scholarly journals Congenital Adrenal Hyperplasia: clinical symptoms and diagnostic methods

2018 ◽  
Vol 65 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Rafał Podgórski ◽  
David Aebisher Aebisher ◽  
Monika Stompor ◽  
Dominika Podgórska ◽  
Artur Mazur
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Clinical Symptoms ◽  
Hydroxysteroid Dehydrogenase ◽  
Diagnostic Methods ◽  
Screening Tests ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Screening Programs ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

The aim of this paper is a straightforward presentation of the steroidogenesis process and the most common type of congenital adrenal hyperplasia (CAH) 21-hydroxylase deficiency as well as the analytical diagnostic methods that are used to recognize this disease. CAH is a family of common autosomal recessive disorders characterized by impaired adrenal cortisol biosynthesis with associated androgen excess due to a deficiency of one or more enzymes in the steroidogenesis process within the adrenal cortex. The most common and prototypical example of this group of CAH disorders (90-95%) are caused by 21-hydroxylase deficiency. Less frequent types of CAH are 11β-hydroxylase deficiency (up to 8% of cases), 17α-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, P450 oxidoreductase deficiency and StAR deficiencies. In the 21-hydroxylase and 11β-hydroxylase deficiency only adrenal steroidogenesis is affected, whereas a defect in 3β-hydroxysteroid dehydrogenase or 17α-hydroxylase also involves gonadal steroid biosynthesis. Many countries have introduced newborn screening programs based on immunoassays measuring 17-hydroxyprogesterone from blood spots used for other neonatal screening tests which enable faster diagnosis and treatment of CAH. Currently, chromatographic techniques coupled with mass spectrometry are gaining in popularity due to an increase in the reliability of test results.

scholarly journals Failure of Cortisone Acetate Treatment in Congenital Adrenal Hyperplasia because of Defective 11β-Hydroxysteroid Dehydrogenase Reductase Activity*

1999 ◽  
Vol 84 (4) ◽  
pp. 1210-1213 ◽  
Author(s):  
Anna Nordenström ◽  
Claude Marcus ◽  
Magnus Axelson ◽  
Anna Wedell ◽  
E. Martin Ritzén
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Reductase Activity ◽  
Urinary Metabolites ◽  
Hydroxysteroid Dehydrogenase ◽  
Cortisone Acetate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genetic Lesion ◽  
21 Hydroxylase Deficiency ◽  
Very High

Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone. It is known that certain patients with congenital adrenal hyperplasia require very high substitution doses of cortisone acetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2·day), was examined. The activation of cortisone to cortisol was assessed by measuring urinary metabolites of cortisone and cortisol. The patient’s inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11β-hydroxysteroid dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron junctions of the 11β-hydroxysteroid dehydrogenase type1 gene (HSD11L) were sequenced without finding any mutations, but a genetic lesion in the promoter or other regulatory regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of hydrocortisone, rather than cortisone acetate, for substitution therapy in adrenal insufficiency.

scholarly journals Delayed Diagnosis of Congenital Adrenal Hyperplasia with Salt Wasting Due to Type II 3β-Hydroxysteroid Dehydrogenase Deficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2076-2080 ◽  
Author(s):  
Trine H. Johannsen ◽  
Delphine Mallet ◽  
Harriet Dige-Petersen ◽  
Jørn Müller ◽  
Katharina M. Main ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Delayed Diagnosis ◽  
Bone Age ◽  
Hydroxysteroid Dehydrogenase ◽  
Type Ii ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency ◽  
Premature Pubarche

Abstract Classical 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3β-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17α-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3β-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly elevated Δ5-steroids, in particular 17α-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated Δ5-/Δ4-steroid ratios. Sequencing of the type II 3β-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17α-hydroxyprogesterone were found on blood spots from Guthrie’s test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3β-HSD gene. Because neonatal diagnosis could have prevented life-threatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology.

Development of a Direct Fluoroimmunoassay for Serum Levels of 17-Hydroxyprogesterone

1988 ◽  
Vol 25 (1) ◽  
pp. 35-41 ◽  
Author(s):  
B A El-Gamal ◽  
S A Eremin ◽  
D S Smith ◽  
J Landon
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Sodium Salicylate ◽  
Serum Levels ◽  
Adrenal Hyperplasia ◽  
Initial Sample ◽  
Hydroxylase Deficiency ◽  
Sample Extraction ◽  
Analytical Recovery ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

A direct, rapid and highly specific fluoroimmunoassay for determining serum levels of 17-hydroxyprogesterone has been developed. It is based on the use of a sheep antiserum covalently coupled to magnetisable particles and fluorescein-labelled steroid. Sodium salicylate is employed to eliminate interference from endogenous binding proteins in serum. The sensitivity of 0·5 nmol/L is adequate for clinical purposes. Analytical recovery, linearity and precision are satisfactory and the results obtained correlate closely with those of an established radioimmunoassay using 3H-labelled steroid and the same antiserum after initial sample extraction and chromatography. The values found for serum from normal adult subjects ranged from 1·0 to 12·6 nmol/L while those from treated and untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency were 1·5 to 190 and 28·0 to 655 nmol/L, respectively.

17-HYDROXYPROGESTERONE IN THE COSYNTROPIN TEST: RESULTS IN NORMAL AND HIRSUTE WOMEN AND IN MILD CONGENITAL ADRENAL HYPERPLASIA

1979 ◽  
Vol 90 (3) ◽  
pp. 481-489 ◽  
Author(s):  
M. Gourmelen ◽  
M. T. Pham-Huu-Trung ◽  
M. G. Bredon ◽  
F. Girard
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Individual Values ◽  
Minimum Concentration ◽  
The Mean ◽  
17 Hydroxyprogesterone ◽  
The Individual ◽  
21 Hydroxylase Deficiency

ABSTRACT The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.

Management of Congenital Adrenal Hyperplasia Using Serum Dehydroepiandrosterone Sulfate and 17-Hydroxyprogesterone Concentrations

PEDIATRICS ◽  
1978 ◽  
Vol 61 (6) ◽  
pp. 867-871
Author(s):  
Michael P. Golden ◽  
Barbara M. Lippe ◽  
Solomon A. Kaplan ◽  
Norman Lavin ◽  
John Slavin
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Good Control ◽  
Dehydroepiandrosterone Sulfate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Exact Evaluation ◽  
Degree Of Control ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Urine Steroid

Simultaneous serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) and 17-hydroxyprogesterone (17-OHP) were compared with urinary 17-ketosteroid (17-KS) and pregnanetriol (PT) excretion during therapy in 18 prepubertal patients with the 21-hydroxylase deficiency form of congenital adrenal hyperplasia (CAH). Patients were classified into those in good, poor, or questionable control on the basis of clinical examination, skeletal age, and 17-KS and PT excretion. During therapy, use of serum steroid concentrations was found to be nearly as accurate in judging adequacy of control as use of urine steroid concentrations. Of 34 evaluations, a definite assessment of adequacy of control could be arrived at 25 times using urinary values and 22 times using both serum DHEA-S and 17-OHP concentrations. DHEA-S concentration responded sluggishly when treatment was not adequate, being greater than 100 µg/dl only in patients significantly undertreated. It was never elevated in well-controlled patients. Mid-afternoon 17-OHP concentrations were less than 200 ng/dl in well-controlled patients but readily escaped suppression and could not be used to differentiate poor from borderline control or from temporary noncompliance. Therefore, an increased DHEA-S concentration indicated poor control and a suppressed 17-OHP concentration indicated good control. The combination of normal DHEA-S level with elevated 17-OHP level, however, did not permit exact evaluation of the degree of control. Of significance is that not all patients with CAH present with an elevated DHEA-S concentration, and only in those in whom an elevated level has been documented can DHEA-S level be used as an index of control during therapy.

Influence of different genotypes on 17-hydroxyprogesterone levels in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

2000 ◽  
Vol 52 (5) ◽  
pp. 601-607 ◽  
Author(s):  
Tânia A. S. S. Bachega ◽  
Ana E. C. Billerbeck ◽  
José A. M. Marcondes ◽  
Guiomar Madureira ◽  
Ivo J. P. Arnhold ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Serum 3α-androstanediol glucuronide measurements in children with congenital adrenal hyperplasia

1994 ◽  
Vol 131 (5) ◽  
pp. 504-508 ◽  
Author(s):  
Sükrü Hatun ◽  
Nurşen Yordam ◽  
Ali Süha Çalikoǧlu
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Control Group ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Female Children ◽  
The Mean ◽  
Simple Virilizing ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Androstanediol Glucuronide

Hatun Ş, Yordam N, Çalikoǧlu AS. Serum 3α-androstandiol glucuronide measurements in children with congenital adrenal hyperplasia. Eur J Endocrinol 1994;131:504–8. ISSN 0804–4643 To determine the value of 3α-androstanediol glucuronide (3-AG) measurements in children with congenital adrenal hyperplasia, we compared serum 3AG, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) levels and 24-h urinary 17-ketosteroid (17-KS) excretion in 42 female children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, including 27 with the simple virilizing and 15 with the salt-losing form. Their mean age was 74.5 ±48.5 months (range, 6–194 months). Twenty-four-hour urinary 17-KS excretion and serum 3-AG, A, T, DHT and 17-OHP levels were measured in the patients. The values were less than the mean + 2 sd of the control group in 63%, 74%, 67%, 69%, 60% and 31% of the patients, respectively. Serum 3-AG levels correlated with 24-h urinary 17-KS excretion (r = 0.66) and plasma A (r = 0.80), 17-OHP (r = 0.56), T (r = 0.79) and DHT (r = 0.62) levels. We conclude that serum 3-AG is a useful metabolic index in the management of children with congenital adrenal hyperplasia. Şükrü Hatun, Türk-İş Blk, 274/7, Aydinlikevler, Ankara, Turkey

Sign in / Sign up

Export Citation Format

Share Document