Mutation distributions among patients with congenital adrenal hyperplasia from five regions of Brazil: a systematic review

ABSTRACT Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by CYP21A2 gene mutations, and its molecular diagnosis is widely used in clinical practice to confirm the hormonal diagnosis. Hence, considering the miscegenation of the Brazilian population, it is important to determine a mutations panel to optimise the molecular diagnosis. The objective was to review the CYP21A2 mutations' distribution among Brazilian regions.Two reviewers screened Brazilian papers up to February 2020 in five databases. The pair-wise comparison test and Holm method were used in the statistical analysis. Nine studies were selected, comprising 769 patients from all regions. Low proportion of males and salt-wasters was identified in the North and Northeast regions, although without significant difference. Large gene rearrangements also had a low frequency, except in the Center-West and South regions (p < 0.05). The most frequent mutations were p.I172N, IVS2-13A/C>G, p.V281L and p.Q318X, and significant differences in their distributions were found: p.V281L was more frequent in the Southeast and p.Q318X in the Center-West and Northeast regions (p < 0.05). Thirteen new mutations were identified in 3.8%-15.2% of alleles, being more prevalent in the North region, and six mutations presented a founder effect gene. Genotype-phenotype correlation varied from 75.9%-97.3% among regions. The low prevalence of the salt-wasting form, affected males and severe mutations in some regions indicated pitfalls in the clinical diagnosis. The good genotype-phenotype correlation confirms the usefulness of molecular diagnosis; however, the Brazilian population also presents significant prevalence of novel mutations, which should be considered for a molecular panel.

Corticotropin releasing factor type 1 receptor antagonist: a promising therapy for 21-hydroxylase deficiency / 中华实用儿科临床杂志

21-hydroxylase deficiency(21-OHD) is mainly characterized by cortisol deficiency with or without aldosterone deficiency and hyperandrogenemia.The disease requires lifelong exogenous glucocorticoid/salt supplementation.Excessive doses of exogenous glucocorticoids are often needed to control hyperandrogenemia, but the effect is not satisfactory.Corticotropin releasing factor (CRF) type 1 receptor antagonist can directly block the production of adrenocorticotropin, inhibit the generation of adrenogenic androgen, reduce the dose of glucocorticoid therapy, and thus lower the incidence of adverse reactions.In this article, the current research progress on 21-OHD therapy and CRF1 receptor antagonist was reviewed.

Irregular Menstruation-Hirsutism-Infertility: Clinical Management of Non-Classic Congenital Adrenal Hyperplasia / 罕见病研究

A 38-year-old female presented with irregular menstruation and hirsutism that started at age of 16 and diagnosed with polycystic ovary syndrome at age of 29 with elevated testosterone. When treated with ethinestradiol cyproterone tablets, her menstruation returned to normal and androgen levels was not changed. At age of 38 she was referred to the hospital with infertility, a diagnosis of nonclassical 21-hydroxylase deficiency was confirmed using 17-hydroxyprogesterone, dehydroepiandrosterone-sulfate, a cosyntropin-stimulation test and genetic test. This case suggested that nonclassical congenital adrenal hyperplasia should be considered when a patient is presented with oligomenorrhea, hirsutism with hyperandrogenemia and infertility.

Genetic diagnosis of non-classical 21-hydroxylase deficiency by the new nanopore sequencing detection method / 中华检验医学杂志

Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.

Effects of 21-hydroxylase deficiency on male fertility / 中华内分泌代谢杂志

Congenital adrenal hyperplasia(CAH) is a group of autosomal recessive disorders caused by deficiency of specific enzymes in the adrenocortical hormone synthesis pathway, resulting in impaired corticosteroid synthesis. 21-hydroxylase deficiency is the most common type of CAH, and the disorder can lead to impaired fertility in patients. Most current studies have focused on fertility problems in female CAH patients. The most common causes of impaired fertility in men with 21-OHD include testicular adrenal rest tumors(TART), low gonadotropin secretion, and inappropriate glucocorticoid therapy. This article reviews the causes of impaired fertility and its treatment in male patients with 21-OHD, with the aim of providing guidance for improving the fertility of male patients with 21-OHD.

Anthropometric and Pubertal Outcomes in Girls With Classical Congenital Adrenal Hyperplasia

Objective: To evaluate the anthropometric and pubertal outcomes, over a spectrum of treatment regimens and compliance. Methods: We reviewed records of the patients with classical CAH seen at the endocrinology clinic of a tertiary care center between 1995 and 2016. Results: 25 females were included in the study, the majority (80%) with simple virilizing variant. All patients had genital ambiguity since birth, yet 40% (10/25) presented much later with menstrual complaints. All patients received hydrocortisone, but some switched to dexamethasone (n=7) or prednisolone (n=4). 7/9 (77.9%) girls who achieved target height, were on hydrocortisone. Menarche occurred with corticosteroid treatment in 60% (15/25) patients at a median (IQR) age of 16 (12-22) years. Conclusion: Hydrocortisone seems to have a beneficial effect on linear growth. Once target height is achieved, dexamethasone may be considered as an alternative.

Diagnosis and treatment of 21-hydroxylase deficiency with testicular adrenal rest tumors:a report of three cases and literature review / 中华内科杂志

Objective:To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed.Methods:The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up.Results:All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia.Conclusions:Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

Phenotype and genotype analysis of 6 patients with 21-hydroxylase deficiency / 中华全科医师杂志

The clinical data of 6 patients with 21-hydroxylase deficiency(21-OHD) diagnosed in The People′s Hospital of Xinjiang Uygur Autonomous Region from 2015 to 2020 were retrospectively analyzed. There were 2 male cases manifesting shorter height, high progesterone level and infertility. And 4 cases were females, manifesting primary amenorrhea, heterosexual precocious puberty, fatigue during emergency, decreased physical strength, dark skin, clitoral hypertrophy and vulva fusion. None of the parents had a history of consanguinity. All but one patient received glucocorticoid replacement therapy. The sequencing of exons and introns of 21CYPA2 gene showed tuat 1 case was homozygous mutation and 5 cases were complex heterozygous mutation. In terms of clinical phenotype, 1 case was non-classical (complex heterozygous mutation) and 5 cases were simple virilizing phenotype.

Abordagem da hiperplasia adrenal congênita pela deficiência da enzima 21-hidroxilase em crianças e adolescentes: revisão / Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents: review

Objetivo: Descrever o diagnóstico e manejo clínico da deficiência da 21-hidroxilase (D-21OH), no contexto atual de inclusão da doença nos programas de triagem neonatal, bem como características genéticas, fisiopatológicas e manifestações na infância e adolescência. Fonte de Dados: Revisão integrativa realizada nas bases de dados MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science nos últimos vinte anos, em língua inglesa e portuguesa; população-alvo: crianças da primeira infância à adolescência; com o uso dos termos "triagem neonatal", "hiperplasia adrenal congênita", "deficiência da 21-hidroxilase", "glucocorticoide" e "polimorfismos do gene NR3C1". Síntese de Dados: A hiperplasia adrenal congênita (HAC) constitui um grupo de doenças caracterizadas por deficiências enzimáticas na esteroidogênese do córtex adrenal. A D-21OH é responsável por 95% dos casos e, se não tratada precocemente, pode levar ao óbito no período neonatal em sua forma clássica. A triagem neonatal para a HAC consiste na dosagem do precursor 17-hidroxiprogesterona (17OHP) no sangue de recém-nascidos, permitindo rápida confirmação diagnóstica e instituição da terapêutica. A implantação da triagem neonatal constitui um avanço, mas o controle dos pacientes pediátricos com D-21OH é complexo e deve ser sempre individualizado. Conclusão: A instituição dos programas de triagem neonatal para HAC tem trazido benefícios para o prognóstico das crianças com D-21OH. Seu manejo é multiprofissional, individualizado e ainda um desafio mesmo para o especialista. Ampla divulgação do conhecimento sobre a doença é desejável para permitir melhor condução dessas crianças, especialmente de meninas com a doença que apresentam genitália atípica.

Objective: To describe the diagnosis and clinical management of 21-hydroxylase deficiency (21OH-D), in the current context of including the disease in neonatal screening programs, as well as genetic, pathophysiological characteristics, and manifestations in childhood and adolescence. Data Source: Integrative review performed in MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science databases in the last twenty years, in English and Portuguese; target population: children from early childhood to adolescence; with the use of the terms "neonatal screening"; "congenital adrenal hyperplasia"; "21-hydroxylase deficiency"; "glucocorticoid"; "polymorphisms of the NR3C1 gene". Data Synthesis: Congenital adrenal hyperplasia (CAH) is a group of diseases characterized by enzyme deficiencies in adrenal cortex steroidogenesis. 21OH-D is responsible for 95% of cases and, if not treated early, can lead to death in the neonatal period in its classic form. Neonatal screening for CAH consists of measuring the precursor 17-hydroxyprogesterone (17OHP) in the blood of newborns, allowing rapid diagnostic confirmation and institution of therapy. The implementation of neonatal screening is an advance, but the control of pediatric patients with 21OH-D is complex and must always be individualized. Conclusion: The institution of newborn screening programs for CAH has benefits for the prognosis of children with 21OH-D. Its management is multi-professional, individualized and still a challenge even for the specialist. Wide dissemination of knowledge about the disease is desirable to allow better management of these children, especially girls with the disease who have atypical genitalia.

Research on the follow-up value of steroid hormones for 21-hydroxylase deficiency / 中华检验医学杂志

Objective:This study explored the consistency of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay for the detection of steroid hormones. The diagnostic value of multiple steroid hormones in 21-hydroxylase deficiency (21-OHD) was investigated and the follow-up indicators were screened.Methods:This experimental group included 109 patients with typical 21-OHD who received standard treatment, and the control group included 94 normal children. 17-hydroxyprogesterone (17-OHP), androstenedione (Δ4-A), testosterone and cortisol were detected by immunoassay and LC-MS/MS method. At the same time, 16 other adrenal steroids were detected by LC-MS/MS method. The experimental group was divided into: (1) overtreatment group: 17OHP<4 ng/ml; (2) well controlled group: 4 ng/ml≤17-OHP<12 ng/ml; (3) poorly controlled group: 17-OHP≥12 ng/ml. The following studies were carried out. (1) The consistency of immunoassay and LC-MS/MS detection results was analyzed; (2) The serum concentrations of various steroid hormones in patients with 21-OHD and the control group were compared to explore the diagnostic value of multiple steroid hormones detection; (3) The concentration differences of 20 kinds of steroid hormones in 21-OHD patients with different therapeutic effects were compared to screen more valuable follow-up indicators.Results:(1) among the four indicators detected by LC-MS/MS and immunoassay, the consistency of T and 17-OHP was high. The concentrations of cortisol and Δ4-A determined by immunoassay were higher than those determined by LC-MS/MS. (2) Among the 20 kinds of steroid hormones secreted by adrenal gland detected by LC-MS/MS, 6 kinds of hormones were significantly higher and 6 kinds of hormones were significantly lower in 21-OHD patients compared with the control group, ,and 8 kinds of steroids showed no statistical difference. (3) 17-OHP decreased and 11-deoxycortisol increased in over-inhibition group, while 17-OHP, pregnenolone, progesterone, 17-hydroxypregnenolone, 21-deoxycortisol, Δ4-A and estrone increased in the poorly controlled group.Conclusions:LC-MS/MS can detect many kinds of steroid hormones at one time with better evaluate dimensions. During the follow-up, only 8 of the 20 hormones were closely related to the control status of patients, suggesting that unnecessary testing work could be reduced.

Analysis of CYP21A2 gene mutation and phenotype in patients with 21-hydroxylase deficiency / 中华内分泌代谢杂志

Objective To investigate the spectrum of CYP21A2 gene mutation and the correlation between genotype and phenotype in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas.Methods Genomic DNA was extracted from the peripheral blood samples of the proband.Locus-specific PCR,direct sequencing of PCR amplification products,and multiplex ligation-dependent probe amplification were applied to detect pathogenic gene CYP21A2 and the relationship between genotypes and phenotypes was analyzed.Results (1) Of 35 patients with 21-hydroxylase deficiency,25 were classified as salt-wasting phenotype and 10 were simple virilizing phenotype.(2) 69 mutant alleles were detected in a total of 70 alleles in 35 patients.Only one mutant allele was detected in one patient.Two mutant alleles were detected in all other patients,with the mutation detection rate 98.6％.(3) A total of 6 types of mutations were detected,of which c.293-13C/A＞G (I2G) was the most common,accounting for 57.1％ (40/70),followed by 18.6％ (13/70) for large gene deletion or conversion,and 14.3％ (10/70) for p.I173N.In addition,a novel mutation,c.949C＞T (p.R317X),which has not been reported previously,was detected as a pathogenic mutation.(4) Correlation analysis of genotype and phenotype in 35 children showed that the phenotype predicted by genotype was consistent with the actual salt-wasting phenotype in 31 children,and those in three children were inconsistent with the actual clinical phenotype.Conclusion The mutation characteristics of CYP21A2 gene in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas are slightly different from those reported in other regions in China.A mutation c.949C＞T has not been reported,which enriches the mutation spectrum of CYP21A2 gene and provide the foundation for genetic counseling and prenatal diagnosis.

New advances in diagnosis and treatment of 21-hydroxylase deficiency / 中华实用儿科临床杂志

21-hydroxylase deficiency (21-OHD) is an autosomal recessive hereditary disease, which results in reduced synthesis of aldosterone and cortisol and increased adrenal androgens due to lack or reduced activity of 21-hydroxylase during the synthesis of adrenal steroids.In recent years, the " backdoor" metabolic pathway of adrenal androgen synthesis and the role of adrenal specific 11-oxygenated C19 steroid in 21-OHD have been recognized, and some adrenal specific androgen sources are gradually becoming diagnostic and therapeutic indicators for 21-OHD.On basis of original glucocorticoid and salt corticosteroid replacement therapy, new drugs and treatments are gradually developed and applied in clinical practice.Nov, the latest progress in diagnosis, treatment and monitoring of 21-OHD is reviewed.

Non-classical 21-hydroxylase deficiency of a pedigree and related literature review / 中华内分泌代谢杂志

The clinical data of a patient with non-classical 21-hydroxylase deficiency ( 21-OHD) were retrospectively analyzed. The CYP21A2 gene analysis was performed on the patient and his family members by PCR-DNA direct sequencing. It was found that the proband had a heterozygous mutation [ point mutation:p.Ile173Asn, p. ( Ile237Asn, Val238Glu, Met240Lys ), p. Val282Leu, p. Gln319Ter, p. Arg357Trp, insertion mutation: p.Leu308Phefs?6, deletion/insert mutation: p. Arg484Profs]. Among the members of the family, the patient's eldest sister and three paternal members all carried the p.Val282Leu heterozygous mutation, and the patient's second sister and two maternal members carried the same p. Val282Leu homozygous mutation and other compound heterozygous mutations just as the proband. The proband presented a non-classical phenotype with ultimately normal height and fertility. It is suggested that the potential phenotype of the disease is related to the residual activity of its allele, and there exists a good genotype-phenotype correlation.

New advances in diagnosis and treatment of 21-hydroxylase deficiency / 中华实用儿科临床杂志

21-hydroxylase deficiency (21-OHD) is an autosomal recessive hereditary disease,which results in reduced synthesis of aldosterone and cortisol and increased adrenal androgens due to lack or reduced activity of 21-hydroxylase during the synthesis of adrenal steroids.In recent years,the " backdoor" metabolic pathway of adrenal androgen synthesis and the role of adrenal specific 11-oxygenated C19 steroid in 21-OHD have been recognized,and some adrenal specific androgen sources are gradually becoming diagnostic and therapeutic indicators for 21-OHD.On basis of original glucocorticoid and salt corticosteroid replacement therapy,new drugs and treatments are gradually developed and applied in clinical practice.Nov,the latest progress in diagnosis,treatment and monitoring of 21-OHD is reviewed.

Clinical features and genetic characteristics of 33 patients with simple virilizing form of 21-hydroxylase deficiency / 中华内科杂志

Objective To analyze the clinical features and genotypes of adult patients with simple virilizing form of 21-hydroxylase deficiency (SV 21-OHD).Methods This is a retrospective study including 33 patients with SV 21-OHD from January 2015 to March 2018 in the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine.Results The diagnostic age of the patients was (26.3± 6.5) years old.All patients presented with signs of masculinization,such as short stature (100％),clitoromegaly/microphallus (89.65％,26/29),undeveloped breasts (82.76％,24/29),deep voice (55.17％,16/29) and primary amenorrhea (89.65％,26/29).The serum levels of 17-hydroxyprogesterone (17-OHP),androstenedione (AD) and testosterone were significantly elevated in 90.9％,93.9％ and 91.2％ of the patients,respectively.Thirteen types of mutations were identified in CYP21A2 from these patients.Among them,I173N accounted for 40％ and I2 G accounted for 18.33％.Four patients were found with multiple mutations in CYP21A2.Conclusions Short stature,clitoromegaly/microphallus and primary amenorrhea are the most common clinical features in adult patients with SV 21-OHD.Serum levels of 17-OHP and AD are important indices for the diagnosis and monitoring of the patients.I173N and I2 G are the two most prevalent mutations in patients of the present study.Limitation of clinical recognition and delay in treatment contribute to the short stature of the SV 21-OHD patients.

An evaluation of the risk factors for orchidism and the efficacy of intensive corticosteroids therapy for the complicating testicular adrenal rest tumors in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency during the childhood and pubescent stages / 中华内分泌代谢杂志

Objective To explore the risk factors for orchidism and the curative efficacy of intensive corticosteroids therapy for the testicular adrenal rest tumors ( TART ) in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency ( 21OHD) during childhood and pubescent periods. Methods A total 12 cases (27 case-times) with TART were adopted in intensive corticosteroids therapy, 7 cases (7case-times) as control group without intensive therapy. Retrospective analysis following parameters:( 1) The testicular volume and the echogenic characteristics of TART by B-mode ultrasound. ( 2 ) Serum levels of FSH, LH, testosterone, 17-hydroxyprogesterone, androstendion, and inhibin-B were measured. ( 3 ) Orchidism was defined by one of following events:serum level of inhibin-B≤3rd％ for norm, and/or serum level of testosterone<1. 47 ng/ml for the individual which is already in TannerⅣstage. ( 4) The relationship between regression of TART and intensive therapy project. Results The prevalence of TART in 21-OHD was 28.18％during 2-18 years old, and the youngest age with TART was 2. 48 year of old. The regression rate of TART by intensive therapy was higher than that of the control significantly, 20/30 and 1/11(tumor-times) respectively(P=0.004). When the dose of dexamethasone≥30％ of total doses of corticosteroids, the regression rate of TART was higher than those less than 30％ ones, or adopted hydrocortisone alone, were both respectively 16/20 and 4/10(P=0.045). The risk factors for orchidism related to early diagnosis:The TARTs stages in diagnosis (≥stages III;P=0.003) , the tumor in size, hyperechogenicity in B ultrasound of the tumors ( P = 0. 003 ) . Inhibin-B is the earliest displayed biochemical warker for orchidism. Conclusions The TART could regress when got early diagnosis and adopted intensive corticosteroids therapy on time. Delayed diagnosis was the main risk factor for orchidism. For early diagnosis of TART, we suggest to conduct the scrotal ultrasound regularly started from 2 years of age.

Clinical diagnosis and treatment of 21-hydroxylase deficiency nonclassic congenital adrenal hyperplasia complicated by testicular adrenal rest tumors(one-case report) / 中国基层医药

Objective To assess the clinical diagnosis and treatment of 21-hydroxylase deficiency nonclassic congenital adrenal hyperplasia (NCCAH) complicated by testicular adrenal rest tumors (TART),thus to improve the recognition of the disease.Methods The clinical data of one patient of NCCAH with TART from our department in 2016 were retrospectively studied,and were analyzed combined with related literature,and the diagnosis was established for treatment.Results The patient was a 17 years old boy.At the age of seven began to appear the pubic hair,voice and other secondary sexual performance.More than their big penis development was significantly higher than their peers.At the age of 12 found bilateral testicular gradually enlarged and attendance.Physical examination:bilateral testicular swelling and a sense of nodules,hard texture,epididymis,normal bilateral varicocele.Laboratory exam indications showed increased levels of progesterone(P),adrenocorticotropic hormone(ACTH),17 hydroxyprogesterone(17α-OHP),aaldosterone(ALD),17-hydroxyl corticosteroids(17-OHCS),17-ketone corticosteroids(17-KS).By the ACTH stimulating test,17α-OHP was increased.Bilateral testes MRI:irregular bilateral testes,signal,see in space.Enhanced scan lesions uniform reinforcement,germ cell tumors to row.Adrenal CT:bilateral adrenal hyperplasia.Testicular biopsy:testicular adrenal genital syndrome tumor.Genetic testing:CYP21A2 heterozygous mutations.The above test results were diagnosed of NCCAH 21-OHD with TART.The patient was orally given 10mg/d prednisone 2 time.3 months after treatment,the 17α-OHP,CO and sex hormones returned to normal.Review the adrenal CT showed significant bilateral adrenal shrink,Pa/testis tubercle was narrow,but not obvious.Semen routine still suggested no sperm,considering the TART medical treatment effect was poor.Hence,further line tumor removed,followed up for 3 months without tumor recurrence at present.Conclusion NCCAH complex and varied clinical manifestations and hidden.Not easy to be noticed by patients and clinicians.For the early childhood in pubic hair growth accelerated leading to premature epiphyseal fusion and make the adult height is short stature consideration should be given to the disease.Further lines of sex hormones,adrenal related endocrine examination,genetic testing and ACTH stimulating test,etc.If concurrent bilateral testicular nodules,should consider to merge TART may.Testicular biopsy can be clear.Treatment can choose according to TART classification of glucocorticoid (a hormone steroid) or surgical treatment,concrete scheme should be individualized.

A case of 21-hydroxylase deficiency in Turner's syndrome and literature review / 中华内分泌代谢杂志

To improve the recognition and treatment of the combination of classical congenital adrenal hyperplasia (CAH) and Turner's syndrome. A case of 21-hydroxylase deficiency (21-OHD) in 45,X[3] / 46,XX [47] was reported,and the related literatures were reviewed. A 29-year-old woman with 45,X[3] / 46,XX[47] was referred with clitorimegaly and primary amenorrhea. Her height was 150 cm with a weight of 56 kg. Physical examination revealed a Tanner stage Ⅵ for both breast development and pubic hair development. She showed a little signs of Turner' s syndrome, such as cubitus valgus. Lab findings: sex hormones are significantly increased, including progesterone, testosterone, dehydroepiandrosterone, 17 hydroxyprogesterone, dihydrotestosterone, and androstendione. Enhanced CT scan showed bilateral adrenal hyperplasia. Gynecological ultrasound showed that the size of the uterus and ovary were near normal and the endometrium was not clear. By gene mutation screening, two mutation sites were found in CYP21A2 gene, such as IVS2-13C/ A→G and p. Ile173Asn( c. 518T→A). Taken together, the patient was diagnosed as a combination of 21-OHD and Turner syndrome. A total of ten patients associated with CAH in Turner's syndrome have been reported so far. The findings showed that routine karyotyping during investigations of patients presenting with ambiguous genitalia or with a diagnosis of CAH may reveal the concomitant presence of Turner's syndrome. We should make a definite diagnosis and give early treatment as soon as possible.

A case of 21-hydroxylase deficiency in Turner's syndrome and literature review / 中华内分泌代谢杂志

To improve the recognition and treatment of the combination of classical congenital adrenal hyperplasia (CAH) and Turner's syndrome. A case of 21-hydroxylase deficiency (21-OHD) in 45,X[3] / 46,XX [47] was reported,and the related literatures were reviewed. A 29-year-old woman with 45,X[3] / 46,XX[47] was referred with clitorimegaly and primary amenorrhea. Her height was 150 cm with a weight of 56 kg. Physical examination revealed a Tanner stage Ⅵ for both breast development and pubic hair development. She showed a little signs of Turner' s syndrome, such as cubitus valgus. Lab findings: sex hormones are significantly increased, including progesterone, testosterone, dehydroepiandrosterone, 17 hydroxyprogesterone, dihydrotestosterone, and androstendione. Enhanced CT scan showed bilateral adrenal hyperplasia. Gynecological ultrasound showed that the size of the uterus and ovary were near normal and the endometrium was not clear. By gene mutation screening, two mutation sites were found in CYP21A2 gene, such as IVS2-13C/ A→G and p. Ile173Asn( c. 518T→A). Taken together, the patient was diagnosed as a combination of 21-OHD and Turner syndrome. A total of ten patients associated with CAH in Turner's syndrome have been reported so far. The findings showed that routine karyotyping during investigations of patients presenting with ambiguous genitalia or with a diagnosis of CAH may reveal the concomitant presence of Turner's syndrome. We should make a definite diagnosis and give early treatment as soon as possible.

Management issues of congenital adrenal hyperplasia during the transition from pediatric to adult care / 소아과

Steroid 21-hydroxylase deficiency is the most prevalent form of congenital adrenal hyperplasia (CAH), accounting for approximately 95% of cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, tumor, osteoporosis, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and health-care providers. Psychosocial issues frequently affect adherence to glucocorticoid treatment. Therefore, the safe transition of adolescents to adult care requires regular follow-up of patients by a multidisciplinary team including pediatric and adult endocrinologists. The major goals for management of adults with 21-hydroxylase deficiency are to minimize the long-term complications of glucocorticoid therapy, reduce hyperandrogenism, prevent adrenal or testicular adrenal rest tumors, maintain fertility, and improve quality of life. Optimized medical or surgical treatment strategies should be developed through coordinated care, both during transition periods and throughout patients' lifetimes. This review will summarize current knowledge on the management of adults with CAH, and suggested appropriate approaches to the transition from pediatric to adult care.