Height outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Objective:To retrospectively investigate the height outcome of patients with congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency(21-OHD).Methods:The 135 CAH patients with 21-OHD diagnosed in our hospital from Jan 1980 to Oct 2006 were retrospectively analyzed.The investigated parameters included final height(FH),FH standard deviation score(FH SDS),target height SDS(TH SDS),difference between TH and FH(TH-FH),FH SDS-TH SDS,the age of onset of sexual development,and the difference between bone age and chronological age(BA-CA)when patients got the FH.Results:Among the 135 patients,female/male=108/27.Mean FH was(156.8±5.4)cm(n=14)and(150.8±6.8)cm(n=76)for males and females,respectively.Mean FH SDS was(-0.6±0.8)(n=13)and(0.2±1.2)(n=54)for males and females,respectively.Sexual development began at(5.2±1.7)years old(y/o)(n=13)and(7.9±3.2)y/o(n=43)in males and females,respectively.Conclusions:The FH of CAH patients with 21-OHD was lower than that of the normal range.Effect of the disease on the height growth in male patients was more severe than that in females.All patients began sexual development much earlier than the normal age-matched group.Male patients began their sexual development even earlier.     

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a cross-sectional study of factors involved in bone mineral density

Glucocorticoids are essential in the treatment of patients with congenital adrenal hyperplasia (CAH). The opposite actions of glucocorticoids and androgens in bone mass achievement justify a study of bone mineral density (BMD) in these patients. We evaluated BMD in patients with CAH due to classic 21-hydroxylase (CYP21A2) deficiency and investigated the involvement of clinical and laboratory factors in the BMD. This study assessed the clinical and laboratory factors involved in BMD of 45 patients at the Pediatric Unit of Endocrinology, UNICAMP, who had been diagnosed as having classical CAH due to CYP21A2 deficiency including molecular characterization. The sample consisted of 28 females and 17 males; 23 salt-wasting (SW) and 22 simple virilizing (SV) cases, with average of 9.9 years (ranges, 5.1–16.3 years) when bone densitometry was performed. The DEXA method was used for calculating the areal BMD Z score in L2–L4. The variables were analyzed with reference to the BMD for chronological age (BMD/CA), height age (BMD/HA), and bone age (BMD/BA). The mean Z score for BMD/CA was 0.08 ± 1.21 (–2.55 to 2.64); it was 0.29 ± 1.33 (–2.01 to 4.00) for BMD/HA, and –0.90 ± 1.24 (–3.41 to 1.92) for BMD/BA. The BMD/CA was significantly lower in females and in patients on treatment for a long period and of more advanced chronological age. Weight and body mass index (BMI) Z scores showed a positive correlation with advanced BA. The higher the weight and BMI Z scores, the higher the BMD/HA. The BMD/BA values were significantly higher in the group in which BA was closer to CA. The BMD/BA value was significantly lower when compared to the value obtained with height and chronological ages. Sex, duration of treatment, weight, BMI, and bone age have an effect on areal BMD in patients with CAH due to CYP21A2 deficiency, which may be underestimated when evaluated in relation to CA and HA.     

Congenital adrenal hyperplasia: preliminary observations of the urethra in 9 cases.

PURPOSE: Congenital adrenal hyperplasia is the most common cause of androgen mediated virilization of the genitourinary tract in females. In our study relative lengths of the internal genital duct structure were compared with the degree of virilization of the external genitalia. MATERIALS AND METHODS: The records of 9 consecutive female patients with a median age of 2.6 years with congenital adrenal hyperplasia were studied. There were 4 normal females with a median age of 7.4 months who had a voiding cystourethrogram for urinary tract infection used as controls. The patients with congenital adrenal hyperplasia were stratified into groups as having mild, moderate or severe virilization based on preoperative photographs of external genitalia. By lateral voiding cystourethrograms the length of the proximal urethra, vagina and urogenital sinus was measured and standardized against the femoral metaphysis. The relative length of these internal genital structures was compared to the degree of virilization of the external genitalia. RESULTS: There were 4 cases classified as normal, and 2 mildly, 4 moderately and 3 severely virilized. The urogenital sinus appeared to lengthen, with increasing virilization of the external genitalia. There was no trend for the proximal urethra to shorten with increasing virilization. The vagina also seemed to shorten with increasing virilization. CONCLUSIONS: Our results suggest that the vagina enters the urogenital sinus at a fixed distance from the bladder neck. With increasing virilization, the majority of urethral lengthening occurs primarily distal to the vaginal opening, that is urogenital sinus lengthening.     

Genital sensation after feminizing genitoplasty for congenital adrenal hyperplasia: a pilot study

OBJECTIVE: To assess sensation in the clitoris and vagina in women with congenital adrenal hyperplasia (CAH) who have previously had genital surgery, and to evaluate sexual function in this group as the latter, and particularly the experience of orgasm, appear to be closely related to sensitivity. PATIENTS AND METHODS: Six women were recruited from a multidisciplinary clinic specialising in intersex conditions, and representing an initial cohort from a larger ongoing study. The patients were asked to complete a postal questionnaire with a specialized sexual function assessment. Thermal, vibratory and light-touch sensory thresholds were assessed in the clitoris and vagina using a genito-sensory analyser and Von Frey filaments. RESULTS: All six women had highly abnormal results for sensation in the clitoris. Only three of them had an introitus capable of admitting the vaginal probe, and the vaginal sensory data of all three were within the validated ranges. A self-administered sexual function assessment was completed by the five women who were sexually active. The scores indicated sexual difficulties, particularly in the areas of infrequency of intercourse and anorgasmia. CONCLUSIONS: The sensory data for all six women were outside the normal range for the clitoris. The results for the upper vagina, which had not had surgery, were within normal ranges. These findings suggest that genital surgery may disrupt sensory input. Sexual function also appears to be impaired and this may relate to the compromised sensitivity and restricted introitus. The possibility that women with CAH have deficient clitoral sensation ab initio cannot be excluded. These striking findings must be evaluated further in the light of the controversy about the issue of genital surgery in children with CAH.     

Bilateral ovarian cysts in a neonate with salt-wasting congenital adrenal hyperplasia

Congenital adrenal hyperplasia is by far the most common cause of ambiguous genitalia. The occurrence of ovarian cysts has not been previously described in the classical salt-wasting form of 21-hydroxylase-deficient congenital adrenal hyperplasia. We report a very rare case of bilateral ovarian cysts in one such neonate.     

Cardiac arrest in an infant with congenital adrenal hyperplasia

We report a 3-month-old boy who suffered an out-of-hospital cardiac arrest. During resuscitation, the medical team was informed that he was receiving hydrocortisone treatment. The possibility of adrenal insufficiency with hyperkalemic cardiac arrest prompted the administration of calcium, which resulted in the return of spontaneous circulation. The infant's diagnosis of congenital adrenal hyperplasia was not spontaneously mentioned by the parents. This case illustrates the importance of obtaining adequate parental information and considering hyperkalemia as a possible cause of cardiac arrest.     

迟发型先天性肾上腺皮质增生合并睾丸结节分析(附7例报告)

目的提高对迟发型先天性肾上腺皮质增生(CAH)合并睾丸结节的认识和早期诊治水平。方法对我院近10余年诊断的7例迟发型CAH合并睾丸结节患者的临床资料进行分析。结果7例男性患者平均年龄(21.4±5.3)岁,血促肾上腺皮质激素(ACTH)(17.2±2.5)pmol/L,17-羟孕酮(17-OHP)(1.9±0.4)pmol/L,24 h尿游离皮质醇(UFC)(25.0±9.0)nmol/24 h。其中有5例患者先诊断为迟发型CAH,行双侧睾丸B超检查发现双侧睾丸结节,1例因为疑诊Leydig细胞肿瘤行单侧睾丸切除,病理证实良性睾丸结节,另1例在B超下穿刺病理确诊。B超检查示双侧结节为6例而且均为多个结节,仅有1例为单侧结节。结节均为圆形或椭圆形,质地中等,仅有1例患者有压痛。共有3例患者治疗前进行精液常规检查,均表现为无精子症,经过足量糖皮质激素替代治疗12个月后,1例患者精液检查示精子总数达80×109/L,另2例患者无明显改善,但其睾丸结节缩小。结论迟发型CAH患者中,在高水平ACTH持续刺激下导致睾丸结节,但经过足量糖皮质激素替代治疗可使生精功能恢复正常,睾丸结节缩小甚至消退。在肾上腺性征综合征患者中睾丸结节往往被误认为肿瘤,甚至有患者行双侧睾丸切除术,因此要求临床医生增加对该病的认识,以免误诊误治。     

Prevalence and ultrasound patterns of testicular adrenal rest tumors in adults with congenital adrenal hyperplasia

BackgroundTesticular adrenal rest tumors (TARTs) are benign neoplasms affecting patients with congenital adrenal hyperplasia (CAH). The prevalence of TART in adult patients with CAH is not well known. Ultrasonography (US) is the main tool for diagnosing TART and the role of contrast-enhanced US (CEUS) is never investigated. The aim of this study was to evaluate the TART prevalence in adults with CAH, by stratifying patients according to disease phenotype and assessing the diagnostic performance of US, color Doppler (CD) US and CEUS.MethodsMale patients >16 years old with certain diagnosis of CAH who underwent US for TARTs, between December 2015 and September 2019 were prospectively enrolled. The control group included patients without CAH affected by testicular lesions at US other than TARTs.ResultsTARTs were identified in 16 of 52 patients (31%), of whom 15 (93.8%) displayed the salt-wasting (SW) form (P<0.001). The prevalence of TARTs in patients with the SW form was 54%. One patient with the non-classic (NC) form (6%) showed TART (likely the first documented case). The mean age of patients upon detection of TARTs was significantly younger compared with the control group (P<0.001); moreover, TARTs were bilateral in 15/16 patients (93.8%; P<0.001) and the largest lesion was more frequent in the medium third of testis in the TART group (87.5%), statistically different from the control group (P=0.013).ConclusionsTARTs almost exclusively affected patients with the SW form of CAH. Age at diagnosis and bilateralism are useful factors for achieving a correct diagnosis of TARTs in CAH adult patients.     

Leydig cell tumor of the spermatic cord in an adolescent affected by congenital adrenal hyperplasia

We report the first case of a patient with extratesticular Leydig cell tumor associated with congenital adrenal hyperplasia. An 18‐year‐old congenital adrenal hyperplasia patient presented with a palpable and asymptomatic right extratesticular mass. Color Doppler sonography confirmed the presence of a capsulated and vascularised lesion. Sieric tumor markers were negative. The patient underwent surgical scrotal exploration through an inguinal right incision. The mass, 18 mm in size and located within the spermatic cord, was removed and final pathology diagnosed a benign Leydig cell tumor.     

Gender assignment in female congenital adrenal hyperplasia: a difficult experience

OBJECTIVE: To report experience of gender (re)assignment in genotypic female (46XX) patients with congenital adrenal hyperplasia (f-CAH), a difficult and stressful experience if complicated with delayed presentation and inadvertent assignment. PATIENTS AND METHODS: Between 1983 and 2002, 70 patients with f-CAH were counselled for gender assignment. The age at diagnosis and operation, the degree of virilization, parental consanguinity, the gender preference of the families, and the factors governing the decision-making process were determined. RESULTS: Forty-one (59%) patients presented after the neonatal period. All parents had already assumed or were advised of a gender for their children, based on the suggestive appearance of the external genitalia. Consequently, 49 patients were reared as female and 21 as "male". Only nine of these "males" could be reassigned as females (mean age at presentation 7.87 months, sd 10.42). Twelve children had to be reared as "male"(mean age at presentation 55.8 months, sd 32.42) in compliance with the parents' and the study group's decision, and appropriate masculinizing reconstructive surgery was undertaken. The difference in the mean age of those reassigned as female and those who remained "male" was significant (P < 0.001). The parental consanguinity rate among the families was especially high in the 'male' patients. CONCLUSIONS It is extremely difficult to correct the gender of patients with f-CAH when they present at >2.5 years old. Furthermore, the delay in diagnosis and the male bias in choice of gender in our population might be a result of strong social pressures on families, influenced by cultural, traditional and economic factors.     

Congenital adrenal hyperplasia and lower urinary tract symptoms

OBJECTIVES: To assess urinary symptoms in adult women with congenital adrenal hyperplasia (CAH), as feminizing surgery in infancy is current standard practice for CAH and one of the indications for surgery is to reduce urinary symptoms. PATIENTS, SUBJECTS AND METHODS: In a case-control study, 19 women with CAH, of whom 16 had had childhood feminizing genital surgery, and age-matched women with no CAH, were evaluated. Subjects and controls completed the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire. RESULTS: Urge incontinence was reported in 13 (68%) patients and three (16%) controls (P = 0.003); stress incontinence was present in 47% and 26%, respectively (P = 0.31). Results from the controls were comparable with those documented in larger studies on normal populations. Nine of the patients felt that their urinary symptoms had an adverse effect on their lives, compared with only one of the controls (P = 0.008). CONCLUSION: Patients with a diagnosis of CAH are more likely to have significant urinary symptoms than normal controls. At present it is not clear whether this is a result of surgery or an effect of CAH. In at least two-thirds of patients surgery did not achieve the objective of reducing urinary symptoms.     

先天性肾上腺皮质增生的产前诊断及治疗

先天性肾上腺皮质增生是肾上腺皮质激素合成途径中酶缺陷所致,是导致新生儿两性畸形的常见原因之一。随着分子遗传学技术的发展,达到了对本病的早期产前诊断。早期官内干预治疗可以有效改善新生儿外生殖器畸形症状。本综述以21-羟化酶缺乏致先天性肾上腺皮质增生为例介绍近年来其产前诊断及早期宫内治疗的进展。     

先天性肾上腺皮质增生致女性假两性畸形的诊治(附四例报告)

目的　报告 4例先天性肾上腺皮质增生所致女性假两性畸形患者的激素替代治疗加手术整形的效果。　方法　 4例患者 ,年龄分别为 11、15、14、2 0岁。通过病史、超声、血清激素测定及染色体分析 ,确诊为先天性肾上腺皮质增生所致女性假两性畸形 ,利用会阴皮瓣行阴蒂和阴道成形术。　结果　术后短期应用雌孕激素调整月经周期 ,终生服用氢化可的松 (10～ 2 0mg ,bid)替代治疗。术后患者均月经来潮 ,乳房发育 ,阴道通畅未发生缩窄。　结论　此病易误诊为男性尿道下裂并双侧隐睾 ,诊断除详细体检外 ,还应进行血清激素测定、腹部超声检查及染色体分析。合理利用会阴和阴蒂皮瓣再造阴唇、阴道和阴蒂 ,同时加强围手术期处理 ,可以取得较满意的疗效。     

迟发型先天性肾上腺皮质增生伴睾丸肾上腺残余肿瘤临床分析(附1例报告)

目的:分析迟发型先天性肾上腺皮质增生(congenital adrenal hyperplasia,CAH)伴睾丸肾上腺残余肿瘤(testicular adrenal rest tumors,TART)的临床诊疗方法。方法:对2009年本院男科门诊收治的1例迟发型CAH伴TART的患者临床资料进行回顾性分析。结果:患者年龄15岁,身材矮小,皮肤黝黑,牙龈及外生殖器等皮肤色素沉着,第二性征呈成人型,双侧睾丸触及不规则肿大质硬结节。血促肾上腺皮质激素(ACTH)、尿17-酮类固醇(17-KS)、硫酸脱氢表雄酮(DHEA-S)、血孕酮(PRGE)明显升高。卵泡刺激素(FSH)、黄体生成素(LH)、皮质醇(CO)明显降低。小剂量地塞米松抑制试验ACTH、DHEA-S降至正常水平。影像学检查双侧肾上腺软组织密度影,右侧较为明显。双侧睾丸见不规则增大,左侧较为明显,信号不均,内见分隔,周围见液性信号环绕。病理学示嗜酸性胞质呈多角形或圆形,间质样细胞条索状排列,胞质内含有脂色素,免疫组化示排除睾丸间质细胞瘤。地塞米松替代治疗3个月后临床症状逐渐改善,睾丸结节左侧明显缩小,右侧消失,肾上腺增生结节9个月时消失。结论:根据以上临床表现和辅助检查,诊断为迟发型CAH伴TART,因肾上腺皮质功能不足致ACTH的持续大量分泌,最终导致肾上腺皮质增生和TART发生,通过足量的地塞米松替代治疗后TART缩小或消失,肾上腺增生结节消失,临床症状改善,各项实验室指标恢复正常。     

Infertility in a man with 21-hydroxylase deficient congenital adrenal hyperplasia

Congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency in men can cause profound oligospermia. The mechanism for this condition is overproduction of adrenal androgens, which in turn inhibit gonadotropin secretion. Men with a mild subclinical form of congenital adrenal hyperplasia may remain undiagnosed until adulthood. We report on a man who presented with infertility secondary to profound oligospermia. The treatment of this condition resulted in improved semen quality and subsequent conception. The importance of family history and determining whether precocious puberty was present, as well as obtaining appropriate laboratory tests is discussed.     

非典型先天性肾上腺皮质增生症误诊为多囊卵巢综合征二例报告

目的总结分析避孕药引起高孕酮血症患者的临床特征,探讨其诊治要点、鉴别诊断及治疗。方法两例患者因月经紊乱及不育而就诊,误诊为多囊卵巢综合征。口服避孕药治疗后孕酮值异常升高,以此为线索最终确诊为非典型先天性肾上腺皮质增生症。结果明确诊断后进行强的松类药物治疗,一例有3次试管婴儿治疗失败史的患者,治疗控制病情后一次试管婴儿即成功。另一例经强的松治疗后疗效明显,月经恢复正常。结论非典型先天性肾上腺皮质增生误诊为多囊卵巢综合征二例报告,提示早卵泡期血清孕酮水平的升高可作为诊断线索,口服避孕药使孕酮水平升高的案例非常罕见,发生这种情况必须进一步进行排除诊断。     

Testicular adrenal rest tumours in young adult males with congenital adrenal hyperplasia: prevalence and impact on testicular function

Testicular adrenal rest tumours (TARTs) have been described in patients with congenital adrenal hyperplasia (CAH). The aim of the study was to determine the prevalence of TARTs in patients with CAH, the associated factors and their impact on gonadal function. It is a prospective study concerning six young adult men with CAH, four cases with 21‐hydroxylase deficiency and two cases with 11‐hydroxylase deficiency. All patients were under glucocorticoid therapy. The mean age was 25 years (range: 20–31). All patients underwent a physical examination with testicular palpation, scrotal ultrasonography, a blood sample for serum testosterone, FSH, LH, inhibin B, ?4‐androstenedione and 17‐OH‐progesterone measurements and a semen analysis. Ultrasound revealed TARTs in four patients; three were bilateral. The mean tumour size was 6.3 ml (range: 0.02–14.1). The tumours were palpable in two cases. 17‐OH‐progesterone was <10 ng/ml in all cases. Decreased testosterone level was found in one case. The semen analysis revealed azoospermia in one case and poor semen quality in four patients. TARTs were common and associated with impaired spermatogenesis.