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.

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).

scholarly journals High Reliability of Neonatal Screening for Congenital Adrenal Hyperplasia in Switzerland

2002 ◽  
Vol 87 (9) ◽  
pp. 4106-4110 ◽  
Author(s):  
Michael Steigert ◽  
Eugen J. Schoenle ◽  
Anna Biason-Lauber ◽  
Toni Torresani
Keyword(s):  
Positive Predictive Value ◽  
Congenital Adrenal Hyperplasia ◽  
Predictive Value ◽  
Neonatal Screening ◽  
Screening Program ◽  
High Reliability ◽  
Dried Blood Spots ◽  
Recall Rate ◽  
Adrenal Hyperplasia ◽  
Salt Wasting

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children’s Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.

scholarly journals Ten-year evaluation of a Neonatal Screening Program for Congenital Adrenal Hyperplasia

2014 ◽  
Vol 58 (7) ◽  
pp. 765-771 ◽  
Author(s):  
Marilza Leal Nascimento ◽  
Anísia Nhelety Baptista Cristiano ◽  
Tatiane de Campos ◽  
Masanao Ohira ◽  
Edson Cechinel ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Screening Program ◽  
Clinical Manifestations ◽  
The State ◽  
Adrenal Hyperplasia ◽  
Santa Catarina ◽  
Salt Wasting ◽  
Neonatal Screening Program ◽  
Treatment Onset

Objective Evaluate the Neonatal Screening Program (NSP) for congenital adrenal hyperplasia (CAH) of the Department of Health of the State of Santa Catarina (Secretaria de Estado da Saúde de Santa Catarina, SES/SC), and provide information to improve the program. Subjects and methods Descriptive, retrospective study of 748,395 children screened between January 2001 and December 2010. We analyzed the coverage of the NSP-SES/SC prevalence of CAH, child’s age when the first sample for 17-hydroxyprogesterone (17OHP) measurement was collected, levels of 17OHP, mean age at treatment onset and main clinical manifestations. Results The NSP-SES/SC covered 89% of the live newborns in the State. It diagnosed 50 cases of CAH, yielding an incidence of 1:14,967. Mean age at collection of the first sample was 7.3 days and mean level of 17OHP was 152.9 ng/mL. The most frequent manifestations were virilized genitalia with nonpalpable gonads, clitoromegaly and genital hyperpigmentation. In three girls, the genre established at birth was incorrect. The salt-wasting form was present in 74% of the cases. There was no occurrence of shock or death. Mean age at treatment onset in the salt-wasting form was 17.4 days compared with 54.9 days in those without the salt-wasting form of the disease. All children were treated with hydrocortisone, and those with salt-wasting CAH were also treated with fludrocortisone. Conclusions The incidence of CAH was 1 case to 14,967 live newborns. Collection of the first sample occurred outside the recommended time, resulting in delays in treatment onset.

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 SAT-098 The Impact of 17-OHP Cutoffs Determination in a Public Newborn Screening Program for Congenital Adrenal Hyperplasia in Southern Brazil: A Three Years’ Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Cristiane Kopacek ◽  
Paloma Wiest ◽  
Simone Martins de Castro ◽  
Poli Mara Spritzer
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
False Positive ◽  
Neonatal Screening ◽  
Screening Program ◽  
Southern Brazil ◽  
Adrenal Hyperplasia ◽  
Predictive Values ◽  
Live Births ◽  
Classic Cah ◽  
Weight Groups

Abstract Congenital adrenal hyperplasia (CAH), an autosomal recessive disease, is characterized by impairment of metabolic cortisol synthesis, with or without insufficient aldosterone production. It is caused by mutations in the CYP21A2 gene in approximately 90% of all cases, leading to 21-hydroxylase deficiency and androgen precursors elevation. The main disease marker is 17-hydroxyprogesterone (17-OHP). Early diagnosis through neonatal screening (NS) allows proper treatment and reduces mortality. In Brazil, the average incidence of the classic form of CAH ranges from 1: 7,500 to 1: 18,000 live births. Objective: To determine the 17-OHP cutoffs ​​for newborn screening to diagnose Congenital Adrenal Hyperplasia (CAH) in a Public Neonatal Screening Program in Southern Brazil. Materials and Methods: A retrospective, descriptive, cross-sectional study was carried out for analysis of dried blood test results on the 17-OHP paper filter of 317,745 newborns screened by a public neonatal screening center from May 2014 to April 2017. CAH-C was defined as NB with elevation of 17-OHP confirmed by retest and/or clinical evaluation, followed by genotype study. False positive cases (FP) were characterized by absence of genital alterations and/or loss of salt, with normalization of 17-OHP levels on retest. For the determination of the cutoffs ​​according to the four weight groups (WG) (WG1 ≤1,500 g, WG2 1,501 to 2,000 g, WG3 2,001 to 2,500 g and WG4 ≥ 2,501 g), the percentiles 97.5, 98.5, 99.5 and 99.8 were calculated. Sensitivity, specificity, positive predictive values ​​(PPV), negative predictive values ​​(NPV) were performed for the four WG. Results: Based on the descriptive analysis of the data, the incidence of CAH for the state of Rio Grande do Sul was 1:15,887 live births, with 20 cases of classic CAH being diagnosed during this period, and 17-OHP values ​​ranged from 32.50 ng/mL to 733.00 ng/mL in WG 2,000 g to 2,500 g and WG ≥ 2,501 g. No confirmed cases of CAH were detected for WG ≤ 1,500 g and 1,501 g at 2,000 g until the time of analysis of this study. Most (80.73%) newborns were caucasian and prematurity rate was 9.8% of the study population. The median and average (days) of first sample collection was 5 and 5.83, while for retest was 21 and 25.97 respectively. The cutoffs change from the 99th percentile to the 98.5 for the weight group between 2,001 g and 2,500 g and to the 99.8 for the other weight groups, decreasing false positive results and increasing specificity compared to current reference values ​​to identify classic CAH cases. Conclusion: The new 17-OHP cutoffs ​​specified were, for all weight groups, higher than currently used by this screening program. The calculation of reference values ​​from local population data and the combination of percentages prove to be an important tool for proper diagnosis of CAH cases and reduction of the number of FP newborns.

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