Biochemical aspects of congenital adrenal hyperplasia (original) (raw)
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Clinical endocrinology, 2016
The primary concern related to CAH newborn screening (NBS) is the high rate of false-positive results (FPR) associated with prematurity; false-negative results (FNR) can also occur due to precocious sample collection OBJECTIVE: To determine the neonatal 17-hydroxyprogesterone (N17OHP) normal range in newborns in Sao Paulo using different references according to age and birth-weight, and to establish the optimal NBS cut-off levels METHODS: N17OHP levels from 271,810 newborns (NBs) according to sample collection time (G1: 48-<72 hs and G2: ≥72 hs) and birth-weight (≤1,500g, 1,501-2,000g, 2,001-2,500 and >2,500g) were evaluated. N17OHP was measured by an immunofluorimetric assay, and serum 17OHP was measured by liquid chromatography-mass spectrometry. Affected and asymptomatic NBs with persistently increased 17OHP levels were submitted to CYP21A2-sequencing RESULTS: N17OHP levels in G1 were lower than G2 in all birth-weight groups (p<0.001). The FPR rate in G1/G2 was 0.2% usin...
Neonatal screening for congenital adrenal hyperplasia
Archives of Disease in Childhood, 1983
SUMMIARY Capillary blood samples from 42 930 infants born in the Italian region of Emilia-Romagna were collected for 17-hydroxyprogesterone radioimmunoassays on days 2, 3, 4, 5, 6, and 7, or between days 7 and 15 of life. A microfilter paper method modified from that of Pang et al.1 was used for this assay. Pathologic values of 17-hydroxyprogesterone were found in 5 infants giving an incidence in this homogeneous Caucasian population of 1:8586. We also investigated 17-hydroxyprogesterone values in relation to the day of sampling and the possible correlation between 17-hydroxyprogesterone values and birthweight and gestational age. We concluded that neonatal screening for congenital adrenal hyperplasia caused by 21-hydroxylase deficiency was possible by this method and that the infants' maturity and the particular day of collection of the samples affect the values but not the validity of the screening.
International Journal of Neonatal Screening, 2015
Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessively inherited disorders of cortisol biosynthesis in the adrenal cortex. More than 95% are based on a defect in the CYP21A2 gene causing 21-hydroxylase deficiency. Newborn screening (NBS) for CAH by means of 17-hydroxy-progesterone (17-OHP) determination in dried whole blood on filter paper has been introduced as part of the NBS in many countries worldwide. The goals of CAH screening are early detection of the severe, salt-wasting form, therefore prevention of adrenal crisis or death, early detection of the simple virilizing form, and prevention or shortening of the period of incorrect gender assignment in females. Methodological problems of false-positive samples, especially in pre-term infants, can be corrected by adapting the cutoff values for 17-OHP to birth weight, gestational age and age at the time of collection and by performing a second tier screening. Despite a positive voting for newborn CAH screening by the European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society, it is obvious that the acceptance of CAH screening varies worldwide.
Journal of Clinical Laboratory Analysis, 2002
A rapid, simple, and specific method was developed for the diagnosis of congenital adrenal hyperplasia (CAH) from dried blood spots on newborn screening cards based on high-performance liquid chromatography/ electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). The usefulness of 17α-hydroxyprogesterone (17OH-P) determination on dried filter-paper blood samples from patients with CAH caused by 21-hydroxylase deficiency was evaluated. The LC/MS/MS detection of 17OH-P was rapid, <4 min. The intra-and interday accuracy and precision of the method were <7%. Our procedure maintained good linearities (R 2 > 0.992) and recovery rate (>83%). We used this new method to directly determine the 17OH-P levels in dried blood specimens from abnormal children of various ages, with a detection limit of 20 ng/ml (~240 pg), to avoid the time-consuming derivatization steps required by the gas-chromatography/ mass spectrometry (GC/MS) method. Four dried filter-paper blood samples of CAH patients (three girls and one boy, 1-14 years old) were all quantified in an LC/MS/MS study and revealed high 17OH-P levels (>90 ng/ ml). After treatment, all of the elevated 17OH-P levels either decreased or disappeared. Compared with CAH patients, 17OH-P was nearly undetectable (<20 ng/ml) in the normal infants by LC/MS/MS. This LC/MS/MS assay is not only useful for both diagnosis and monitoring of treatment of CAH in all other age groups, it also can be used as a screening test for CAH infants. In this study, we provided the first data on 17OH-P in dried blood specimens affected with CAH using HPLC/ESI-MS/MS.
Neonatal Screening Program for Congenital Adrenal Hyperplasia in a Homogeneous Caucasian Population
Annals of the New York Academy of Sciences, 1985
The considerable variation in the reported incidence of congenital adrenal hyperplasia (CAH)'-7 may be explained partially by the lack of a valid screening method. To evaluate the true prevalence of CAH, we examined all the newborns in the Emilia Romagna region during a period of approximately three years. Emilia Romagna is situated in northern Italy and is a homogeneous sample of a Caucasian population.
Monitoring congenital adrenal hyperplasia using blood spot 17-hydroxyprogesterone assay
The Southeast Asian journal of tropical medicine and public health, 2003
Blood spots taken by finger prick collected on filter paper cards can provide an option to venous blood extraction in monitoring 17-OHP levels in children with Congenital Adrenal Hyperplasia (CAH). This study was done to evaluate the usefulness of blood spot 17-OHP in monitoring disease control in pre-pubertal children with CAH, to correlate it with simultaneously extracted venous 17-OHP levels, and to compare blood spot levels of children with CAH with that of normal non-virilized children. Nine pre-pubertal children with CAH (1 male; 8 females) were enrolled in the study. Age, sex, growth velocity, height age and bone age were determined. Simultaneous venous and blood spot specimens were taken between 0800 and 0900 hours. Nine pre-pubertal, age- and sex-matched normal non-virilized children served as controls. COAT-A-COUNT was used to measure venous 17-OHP levels, and AutoDELFIA Neonatal 17alpha-OH-progesterone was employed for blood spot specimens. Mean age of patients with CAH w...
Arquivos Brasileiros de Endocrinologia & Metabologia, 2011
OBJECTIVE: To evaluate weight-adjusted strategy for levels of neonatal-17OHP in order to improve newborn screening (NBS) efficiency. SUBJECTS AND METHODS: Blood samples collected between 2-7 days of age from 67,640 newborns were evaluated. When N17OHP levels were > 20 ng/mL, and a second sample was requested. We retrospectively analyzed neonatal-17OHP levels measured by Auto DELFIA- B024-112 assay, grouped according to birth-weight: G1: < 1,500 g, G2: 1,501-2,000 g, G3: 2,000-2,500 g and G4: > 2,500 g. 17OHP cutoff values were determined for each group using the 97.5th, 99th, 99.5th and 99.8th percentiles. RESULTS: 0.5% of newborns presented false-positive results using the cutoff level > 20 ng/mL for all groups. Neonates of low birthweight made up 69% of this group. Seven full-term newborns presented congenital adrenal hyperplasia (CAH) and, except for one of them, 17OHP levels were > 120 ng/mL. Only the 99.8th percentile presented higher predictive positive value (2...
The Turkish journal of pediatrics
To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP < 10 ng/ml. A cutoff of 1.55 ng/ml for basal 17-OHP together with bone SDS > 2 in those with lower basal ...
Neonatal screening programme for congenital adrenal hyperplasia in a homogenous Caucasian population
Journal of Inherited Metabolic Disease, 1986
The considerable variation in the reported incidence of congenital adrenal hyperplasia (CAH 1, McKusick 20191) may be explained partially by the lack of a valid screening method. To evaluate the true prevalence of CAH, we examined all the newborns in the Emilia Romagna region of Italy during a period of approximately three years. Emilia Romagna is situated in northern Italy and our sample there was of a homogenous Caucasian population. For the screening programme we took advantage of the specimens collected on filter paper for neonatal screening of hypothyroidism and phenylketonuria. For the 17-OH-progesterone assay, the microfilter paper method modified from that of Pang and colleagues Piazzi et al., 1981; was used.
Diagnosis of 21-hydroxylase deficiency in newborn infants by GC-MS of urinary steroids
Journal of Paediatrics and Child Health, 1988
In a study using gas chromatography-mass spectrometry (GC-MS) on urine specimens from 16 normal infants and 16 infants with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (aged 1 day to 4 weeks), the major steroids recognized in all infants were: 16a-hydroxydehydroepiandrosterone, 168-hydroxy-dehydroepiandrosterone, 16-oxo-androstenediol, androstenetriol, 15~,17~dihydroxy-pregnenolone and 16a-hydroxy-pregnenolone.