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一大群中国肿瘤诱导性骨软化症患者的甲状旁腺功能亢进症

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

作者信息

Ni Xiaolin, Liu Wei, Zhang Dingding, Li Xiang, Chi Yue, Feng Juan, Jin Chenxi, Pang Qianqian, Gong Yiyi, Cui Lijia, Jiajue Ruizhi, Yu Wei, Wu Huanwen, Huo Li, Liu Yong, Jin Jin, Zhou Xi, Lv Wei, Zhou Lian, Xia Yu, Wang Ou, Li Mei, Xing Xiaoping, Jiang Yan, Xia Weibo

机构信息

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

J Clin Endocrinol Metab. 2023 Apr 13;108(5):1224-1235. doi: 10.1210/clinem/dgac650.

Abstract

CONTEXT

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented.

OBJECTIVES

To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective study enrolled 202 patients with TIO.

MAIN OUTCOME MEASUREMENTS

Occurrence of HPT in patients with TIO.

RESULTS

HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels.

CONCLUSIONS

HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

摘要

背景

肿瘤诱导的骨软化症(TIO)是一种罕见的副肿瘤综合征,由肿瘤过度分泌成纤维细胞生长因子23(FGF23)引起。TIO患者中的甲状旁腺功能亢进症(HPT),包括继发性甲状旁腺功能亢进症(SHPT)和三发性甲状旁腺功能亢进症(THPT),被认为与补充磷酸盐有关,但相关报道并不充分。

目的

明确我院一大群中国TIO患者中HPT的患病率、临床特征及危险因素。

设计、地点和参与者:这项回顾性研究纳入了202例TIO患者。

主要观察指标

TIO患者中HPT的发生情况。

结果

91例患者(91/202,45.1%)出现HPT:84例(41.6%)为SHPT,7例(3.5%)为THPT。所有THPT患者均接受了甲状旁腺切除术,仅有1例复发。与无HPT的患者相比,SHPT患者病程更长,补充磷酸盐和骨化三醇的比例更高,血清钙更低,尿钙排泄更低,尿磷排泄更高。与SHPT患者相比,THPT患者病程更长,补充磷酸盐和骨化三醇的比例更高。TIO患者中,甲状旁腺激素(PTH)水平与完整FGF23和1,25-二羟基维生素D水平呈正相关,但与25-羟基维生素D水平无关。多因素logistic回归分析显示,病程长和补充磷酸盐是TIO患者发生HPT的独立相关因素。进一步的logistic回归分析和限制性立方样条模型显示,磷酸盐补充累积剂量与PTH水平之间存在剂量反应关系。

结论

HPT在TIO患者中很常见。为避免TIO患者发生HPT,及时诊断和切除肿瘤是必要的,术前不建议过量补充磷酸盐。

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