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

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.

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Salivary morning androstenedione and 17α-OH progesterone levels in childhood and puberty in patients with classic congenital adrenal hyperplasia

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-0375 ◽

2015 ◽

Vol 53 (3) ◽

Cited By ~ 3

Author(s):

Monique J.M. de Groot ◽

Karijn J. Pijnenburg-Kleizen ◽

Chris M.G. Thomas ◽

Fred C.G.J. Sweep ◽

Nike M.M.L. Stikkelbroeck ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Term Treatment ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Classic Congenital Adrenal Hyperplasia ◽

Paediatric Patients ◽

Long Term Treatment ◽

Target Values ◽

21 Hydroxylase Deficiency

AbstractTreatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be monitored by salivary androstenedione (A-dione) and 17α-hydroxyprogesterone (17OHP) levels. There are no objective criteria for setting relevant target values or data on changes of 17OHP and A-dione during monitoring.We evaluated A-dione and 17OHP levels in nearly 2000 salivary samples collected during long-term treatment of 84 paediatric patients with classic 21-hydroxylase deficiency.A-dione and 17OHP levels and its ratio 17OHP/A-dione remained constant from 4 to 11 years with no sex-related differences. During puberty, A-dione and 17OHP levels both increased, starting at earlier age in girls than in boys. The ratio 17OHP/A-dione declined. Normalised A-dione concomitant with elevated 17OHP [1.43 nmol/L (0.46–4.41) during prepuberty; 2.36 nmol/L (0.63–8.89) for boys and 1.99 nmol/L (0.32–6.98) for girls during puberty] could be obtained with overall median glucocorticoid doses of 11–15 mg/mNormalised A-dione consistent with 17OHP three times URL during prepuberty and normalised A-dione consistent with 4–6 times URL during puberty could be obtained by moderate glucocorticoid dosages. A constant 17OHP/A-dione ratio during prepuberty suggested absence of adrenarche. During puberty, a higher percentage of samples met the criteria for undertreatment, especially of boys.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.2.3759 ◽

1997 ◽

Vol 82 (2) ◽

pp. 479-485 ◽

Cited By ~ 2

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.

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