两名携带相同 TBX19 基因同源 c.172A>G,p.(Thr58Ala) 突变的独立患者出现肾上腺功能不全。

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Paul-Martin Holterhus, Claudia Roll, Barbara Gaida, Annette Richter-Unruh, Alexandra E Kulle, Daniel Kaschta, Michaela F Hartmann, Stefan A Wudy, Thomas Reinehr
{"title":"两名携带相同 TBX19 基因同源 c.172A>G,p.(Thr58Ala) 突变的独立患者出现肾上腺功能不全。","authors":"Paul-Martin Holterhus, Claudia Roll, Barbara Gaida, Annette Richter-Unruh, Alexandra E Kulle, Daniel Kaschta, Michaela F Hartmann, Stefan A Wudy, Thomas Reinehr","doi":"10.1159/000539796","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases.</p><p><strong>Case presentation: </strong>Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A&gt;G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency.</p><p><strong>Conclusion: </strong>Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Global Adrenal Insufficiency in Two Independent Patients Carrying the Same Homozygous c.172A&gt;G, p.(Thr58Ala) Mutation in the TBX19 Gene.\",\"authors\":\"Paul-Martin Holterhus, Claudia Roll, Barbara Gaida, Annette Richter-Unruh, Alexandra E Kulle, Daniel Kaschta, Michaela F Hartmann, Stefan A Wudy, Thomas Reinehr\",\"doi\":\"10.1159/000539796\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases.</p><p><strong>Case presentation: </strong>Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A&gt;G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency.</p><p><strong>Conclusion: </strong>Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.</p>\",\"PeriodicalId\":13025,\"journal\":{\"name\":\"Hormone Research in Paediatrics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-06-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hormone Research in Paediatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000539796\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormone Research in Paediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000539796","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

导言 TBX19 基因突变会导致孤立的促肾上腺皮质激素(ACTH)缺乏症。虽然这通常会导致严重的皮质醇分泌过少,但迄今为止还没有描述过矿质类固醇生物合成的潜在后果。液相色谱质谱法(LC-MS/MS)和气相色谱质谱法(GC-MS)使人们对儿科内分泌疾病的类固醇代谢有了新的认识。病例介绍 患者 1(女)出生后即出现低血糖和低钠血症(最低钠含量为 126 毫摩尔/升)。在氢化可的松、氟氢可的松和初始氯化钠的治疗下,她康复了。患者 2(男)出生后出现长期胆汁淤积性黄疸。直到 3 个半月大时,才反复出现低血糖。两名患者的促肾上腺皮质激素均严重减少。对血浆样本进行的 LC-MS/MS 分析表明,糖皮质激素和矿皮质激素的生物合成同时减少,对点滴尿液进行的 GC-MS 分析也证实了这一点。与患者 1 不同,患者 2(现年 8 岁)从未患过低钠血症。结论 孤立的促肾上腺皮质激素缺乏症可能与矿物质皮质激素减少和低钠血症有关。我们推测,充足的垂体促肾上腺皮质激素分泌是肾上腺矿化类固醇正常生物合成的重要前提。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Global Adrenal Insufficiency in Two Independent Patients Carrying the Same Homozygous c.172A>G, p.(Thr58Ala) Mutation in the TBX19 Gene.

Introduction: TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases.

Case presentation: Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A>G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency.

Conclusion: Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信