scholarly journals Carriers of 21-Hydroxylase Deficiency Are Not at Increased Risk for Hyperandrogenism*

1997 ◽  
Vol 82 (2) ◽  
pp. 479-485 ◽  
Author(s):  
E. S. Knochenhauer ◽  
C. Cortet-Rudelli ◽  
R. D. Cunnigham ◽  
B. A. Conway-Myers ◽  
D. Dewailly ◽  
...  
Keyword(s):  
Hormonal Treatment ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Sex Hormone Binding Globulin ◽  
Adrenal Hyperplasia ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency

Abstract A deficiency of 21-hydroxylase activity is one of the most commonly inherited genetic disorders in man, with heterozygosity for CYP21 mutations affecting approximately 1 in 60 of the non-Jewish Caucasian population. We have hypothesized that heterozygosity for CYP21 mutations in women increases their risk of developing clinically evident hyperandrogenism, and that this risk is related to the severity of the mutation of CYP21 and/or the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation. To test these hypotheses, we studied 38 obligate carriers for 21-hydroxylase deficiency (i.e. mothers of children with congenital adrenal hyperplasia or nonclassic congenital adreanl hyperplasia), comparing them to 27 weight-, parity-, and age-matched controls. Premenopausal carriers, not receiving hormonal treatment (n = 27), had higher mean total and free testosterone [T; 2.02 ± 0.55 vs. 1.56 ± 0.65 nmol/L (P < 0.007) and 0.018 ± 0.007 vs. 0.012 ± 0.006 nmol/L (P < 0.007), respectively] and lower mean sex hormone-binding globulin (214 ± 62 vs. 277 ± 129 nmol/L; P < 0.03) levels compared to controls. There was no difference in the mean basal levels of dehydroepiandrosterone sulfate, androstenedione (A4), or 17-OHP between carriers and controls. As expected, carriers exhibited higher stimulated and net increment 17-OHP levels than controls [21.1 ± 27.1 vs. 6.2± 3.1 nmol/L (P < 0.01) and 19.0 ± 26.5 vs. 4.4 ± 2.8 nmol/L (P < 0.009), respectively]. However, no difference was observed in the response of A4 to ACTH-(1–24) stimulation. Of the 27 carriers studied biochemically, 2 (7.4%) had a stimulated 17-OHP value between 30.3–60.6 nmol/L, and 1 (3.7%) had a 17-OHP level above 60.6 nmol/L, suggestive of nonclassic adrenal hyperplasia. Of all carriers studied genetically (n = 36), 50.0% (18 of 36) had 1, 33% (12 of 36) had 2, and 16.7% (6 of 36) had 3 or more mutations. In 27.8% (10 of 36) of carriers, the mutations were contiguous, consistent with a large gene conversion. All 38 carriers were examined for historical and physical features of hyperandrogenism. Hirsutism was defined as a Ferriman-Gallwey score of 6 or more, menstrual/ovulatory dysfunction as a history of menstrual cycles of more than 35-day, and hyperandrogenemia as total or free T, A4, and/or dehydroepiandrosterone sulfate levels above the upper 95th percentile of control values. Further, defining functional androgen excess (FAE) as the presence of at least 2 of the 3 hyperandrogenic features, 4 of 38 (10.5%) of carriers appeared to be affected (95% confidence interval, 2.9–24.8%). Assuming an expected prevalence rate of FAE in the general population of 5–20%, the frequency of FAE among our carriers was not significantly higher than expected. In conclusion, heterozygosity for CYP21 mutations does not appear to increase the risk of clinically evident hyperandrogenism, although carrying the defect was associated with higher mean and free T levels. Finally, due to the low frequency of androgen excess in our heterozygote population, we were unable to correlate the severity of the CYP21 mutation and/or the 17-OHP response to ACTH stimulation with the presence of the phenotype.

scholarly journals Long-Term Health Outcomes of Korean Adults With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Seung Gyun Lim ◽  
Young Ah Lee ◽  
Han Na Jang ◽  
Sung Hye Kong ◽  
Chang Ho Ahn ◽  
...  
Keyword(s):  
Dehydroepiandrosterone Sulfate ◽  
Metabolic Risk ◽  
Menstrual Irregularity ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency ◽  
Age And Sex

There is a lack of studies regarding the long-term outcomes of Asian adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. We hypothesized that adults with CAH are at higher metabolic risk than their age-, and sex-matched controls. We further investigated the long-term health outcome-related factors in adults with CAH. We compared metabolic risk between adults with CAH (71 men, 93 women) and age-, and sex-matched controls (190 men, 261 women) from the Korean National Health and Nutrition Examination Survey data. The presence of obesity, testicular adrenal rest tumors (TARTs), and menstrual irregularity was assessed. Hormone status and treatment regimens were compared according to the presence of adverse outcomes. The median age was 27.0 y and 28.0 y for men and women, respectively. Adults with CAH had a higher waist circumference (88.0 vs. 82.3 cm in men, and 83.5 vs. 72.3 cm in women), and blood pressure (125.0 vs. 113.0 mmHg in men, and 120.0 vs. 104.0 mmHg in women) than age- and sex-matched controls (P<0.05 for all). The 2.7-fold increased risk for hypertension (men) and 2.0-fold increased risk for obesity (women) was significant in patients with CAH (P<0.05 for both). Obese adults with CAH showed significantly higher adrenal limb thicknesses (men) and 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels (women) (P<0.05 for both). TARTs occurred in 58.1% of men and did not differ by hormone or treatment regimen. Irregular menstruation was observed in 57.1% of women, with higher dehydroepiandrosterone sulfate levels in those with irregular periods. Adults with CAH had a higher metabolic risk than the general population. Poor disease control may increase their risk of metabolic morbidity and menstrual irregularity.

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.

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

1997 ◽  
pp. 670-674 ◽  
Author(s):  
Y Sahin ◽  
F Kelestimur
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Late Onset ◽  
Polycystic Ovary ◽  
Serum Testosterone ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Ovary Syndrome ◽  
Biochemical Features

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment

2017 ◽  
Vol 176 (4) ◽  
pp. R167-R181 ◽  
Author(s):  
Anne Bachelot ◽  
Virginie Grouthier ◽  
Carine Courtillot ◽  
Jérôme Dulon ◽  
Philippe Touraine
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Management Strategies ◽  
The United States ◽  
Fertility Treatment ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency ◽  
And Control

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge.

Hormonal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

2007 ◽  
Vol 68 (4) ◽  
pp. 274-280 ◽  
Author(s):  
A. Bachelot ◽  
Z. Chakhtoura ◽  
A. Rouxel ◽  
J. Dulon ◽  
P. Touraine
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hormonal Treatment ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
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.

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.

Low Adrenomedullary Function Predicts Acute Illness in Infants with Classical Congenital Adrenal Hyperplasia

2021 ◽  
Author(s):  
Jonathan Weber ◽  
Veeraya K Tanawattanacharoen ◽  
Amy Seagroves ◽  
Mark C Liang ◽  
Christina M Koppin ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Acute Illness ◽  
First Year ◽  
Plasma Epinephrine ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Young Infants ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency ◽  
First Year Of Life

Abstract Context Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective To study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. Design Prospective cohort study. Setting Study participants were recruited from a pediatric tertiary care center. Patients or Other Participants 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main Outcome Measures Plasma epinephrine levels (N=27), CYP21A2 genotype (N=15), and incidence of acute illnesses from birth to 1 year of age (N=28). Results Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (β=-0.018, R=-0.45, P=0.02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R=-0.51, P=0.007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P=0.02). CAH patients had lower epinephrine as newborns than controls (P=0.007) and showed decreases in epinephrine from birth to 1 year of age (P=0.04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Conclusions Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

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