Cognitive and Behavioral Aspects of Congenital Adrenal Hyperplasia

2010 ◽  
Author(s):  
Sheri A. Berenbaum
Keyword(s):  
Adrenal Gland ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Late Onset ◽  
Adrenal Hyperplasia ◽  
Inborn Errors ◽  
Salt Wasting ◽  
Additional Information ◽  
Classic Cah ◽  
Simple Virilizing

Congenital adrenal hyperplasia (CAH) is a family of genetic disorders involving enzyme defects in the synthesis of cortisol in the adrenal gland (for reviews and additional information, see Grumbach, Hughes, and Conte 2003; Merke and Bornstein 2005; Speiser 2001). The most common defect is in 21-hydroxylase (21-OH), which accounts for 90% of cases of CAH and results in physical signs of androgen excess. Congenital adrenal hyperplasia is heterogeneous, with the phenotype usually classified as nonclassic (NC), a mild, often late-onset form, or classic, a severe form. Classic CAH consists of the salt-wasting (SW) and simple-virilizing (SV) forms, which reflect degree of aldosterone deficiency (mineralocorticoid disturbance), with a SW:SV ratio of approximately 2:1. It is likely that the three forms of CAH (NC, SV, SW) reflect an underlying continuum. Individuals with classic CAH due to 21-OH deficiency are unable to produce enough cortisol to suppress the release of adrenocorticotropic hormone (ACTH). This results in an accumulation of cortisol precursors, leading to increased production of androgen from the adrenal gland beginning early in gestation and continuing until the disorder is diagnosed and treated with cortisol replacement, usually in the newborn period. Classic CAH is usually detected through newborn screening in the United States and in some other countries (Therrell 2001). Untreated classic CAH causes rapid growth (and ultimately short stature), precocious puberty, and physical virilization. Aldosterone deficiency can cause hypoglycemia, and potentially life-threatening episodes of hyponatremia and hyperkalemia. The defects in CAH also have consequences for behavior and cognition, as will be discussed throughout this chapter. Individuals with nonclassic CAH due to 21-OH deficiency do not have the significant cortisol deficiency characteristic of classic CAH. Nevertheless, they do have increased androgen, usually beginning in childhood or in adulthood. The excess androgen is associated with an increased likelihood of early puberty, infertility, and in women, hirsutism, menstrual irregularities, and polycystic ovaries. Classic CAH is one of the most common inborn errors of metabolism and the most common cause of ambiguous genitalia. Data from newborn screening show the incidence to be approximately 1 in 15,000 live births with some variations across countries and ethnic groups (Therrell 2001).

Evaluation of the Dutch neonatal screening for congenital adrenal hyperplasia

2019 ◽  
Vol 104 (7) ◽  
pp. 653-657 ◽  
Author(s):  
Annelieke A A van der Linde ◽  
Yvonne Schönbeck ◽  
Hetty J van der Kamp ◽  
Erica L T van den Akker ◽  
Mirjam E van Albada ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
High Specificity ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Period 2 ◽  
Classic Cah ◽  
Screening Sensitivity ◽  
Simple Virilizing ◽  
Screening Result

BackgroundIn 2002, a nationwide screening for congenital adrenal hyperplasia (CAH) was introduced in the Netherlands. The aim of our study is to evaluate the validity of the neonatal screening for CAH and to assess how many newborns with salt-wasting (SW) CAH have already been clinically diagnosed before the screening result was known.MethodsRetrospective, descriptive study. The following data of patients with positive screening results since implementation of the screening programme were collected (1 January 2002 up until 31 December 2013): gestational age, sex, diagnosis, clinical presentation and contribution of screening to the diagnosis.ResultsIn the evaluated period, 2 235 931 newborns were screened. 479 children had an abnormal screening result, 133 children were diagnosed with CAH (114 SW, 14 simple virilizing (SV)), five non-classic CAH. During this period, no patients with SW CAH were missed by neonatal screening (sensitivity was 100%). After exclusion of 17 cases with missing information on diagnosis, specificity was 99.98% and positive predictive value was 24.7%. Most false positives (30%) were attributable to prematurity. Of patients with SW CAH, 68% (71/104) patients were detected by neonatal screening and 33 (33/104) were clinically diagnosed. Of girls with SW CAH, 38% (14/37) were detected by neonatal screening and 62% (23/37) were clinically diagnosed.ConclusionThe Dutch neonatal screening has an excellent sensitivity and high specificity. Both boys and girls can benefit from neonatal screening.

scholarly journals Nonvirilized Genitalia in 3 Female Newborns With the Salt-Wasting Congenital Adrenal Hyperplasia Phenotype

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Lauren Yauch ◽  
Allison Mayhew ◽  
Veronica Gomez-Lobo ◽  
Kim Shimy ◽  
Kyriakie Sarafoglou
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Cortisol Secretion ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Salt Wasting ◽  
Newborn Screen ◽  
Classic Cah ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Abstract Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a form of primary adrenal insufficiency characterized by impaired cortisol secretion and elevated androgen production, is the leading cause of atypical genitalia in the female newborn. Females with classic CAH, either salt-wasting or simple-virilizing form, usually present at birth with atypical genitalia ranging from clitoromegaly to male-appearing genitalia, due to in utero to elevated androgens (androstenedione and testosterone). Females with mild nonclassic CAH usually present with typical genitalia. Proving the importance of always keeping an open mind for exceptions to the rule, we report on 3 female newborns who presented with the nonvirilized genitalia, salt-wasting CAH phenotype and genotype most consistent with simple-virilizing CAH. It is only through a positive newborn screen identifying the females with CAH that they were diagnosed before developing adrenal and/or salt-wasting crisis.

scholarly journals Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry

2021 ◽  
Author(s):  
Heike Hoyer-Kuhn ◽  
Angela Huebner ◽  
Annette Richter-Unruh ◽  
Markus Bettendorf ◽  
Tilman Rohrer ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Daily Practice ◽  
Linear Regression Models ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Comprehensive Information ◽  
Custom Made ◽  
Classic Cah ◽  
Simple Virilizing

Objective: Treatment in classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH, but recommendations regarding dosage/administration are inconsistent. Aim of the study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicentre CAH registry. Design: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. Methods: A custom-made electronic health record software is used at the participating centres. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. Results: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean [lower-upper quartiles] daily HC dose [mg/m² body surface area] was 19.4 [18.9-19.8] for patients <3 months (n=329), 15.0 [14.6-15.3] age ≥3-12 months (n=463), 14.0 [13.7-14.3] age 1-5.9 years (n=745), 14.2 [14.0-14.5] age 6 years-puberty entry (n=669), and 14.9 [14.6-15.2] during puberty-18 years (n=801). Fludrocortisone was administered in 74.1% of patients (median daily dosage 88.8 µg). Conclusion: Our analyses demonstrated still a high proportion of children with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

scholarly journals Adverse Outcomes and Economic Burden of Congenital Adrenal Hyperplasia Late Diagnosis in the Newborn Screening Absence

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Mirela Costa De Miranda ◽  
Luciana Bertocco de Paiva Haddad ◽  
Guiomar Madureira ◽  
Berenice Bilharinho de Mendonca ◽  
Tania A S S Bachega
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Adverse Outcomes ◽  
Late Diagnosis ◽  
Adrenal Hyperplasia ◽  
Gnrh Analog ◽  
Mortality And Morbidity ◽  
Salt Wasting ◽  
Life Years ◽  
Simple Virilizing

Abstract Objective To establish short- and long-term adverse outcome frequencies related to a late diagnosis of congenital adrenal hyperplasia (CAH) in the absence of newborn screening (NBS) and to determine respective treatment costs, which have never been reported. Design A retrospective analysis of a CAH cohort diagnosed without NBS. Methods We evaluated medical record data concerning 195 patients (141 females) diagnosed with CAH through clinical suspicion and confirmed using hormonal and CYP21A2 analysis, who were followed from 1980 to 2016 at Sao Paulo University. We measured mortality, dehydration, mental impairment frequencies, and hospitalization length outcomes in the salt-wasting form; the frequency of genetic females raised as males in both forms, frequency of depot GnRh analog (GnRha) and GH therapies in the simple virilizing form, and related outcome costs were calculated. Results Mortality rates and associated costs, varying from 10% to 26% and from $2,239,744.76 to $10,271,591.25, respectively, were calculated using the Brazilian yearly live-births rate, estimated productive life years, and gross domestic product. In the salt-wasting form, 76% of patients were hospitalized, 8.6% were mentally impaired, and 3% of females were raised as males (total cost, $86,230/salt-wasting patient). GnRha and growth hormone were used for 28% and 14% of simple virilizing patients, respectively, and 18% of females were raised as males (preventable cost, $4232.74/simple virilizing patient). Conclusions A late CAH diagnosis leads to high mortality and morbidity rates, notably increasing public health costs, and may result in physical and psychological damage that is not easily measurable.

scholarly journals High Prevalence of Reduced Fecundity in Men with Congenital Adrenal Hyperplasia

2009 ◽  
Vol 94 (5) ◽  
pp. 1665-1670 ◽  
Author(s):  
Nicole Reisch ◽  
Linda Flade ◽  
Michael Scherr ◽  
Marietta Rottenkolber ◽  
Francesco Pedrosa Gil ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Semen Quality ◽  
Semen Analysis ◽  
Hormonal Control ◽  
Inhibin B ◽  
The Other ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
High Prevalence ◽  
Simple Virilizing

Abstract Context: Testicular adrenal rest tumors (TARTs) are regarded to contribute to the high prevalence of subfertility in males with congenital adrenal hyperplasia (CAH). Objectives: Our objectives were to evaluate reduced fecundity and its possible causes in well-controlled adult males with CAH, and to investigate diagnostic tools for improved treatment monitoring with respect to fertility outcomes. Design: In a cross-sectional study at the Department of Endocrinology at the University Hospital München, Germany, 22 adult male CAH patients (15 salt wasting and seven simple virilizing, age 19–48 yr) were clinically assessed according to their hormonal control. We performed testicular ultrasound (22 of 22), magnetic resonance imaging (18 of 22), and a semen analysis (19 of 22) in the participants. Results: All patients had a pathological semen analysis. TART prevalence was 10 of 22 (eight salt wasting, two simple virilizing). Poor therapy control was present in five patients, and all five had TARTs. Of the other 17 well-controlled patients with normal or suppressed adrenal androgens and 17-hydroxyprogesterone levels, five presented with TARTs. There was a significant correlation between sperm concentration and functional testicular volume (r = 0.70; P = 0.002), TART volume (r = −0.70; P = 0.036), as well as inhibin B levels (r = 0.75; P &lt; 0.0001), respectively. In several men, hormonal control parameters suggested hypogonadism, with glucocorticoid overtreatment as a relevant factor for poor semen quality. Conclusions: Poor semen parameters are common in male CAH patients. TARTs, most likely reflecting undertreatment, as well as inhibin B are important indicators of fecundity. On the other hand, long-term glucocorticoid overtreatment also seems to contribute to low semen quality.

scholarly journals Impact of Newborn Screening on Clinical Presentation of Congenital Adrenal Hyperplasia

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1035
Author(s):  
Rūta Navardauskaitė ◽  
Kornelija Banevičiūtė ◽  
Jurgita Songailienė ◽  
Kristina Grigalionienė ◽  
Darius Čereškevičius ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Sensitivity And Specificity ◽  
Serum Potassium ◽  
Predictive Value ◽  
Clinical Presentation ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Screening Programs

Background and Objectives: The main reason for Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) is to prevent adrenal insufficiency that can lead to life-threatening conditions. On the other hand, screening programs are not always sensitive and effective enough to detect the disease. We aimed to evaluate impact of the national NBS on the clinical presentation of patients with CAH in Lithuania. Materials and Methods: A retrospective study was performed on data of 88 patients with CAH from 1989 to 2020. Patients with confirmed CAH were divided into two groups: (1) 75 patients diagnosed before NBS: 52 cases with salt-wasting (SW), 21 with simple virilising (SV) and two with non-classical (NC) form; (2) 13 patients diagnosed with NBS: 12 cases with SW and 1 case with SV form. For the evaluation of NBS effectiveness, data of only male infants with salt-wasting CAH were analysed (n = 36, 25 unscreened and nine screened). Data on gestational age, birth weight, weight, symptoms, and laboratory tests (serum potassium and sodium levels) on the day of diagnosis, were analysed. Results: A total of 158,486 neonates were screened for CAH from 2015 to 2020 in Lithuania and CAH was confirmed in 13 patients (12 SW, one–SV form), no false negative cases were found. The sensitivity and specificity of NBS program for classical CAH forms were 100%; however, positive predictive value was only 4%. There were no significant differences between unscreened and screened male infant groups in terms of age at diagnosis, serum potassium, and serum sodium levels. Significant differences were found in weight at diagnosis between the groups (−1.67 ± 1.12 SDS versus 0.046 ± 1.01 SDS of unscreened and screened patients respectively, p = 0.001). Conclusions: The sensitivity and specificity of NBS for CAH program were 100%, but positive predictive value—only 4%. Weight loss was significantly lower and the weight SDS at diagnosis was significantly higher in the group of screened patients.

scholarly journals Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

2016 ◽  
Vol 174 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Brigitte Odenwald ◽  
Uta Nennstiel-Ratzel ◽  
Helmuth-Günther Dörr ◽  
Heinrich Schmidt ◽  
Manfred Wildner ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hospital Admissions ◽  
Discharge Summary ◽  
Severe Illness ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency

ObjectiveTo evaluate adrenal crises after the start of treatment up to the age of 6 years in children with classic congenital adrenal hyperplasia (CAH).DesignAnalysis of data extracted from a population-based prospective long-term follow-up study of children detected in neonatal screening.MethodsData of 102 Bavarian children with classic CAH due to 21-hydroxylase deficiency were analyzed, using parental questionnaires and medical reports. Parent-reported hospital admissions of children diagnosed with acute health impairment were included in the analysis if salt loss (hyponatremia) or hypoglycemia was documented in the discharge summary.ResultsA total of 74 children (72.5%) had no report of hospital admissions with salt loss or hypoglycemia during the observational period. However, in 27.5% of the children, 22 salt-wasting crises (seven of these also with low blood glucose) and 16 hypoglycemic episodes without salt loss were reported. Furthermore, the cumulative incidence for seizures was elevated; 13 children experienced seizures during hyponatremia or hypoglycemia. Most adrenal crises were triggered by infections, often with inappropriate emergency management, but in 11 cases hypoglycemia occurred unexpectedly, without evidence of severe illness and without any management errors. Frequency of adrenal crises was 6.5 per 100 patient years (95% CI: 4.6–8.8).ConclusionsCrisis prevention remains a permanent challenge for families and physicians caring for children with classic CAH. Expert care and compliance with emergency recommendations are crucial. Further research on the interactions among glucocorticoid deficiency, adrenomedullary dysfunction, and glucose metabolism is necessary for the prevention of hypoglycemia, especially in young CAH patients.

Sign in / Sign up

Export Citation Format

Share Document