Salt-wasting 21-hydroxylase Deficiency Research Articles

LBODP087 Unusual Presentation Of Salt-wasting 3-beta-hydroxysteroid Dehydrogenase-2 Deficiency

Abstract Background Biallelic pathogenic variants of HSD3B2 cause 3-beta-hydroxysteroid dehydrogenase-2 (3BHSD2) deficiency. 3BHSD2 is a rare cause of congenital adrenal hyperplasia (CAH) with two presentations in infancy including salt-wasting and a non-salt wasting with variable virilization of females and undervirilization of males (1). The salt-wasting form is usually not detected on newborn screen (NBS) and often presents with a potentially fatal adrenal crisis. We report a case of salt-wasting 3BHSD2, initially diagnosed as salt-wasting 21-hydroxylase deficiency following an abnormal newborn screen. Clinical case: A now 5.3 year old female was born at term, birthweight 3.44 kg, with no known pregnancy or neonatal problems. The first NBS at two days old was normal. The second NBS at 16 days old showed very high 17-hydroxyprogesterone (17OHP). She was clinically healthy with mild labial hyperpigmentation and rugation, and her clitoris was 1 cm in length. However, she had low sodium, elevated potassium, and elevated 17OHP with Na 127 mmol/L (RR 134-144), K 9.1 mmol/L (RR 3.5-5.2), and 17-OHP 5440 ng/dL (HPLC-MS/MS; RR 7-106). Glucocorticoid and mineralocorticoid replacement was initiated. She remained healthy with suppressed 17OHP and renin and full regression of virilization led to suspicion of the presumptive diagnosis of 21-hydroxylase deficiency. At 3 to 4 years old, CYP21A2 and CYP11B1 analyses were both resulted normal. At 4.5 years old following a two day therapeutic withdrawal test, her labs were as follows: ACTH 1940 pg/mL (RR 7-63), 17OHP 147 ng/dL (RR <299), DHEA 7240 ng/mL (RR 50-995), 17-hydroxypregnenolone 10405 ng/dL (RR ≤280) and pregnenolone 1352 ng/dL (RR 15-125). Her electrolytes were normal and all other adrenal precursors were within the normal reference range. Her diagnosis has since been revised to 3BHSD2 deficiency. At the time of submission, genetic confirmation is pending. Conclusion This case illustrates the variable presentation of this rare condition, and the value of genetic testing in CAH. The cause of the transient 17OHP elevation and mild virilization is uncertain; however, a possible relationship to persistent fetal adrenal is postulated.

A Case of Salt-Wasting 21-Hydroxylase Deficiency With Resistance to Aldosterone due to Urinary Tract Infection

Classic salt-wasting 21-hydroxylase deficiency (21-OHD) often requires fludrocortisone (FC) replacement. However, the optimal dose of FC varies between patients and the dose needs to be adjusted depending on the degree of symptoms. Further, the aldosterone resistance due to urinary tract infections causes salt-wasting symptoms. We recently encountered a patient with 21-OHD who required up to 0.36 mg/day of FC in order to control hyperkalemia despite adequate hydrocortisone (HC) administration. This condition was presumed to be due to aldosterone resistance complications associated with urinary tract infections. Thus, if the initial treatment of 21-OHD with HC and FC is resistant, then one should consider complications that may cause aldosterone resistance, such as urinary tract infections.

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants

Objective:Congenital adrenal hyperplasia (CAH) is the most common form of primary adrenal insufficiency in children. Neonatal screening for CAH is effective in detecting the salt-wasting (SW) form and in reducing mortality. In this study, our aim was to estimate the incidence of CAH in Turkey and to assess the characteristics and efficacy of the adopted newborn CAH screening strategy.Methods:A pilot newborn CAH screening study was carried out under the authority of the Turkish Directorate of Public Health. Newborn babies of ≥32 gestational weeks and ≥1500 gr birth weight from four cities, born between March 27-September 15, 2017 were included in the study. Screening protocol included one sample two-tier testing. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. The cases with positive initial screening were tested by steroid profiling in DBS using a liquid chromatography-tandem mass spectrometry method to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione as a second-tier test. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.5 were referred to pediatric endocrinology clinics for diagnostic assessment.Results:38,935 infants were tested, 2265 (5.82%) required second-tier testing and 212 (0.54%) were referred for clinical assessment, six of whom were diagnosed with CAH (four males, two females). Four cases were identified as SW 21-hydroxylase deficiency (21-OHD) (two males, two females). One male baby had simple virilizing 21-OHD and one male baby had 11-OHD CAH. The incidence of classical 21-OHD in the screened population was 1:7,787.Conclusion:The incidence of CAH due to classical 21-OHD is higher in Turkey compared to previous reports. We, therefore, suggest that CAH be added to the newborn screening panel in Turkey. The use of steroid profiling as a second-tier test was found to improve the efficacy of the screening and reduce the number of false-positives.

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia. Methods. Retrospective study during 23 years at outpatient clinic of a referral center. Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment. Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD.

A unique case of a child with two inherited salt-losing conditions

A Unique Case of a Child with Two Inherited Salt-Losing Conditions DS Gurudutt1, H McCabe2, C O’Brien2, DSF Matthews1 1 Dept of Paediatric Endocrinology, 2 Dept of Paediatric Respiratory Medicine Introduc*on Salt losing conditions can be challenging to manage well during infancy and childhood. Prolonged sodium depletion is known to be associated with growth failure and other problems in young animals1. We describe a unique case of a child with both Salt-Wasting 21-Hydroxylase Deficiency (SW21OHD) and Cystic Fibrosis (CF).

A Retrospective Analysis of the Growth Pattern in Patients with Salt-wasting 21-Hydroxylase Deficiency.

The objective of this study was to investigate the growth pattern of children with the salt-wasting form of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (21-OHD). We reviewed the medical records of 13 patients in whom salt-wasting 21-OHD was diagnosed during the first 2 mo of life at our hospital from 1980 through 2008. Six reached adult height. Growth patterns, bone age, biochemical data, and the hydrocortisone dose at each growth stage were analyzed retrospectively. The mean adult height was 155.1 ± 6.5 cm (mean ± SD) in females and 158.1 ± 7.1 cm in males. Although length at birth was normal or longer than the national mean in almost all patients, the mean height SD score of both boys and girls decreased to below 0 SD during infancy. Subsequently, both boys and girls transiently showed growth acceleration and reached their peak growth velocity at 3–10 yr of age. In conclusion, in addition to suppression of growth during infancy, there was inappropriate growth acceleration during childhood. Especially from 3 mo to 3 yr of age, decreasing the hydrocortisone dose in patients who exhibit slower growth may lead to satisfactory height outcomes. Also, strict adjustment of the hydrocortisone dose to avoid accelerated growth from childhood to adolescence might improve adult height outcomes of patients with 21-OHD.

Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency

OBJECTIVE:The protocols for glucocorticoid replacement in children with salt wasting 21-hydroxylase deficiency are well established; however, the current recommendation for mineralocorticoid replacement is general and suggests individualized dose adjustments. This study aims to retrospectively review the 9-∝-fludrocortisone dose regimen in salt wasting 21-hydroxylase deficient children who have been adequately treated during infancy.METHODS:Twenty-three salt wasting 21-hydroxylase deficient patients with good anthropometric and hormonal control were followed in our center since diagnosis. The assessments of cortisone acetate and 9-∝-fludrocortisone doses, anthropometric parameters, and biochemical and hormonal levels were rigorously evaluated in pre-determined intervals from diagnosis to two years of age.RESULTS:The 9-∝-fludrocortisone doses decreased over time during the first and second years of life; the median fludrocortisone doses were 200 μg at 0-6 months, 150 μg at 7-18 months and 125 μg at 19-24 months. The cortisone acetate dose per square meter was stable during follow-up (median = 16.8 mg/m2/day). The serum sodium, potassium and plasma rennin activity levels during treatment were normal, except in the first month of life, when periodic 9-∝-fludrocortisone dose adjustments were made.CONCLUSIONS:The mineralocorticoid needs of salt wasting 21-hydroxylase deficient patients are greater during early infancy and progressively decrease during the first two years of life, which confirms that a partial aldosterone resistance exists during this time. Our study proposes a safety regiment for mineralocorticoid replacement during this critical developmental period.

Use of PET/CT with Cosyntropin Stimulation to Identify and Localize Adrenal Rest Tissue following Adrenalectomy in a Woman with Congenital Adrenal Hyperplasia

Adrenalectomy is an experimental treatment option for select patients with congenital adrenal hyperplasia who have failed medical therapy. After adrenalectomy, adrenal rest tissue can remain in extraadrenal locations, cause recurrent hyperandrogenism, and be difficult to localize. The aim of the study was to investigate the usefulness of positron emission tomography/computerized tomography (PET/CT) in identifying adrenal rest tissue. A female with salt-wasting 21-hydroxylase deficiency who had bilateral adrenalectomy at age 17 yr presented with hyperandrogenism at age 32 yr. Pelvic magnetic resonance imaging and ultrasound imaging were nondiagnostic for the source of androgen production. A baseline F-18 labeled fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT scan showed no active uptake; however, a second scan preceded by a 250-μg cosyntropin injection identified three areas of active uptake near both ovaries. Subsequent ovarian venous sampling showed elevations in 17-hydroxyprogesterone, androstenedione, and 21-deoxycortisol in both ovarian veins compared to a peripheral vein at baseline and more so after cosyntropin administration. At laparoscopy, three well-circumscribed nodules (2.4 × 0.9 × 1.3 cm, 1.2 × 1.5 × 1.5 cm, and 2 × 1.5 × 1 cm) lying lateral to the fallopian tubes adjacent to the broad ligaments were removed. The paraovarian nodules and previously removed adrenal glands had similar histology and immunohistochemistry. Postoperatively, androgen concentrations were undetectable, with no response to cosyntropin stimulation. Patients with CAH after an adrenalectomy may experience recurrent hyperandrogenism due to adrenal rest tissue. 18F-FDG PET/CT with cosyntropin stimulation accurately identified adrenal rest tissue not visualized with conventional imaging, allowing for successful surgical resection.

Newborn screening for congenital adrenal hyperplasia in Srinagarind Hospital, Khon Kaen University, Thailand

Background: Salt wasting 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is the most common cause of adrenal insufficiency during neonatal periods. Newborn screening for CAH will improve case early detection and decrease associated morbidity and mortality. The previous nationwide incidence of CAH in 1999 was 1:19,521. To date, CAH newborn screening has not been included in national newborn screening program. Objective: We evaluated the incidence of CAH in newborns delivered at Srinagarind Hospital. Methods: Between September 2005 and June 2008, the filter paper blood spot 17-hydroxyprogesterone (17-OHP) tests were determined in newborns delivered at Srinagarind Hospital. The tests were concurrently performed with TSH and phenylketonuria screening in national newborn screening program of the Ministry of Public Health of Thailand. Re-evaluation with completed physical examinations, repeated blood test for serum 17-OHP and serum electrolytes were performed in newborns who had 17-OHP levels higher than cut-off values. CAH was indicated in patients who had abnormal high serum 17-OHP concentration with or without hyperpigmentation and/or ambiguous genitalia in affected females and/or electrolyte imbalance. Results: Five thousand seven hundred seventy one of 7,147 (80.74%) live births were screened for CAH. Fourteen infants (0.24%) were recalled for re-evaluation. Eight of fourteen (57.14% response rate) infants had the repeated blood tests. Abnormal elevated serum 17-OHP concentrations were found in two infants. Only one had clinical and laboratory findings indicative of CAH. The incidence of CAH was therefore 1:5,771. Conclusion: The incidence of CAH from newborn screening in Srinagarind Hospital was obviously higher than national incidence of Thailand. The implement of CAH screening for all neonates should be reconsidered. Keywords: Congenital adrenal hyperplasia, newborn screening, salt wasting, 17-hydroxyprogesterone, 21-hydroxylase deficiency

Normalization of height and excess body fat in children with salt-wasting 21-hydroxylase deficiency

To evaluate growth and body composition of patients with the salt wasting form of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and to compare them with healthy children. Twenty-one prepubertal patients (eight boys and 13 girls) between 2.1 and 10.2 years and 67 prepubertal healthy controls (36 boys and 31 girls) between 1.2 and 11.7 years were included. Weight, height, upper-arm circumference, skinfolds, body composition determined by bioimpedance, and bone age were measured. The following data were obtained from the medical records: parents' height, serum levels of 17-hydroxyprogesterone and Δ4-androstenedione, prescribed hydrocortisone doses, weight and length at birth, in the beginning of the treatment, and at 2 years. Patients had lower weight and length z scores at the first appointment compared with the same data at birth, showing recovery after the beginning of the treatment without advanced bone age. Mean height z score was higher in controls (0.28 ± 0.86) than in patients (-0.61 ± 0.99, p < 0.001); this difference disappeared when the patients' height was adjusted to their bone age (0.33 ± 1.68, p = 0.912). Patients had higher body mass index (p < 0.001), fat mass (p < 0.001), and fat mass index (p < 0.001) than controls. There was no difference in the skinfolds between the two groups (p = 0.157). Patients had growth recovery with mean height similar to the general population; however, they had higher body fat, which seems to be visceral, since there was no difference between the skinfolds of both groups.

Early hypertension and prolonged mineralocorticoid therapy discontinuation in a child with salt-wasting 21-hydroxylase deficiency

Early hypertension and prolonged mineralocorticoid therapy discontinuation in a child with salt-wasting 21-hydroxylase deficiency

Novel intronic CYP21A2 mutation in a Japanese patient with classic salt-wasting steroid 21-hydroxylase deficiency

Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder caused by the defective CYP21A2 gene that leads to various degrees of impaired secretion of both cortisol and aldosterone. In the present study, we analyzed the CYP21A2 gene in a Japanese male patient with 21-OHD and functionally characterized the mutant CYP21A2 gene . The patient presented with hypoglycemia and a salt-losing crisis during the neonatal period, and was diagnosed as having the salt-wasting form of 21-OHD based on the clinical and laboratory findings. Analysis of the CYP21A2 gene revealed that the patient is homozygous for a novel C to A conversion at −9 position of intron 9 (IVS9-9C>A) and that his parents are heterozygous for the IVS9-9C>A mutation. Transient expression of the IVS9-9C>A mutant CYP21A2 gene in COS-1 cells demonstrated that the mutation creates an aberrant splice acceptor site at −7 position of intron 9 and totally inactivates the authentic splice acceptor site of intron 9, which results in complete deficiency of 21-hydroxylase activity and loss of immunoreactive 21-hydroxylase protein. Clinical presentations of the patient as the severe salt-wasting form of 21-OHD are in good agreement with these results of the expression study. In conclusion, the patient is a homozygote for the novel intronic IVS9-9C>A mutation, which affects messenger RNA splicing and totally inactivates 21-hydroxylase to give rise to clinically manifest classic salt-wasting 21-OHD.

Congenital Adrenal Hyperplasia and Brain Magnetic Resonance Imaging Abnormalities

A 15-yr-old male patient with congenital adrenal hyperplasia (CAH) was referred to our department with a one year history of gradual worsening of tremors. He was diagnosed with salt-wasting 21-hydroxylase deficiency CAH at 40 d old and was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age. Detailed investigations failed to detect any cause for secondary hypertension. Physical findings on the current hospitalization objectified obesity, blood pressure of 150/80 mmHg, postural and action tremor, left cerebellar syndrome, reflex tetra pyramidal syndrome and mental decline. Brain magnetic resonance imaging (MRI) showed bilateral periventricular white matter hyperintensity that was more pronounced in the posterior regions and associated with cortico-subcortical atrophy and complete agenesis of the corpus callosum. All investigations for leukoencephalopathy were negative. A diagnosis of brain MRI abnormalities related to CAH was made, and the patient received symptomatic treatment of tremors. Our case report provides evidence of an increased frequency of brain MRI abnormalities in CAH. The literature suggests hormonal imbalance and exposure to excess exogenous glucocorticoids as main probable mechanisms. Thus, in clinical practice, CAH should be considered as one of the possible causes of brain white matter involvement associated with or without cerebral atrophy.

Severity of Virilization of External Genitalia in Japanese Patients with Salt-wasting 21-hydroxylase Deficiency

Females with salt-wasting (SW) 21-hydroxylase deficiency (21OHD) may present with mild external genitalia virilization, despite complete or almost complete enzyme inactivation. We therefore analyzed genotype/phenotype correlation in 13 Japanese female patients with SW 21OHD. Criteria for classification into the SW phenotype included history of a salt-losing crisis with documented hyponatremia, hyperkalemia, and markedly elevated plasma renin activity. Urologists and pediatricians determined the Prader genital stage and classified the location of the vaginal entrance into the common urogenital sinus as low, moderate, or high. CYP21A2 gene, coding for 21-hydroxylase, was analyzed with Southern blotting and direct sequencing. Genotypes were categorized into four mutation groups, based on the degree of enzymatic activity (N, complete enzyme inactivation; groups A, < 2%, B, 3-7%, and C > 30%). Basal androgen levels were available from only six out of thirteen patients, so we could not relate androgen levels with the severity of external genitalia virilization. We compared the degree of external genitalia virilization with genotype. The severity of external genitalia virilization varied from Prader stage 1 to 4. One patient who presented with Prader 1 had a genotype consistent with Group B. In addition, discordance between Prader classification and the location of the vaginal entrance was noted; one patient classified as Prader 4 showed low vaginal entrance, while another patient classified as Prader 3 showed high vaginal entrance. The degree of the impairment of 21-hydroxylase activity does not correlate with the severity of virilization of the external genitalia in female patients with the SW type of 21OHD.

Fractures and Bone Mineral Density in Adult Women with 21-Hydroxylase Deficiency

Patients with classical congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacological doses of glucocorticoids are an established risk factor for osteoporosis. Our objective was to evaluate bone mineral density (BMD), fracture prevalence, and markers of bone metabolism in adult females with CAH. This was a cross-sectional observational study. Tertiary care referral centers were used in this study. We studied 61 women, aged 18-63 yr, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt wasting (n = 27), simple virilizing (n = 28), and nonclassical 21-hydroxylase deficiency (n = 6). A total of 61 age-matched women were controls. History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dual-energy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide was studied. The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m2. Patients had lower BMD than controls at all measured sites (P < 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P < 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P < 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. beta-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058). Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.

Salt-wasting 21-hydroxylase deficiency congenital adrenal hyperplasia and pyloric stenosis in two Hispanic brothers

The differential diagnosis of vomiting and dehydration in the first month of life includes congenital adrenal hyperplasia (CAH) and pyloric stenosis (PS). Each diagnosis may mask the presence of the other, requiring careful evaluation and follow-up. We document the occurrence of CAH and PS in two Hispanic siblings.

Monitoring of menstrual cycles, ovulation, and adrenal suppression by saliva sampling in female patients with 21-hydroxylase deficiency

Objective: To investigate the correlation between menstrual cycles, ovulation, and adrenal suppression in congenital adrenal hyperplasia. Design: Prospective observational study. Setting: An academic outpatient clinic. Patient(s): Five females with salt-wasting 21-hydroxylase deficiency, aged 15.5 to 22.9 years; one had amenorrhea, one had irregular bleeding, and three had regular bleeding. Intervention(s): Daily morning saliva sampling for 40 to 280 days. Main outcome measure(s): Salivary levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), and androstenedione. Result(s): In the amenorrheic patient, the elevated P and 17-OHP levels decreased when the glucocorticoid dose was increased, and subsequently menarche occurred. The androstenedione levels were normal. The correlations between P and 17-OHP levels before and after menarche suggest that adrenal progesterone had prevented menarche. The patient with irregular bleeding showed slightly elevated androstenedione levels and increased levels of 17-OHP and P in an irregular pattern, without correlation in time with vaginal bleeding. Three patients with regular cycles showed a biphasic pattern of P levels, indicating ovulation. Conclusion(s): These longitudinal data support the hypothesis that menstrual cycling in females with 21-hydroxylase deficiency can be prevented or disturbed by elevated progesterone levels of adrenal origin, in the absence of androgen excess. Increasing glucocorticoid dose could suppress adrenal progesterone production, resulting in menarche.

Growth inhibition by glucocorticoid treatment in salt wasting 21-hydroxylase deficiency: in early infancy and (pre)puberty.

In patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, adult height is below target height. This may result from growth inhibition by glucocorticoid treatment. Previous studies suggest that glucocorticoids have a dose-dependent negative effect on growth in CAH patients and that this effect is age dependent. This study analyzed the correlation between glucocorticoid dose and growth in these patients. A retrospective study was carried out on growth data from 48 patients with classic salt-wasting 21-hydroxylase deficiency who all had been diagnosed in the first year of life and treated from the moment of diagnosis with glucocorticoids and mineralocorticoids. Analysis of the effect of prescribed glucocorticoid dose on growth was performed in age intervals, by analysis of covariance (ANCOVA). The dependent variables height for age z-score (HAZ), weight for age z-score (WAZ) (both corrected for secular trend), and weight for height z-score (WHZ), at 10 selected ages (1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 yr) were explained by 1) mean daily glucocorticoid dose per body surface in the preceding age interval; 2) HAZ, WAZ, or WHZ value at the beginning of the age interval; 3) HAZ, WAZ, or WHZ value 1 yr before the beginning of the considered age interval; and 4) midparental height (only for HAZ). ANCOVA showed that the daily glucocorticoid dose had significant negative effects on HAZ between the ages of 6 and 12 months and between the age of 8-10 and 12-14 yr (and a trend toward significance between 10-12 yr). The negative glucocorticoid effect on HAZ in the age interval of 12-14 yr was as large as in the interval between 6 and 12 months of age. Weight and weight for height were not significantly influenced by glucocorticoid dose in any of the age intervals. We conclude that in CAH patients in the first year of life and between the ages of 8 and 14 yr, there is a dose-dependent negative effect of glucocorticoids on linear growth. Therefore, the daily glucocorticoid dose in these periods should be sufficient to avoid androgen excess, but as low as possible to allow optimal linear growth and adult height.

Blood pressure in children and adolescents with congenital adrenal hyperplasia (21-hydroxylase deficiency): a preliminary report.

Classical congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, adrenal hyperandrogenism, impaired adrenal medullary function and insulin insensitivity. The latter along with the increased tendency towards obesity raises questions whether other cardiovascular risk factors are altered in CAH. To evaluate 24-h ambulatory blood pressure and obesity in patients with salt-wasting 21-hydroxylase deficiency diagnosed in the neonatal period and treated with hydrocortisone and 9alpha-fludrocortisone thereafter. Thirty-eight children (15 males) aged 11.2 years (range 6.1-18.2 years) underwent 24-h ambulatory blood pressure monitoring in the hospital setting. Standard anthropometric measures of height, weight and skinfold thickness were undertaken and body mass index (BMI) derived. All data were expressed as standard deviation scores (SDS) using the UK Growth Reference data. Mean daytime systolic blood pressure SDS (1.8, SD 1.1) was significantly higher than the reference population (P < 0.001), and 58% of patients (67% males; 52% females) had systolic hypertension. Mean daytime diastolic blood pressure SDS (0.8, SD 0.8) was also elevated and 24% (13% males; 37% females) had diastolic hypertension. Eighty-four per cent had absence of the physiological nocturnal dip in systolic blood pressure. Height SDS was similar to the reference population but BMI SDS was higher (P < 0.001). BMI SDS was related to systolic blood pressure SDS (r = 0.34; P = 0.03) and the effect was most marked in females where it was related to measures of truncal fat (r = 0.82; P = 0.002). Children with salt-wasting 21-hydroxylase deficiency have elevated 24-h ambulatory blood pressure and absence of the physiological nocturnal dip in blood pressure. These abnormalities are associated with a raised BMI, particularly in females. Regular measurement and plotting of blood pressure should be part of the management of children with classical CAH.

CLITOROPLASTY WITH PRESERVATION OF NEUROVASCULAR PEDICLES

In Brief Background: Optimal sexual function after surgical correction of clitoral hypertrophy requires an adequate postoperative innervation and vascular supply to the glans clitoris. Several clitoroplasty methods have been reported, but few describe preservation of dorsal and ventral neurovascular bundles in sexually mature women. Case: A 22-year-old woman with clitoromegaly caused by non–salt-wasting classic 21-hydroxylase deficiency presented for a second surgical procedure after an operation in her infancy. The erect clitoral length exceeded 7.5 cm. Clitoral reduction was done through a semicircular incision in the phallus, with preservation of dorsal and ventral neurovascular pedicles. Conclusion: Preservation of ventral and dorsal vascular pedicles at clitoroplasty had a satisfactory result in sexually mature women. Preservation of dorsal and ventral neurovascular pedicles can be accomplished at clitoroplasty.