17α-羟化酶缺陷症的临床研究进展
|
摘要
17α-羟化酶(17OHD)是先天性肾上腺皮质增生(CAH)的少见类型。该文就17OHD的流行病学、病因与发病机制、临床特点、诊断与鉴别诊断及治疗进行最新的文献学习及总结。该疾病的独特之处在于患者无论核型如何均为女性表型,常表现出假两性畸形、第二性征不发育等生殖腺异常,及低肾素性高血压、低醛固酮、低血钾的肾上腺异常。由于临床表现多样且诊断复杂,很多患者症状不明显,故不能及时就诊。综述期望对临床医生有所启迪并对该病加深认识。
The 17α-hydroxylase (17OHD) is a rare type of congenital adrenal cortical hyperplasia (CAH). This article reviews and summarizes the latest literature on the epidemiology,etiology and pathogenesis,clinical characteristics,diagnosis and differential diagnosis and treatment of 17OHD. The uniqueness of the disease lies in the fact that the patients are female phenotypes regardless of their karyotype,often showing genital abnormalities such as pseudohermaphroditism,secondary sexual dysplasia,and adrenal abnormalities such as low renaline hypertension,low aldosterone and low blood potassium. Because of the diversity of clinical manifestations and the complexity of diagnosis,many patients have no obvious symptoms and can not see a doctor in time. The review is expected to give some inspiration to clinicians and deepen their understanding of the disease.
The 17α-hydroxylase (17OHD) is a rare type of congenital adrenal cortical hyperplasia (CAH). This article reviews and summarizes the latest literature on the epidemiology,etiology and pathogenesis,clinical characteristics,diagnosis and differential diagnosis and treatment of 17OHD. The uniqueness of the disease lies in the fact that the patients are female phenotypes regardless of their karyotype,often showing genital abnormalities such as pseudohermaphroditism,secondary sexual dysplasia,and adrenal abnormalities such as low renaline hypertension,low aldosterone and low blood potassium. Because of the diversity of clinical manifestations and the complexity of diagnosis,many patients have no obvious symptoms and can not see a doctor in time. The review is expected to give some inspiration to clinicians and deepen their understanding of the disease.
引文
[1]El-Maouche D,Arlt W,Merke DP.Congenital adrenal hyperplasia[J].The Lancet,2017,390(10108):2194-2210.DOI:10.1016/s0140-6736(17)31431-9.
[2]Fontenele R,Costa-santos M,Kater C.17α-Hydroxylase deficiency is an underdiagnosed disease:hioh frequency of misdiagnoses in a large cohort of brazilian patients[J].Endocrine Practice,2018,24(2):170-178.DOI:10.4158/EP171987.OR.
[3]Yao F,Huang S,Kang X,et al.CYP17A1 mutations identified in 17Chinese patients with 17α-hydroxylase/17,20-lyase deficiency[J].Gynecol Endocrinol,2013,29(1):10-15.DOI:10.3109/09513590.2012.705373.
[4]Zhang M,Sun S,Liu Y,et al.New,recurrent,and prevalent mutations:Clinical and molecular characterization of 26 Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency[J].J Steroid Biochem Mol Biol,2015,150(1):11-16.DOI:10.1016/j.jsbmb.2015.02.007.
[5]Zhang Y,Zhang X,Wang Y,et al.Genetic defect of a combined 17α-hydroxylase/17,20-lyase deficiency patient with adrenal crisis[J].Gynecol Endocrinol,2018,34(6):540-544.DOI:10.1080/09513590.2017.1417981.
[6]杨军,李小英,孙首悦,等.10例17α羟化酶/17,20碳链裂解酶缺陷症临床和遗传学研究[J].上海交通大学学报:医学版,2006,26(1):17-21.DOI:10.3969/j.issn.1674-8115.2006.01.005.
[7]Kim Y,Kang M,Choi J,et al.A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency,a case series of such mutations among Koreans and functional characteristics of a novel mutation[J].Metab Clin Exp,2014,63(1):42-49.DOI:10.1016/j.metabol.2013.08.015.
[8]Wolthers O,Rlimsby G,Techatraisak K,et al.17-Hydroxylase/17,20 lyase deficiency diagnosed during childhood[J].Horm Res,2002,57(3-4):133-136.DOI:10.1159/000057964.
[9]Huang N,Pandey A,Agrawal V,et al.Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis[J].Am J Hum Genet,2005,76(5):729-749.DOI:10.1086/429417.
[10]Aydin Z,Ozturk S,Gursu M,et al.Male pseudohermaphroditism as a cause of secondary hypertension:a case report[J].Endocrine,2010,38(1):100-103.DOI:10.1007/s12020-010-9357-x.
[11]Hinz L,Pacaud D,Kline G.Congenital adrenal hyperplasia causing hypertension:an illustrative review[J].Journal of Human Hypertension,2018,32(2):150-157.DOI:10.1038/s41371-017-0002-5.
[12]Wang Y,Li J,Li J,et al.Three novel CYP17A1 gene mutations(A82D,R125X,and C442R)found in combined 17α-hydroxylase/17,20-lyase deficiency[J].Metab Clin Exp,2011,60(10):1386-91.DOI:10.1016/j.metabol.2011.03.008.
[13]Toh V,Yung C.A young woman with hypogonadism,hypertension and hypokalaemia[J].Med J Malaysia,2009,64(3):242-243.
[14]王彬,宋康兴,冯丽洁,等.17α-羟化酶缺陷症的早期诊断与干预[J].中国全科医学,2013,16(23):2738-2739.DOI:10.3969/j.issn.1007-9572.2013.23.022.
[15]史轶蘩.协和内分泌和代谢学[M].北京:科学出版社,1999:1165-1172.
[16]Akyiirek N,Atabek M,Eklio4lu B,et al.Ambulatory blood pressure and subclinical cardiovascular disease in patients with congenital adrenal hyperplasia:a preliminary report[J].J Clin Res Pediatr Endocrinol,2015,7(1):13-18.DOI:10.4274/jcrpe.1658.
[17]魏红玲,鲁珊,王新利,等.以严重高血压就诊的17α-羟化酶缺乏症[J].中国当代儿科杂志,2018,20(8):675-679.DOI:10.7499/j.issn.1008-8830.2018.08.014.
[18]郭媛博,闫朝丽,张丽娟,等.原发性醛固酮增多症46例临床分析[J].疑难病杂志,2014,(3):256-258.DOI:10.3969/j.issn.1671-6450.2014.03.013.
[19]赵芳玉,王亮亮,赵红丽,等.糖尿病合并原发性醛固酮增多症疑难病例一例报告[J].新疆医学,2018,48(3):334-335.
[20]Fang DC,Xiang X,Ma YT,et al.Relationship between CYP17A1Genetic Polymorphism and Essential Hypertension in a Chinese Population[J].Aging Dis,2015,6(6):486-498.DOI:10.14336/AD.2015.0505.
[21]Rubtsov P,Nizhnik A,Dedov I,et al.Partial deficiency of 17alphahydroxylase/17,20-lyase caused by a novel missense mutation in the canonical cytochrome heme-interacting motif[J].European Journal of Endocrinology,2015,172(5):K19-25.DOI:10.1530/eje-14-0834.
[22]Miguel D,Ashwini M,Verena G,et al.Hormonal circadian rhythms in patients with congenital adrenal hyperplasia:identifying optimal monitoring times and novel disease biomarkers[J].Eur J Endocrinol,2015,173(6):727-737.DOI:10.1530/EJE-15-0064.
[23]Wu C,Fan S,Qian Y,et al.17α-Hydroxylase/17,20-lyase deficiency:clinical and moleolecular characterization of eight chinese patients[J].Endocrine Practice,2017,23(5):576-582.DOI:10.4158/EP161610.
[24]Nella A,Mallappa A,Perritt A,et al.A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia[J].J Clin Endocrinol Metab,2016,101(12):4690-4698.DOI:10.1210/jc.2016-1916.
[25]Ruiz-babot G,Hadjidemetriou I,King P,et al.New directions for the treatment of adrenal insufficiency[J].Front Endocrinol(Lausanne),2015,6:70.DOI:10.3389/fendo.2015.00070.
[26]Kamrath C,Wettstaedt L,Boettcher C,et al.Androgen excess is due to elevated 11-oxygenated androgens in treated children with congenital adrenal hyperplasia[J].J Steroid Biochem Mol Biol,2018,178:221-228.DOI:10.1016/j.jsbmb.2017.12.016.
[2]Fontenele R,Costa-santos M,Kater C.17α-Hydroxylase deficiency is an underdiagnosed disease:hioh frequency of misdiagnoses in a large cohort of brazilian patients[J].Endocrine Practice,2018,24(2):170-178.DOI:10.4158/EP171987.OR.
[3]Yao F,Huang S,Kang X,et al.CYP17A1 mutations identified in 17Chinese patients with 17α-hydroxylase/17,20-lyase deficiency[J].Gynecol Endocrinol,2013,29(1):10-15.DOI:10.3109/09513590.2012.705373.
[4]Zhang M,Sun S,Liu Y,et al.New,recurrent,and prevalent mutations:Clinical and molecular characterization of 26 Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency[J].J Steroid Biochem Mol Biol,2015,150(1):11-16.DOI:10.1016/j.jsbmb.2015.02.007.
[5]Zhang Y,Zhang X,Wang Y,et al.Genetic defect of a combined 17α-hydroxylase/17,20-lyase deficiency patient with adrenal crisis[J].Gynecol Endocrinol,2018,34(6):540-544.DOI:10.1080/09513590.2017.1417981.
[6]杨军,李小英,孙首悦,等.10例17α羟化酶/17,20碳链裂解酶缺陷症临床和遗传学研究[J].上海交通大学学报:医学版,2006,26(1):17-21.DOI:10.3969/j.issn.1674-8115.2006.01.005.
[7]Kim Y,Kang M,Choi J,et al.A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency,a case series of such mutations among Koreans and functional characteristics of a novel mutation[J].Metab Clin Exp,2014,63(1):42-49.DOI:10.1016/j.metabol.2013.08.015.
[8]Wolthers O,Rlimsby G,Techatraisak K,et al.17-Hydroxylase/17,20 lyase deficiency diagnosed during childhood[J].Horm Res,2002,57(3-4):133-136.DOI:10.1159/000057964.
[9]Huang N,Pandey A,Agrawal V,et al.Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis[J].Am J Hum Genet,2005,76(5):729-749.DOI:10.1086/429417.
[10]Aydin Z,Ozturk S,Gursu M,et al.Male pseudohermaphroditism as a cause of secondary hypertension:a case report[J].Endocrine,2010,38(1):100-103.DOI:10.1007/s12020-010-9357-x.
[11]Hinz L,Pacaud D,Kline G.Congenital adrenal hyperplasia causing hypertension:an illustrative review[J].Journal of Human Hypertension,2018,32(2):150-157.DOI:10.1038/s41371-017-0002-5.
[12]Wang Y,Li J,Li J,et al.Three novel CYP17A1 gene mutations(A82D,R125X,and C442R)found in combined 17α-hydroxylase/17,20-lyase deficiency[J].Metab Clin Exp,2011,60(10):1386-91.DOI:10.1016/j.metabol.2011.03.008.
[13]Toh V,Yung C.A young woman with hypogonadism,hypertension and hypokalaemia[J].Med J Malaysia,2009,64(3):242-243.
[14]王彬,宋康兴,冯丽洁,等.17α-羟化酶缺陷症的早期诊断与干预[J].中国全科医学,2013,16(23):2738-2739.DOI:10.3969/j.issn.1007-9572.2013.23.022.
[15]史轶蘩.协和内分泌和代谢学[M].北京:科学出版社,1999:1165-1172.
[16]Akyiirek N,Atabek M,Eklio4lu B,et al.Ambulatory blood pressure and subclinical cardiovascular disease in patients with congenital adrenal hyperplasia:a preliminary report[J].J Clin Res Pediatr Endocrinol,2015,7(1):13-18.DOI:10.4274/jcrpe.1658.
[17]魏红玲,鲁珊,王新利,等.以严重高血压就诊的17α-羟化酶缺乏症[J].中国当代儿科杂志,2018,20(8):675-679.DOI:10.7499/j.issn.1008-8830.2018.08.014.
[18]郭媛博,闫朝丽,张丽娟,等.原发性醛固酮增多症46例临床分析[J].疑难病杂志,2014,(3):256-258.DOI:10.3969/j.issn.1671-6450.2014.03.013.
[19]赵芳玉,王亮亮,赵红丽,等.糖尿病合并原发性醛固酮增多症疑难病例一例报告[J].新疆医学,2018,48(3):334-335.
[20]Fang DC,Xiang X,Ma YT,et al.Relationship between CYP17A1Genetic Polymorphism and Essential Hypertension in a Chinese Population[J].Aging Dis,2015,6(6):486-498.DOI:10.14336/AD.2015.0505.
[21]Rubtsov P,Nizhnik A,Dedov I,et al.Partial deficiency of 17alphahydroxylase/17,20-lyase caused by a novel missense mutation in the canonical cytochrome heme-interacting motif[J].European Journal of Endocrinology,2015,172(5):K19-25.DOI:10.1530/eje-14-0834.
[22]Miguel D,Ashwini M,Verena G,et al.Hormonal circadian rhythms in patients with congenital adrenal hyperplasia:identifying optimal monitoring times and novel disease biomarkers[J].Eur J Endocrinol,2015,173(6):727-737.DOI:10.1530/EJE-15-0064.
[23]Wu C,Fan S,Qian Y,et al.17α-Hydroxylase/17,20-lyase deficiency:clinical and moleolecular characterization of eight chinese patients[J].Endocrine Practice,2017,23(5):576-582.DOI:10.4158/EP161610.
[24]Nella A,Mallappa A,Perritt A,et al.A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia[J].J Clin Endocrinol Metab,2016,101(12):4690-4698.DOI:10.1210/jc.2016-1916.
[25]Ruiz-babot G,Hadjidemetriou I,King P,et al.New directions for the treatment of adrenal insufficiency[J].Front Endocrinol(Lausanne),2015,6:70.DOI:10.3389/fendo.2015.00070.
[26]Kamrath C,Wettstaedt L,Boettcher C,et al.Androgen excess is due to elevated 11-oxygenated androgens in treated children with congenital adrenal hyperplasia[J].J Steroid Biochem Mol Biol,2018,178:221-228.DOI:10.1016/j.jsbmb.2017.12.016.