Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography–tandem mass spectrometry

Janzen, Nils; Sander, Stefanie; Terhardt, Michael; Steuerwald, Ulrike; Peter, Michael; Das, Anibh M.; Sander, Johannes

doi:10.1016/j.steroids.2011.07.013

Cited by 59 publications

(46 citation statements)

References 31 publications

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“…However, by using 17OHP cutoff values adjusted by birthweight and/or gestational age, it was possible to reduce the recall rate from 1.12% to 0.5% in Germany [28]. Other newborn CAH screening protocols with second tier steps such as re-measuring first-tier elevated 17-OHP levels by liquid chromatography-tandem mass spectrometry [38], by steroid profiling of steroids such as 17-OHP, androstenedione, and cortisol [39][40][41][42] and/or by molecular-genetic analyses [43] improve screening effectiveness. According to the results of Kosel et al, further reduction of the recall rates of around 90% without loss of sensitivity was possible by analyzing the CYP21A2-gene as second-tier [44].…”

Section: Problems With False-positive and False Negative-resultsmentioning

confidence: 99%

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Dörr

Odenwald²,

Nennstiel-Ratzel³

2015

IJNS

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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 cut-off 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.

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Section: Problems With False-positive and False Negative-resultsmentioning

confidence: 99%

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Dörr

Odenwald²,

Nennstiel-Ratzel³

2015

IJNS

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“…1), in contrast with the only two assays previously reported to use DBSs for the determination of these analytes [16,17]. Our assay was successfully applied in the cross-border cooperation for newborn screening of CAH.…”

Section: Discussionmentioning

confidence: 95%

“…This requires separation of the isobaric analytes 21-deoxycortisol (21-Deox) and 11-deoxycortisol (11-Deox), specific to these two forms of CAH [1,2,3]. Most previous assays for 21-Deox and 11-Deox did not allow an analysis of DBSs [9,10,11,12,13,14,15], and those which did achieved acceptable but not baseline resolution of these isobaric compounds [16,17]. …”

Section: Introductionmentioning

confidence: 99%

Concurrent Confirmation and Differential Diagnosis of Congenital Adrenal Hyperplasia from Dried Blood Spots: Application of a Second-Tier LC-MS/MS Assay in a Cross-Border Cooperation for Newborn Screening

et al. 2015

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Background/Aims: Newborn screening for congenital adrenal hyperplasia (CAH) is generally performed using 17- hydroxyprogesterone dissociation-enhanced, lanthanide fluorescence immunoassay (DELFIA®). The primary screening results must be confirmed due to high false-positive rates; however, the need to obtain a separate specimen can hamper early recognition, differential diagnosis and treatment. We aimed to develop a single liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that allows both the confirmation and differential diagnosis of CAH using the same dried blood spot (DBS) as in primary screening. Methods: An LC-MS/MS assay for cortisol, 21-deoxycortisol, 11-deoxycortisol, 4-androstenedione and 17-hydroxyprogesterone was developed, validated and applied to a total of 163 DBS samples tested positive in primary newborn screening in a cross-border cooperation. Results: Excellent baseline resolution and reliable determination of all analytes were achieved in DBS samples following simple sample preparation without derivatization. Of a total of 163 DBS samples tested positive in primary screening, the 21-hydroxylase-deficient form of CAH was confirmed in 1 sample. Conclusions: The present LC-MS/MS assay was successfully applied as a second-tier test in a cross-border cooperation for newborn screening. The assay allows concurrent confirmation and differential diagnosis of CAH and can be performed on the same DBS samples as in primary screening, enabling early diagnosis and treatment.

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“…104 Mass spectrometric methods have been introduced as second tier tests. [105][106][107][108] Transient high 17-OHP has been seen in premature infants. 109 Since the clinical condition will require life-long treatment, a sound confirmation of the defect is required.…”

Section: Clinical Uses and Limitations Of 17-ohp Measurements Classicmentioning

confidence: 99%

17-Hydroxyprogesterone in children, adolescents and adults

Honour

2014

Ann Clin Biochem

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17-Hydroxyprogesterone (17-OHP) is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase. An inherited deficiency of 21-hydroxylase leads to greatly increased serum concentrations of 17-OHP, while the absence of cortisol synthesis causes an increase in adrenocorticotrophic hormone. The classical congenital adrenal hyperplasia (CAH) presents usually with virilisation of a girl at birth. Affected boys and girls can have renal salt loss within a few days if aldosterone production is also compromised. Diagnosis can be delayed in boys. A non-classical form of congenital adrenal hyperplasia (NC-CAH) presents later in life usually with androgen excess. Moderately raised or normal 17-OHP concentrations can be seen basally but, if normal and clinical suspicion is high, an ACTH stimulation test will show 17-OHP concentrations (typically >30 nmol/L) above the normal response. NC-CAH is more likely to be detected clinically in females and may be asymptomatic particularly in males until families are investigated. The prevalence of NC-CAH in women with androgen excess can be up to 9% according to ethnic background and genotype. Mutations in the 21-hydroxylase genes in NC-CAH can be found that have less deleterious effects on enzyme activity. Other less-common defects in enzymes of cortisol synthesis can be associated with moderately elevated 17-OHP. Precocious puberty, acne, hirsutism and subfertility are the commonest features of hyperandrogenism. 17-OHP is a diagnostic marker for CAH but opinions differ on the role of 17OHP or androstenedione in monitoring treatment with renin in the salt losing form. This review considers the utility of 17-OHP measurements in children, adolescents and adults.

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Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography–tandem mass spectrometry

Cited by 59 publications

References 31 publications

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Concurrent Confirmation and Differential Diagnosis of Congenital Adrenal Hyperplasia from Dried Blood Spots: Application of a Second-Tier LC-MS/MS Assay in a Cross-Border Cooperation for Newborn Screening

17-Hydroxyprogesterone in children, adolescents and adults

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