The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis

2015 ◽  
Vol 84 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Urszula Ambroziak ◽  
Anna Kępczyńska-Nyk ◽  
Alina Kuryłowicz ◽  
Ewa Maria Małunowicz ◽  
Anna Wójcicka ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
False Positive ◽  
Adrenal Hyperplasia ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Positive Diagnosis ◽  
False Positive Diagnosis ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

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.

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.

scholarly journals Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy

2020 ◽  
Vol 6 (3) ◽  
pp. 67 ◽  
Author(s):  
Patrice K. Held ◽  
Ian M. Bird ◽  
Natasha L. Heather
Keyword(s):  
United States ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
False Positive ◽  
Primary Care Physicians ◽  
The United States ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency ◽  
Screening Accuracy

Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.

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.

scholarly journals SUN-172 A False Positive Result in Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in a Girl with Beckwith Wiedemann Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Barbara Leitao Braga ◽  
Klevia N Feitosa ◽  
Thamiris Freitas Maia ◽  
Guiomar Madureira ◽  
Mirian Yumie Nishi ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
False Positive ◽  
Wilms Tumor ◽  
Total Testosterone ◽  
Adrenal Hyperplasia ◽  
Chromosome 11P15 ◽  
Positive Diagnosis ◽  
False Positive Diagnosis ◽  
Increased Risk

Abstract Background: Congenital Adrenal Hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases, resulting in enzymatic defects in the cortisol secretion. CAH newborn screening can avoid neonatal mortality in children with the salt-wasting form and prevent incorrect gender assignments in females. The occurrence of false-positive results creates diagnostic difficulties presenting therapeutic implications. Beckwith Wiedemann Syndrome (BWS) is a congenital disease characterized by somatic overgrowth, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS is due to (epi)genetic changes involving growth-regulating genes with good genotype-phenotype correlation. The adrenal gland is frequently involved and may present diffuse cytomegaly of the adrenal cortex1. We reported a BWS newborn girl with a false-positive diagnosis of CAH in the screening. Case report: The patient was born at 39 weeks from an uneventful cesarean section, 5.6kg (>p97) and 52cm (>p97), referred to the Endocrinology service due to abnormal neonatal tests (neonatal 17-OHP: 96ng/mL) collected at 6 days old. At 14 days old, she was 6.3 kg (Z:+5.59), and 58cm (Z:+2.47), BMI: 18.7 kg/m2 (Z:+4.45), and with typical female external genitalia, ruling out the diagnosis of classic CAH. She presented some syndromic characteristics as macroglossia, ogival palate, orbital hypertelorism, hepatomegaly, and umbilical hernia. At 1 month and 14 days old, serum 17OHP was 7.4ng/mL, androstenedione: 6.1 ng/mL, total testosterone: 279ng/dL, 11-deoxycortisol: 2.11ng/mL, cortisol: 5.0ug/dL, and ACTH: 54pg/mL. At five months old she evolved with normalization of serum 17OHP, androstenedione and testosterone levels (1.36ng/mL, <0.50ng/mL, and 37ng/dL, respectively), but still with high DHEAS levels: 2913ng/mL. At 11 months old, DHEAS also normalized, confirming that it was transient hyperactivity of the zona reticulata. A molecular test was performed in a blood sample by MLPA, showing a gain of methylation in the imprinting control region 1 (ICR1) of chromosome 11p15, which controls two imprinted genes, H19 and IGF-2, confirming the clinical diagnosis of BWS. The hypermethylation of ICR1 is largely related to the Wilms tumor. The patient was diagnosed with bilateral Wilms tumor at 11 months old and undergone chemotherapy without adequate response requiring left nephrectomy at 1 year and 5 days old. Conclusion: We presented the first description of false-positive diagnosis of CAH in the newborn screening of a girl with Beckwith Wiedemann syndrome, probably due to a transient overactivation of the zona reticulata. References: 1.Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14(4):229-49.

THE EXCRETION OF TWO Δ5-3β-OH, 16α-HYDROXYSTEROIDS BY PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA

PEDIATRICS ◽  
1965 ◽  
Vol 36 (4) ◽  
pp. 583-591
Author(s):  
John W. Reynolds
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Urine Samples ◽  
Normal Infant ◽  
Adrenal Hyperplasia ◽  
Normal Range ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Young Infants ◽  
Deficiency Type ◽  
21 Hydroxylase Deficiency

The urinary excretion of two Δ5-3β-OH, 16α-hydnoxysteroids, 16-OH-pregnenolone (16-OH-PG), and 16-OH-dehydroepiandrosterone (16-OH-DHA), has been determined in 18 patients with the C-21 hydroxylase deficiency type of congenital adrenal hyperplasia (CAH). The excretion of 16-OH-PG was generally above the normal range in young infants, fell over the first 4 months and was present in only one of eight control urine samples from patients with CAH over 5 months of age. The excretion of 16-OH-DHA was generally within the normal range in the young infants, fell over the first 4 months, and was not found in urine samples from CAH patients over 5 months of age. ACTH was administered to eight of the CAH patients and caused an increased excretion of both steroids when they were present in control urine samples. Of the five patients receiving ACTH who had neither steroid present in control urine, 16-OH-PG appeared in the two youngest but 16-OH-DHA appeared in none. The ratio of urinary 16-OH-PG/16-OH-DHA was significantly greater in the CAH patients than in the endocninologically normal patients. It was concluded that the pattern of excretion of 16-OH-PG and i6-OH-DHA in patients with CAH is an exaggeration of the normal infant pattern caused by the endogenous ACTH stimulation. The possible role of the fetal zone of the adrenal cortex in the secretion of these steroids was considered but the available evidence indicated that the permanent cartical zone was the site of origin.

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.

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