STEROID EXCRETION PATTERNS IN URINE FROM TWO BOYS IN THE NEONATAL PERIOD WITH CONGENITAL ADRENAL HYPERPLASIA DUE TO 21-HYDROXYLASE DEFICIENCY

1972 ◽  
Vol 71 (2) ◽  
pp. 353-364 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Sven Gustafsson ◽  
Patrick Olin
Keyword(s):  
Mass Spectrometry ◽  
Neonatal Period ◽  
Clinical Signs ◽  
Normal Subjects ◽  
Gas Chromatography Mass Spectrometry ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Steroid Excretion ◽  
21 Hydroxylase Deficiency ◽  
Adrenal Secretion

ABSTRACT Gas chromatography-mass spectrometry was used in a study of the excretion of steroids in urine in two normal boys one month of age and in two boys of the same age with clinical signs of 21-hydroxylase deficiency. A similar pattern of 3β-hydroxy-Δ5-steroids – including 3β,21-dihydroxy-5-pregnen-20-one and 5-pregnene-3β,20α,21-triol – was unexpectedly found in the mono- and disulphate fractions of urine from both the normal subjects and the patients. However, only the patients excreted saturated steroids in the urine indicating the adrenal secretion of progesterone and 17α-hydroxyprogesterone. The results indicate the presence in the adrenal cortex of at least two separate 21-hydroxylase systems, one active on pregnenolone and one on 17α-hydroxyprogesterone. Furthermore, the excretion of large amounts of saturated steroids in the urine of the patients indicates a high activity of adrenal 3β-hydroxy-Δ5-steroid oxidoreductase.

scholarly journals Mass spectrometry: an essential tool to be used in discrimination between causes of congenital adrenal hyperplasia, and its benefits versus radioimmunoassay

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Heba Asfour ◽  
Heba Baz ◽  
Hend Soliman ◽  
Yasmine Elshiwy ◽  
Marwa Elsharkawy ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Congenital Adrenal Hyperplasia ◽  
Predictive Accuracy ◽  
Cost Effective ◽  
Tandem Mass ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract Background Measurement of multiple steroids, 17 hydroxyprogesterone, 11 deoxycortisol, and 21 deoxycortisol, is required to discriminate between congenital adrenal hyperplasia due to 21 hydroxylase deficiency and that due to 11 beta hydroxylase deficiency. This work aims at the selection of the more appropriate, cost-effective method among either mass spectrometry or radioimmunoassay for the quantitation of the previous steroids. In this study, blood samples were collected from 31 patients that were newly diagnosed with congenital adrenal hyperplasia; 17 hydroxyprogesterone and 21 deoxycortisol were assayed using tandem mass spectrometry. Eleven deoxycortisol was assayed using 2 methods: radioimmunoassay and tandem mass spectrometry. Results Measuring 11 deoxycortisol using tandem mass spectrometry could significantly discriminate patients with 11 beta hydroxylase deficiency from those with 21 hydroxylase deficiency (p = 0.002), whereas radioimmunoassay failed (p = 0.095). Moreover, the former was highly predictive of 11 beta hydroxylase deficiency at a cutoff ≥ 11 ng/ml with 100% sensitivity and 92.3% specificity. Simultaneous measurement of 21 deoxycortisol and 11 deoxycortisol and their enrollment in an equation yielded an overall predictive accuracy 96.8% for diagnosis of CAH due to both enzymatic deficiencies. Conclusions Measurement of 11 deoxycortisol using mass spectrometric approach is mandated as a part of work up to differentiate types of congenital adrenal hyperplasia.

scholarly journals Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia

2009 ◽  
Vol 161 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Paolo Cavarzere ◽  
Dinane Samara-Boustani ◽  
Isabelle Flechtner ◽  
Michèle Dechaux ◽  
Caroline Elie ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
False Positive ◽  
Neonatal Screening ◽  
False Positive Rate ◽  
Clinical Signs ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Hydroxylase Gene ◽  
21 Hydroxylase Deficiency ◽  
L 14

ObjectiveNeonatal screening for congenital adrenal hyperplasia (CAH) is characterized by a high false-positive rate, mainly among preterm and low birth weight infants. The aims of this study were to describe a subgroup of infants with transient serum hyper-17-hydroxyprogesteronemia (hyper-17-OHPemia) and to compare them with false positive and affected by 21-hydroxylase deficiency newborns.MethodsWe retrospectively analyzed the clinical data of all newborns positive at CAH neonatal screening, who were referred to our hospital to confirm the diagnosis from 2002 to 2006. They were submitted to clinical investigations and blood tests to evaluate 17-hydroxyprogesterone (17-OHP), renin, and electrolyte levels. CAH-unaffected newborns with increased serum 17-OHP were submitted to strict follow-up monitoring, which included an ACTH-stimulating test and genetic analysis of the 21-hydroxylase gene, until serum 17-OHP decreased.ResultsThirty-seven newborns with gestational ages ranging from 33 to 40 weeks were studied. Eight infants (three male and five female) were affected by CAH (serum 17-OHP: 277.5 (210–921) nmol/l), 14 (ten male and four female) were false positives (17-OHP: 3.75 (0.3–8.4) nmol/l), and 15 (ten male and five female) showed a serum hyper-17-OHPemia (17-OHP: 15.9 (9.9–33) nmol/l). No mutations of the 21-hydroxylase gene were found in infants with hyper-17-OHPemia and their serum 17-OHP levels were normalized by the third month of life.ConclusionWe identified a population of infants with transient serum hyper-17-OHPemia, and no clinical signs of disease or 21-hydroxylase gene mutations. No further investigations are necessary after birth in these newborns if 17-OHP levels decrease, other confirmatory tests such as ACTH-stimulation test or genotyping analysis are necessary only if symptoms appear.

scholarly journals Hormonal diagnosis of 21-hydroxylase deficiency in plasma and urine of neonates using benchtop gas chromatography-mass spectrometry

2000 ◽  
Vol 165 (3) ◽  
pp. 679-683 ◽  
Author(s):  
SA Wudy ◽  
M Hartmann ◽  
J Homoki
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Cord Blood ◽  
Plasma Concentrations ◽  
Gas Chromatography Mass Spectrometry ◽  
Confirmatory Test ◽  
Hydroxylase Deficiency ◽  
Chromatography Mass Spectrometry ◽  
Steroid Profiling ◽  
21 Hydroxylase Deficiency

We aimed at measuring the first plasma concentrations of 17-hydroxyprogesterone (17OH-P) determined by benchtop isotope dilution/gas chromatography-mass spectrometry (ID/GC-MS) in term neonates with or without 21-hydroxylase deficiency. Plasma samples from normal cord blood specimens (n=30), unaffected neonates (n=38) and neonatal patients with classical 21-hydroxylase deficiency (eight salt-wasters, three simple virilizers) were analyzed. Steroid profiling of random urinary specimens by GC-MS served as a confirmatory test for 21-hydroxylase deficiency. 17OH-P (nmol/l) in cord blood plasma lay between 11.66 and 75.92 (median 24.74). It declined shortly after birth. In the first 8 days of life, the time that screening for 21-hydroxylase deficiency is performed, 17OH-P ranged between undetected levels and an upper limit of 22.87 (median 4.11). Thereafter (days 9-28) its concentrations lay between 2.18 and 20.30 (median 6.22). Except one simple virilizer, all other patients with 21-hydroxylase deficiency had clearly elevated plasma 17OH-P at the time that screening for 21-hydroxylase deficiency would be performed. We suggest ID/GC-MS, which provides the highest specificity in steroid analysis, for checking suspicious concentrations of 17OH-P in neonates and underscore the potential of urinary steroid profiling by GC-MS as a rapid, non-invasive and non-selective confirmatory test for congenital adrenal hyperplasia.

Radioimmunoassay for 21-deoxycortisol: clinical applications

1985 ◽  
Vol 108 (4) ◽  
pp. 537-544 ◽  
Author(s):  
B. Gueux ◽  
J. Fiet ◽  
M. T. Pham-Huu-Trung ◽  
J. M. Villette ◽  
M. Gourmelen ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Normal Subjects ◽  
Ethyl Acetate Fraction ◽  
Adrenal Hyperplasia ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Heterozygous Carriers ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract. A radioimmunoassay for 21-deoxycortisol is described. The immunogen, 21-deoxycortisol-3-(O-carboxymethyl) oxime-bovine serum albumin, was prepared, the antisera raised against it were studied and the reliability of the assay was checked. The antiserum selected cross-reacted with 11-deoxycortisol (0.08%), corticosterone (0.25%), cortisol (0.6%) and 17-hydroxyprogesterone (1.6%). 21-deoxycortisol was separated by celite partition chromatography and eluted in the 70/30 (v/v) isooctane/ethyl acetate fraction together with 11-deoxycortisol and corticosterone. The radioimmunoassay was used to measure 21-deoxycortisol in the plasma of normal subjects and patients with androgen excess. In normal subjects, men (0.19 ng/ml ± 0.08) and women (0.18 ng/ml ± 0.09) had similar basal levels (mean ± sd). One hour after ACTH stimulation, these levels were increased by a factor of 3.5. In 7 patients treated for classical congenital adrenal hyperplasia associated with 21-hydroxylase deficiency, basal values varied between 9.1 and 39.9 ng/ml (measured at 8 a.m.). In 7 untreated women with lateonset congenital adrenal hyperplasia (with 21-hydroxylase deficiency), ACTH-stimulated levels were increased to between 9 and 25.5 ng/ml. In 14 heterozygous carriers of 21-hydroxylase deficiency, diagnosed by HLA genotyping, all ACTH-stimulated levels were well above the highest corresponding levels in normal subjects, whereas 17-hydroxyprogesterone levels remained within the normal range in 9 of the cases.

A neonatal mass-screening for congenital adrenal hyperplasia in Japan

1984 ◽  
Vol 107 (4) ◽  
pp. 513-518 ◽  
Author(s):  
Kazuhiko Shimozawa ◽  
Sumitaka Saisho ◽  
Nobuchika Saito ◽  
Jun-ichi Yata ◽  
Yoshio Igarashi ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Mass Screening ◽  
Screening Program ◽  
Clinical Signs ◽  
Plasma Sodium ◽  
Adrenal Hyperplasia ◽  
Perinatal Complications ◽  
Hydroxylase Deficiency ◽  
Urine Metabolites ◽  
21 Hydroxylase Deficiency

Abstract. A pilot neonatal mass-screening for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) was performed in the western region of Shizuoka Prefecture, Japan, using a simplified radioimmunoassay method for 'Disc-17-hydroxyprogesterone (17-OHP)' determination. The results obtained during a 30-month period indicated that 3 infants out of the 34314 neonates examined were proved to have 21-OHD, and the incidence of homozygotes and heterozygotes were estimated to be 1:11438 and 1:54, respectively. At the time of recall, the concentrations of plasma 17-OHP and 21-deoxycortisol and their urine metabolites as well as plasma sodium levels were quite applicable to diagnosis, while the clinical signs that may be manifest in 21-OHD were of little value in this connection. Prematurity and perinatal complications of neonates tended to give false-positive results, being secondary to the function of the residual foetal adrenal cortex and non-specific stimulatory effects of various stresses. Despite several technical and practical problems to be solved, the present study demonstrated the importance and validity of a neonatal mass-screening program for CAH.

A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing

2019 ◽  
Vol 32 (3) ◽  
pp. 253-258 ◽  
Author(s):  
Li-fei Gong ◽  
Xiao Gao ◽  
Nan Yang ◽  
Jin-qi Zhao ◽  
Hai-he Yang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Clinical Characteristics ◽  
Skin Pigmentation ◽  
Clinical Signs ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Feeding Difficulties ◽  
21 Hydroxylase Deficiency

Abstract Background A provisionary screening programme for 21-hydroxylase deficiency (21-OHD) was initiated in Beijing in 2014. The aim of this study was to investigate the incidence and the associated clinical characteristics of neonatal congenital adrenal hyperplasia (CAH) in Beijing and to provide evidence-based guidance for its application in CAH screening. Methods Live birth newborns (n=44,360) were screened for CAH in Beijing from July 2014 to April 2018. The levels of 17-hydroxyprogesterone (17-OHP) in the blood were estimated using the time-resolved fluoroimmunoassay. Neonates with a positive result and a level >30 nmol/L of 17-OHP were called for a retest. CAH was diagnosed based on further laboratory findings combined with clinical signs, such as weight loss, feeding difficulties, skin pigmentation, and atypical genitalia. Through a review of medical records, the clinical findings including molecular data were reported. Results Of the 44,360 neonates screened, 280 cases were deemed positive. Of these, 203 neonates were recalled for further tests and six patients (three boys and three girls) were diagnosed with CAH. Five cases of classic salt-wasting and one case of simple virilising 21-OHD were identified. The incidence of CAH in Beijing was 1:7393. The most frequent 21-OHD mutation was c.293-13C/A>G. Conclusions The incidence of CAH in Beijing was higher than the national average. The results support the need for neonatal CAH screening in Beijing. This pilot study demonstrates the clinical characteristics of 21-OHD through newborn screening. Early detection and treatment through neonatal screening may reduce mortality rates and optimise developmental outcomes.

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