Assessment of retinal thickness as a marker of brain masculinization in children with congenital adrenal hyperplasia: a pilot study.

Objective To investigate the relationship between brain masculinization and retinal thickness in children with congenital adrenal hyperplasia (CAH). Methods Forty-five patients with CAH aged between 4 and 18 years and 30 age-matched healthy controls were included in this prospective study. Macular area was examined with optical coherence tomography (OCT); central subfield thickness (CST), cube volume (CV) and macular retinal thickness (MT) were measured in each subject. A gender identity questionnaire (GIQ) was used for the evaluation of gender happiness index. Results Girls with CAH had a higher CV (p = 0.002) and MT (p = 0.003) than healthy girls. No significant difference was found between boys with CAH and healthy boys regarding the retinal thickness measurements. Mean CST, CV and MT were significantly higher in boys than in girls in the control group (p = 0.013, p < 0.001, respectively), but there was no significant difference in those parameters between girls and boys with CAH. The gender happiness index was not different between healthy boys and boys with CAH, but was significantly lower in girls with CAH than healthy girls (p = 0.01). Conclusions As retina is part of the brain, our finding appears to be a morphological evidence of the excess androgen exposure on brain structures in girls with CAH. In addition, we suggest using retinal thickness measurements as a marker of prenatal excess androgen exposure in future studies.

Virilized external genitalia in young girls: clinical characteristics and management challenges in a low-resource setting.

OBJECTIVE: Virilization of the external genitalia in young girls (VEG) manifests mostly as ambiguity of the genitalia and elicits concerns and uncertainties especially in settings with poor awareness. This study evaluates the profile and challenges of VEG in southeast Nigeria. METHODS: We analyzed 23 children with VEG managed in 2 referral centers in southeast Nigeria from June 2005 to January 2013. RESULTS: They presented at median age of 13.3 months (interquartile range [IQR] 3 months-3 years). The cases included 3 (13%) of Prader type 1, 6 (26%) of type 2, 11 (48%) of type 3, and 3 (13%) of type 4. Five of the Prader type 3 and all 3 cases of Prader type 4 were reared as male prior to presentation. Following evaluation, all the cases were assigned female gender at a mean age of 2.7 years (range 2 months-10.5 years). Appropriate feminizing genitoplasty was undertaken in all the cases and after a follow-up period of 3 months to 5 years (mean 2 years), 2 patients developed vaginal stenosis, and 3 cases had surgical wound infection. Poor awareness, delayed presentation, inadequate facilities, and lack of trained manpower were the challenges in the management of the cases. CONCLUSION: VEG in our setting is associated with delayed management. Focused health education and public awareness programs, and improved healthcare funding may improve outcome and minimize the need for gender reassignment.

External quality assessment of urinary steroid profile analysis.

BACKGROUND: Clinical samples were distributed on 10 occasions to six UK laboratories that perform urinary steroid profile analysis. Urine samples were from normal adult men and women, normal children and neonates. Samples from patients with Cushing's syndrome, virilization, adrenarche, obesity and congenital adrenal hyperplasia (21 and 17-hydroxylase defects) were also used for evaluation. METHODS: Samples were analysed by capillary column gas chromatography (all laboratories) after hydrolysis of conjugates and derivative formation (five laboratories) or by variation of 17-oxogenic steroid methodology (one laboratory). RESULTS: For each distribution of samples, the performance of the participants was compared for quantitative analysis, and user comments were summarized. Quantitative results showed variation without necessarily biasing the result. Comments varied considerably in length. The interpretations did not always lead to a clear diagnosis or advise about appropriate further tests. CONCLUSIONS: This pilot urine steroid profiling scheme has clearly identified the requirement for external quality assessment. It is now hoped to offer this scheme worldwide in collaboration with the European Research Network for the Evaluation and Improvement of Screening, Diagnosis and Treatment of Inherited Disorders of Metabolism (ERNDIM).

MIS/AMH in the assessment of cryptorchidism and intersex conditions.

Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), causes Mullerian duct involution during male sexual differentiation and also has a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific pattern of expression and its concentrations are sexually dimorphic in children; hence measurement of serum MIS/AMH helps in the evaluation of children with gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum MIS/AMH correlates with testicular tissue. A measurable value is predictive of undescended testes while an undetectable value is highly suggestive of anorchia. In minimally virilized phenotypic females, MIS/AMH helps differentiate between gonadal and non-gonadal causes of virilization. In children with intersex conditions, MIS/AMH values assist differential diagnosis: a value above the normal female range is predictive of testicular tissue, while an undetectable value is suggestive of absent testicular tissue. Thus, MIS/AMH is useful for delineating gonadal pathology and facilitates the differential diagnosis and management of children with diverse gonadal disorders.

Newborn screening for congenital adrenal hyperplasia in New Zealand.

OBJECTIVE: To evaluate the efficacy and efficiency of newborn screening for classic congenital adrenal hyperplasia (CAH) in New Zealand. DESIGN: All infants younger than 6 weeks of age identified by newborn screening between December 1984 and December 1993 were included. RESULTS: 23 cases of classic CAH (20 salt-losers) were identified. The incidence of classic CAH was 1 in 23,344. Screening identified 3 of 9 virilized female infants whose disease had not been detected clinically. Screening alone identified all 11 male infants. Notification of cases occurred at 11 +/- 3 days of age. There was a delay in treatment of the group identified by screening alone (n = 14) until 13 days of age (range, 4 to 35 days); at that time 11 infants had hyponatremia and 10 had hyperkalemia. Symptoms of vomiting, poor feeding, and shock were common after 10 days of age (2/10, < 10 days, and 8/8, 11 to 16 days of age). CONCLUSIONS: Newborn CAH screening is the only method of identifying male infants with classic CAH without a family history of CAH before symptoms develop, as well as a significant portion of overlooked virilized female infants. So that clinical or significant biochemical deterioration can be avoided, pediatrician notification of screening results and treatment should be started before 10 days of age.

The significance of the combined dexamethasone-HCG test for the assessment of hyperandrogenism.

The combined dexamethasone-HCG test was employed in 57 patients with excessive androgen secretion in order to differentiate the Stein-Leventhal syndrome from other disorders associated with increased androgen production. The patients were classified according to the test results. All except two of the patients gave a test result typical for the Stein-Leventhal syndrome.