伴多内分泌腺瘤病的促肾上腺皮质激素依赖性库欣综合征临床特点分析

doi:10.3969/j.issn.1672-6731.2021.03.008

中国现代神经疾病杂志 ›› 2021, Vol. 21 ›› Issue (3): 170-176. doi: 10.3969/j.issn.1672-6731.2021.03.008

2 伴多内分泌腺瘤病的促肾上腺皮质激素依赖性库欣综合征临床特点分析

郑光耀¹, 包旭东², 卢琳², 冯铭³, 朱惠娟², 姚勇³, 王任直³

1. 261053 潍坊医学院临床医学院2019级;
2. 100730 中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生健康委员会内分泌重点实验室协和转化医学中心;
3. 100730 中国医学科学院北京协和医学院神经外科

收稿日期:2021-03-19 出版日期:2021-03-25 发布日期:2021-04-02
通讯作者: 卢琳,Email:lulin88@sina.com
基金资助:
国家重点研发计划项目（项目编号：2016YFC0901500）；中国医学科学院医学与健康科技创新工程项目（项目编号：2017-I2M-1-011）；中国医学科学院中央级公益性科研院所基本科研业务费专项资助项目（项目编号：2017PT32020）；中国医学科学院中央级公益性科研院所基本科研业务费专项资助项目（项目编号：2018PT32001）

Clinical characteristics of adrenocorticotropic hormone-dependent Cushing's syndrome complicated with multiple endocrine neoplasia

ZHENG Guang-yao¹, BAO Xu-dong², LU Lin², FENG Ming³, ZHU Hui-juan², YAO Yong³, WANG Ren-zhi³

1 Grade 2019, Clinical Medical College of Weifang Medical University, Weifang 261053, Shandong, China;
2 Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translational Medicine Center of Peking Union College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;
3 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

Received:2021-03-19 Online:2021-03-25 Published:2021-04-02
Supported by:
This study was supported by the National Key Research and Developement Program of China (No. 2016YFC0901500), the Chinese Academy of Medical Sciences Innovation Fund for Medical Science (No. 2017-I2M-1-011), and Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2017PT32020, 2018PT32001).

摘要/Abstract

摘要：

目的总结伴多内分泌腺瘤病（MEN）的促肾上腺皮质激素（ACTH）依赖性库欣综合征的临床特点。方法纳入中国垂体疾病注册中心中国医学科学院北京协和医院分中心垂体瘤数据库1984年1月至2020年9月确诊的伴多内分泌腺瘤病的促肾上腺皮质激素依赖性库欣综合征患者18例，回顾分析其人口统计学、临床表现、实验室和影像学特征。结果 18例患者中库欣病13例，异位促肾上腺皮质激素综合征5例；MEN1型15例，MEN2型2例，MEN4型1例；临床表现为亚临床库欣综合征6例，显性库欣综合征12例；合并骨量减少或骨质疏松占18/18，泌尿系统结石占11/18；根据受累内分泌腺体，垂体促肾上腺皮质激素腺瘤占13/18，垂体催乳素（PRL）腺瘤占4/18，甲状旁腺功能亢进症占15/18，胰腺神经内分泌肿瘤占13/18，肾上腺腺瘤及增生占10/18。实验室检查，清晨血清皮质醇平均为（652.90±254.90）nmol/L，ACTH为（13.38±8.73）pmol/L，24 h尿游离皮质醇446.35（233.08，531.10）μg；2例血清PRL升高，13例甲状旁腺激素升高，11例钙离子升高。影像学检查，12例为垂体微腺瘤，3例为垂体大腺瘤；8例为肾上腺腺瘤，4例为肾上腺增粗，2例为肾上腺嗜铬细胞瘤，1例为腹主动脉旁副神经节瘤。基因检测，3例存在MEN1基因突变，分别为c.1183C > T、c.1579C > T和c.1174G > T突变。结论伴多内分泌腺瘤病的促肾上腺皮质激素依赖性库欣综合征临床罕见且表现复杂，主要表现为骨量减少和（或）骨质疏松；库欣综合征的最常见病因为垂体微腺瘤；MEN1型最多见，其他受累内分泌腺体主要为原发性甲状旁腺功能亢进症，其次为胰腺神经内分泌肿瘤。

关键词: 库欣综合征, 多发性内分泌腺瘤病, ACTH综合征, 异位, 诊断

Abstract:

Objective To summarize the clinical features of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) with multiple endocrine neoplasia (MEN). Methods Based on the pituitary tumor database of Peking Union Medical College Hospital of China Pituitary Disease Register Network (CPDRN), 18 patients with ACTH-dependent CS complicated with MEN from January 1984 to September 2020 were collected. The clinical manifestations, involved other endocrine glands, laboratorial and imageological examinations were analyzed. Results Among 18 patients, 13 cases were Cushing's disease and 5 cases were ectopic ACTH syndrome (EAS); 15 cases were MEN1 type, 2 cases were MEN2 type and one case was MEN4 type. The clinical manifestations were subclinical CS in 6 cases and overt CS in 12 cases. All cases had osteopenia or osteoporosis. Urolithiasis accounted for 11/18 cases. Regarding the involved endocrine glands, pituitary ACTH adenoma accounted for 13/18 cases, prolactinoma accounted for 4/18 cases, hyperparathyroidism accounted for 15/18 cases, pancreatic neuroendocrine tumors accounted for 13/18 cases and adrenal adenomas and hyperplasia accounted for 10/18 cases. Laboratorial examinations showed the average morning serum cortisol was (652.90 ±254.90) nmol/L, the morning ACTH was (13.38 ±8.73) pmol/L and the 24 h urinary free cortisol was 446.35 (233.08, 531.10) μg. Serum prolactin was elevated in 2 cases, parathyroid hormone was elevated in 13 cases and serum calcium was elevated in 11 cases. In imageological examinations, there were pituitary microadenoma in 12 cases, pituitary macroadenoma in 3 cases, adrenal adenoma in 8 cases, thickened adrenal in 4 cases, adrenal pheochromocytoma in 2 cases, and paraganglioma in one case. Genetic test showed 3 cases had MEN1 gene mutation including c.1183C > T, c.1579C > T and c.1174G > T. Conclusions ACTH -dependent CS with MEN is a rare disease with complex manifestations. The most common symptom is osteopenia/osteoporosis. The most common cause of CS is pituitary microadenoma. MEN1 is the most common MEN type, and primary hyperparathyroidism is the most common type of affected endocrine glands, followed by pancreatic neuroendocrine tumors.

Key words: Cushing syndrome, Multiple endocrine neoplasia, ACTH syndrome, ectopic, Diagnosis

郑光耀, 包旭东, 卢琳, 冯铭, 朱惠娟, 姚勇, 王任直. 伴多内分泌腺瘤病的促肾上腺皮质激素依赖性库欣综合征临床特点分析[J]. 中国现代神经疾病杂志, 2021, 21(3): 170-176.

ZHENG Guang-yao, BAO Xu-dong, LU Lin, FENG Ming, ZHU Hui-juan, YAO Yong, WANG Ren-zhi. Clinical characteristics of adrenocorticotropic hormone-dependent Cushing's syndrome complicated with multiple endocrine neoplasia[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(3): 170-176.

http://journal11.magtechjournal.com/cjcnn/CN/Y2021/V21/I3/170

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2 伴多内分泌腺瘤病的促肾上腺皮质激素依赖性库欣综合征临床特点分析

Clinical characteristics of adrenocorticotropic hormone-dependent Cushing's syndrome complicated with multiple endocrine neoplasia

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