Synthetic glucocorticoids instead of hydrocortisone do not increase mineralocorticoid needs in adult patients with salt wasting congenital adrenal hyperplasia.

It has been postulated that in patients with congenital adrenal hyperplasia (CAH) with salt wasting (SW), fludrocortisone needs might be higher in those on synthetic glucocorticoid replacement therapy in comparison to conventional hydrocortisone due to the lower mineralocorticoid activity. Here we report the results of a cross-sectional single center study comparing mineralocorticoid needs between patients taking synthetic glucocorticoids (S-GC) (N = 24) and those on conventional hydrocortisone (HC) (N = 16). We could show that while both groups took comparable HC-equivalent dosages, there was no significant difference in FC dosage (GC: 0.075 mg; IQR 0.05-0.1; HC: 0.1 mg; IQR 0.05-0.1; p = 0.713). Although there was a trend for higher renin levels in the S-GC group (67.1 µU/ml; IQR 40.5-113.9 vs. 40.4 IQR 14.2-73.1; p = 0.066), this failed to reach significance. With regard to blood pressure, those taking S-GC had even significantly elevated mean systolic (125.0 mmHg, IQR 117.5-130.0 vs 116.5 mmHg IQR 111.8-124.8; p = 0.036) and diastolic (78.0 mmHg, IQR 74.3-83.8 vs 74.5mmHG, IQR 69.3-76.0; p = 0.044) during the day. Systolic dipping was however more pronounced in those on GC in comparison to those taking HC (11.3%; IQR 8.7-14.6 vs. 6.4 IQR 3.4-12.7; p = 0.031). In conclusion, we could show in this small, albeit well-balanced cohort that mineralocorticoid dosage does not significantly differ between patients receiving synthetic glucocorticoids or conventional hydrocortisone. Higher blood pressure values despite the tendency for higher renin levels in those on S-GC support the notion that the assessment of MR adequacy should be guided by the clinical picture and blood pressure on a regular basis.

11-oxygenated androgens and their relation to hypothalamus-pituitary-gonadal-axis disturbances in adults with congenital adrenal hyperplasia.

CONTEXT: Hypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context. DESIGN: Cross-sectional single center study including 89 patients (N = 42 men, N = 55 women) with classic CAH. MAIN OUTCOME MEASURES: Differences in steroid markers in men with hypogonadism and women with secondary amenorrhea with a special focus on 11-ketotestosterone (11KT) and 11ß-hydroxyandrostenedione (11OHA4). RESULTS: Hypogonadotropic hypogonadism was present in 23 % of men and 61 % of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28 % of men. 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism and in women with amenorrhea in comparison to those with a regular cycle (11KT: 5.2x; 11OHA4: 3.7x). 11-oxygenated androgens were not higher in men with TART than in those without. There was a negative association of 11KT and 11OHA4 with FSH but not with LH in men. As expected, all steroids were strongly correlated with each other and cases of disproportionally elevated 11-oxygenated androgens that could explain for HPG-disturbances or TART in otherwise controlled patients were rare and also found in eugonadal individuals. CONCLUSIONS: In CAH, 11-oxygenated androgens are elevated in women with menstrual disturbances and in men with hypogonadotropic hypogonadism. Due to the close correlation of 11-oxygenated androgens with other adrenal steroids it remains to be shown if their measurement is superior to conventional markers of androgen control.

Effects of androgen excess and glucocorticoid exposure on bone health in adult patients with 21-hydroxylase deficiency.

CONTEXT: This study aimed to determine the role of modifiable predictors on bone health in congenital adrenal hyperplasia (CAH). DESIGN: Cross-sectional, single center study, including 97 patients (N = 42 men) with classic CAH due to 21-hydroxylase deficiency (N = 65 salt wasting, N = 32 simple virilizing). MAIN OUTCOME MEASURES: Treatment-related predictors of bone health. RESULTS: Average T scores (-0.9 ± 1.4 vs. -0.4 ± 1.4; p = 0.036) as well as Z scores (-1.0 ± 1.3 vs. -0.1 ± 1.4; p = 0.012) at the spine in patients with CAH were significantly lower in men than women. While osteoporosis was rare in women, it was documented in 9.1% of men with CAH. There was a significant positive correlation of Z scores at the spine with advancing age in women with CAH (R² = 0.178; p = 0.003). In multivariate analysis, the intake of conventional hydrocortisone (HC) instead of synthetic glucocorticoids was independently associated with a higher bone mineral density (BMD) at the hip region in both sexes. In women, there was a positive association with vitamin D concentrations. Interestingly, higher sodium levels were associated with a lower BMD independent of renin levels and fludrocortisone dosage. Neither in men nor in women, markers of androgen control were predictive for BMD at any site. Markers of bone turnover indicated low bone turnover. No pathological fractures were documented. CONCLUSIONS: Men with CAH are particularly prone to low bone density, while women seem to be relatively protected by androgen excess compared to the general female population. The use of HC instead of synthetic GCs for hormone replacement may translate into better bone health.

Effect of androgen excess and glucocorticoid exposure on metabolic risk profiles in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Data on cardiovascular morbidity in adults with congenital adrenal hyperplasia (CAH) is sparse. We therefore aimed to determine the role of androgen control and glucocorticoid therapy on metabolic health. For that purpose, we included 90 patients (N = 39 men, N = 51 women) with classic CAH due to 21-hydroxylase deficiency (N = 61 salt wasting, N = 29 simple virilizing) and an equal number of controls matched for age, sex, BMI and smoking-habits. We could show that there was no difference in intima-media-thickness between patients and controls and only one patient fulfilled all criteria of the metabolic syndrome. CAH men presented with an increased relative body fat mass in comparison to controls (25.6 % vs. 22.1 %; p = 0.011) while this was not true for CAH women. Body fat was lower in those taking hydrocortisone instead of synthetic glucocorticoids (B = -3.27; p = 0.048). While arterial hypertension was rare, 54 % of patients had an impaired systolic drop at night or were classified as non-dippers (17 %). Impaired dipping was not associated with evening glucocorticoid and fludrocortisone intake but mediated by sodium levels. Insulin resistance was more common in CAH women (B = 1.689; p = 0.036) and in those with poor androgen control (B = 0.823; p = 0.046). In summary, we could show that good cardiovascular health outcome in adult CAH patients can be achieved. Hydrocortisone is superior in terms of body composition. It is yet unclear how non-dipping will translate into cardiovascular morbidity in the long-term.