一例儿童醛固酮和皮质醇共分泌肾上腺瘤的临床表现及全外显子测序分析

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (3): 352-357.

一例儿童醛固酮和皮质醇共分泌肾上腺瘤的临床表现及全外显子测序分析

王慧萍^1,2, 文进³, 崔云英², 马晓森², 任卫东¹, 童安莉^2*

1.河北北方学院研究生院, 河北张家口 075000;
2.内分泌科国家卫生健康委员会内分泌重点实验室中国医学科学院北京协和医学院北京协和医院;
3.泌尿外科, 北京 100730 中国医学科学院北京协和医学院北京协和医院

收稿日期:2020-10-26 修回日期:2020-12-24 出版日期:2021-03-05 发布日期:2021-03-01
通讯作者: ^*tonganli@hotmail.com
基金资助:
国家自然科学基金(81770427,82070822);中国医学科学院医学与健康科技创新工程项目(2017-12M-1-001)

Whole-exome sequencing from a case of pediatric aldosterone- and cortisol-coproducing adrenal adenoma

WANG Hui-ping^1,3, WEN Jin³, CUI Yun-ying², MA Xiao-sen², REN Wei-dong¹, TONG An-li^2*

1. Graduate School, Hebei North University,Zhangjiakou 075000;
2. Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission;
3. Department of Urology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China

Received:2020-10-26 Revised:2020-12-24 Online:2021-03-05 Published:2021-03-01
Contact: ^*tonganli@hotmail.com

摘要/Abstract

摘要： 目的对1例儿童醛固酮和皮质醇共分泌瘤患者行全外显子测序,探讨其可能的发病机制。方法收集此例共分泌肾上腺皮质腺瘤患者有关临床资料;提取患者肿瘤组织DNA及外周血DNA,进行全外显子测序,分析胚系及体系突变。结果患者为13岁男孩,因高血压和低血钾就诊;根据临床表现和激素检测的结果,诊断为原发性醛固酮增多症合并亚临床库欣综合征;CT发现右肾上腺4.5 cm×3.6 cm占位,手术病理证实为肾上腺皮质腺瘤。在患者肿瘤组织中发现醛固酮合成酶CTNNB1 c.133T＞C (p.S45P)位点突变。未发现KCNJ5、ATP1A1、ATP2B3和CACNA1D等基因突变。结论此例罕见的儿童醛固酮和皮质醇共分泌肾上腺皮质腺瘤的发生与CTNNB1突变有关,但具体机制仍需要进一步研究。

关键词: 醛固酮和皮质醇共分泌肾上腺皮质腺瘤, 全外显子测序, 质谱分析(LC-MS)

Abstract: Objective To identify the genetic mutations of aldosterone- and cortisol-coproducing adrenal adenoma in a young boy by whole-exome sequencing. Methods The clinical data of a boy with aldosterone- and cortisol-coproducing adrenal adenoma were collected. Whole-exome sequencing was performed with DNA extracted from the blood and tumor tissue to identify germline and somatic mutations. Results A 13-year-old boy with hypertension and hypokalemia was diagnosed as primary aldosteronism complicated with sub-clinical Cushing's syndrome diagnosed by clinical manifestations and adrenal hormone testing. CT scan found a 4.5 cm×3.6 cm mass in right adrenal gland. The mass was surgically removed and adenoma was proved by pathologic microscopy. A somatic CTNNB1 c.133T＞C (p.S45P) mutation was detected in the adenoma tissue. Somatic mutations, such as KCNJ5, ATP1A1, ATP2B3 and CACNA1D were not detected. Conclusions Somatic CTNNB1 mutation is probably the main cause of this rare disease characterized by aldosterone- and cortisol-coproducing adrenal adenoma. But the profound mechanism needs further study.

Key words: aldosterone- and cortisol-coproducing adrenal adenoma, whole-exome sequencing, liquid chromatograph-mass spectrometer(LC-MS)

中图分类号:

R586.9

王慧萍, 文进, 崔云英, 马晓森, 任卫东, 童安莉. 一例儿童醛固酮和皮质醇共分泌肾上腺瘤的临床表现及全外显子测序分析[J]. 基础医学与临床, 2021, 41(3): 352-357.

WANG Hui-ping, WEN Jin, CUI Yun-ying, MA Xiao-sen, REN Wei-dong, TONG An-li. Whole-exome sequencing from a case of pediatric aldosterone- and cortisol-coproducing adrenal adenoma[J]. Basic & Clinical Medicine, 2021, 41(3): 352-357.

参考文献

[1] Mosso L, Carvajal C, González A, et al. Primary aldosteronism and hypertensive disease[J]. Hypertension, 2003, 42: 161-165.
[2] Calhoun DA. Is there an unrecognized epidemic of primary aldosteronism?(Pro)[J]. Hypertension, 2007, 50: 447-453.
[3] Bardet S, Chamontin B, Douillard C, et al. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis[J]. Ann Endocrinol (Paris), 2016, 77: 208-213.
[4] Er LK, Lin MC, Tsai YC, et al. Association of visceral adiposity and clinical outcome among patients with aldosterone producing adenoma[J]. BMJ Open Diabetes Res Care, 2020, 8.doi: 10.1136/bmjdrc-2019-001153.
[5] Uchida N, Amano N, Yamaoka Y, et al. A novel case of somatic KCNJ5 mutation in pediatric-onset aldosterone-producing adenoma[J]. J Endocr Soc, 2017, 1: 1056-1061.
[6] Funder JW, Carey RM, Fardella C, et al. Case detec-tion, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guide-line[J]. J Clin Endocrinol Metab, 2008, 93: 3266-3281.
[7] Allan CA, Kaltsas G, Perry L, et al. Concurrent secretion of aldosterone and cortisol from an adrenal adenoma-value of MRI in diagnosis[J]. Clin Endocrinol (Oxf), 2000, 53: 749-753.
[8] Yang Y, Xiao M, Song Y, et al. H-score of 11β-hydroxylase and aldosterone synthase in the histopathological diagnosis of adrenocortical tumors[J]. Endocrine, 2019, 65: 683-691.
[9] Bhatt PS, Sam AH, Meeran KM, et al. The relevance of cortisol co-secretion from aldosterone-producing adenomas[J]. Hormones (Athens), 2019, 18: 307-313.
[10] Goupil R, Wolley M, Ahmed AH, et al. Does concomi-tant autonomous adrenal cortisol overproduction have the potential to confound the interpretation of adrenal venous sampling in primary aldosteronism?[J]. Clin Endocrinol (Oxf), 2015, 83: 456-461.
[11] Lobo CR, Kolinioti A, Hainsworth AJ, et al. Laparos-copic adrenalectomy for co-secreting aldosterone and cortisol adenomas[J]. Int J Surg, 2012, 10: 555-559.
[12] Späth M, Korovkin S, Antke C, et al. Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism[J]. Eur J Endocrinol, 2011, 164: 447-455.
[13] Funder JW, Carey RM, Mantero F, et al. The manage-ment of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline[J]. J Clin Endocrinol Metab, 2016, 101: 1889-1916.
[14] Stowasser M, Tunny TJ, Klemm SA, et al. Cortisol production by aldosterone-producing adenomas in vitro[J]. Clin Exp Pharmacol Physiol, 1993, 20: 292-295.
[15] Käyser SC, Dekkers T, Groenewoud HJ, et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis[J]. J Clin Endocrinol Metab, 2016, 101: 2826-2835.
[16] Yamada M, Nakajima Y, Taguchi R, et al. KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas[J]. Endocr J, 2012, 59: 735-741.
[17] Åkerström T, Maharjan R, Sven Willenberg H, et al. Activating mutations in CTNNB1 in aldosterone producing adenomas[J]. Sci Rep, 2016, 6: 19546.doi: 10.1038/srep19546.