先天性肾上腺皮质增生症兄弟2例

病例 :例 1:男 ,生后 15天 ,因呕吐、腹泻 7天 ,不哭、不吃1天入院。患儿系第一胎第一产 ,胎龄 40周 ,出生体重 3ｋｇ ,生后即喂水及奶粉 ,第 3天始喂母乳 ,食欲尚可。第 8天始出现吃奶后呕吐 ,非喷射性 ,日 7- 8次 ,同时腹泻 ,为黄色稀水便 ,日 5 - 6次 ,渐消瘦。近 1天来不哭、不吃急入院。父母体健 ,非近亲婚配。查体 :Ｒ 6 0次 /分 ,Ｐ 70次 /分 ,ＢＷ2 8ｋｇ。精神萎糜 ,反应差 ,不哭 ,面色青灰 ,呼吸急促 ,消瘦 ,皮肤弹性差 ,前囟、眼窝明显凹陷 ,口周紫绀 ,双肺呼吸音粗 ,无口罗音。心率 70次 /分 ,律不规整 ,心音低钝 ,无杂音 ,轻…     

先天性肾上腺皮质增生症一家系4例报告

先天性肾上腺皮质增生症系一种少见的遗传性疾病,既往由于认识不足易误诊.我院一家系6名子女中4例发病.现报告如下.     

37例先天性肾上腺皮质增生症治疗和随访分析

目的 探讨先天性肾上腺皮质增生症治疗前后17-羟孕酮(17-αOHP)、促肾上腺皮质激素(ACTH)、睾酮及皮质醇的变化及后期随访的情况.方法 选取2015年1月至2019年12月我院收治的37例先天性肾上腺皮质增生患儿的病史资料,对其进行回顾性分析,对比治疗前后血钠、血钾、17-αtOHP、ACTH、睾酮及皮质醇的变...     

47例先天性肾上腺皮质增生症的临床特点及诊治分析

目的提高对先天性肾上腺皮质增生症（congenital adrenal hyperplasia,CAH）的认识。方法对47例CAH患儿临床资料做回顾性分析。结果失盐型伴高钾、低钠及代谢性酸中毒;多数促肾上腺皮质激素及睾酮升高。皮质醇降低,依从性好者复查该指标基本控制于正常范围。末次随访年龄≥5岁者,初治年龄≤3岁组（6例）末次复诊时骨龄与实际年龄差值[（1．83±3．70）岁]与〉3岁组（10例）[（4．10±1．77）岁]比较差异有统计学意义。初治年龄〉3岁组合并中枢性性早熟5例,≤3岁组2例;男性中枢性性早熟5例,女性2例。结论≤3岁组患儿预测终身高优于〉3岁组;男性CAH可能较女性更易发生性早熟。     

南京地区先天性肾上腺皮质增生症的新生儿筛查和随访

目的总结对新生儿先天性肾上腺皮质增生症(CAH)的筛查和诊治经验.了解南京地区CAH的发病率.方法测定纸片血斑中17羟孕酮(17α-OHP).可疑病例再测静脉中促肾上腺素,睾酮,孕酮,雌二醇,钾钠氯,血糖(ACTH,T,P,E2,K+,Na+,Cl-,GLU)及染色体检查,结合临床确诊本病.结果自1993年～2002年1月,共筛查出5例阳性病例.结论 CAH属于常染色体隐性遗传病,出生时常缺乏症状,极易误诊,故推广此种方法进行大规模新生儿筛查可以早期诊断、及时治疗.预防新生儿生长发育受损及肾上腺危象的发生.     

无锡地区新生儿先天性肾上腺皮质增生症的发病情况探讨

了解无锡市新生儿先天性肾上腺皮质增生症(CAH)的发病情况。方法采用时间分辨荧光免疫法(TRFIA)检测新生儿足跟血17α-OHP浓度,30nmol/m l为阳性切值,经复检阳性者,行确诊试验判断。结果1992年5月至2006年2月共筛查61284例新生儿确诊4例肾上腺皮质增生症(CAH)患者,发病率为1/15321(4/61284)。结论开展新生儿17α-OHP检测以便早期诊治新生儿CAH。     

先天性肾上腺皮质增生症21－羟化酶缺乏2例报道

我院近年来收治的两例先天性肾上腺皮质增生症属２１－羟化酶缺乏，其一表现为男性化伴失盐型，该例曾一度被误诊为营养不良，当高钾低钠难以纠正时查尿１７－ＫＳ为２７．３５μｍｏｌ／２４小时，经氢化可的松试验性治疗２日结果尿１７－ＫＳ下降达对照日的２３．４３％。其二为单纯男性化型，以身高生长停滞为主征，小剂量地塞米松抑制试验尿１７－ＫＳ下降达对照日的１２．８５％。鉴于我们的误诊，总结了点滴经验，供借鉴。     

先天性肾上腺皮质增生症误诊原因初探（附6例分析）

先天性肾上腺皮质增生症误诊原因初探（附６例分析）山东省泰安市儿童医院内科（２７１０００）史宝海，寇红霞先天性肾上腺皮质增生症是由于合成肾上腺皮质激素过程中所需一系列酶先天性缺陷而致的一组临床征候群，为一种少见的常染色体隐性遗传病，表现为吐泻，腹胀和体...     

中山地区新生儿先天性肾上腺皮质增生症的筛查结果分析

目的探讨中山地区先天性肾上腺皮质增生症（CAH）的发病率及治疗情况。方法2008年8月到2010年9月间采集105320名出生48—72h后的新生儿足跟血3滴于滤纸血片上,采用时间分辨荧光免疫法检测血斑中17α羟孕酮（17-α-OHP）的浓度;可疑阳性的召回复查确诊;确诊为CAH的患儿给予规范治疗。结果筛查新生儿105320例,可疑患儿307例,确诊2例,均为男婴,发病率1／52660。结论中山地区CAH发病率低于全国平均水平,早期诊断与治疗对CAH患儿的愈后十分重要。     

先天性肾上腺皮质增生症21—羟化酶缺乏2例报道

我院近年来收治的两例先天性肾上腺皮质增生症属２１－羟化酶缺乏，其一表现为男性化伴失盐型，该例曾一度被误诊为营养不良，当高钾氏钠难以纠正时查尿１７－ＫＳ为２７．３５μｍｏｌ／２４小时，经氢化可的松试验性治疗２日结果尿１７－ＫＳ下降达到照日的２３．４３％，其二为单纯男性化型，以身高生长停滞为主征，小剂量地塞米松抑制试验尿１７－ＫＳ下降对照日的１２．８５％，鉴于我们的误诊，总结了点滴经验，供借鉴。     

Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART.MethodAmong 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded.ResultsTART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro).ConclusionWe found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype–phenotype correlation in TART may benefit further investigations in larger series.     

Testicular Adrenal Rest Tumor (TART) in congenital adrenal hyperplasia

Congenital adrenal hyperplasia is one of the most common autosomal recessive genetic disorders. Testicular adrenal tumors are significant complications of congenital adrenal hyperplasia. We would like to present two patients of testicular adrenal rest tumors. Patient 1 24 year-old male, he was diagnosed with congenital adrenal hyperplasia at the age of 8 due to precocious puberty. He received hydro-cortisone treatment until the age of 18. Testicular mass had been detected and right radical orchiectomy had been applied 6 months ago and reported as testicular adrenal rest tumor. In scrotal ultrasound, a mixed type mass lesion (6 × 4x3 cm) covering a large part of left testis was observed. The imaging findings were consistent with adrenal rest tumor. The patient took adrenocorticotropic hormone supressive therapy with dexamethasone 0.75 mg once a day. Patient 2, 38 year-old male, he had been followed-up as adrenal insufficiency for 35 years. He underwent right orchiectomy operation due to the testicular mass in 2010 and the pathological examination revealed Leydig cell tumor. In scrotal ultrasound, small multifocal lesions were detected on the left testis and resection was done. It was reported as testicular adrenal rest tumor. He is being followed-up with glucocorticoid treatment according to androgen and adrenocorticotropic hormone levels. Early diagnosis of testicular adrenal rest tumor is significant in preventing irreversible testicular damage and infertility. In the differential diagnosis, we should keep in mind that testicular adrenal rest tumor can mimic other testicular tumors such as primary germ cell tumors.     

先天性肾上腺皮质增生症患者21-羟化酶基因启动子区域突变的初步研究

目的研究先天性肾上腺皮质增生症（ｃｏｎｇｅｎｉｔａｌａｄｒｅｎａｌｈｙｐｅｒｐｌａｓｉａ,ＣＡＨ）患者２１－羟化酶基因启动子区域的突变。方法用ＰＣＲ、ＳＳＣＰ、内切酶酶谱分析及测序分析方法对１２例ＣＡＨ患者的２１－羟化酶基因启动子区域进行研究。结果１２例患者中有６例出现异常ＳＳＣＰ条带,其中１例在ＣＫ－２（－１０１）结合区域内的ＫｐｎⅠ内切酶识别位点及其－２０１处的ＴａｑⅠ内切酶识别位点存在突变,并经测序证实。结论在ＣＡＨ患者－２１羟化酶基因启动子区域存在突变,可能为ＣＡＨ发病机理之一。     

临沂地区2009年-2013年新生儿先天性肾上腺皮质增生症的筛查

对严重危害身心健康的先天性或遗传代谢性疾病（新生儿先天性肾上腺皮质增生症（CAH））进行筛检,以便能早期诊断和治疗。目的探讨新生儿先天性肾上腺皮质增生症（CAH）筛查情况,为CAH的早期筛查、确诊和治疗提供依据。方法选择临沂市新生儿疾病筛查中心2009年8月至2013年12月进行CAH筛查的新生儿,采用时间分辨荧光免疫分析方法检测滤纸片17-羟孕酮（17-OHP）浓度,通过数据分析确立实验室筛查的切值。结果研究期间共筛查740730例新生儿,确诊24例CAH。其中市区5例,县城19例。足月儿复查结果显示17-OHP浓度高于30 nm01／L。结论临沂地区CAH发病率低于全国平均水平,早期诊断对CAH患儿的临床治疗具有重要的意义。     

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aimWe aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH).Materials and methods Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system.Results There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status.Conclusion In this study, the CIMT values of CAH cases were similar to those of healthy subjects.     

Acute adrenal crisis complicating hypertensive congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

In its classical form, congenital adrenal hyperplasia due to 11 β-hydroxylase deficiency is characterized by hypertension and abnormal sexual development. Suppression of ACTH secretion by means of administering glucocorticoids fulfills the therapeutic goal of reducing blood pressure and decreasing androgen production. The present report describes the case of a patient suffering from congenital adrenal hyperplasia due to 11β-hydroxylase deficiency who developed an acute adrenal crisis, unprovoked by stress, following interruption of glucocorticoid replacement therapy. It is suggested that patients on a suppressive dose of glucocorticoids for adrenal hyperplasia are at increased risk for acute adrenal insufficiency if therapy is interrupted, and that deoxycorticosterone (DOC) in the absence of a glucocorticoid is insufficient to prevent manifestations of adrenal crisis.     

Ethnic-specific distribution of mutations in 716 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) occurs worldwide. The most common mutations in the CYP21A2 gene in 716 unrelated patients were analyzed and the mutations were grouped by ethnicity, as defined through self-declaration corroborated by review of pedigrees extending to two or three generations. Prevalent allelic mutations and genotypes were found to vary significantly among ethnic groups, and the predominance of the prevalent mutations and genotypes in several of these populations was significant. There are ethnic-specific mutations in the CYP21A2 gene. A large deletion is prevalent in the Anglo-Saxons; a V281L (1685 G to T) mutation is prevalent in Ashkenazi Jews; an R356W (2109 G to A) mutation is prevalent in the Croatians; an IVS2 AS -13 (A/C to G) mutation is prevalent in the Iranians and Yupik-speaking Eskimos of Western Alaska; and a Q318X (1994 C to T) mutation is prevalent in East Indians. Genotype/phenotype non-correlation was seen when at least one IVS2 AS -13 (A/C to G) mutation in the CYP21A2 gene was present.     

CYP21 mutations and congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder caused mainly by defects in the steroid 21-hydroxylase (CYP21) gene. More than 90% of CAH cases are caused by mutations of the CYP21 gene on chromosome 6p21.3. The wide range of CAH phenotypes is associated with multiple mutations known to affect 21-hydroxylase enzyme activity. To date, 56 different CYP21 mutations have been reported, mostly point mutations, but small deletions or insertions have been described too, as well as complete gene deletions. Fifteen mutations, constituting 90-95% of alleles, are derived from intergenic recombination of DNA sequences between the CYP21 gene and the highly homologous CYP21P pseudogene, while the remaining are spontaneous mutations. A reliable and accurate detection of CYP21 mutations is not only important for clinical diagnosis, but also for carrier detection as there is a high variability in the basal level of 17-hydroxyprogesterone between normal and heterozygous individuals. Several strategies based on polymerase chain reaction (PCR)-driven amplification with allele-specific oligonucleotides to the CYP21 gene have been developed. It has been demonstrated that one reaction for PCR amplification of the CYP21 gene and the chimeric CYP21P/CYP21 gene using mixed primers in combination with nested PCR and single-strand conformation polymorphism is considered highly efficient and accurate for molecular diagnosis of CAH due to 21-hydroxylase deficiency.     

Molecular and structural analysis of two novel StAR mutations in patients with lipoid congenital adrenal hyperplasia

Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid congenital adrenal hyperplasia. We report a novel homozygous splice site mutation (IVS1 + 2T --> G) in STAR in two sisters (46XY, 46XX) who presented with primary adrenal insufficiency at birth and a novel homozygous R182H missense mutation in the putative lipid transfer domain of StAR in a phenotypic female (46XY) with adrenal failure and a parotid tumor. These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy and of the critical functional role of R182 in cholesterol transport.     

Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia

We report a case of an adenomatoid tumor (AT) of an adrenal gland with micronodular adrenal cortical hyperplasia (ACH). A 51-year-old man was found to have newly developed hypertension with clinical evidence of primary aldosteronism. A computerized tomogram of the abdomen revealed a solitary mass in the right adrenal gland. He underwent a right adrenalectomy for a presumptive clinical diagnosis of a solitary aldosterone-producing adrenal cortical adenoma. On histopathologic examination, the adrenal gland demonstrated an AT, diagnosed by the characteristic histological features, immunohistochemical stain results, and electron microscopic findings. The surrounding adrenal cortex showed multiple small hyperplastic cortical nodules. After the adrenalectomy, the patient's blood pressure normalized. Primary AT of the adrenal gland coexisting with micronodular ACH associated with hypertension has not been previously reported.