scholarly journals Serum Cortisol and 17-Hydroxyprogesterone Interrelation in Classic 21-Hydroxylase Deficiency: Is Current Replacement Therapy Satisfactory?

2001 ◽  
Vol 86 (10) ◽  
pp. 4679-4685 ◽  
Author(s):  
Evangelia Charmandari ◽  
David R. Matthews ◽  
Atholl Johnston ◽  
Charles G. D. Brook ◽  
Peter C. Hindmarsh
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Serum Cortisol ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Group 2 ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Pituitary Adrenal Axis ◽  
Serum Acth ◽  
Group 1

One of the main aims in the management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency is to achieve adequate suppression of the adrenal cortex with the smallest possible dose of glucocorticoid substitution. To evaluate the administration schedule of current replacement therapy regimens, we investigated the cortisol-17-hydroxyprogesterone interrelation in 36 patients (13 males and 23 females; median age, 12.3 yr; range, 6.1–18.8 yr) with salt-wasting congenital adrenal hyperplasia. As sufficient variation in 17-hydroxyprogesterone concentrations was required to allow analysis of the cortisol-17-hydroxyprogesterone interrelation, patients were divided into 2 groups depending on the adequacy of hypothalamic-pituitary-adrenal axis suppression. The first group consisted of 17 patients with suppressed 17-hydroxyprogesterone concentrations (group 1), and the second group consisted of 19 patients with nonsuppressed 17-hydroxyprogesterone concentrations (group 2). We determined serum cortisol and 17-hydroxyprogesterone concentrations at 20-min intervals for a total of 24 h while patients were receiving their usual replacement treatment with hydrocortisone and 9α-fludrocortisone. We also determined the lowest dose of dexamethasone required to suppress the 0800 h serum ACTH concentrations when administered as a single dose (0.3 or 0.5 mg/m2) the night before. Mean 24-h cortisol and 17-hydroxyprogesterone concentrations were 3.9μ g/dl (sd = 2.1) and 66.2 ng/dl (sd = 92.7), respectively, in group 1 and 4.1 μg/dl (sd = 2.5) and 4865.7 ng/dl (sd = 6951) in group 2. The 24-h 17-hydroxyprogesterone concentrations demonstrated circadian variation, with peak values observed between 0400–0900 h. In group 2, 17-hydroxyprogesterone concentrations decreased gradually in response to the rise in cortisol concentrations during the day, but remained low during the night despite the almost undetectable cortisol concentrations between 1600–2000 h. Mean 0800 h androstenedione concentrations correlated strongly with integrated 17-hydroxyprogesterone concentrations (r = 0.81; P < 0.0001), but not with integrated cortisol concentrations. There was a significant negative correlation between cortisol and 17-hydroxyprogesterone at lag time 0 min (r =− 0.187; P < 0.0001), peaking at lag time 60 min (r = −0.302; P < 0.0001), with cortisol leading 17-hydroxyprogesterone by these time intervals. Finally, 0800 h serum ACTH concentrations were sufficiently suppressed after a dexamethasone dose of 0.3 mg/m2 in all but three patients. These findings indicate that in classic 21-hydroxylase deficiency, hydrocortisone should be administered during the period of increased hypothalamic-pituitary-adrenal axis activity, between 0400–1600 h, with the biggest dose given in the morning. Blood investigations performed as part of monitoring of congenital adrenal hyperplasia patients should include androstenedione and 17-hydroxyprogesterone concentrations determined in the morning before the administration of hydrocortisone. It should also be emphasized that blood investigations are only complementary to the overall assessment of these patients, which is primarily based on the evaluation of growth and pubertal progress.

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

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.

Sign in / Sign up

Export Citation Format

Share Document