Fanconi syndrome, persistence of hypophosphatemia should prompt a workup of TIO, especially in the presence of a tumor.
肿瘤诱导的骨软化症（TIO）是一种极为罕见的副肿瘤性疾病，其特征为低磷血症、骨软化症、脆性骨折和疲劳。一名39岁男性因咯血、病理性肋骨骨折和疲劳接受评估，发现有肺部转移的胸部肿块。肿块活检提示为高级别上皮样和梭形细胞瘤。他最初接受基于异环磷酰胺的方案治疗软组织肉瘤，并出现了范科尼综合征，在停用异环磷酰胺后症状缓解。血清磷酸盐仍低。肾小管对磷酸盐的最大重吸收与肾小球滤过率比值（TmP/GFR）低表明磷酸盐尿不成比例，而成纤维细胞生长因子23（FGF23）水平严重升高则确诊为TIO。开始给他补充磷酸盐和骨化三醇。随后的二代测序显示有一个融合突变，导致其恶性肿瘤重新分类为肉瘤样非小细胞肺癌。他改用塞尔帕替尼，这是一种被批准用于局部晚期或转移性融合阳性实体瘤的靶向激酶抑制剂。这导致肿瘤缓解，随后他的FGF23水平和低磷血症恢复正常。尽管存在如药物诱导的范科尼综合征这样的混杂病因，但低磷血症持续存在应促使对TIO进行检查，尤其是在存在肿瘤的情况下。
