Supplementary Material for: Tumor induced osteomalacia in a patient with Crohn’s disease: A case report and approach to investigating hypophosphatemia

Introduction
Hypophosphatemia occurs commonly in inflammatory bowel disease (IBD) patients, and can cause considerable morbidity. The differential diagnoses in IBD include nutritional causes and hypophosphatemia induced by some formulations of intravenous iron infusions.

Case presentation
We present the case of a 37-year-old man with active Crohn’s disease, presenting with difficulty walking and fractures of the vertebrae and calcaneus. He had long-standing hypophosphatemia. Nutritional causes for hypophosphatemia were considered in the first instance given the presence of chronic diarrhea and Vitamin D deficiency, however there was minimal response to appropriate supplementation with oral phosphorous and Vitamin D. Iron infusion-induced hypophosphatemia was then considered, but the nadir phosphate level preceded any iron infusion. Therefore, work-up was undertaken for less common causes. He was ultimately diagnosed with tumor-induced osteomalacia, caused by excess fibroblast growth factor 23 (FGF23) secretion from a phosphaturic mesenchymal tumor about the knee. He had complete resolution of symptoms and biochemical abnormalities following successful resection of the tumor.

Conclusion
This case illustrates the approach to investigation of hypophosphatemia in IBD patients. If the time course and response to phosphate supplementation are not as expected for nutritional or iron infusion-induced hypophosphatemia, less common causes should be considered.

引言
低磷血症（Hypophosphatemia）在炎症性肠病（IBD）患者中较为常见，且可引发显著的临床发病负担。炎症性肠病患者低磷血症的鉴别诊断包括营养性病因，以及部分静脉补铁输注制剂诱导的低磷血症。

病例报告
本文报告1例37岁活动性克罗恩病男性患者，临床表现为行走困难、椎体及跟骨骨折，且存在长期低磷血症。初始考虑低磷血症的病因为营养性因素，结合患者存在慢性腹泻及维生素D缺乏的情况，但给予口服磷与维生素D的规范补充治疗后，患者症状改善甚微。随后考虑为静脉补铁诱导的低磷血症，但患者血磷最低值出现于首次静脉补铁治疗之前，遂对少见病因开展排查。最终确诊为肿瘤诱导的骨软化症，系膝关节周围泌磷间叶细胞瘤分泌过量成纤维细胞生长因子23（FGF23）所致。患者经手术成功切除肿瘤后，临床症状与生化指标异常均完全缓解。

结论
本案例阐明了炎症性肠病患者低磷血症的诊疗排查思路：若低磷血症的时间进程及磷补充治疗反应不符合营养性或静脉补铁诱导的低磷血症的预期表现，则需考虑少见病因。