cortodoxone and Obesity

The high complexity of pediatric reference ranges across age, sex, and units impairs clinical application and comparability of steroid hormone data, e.g., in congenital adrenal hyperplasia (CAH). We developed a multiples-of-median (MoM) normalization tool to overcome this major drawback in pediatric endocrinology.. Liquid chromatography tandem mass spectrometry data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to > 16 years) from 2 previous datasets were MoM transformed across age and sex. Twenty-three genetically proven CAH patients were included (21-hydroxylase deficiency [21OHD], n = 19; 11β-hydroxylase deficiency [11OHD], n = 4). MoM cutoffs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, n = 8; adrenal cortical carcinoma, n = 6; obesity, n = 40).. 21OHD and 11OHD patients showed disease-typical, easily recognizable MoM patterns independent of age, sex, and concentration units. Two single-steroid cutoffs indicated 21OHD: 3.87 MoM for 17-hydroxyprogesterone (100% sensitivity and 98.83% specificity) and 12.28 MoM for 21-deoxycortisol (94.74% sensitivity and 100% specificity). A cutoff of 13.18 MoM for 11-deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity).. Age- and sex-independent MoMs are straightforward for a clinically relevant display of multi-steroid patterns. In addition, defined single-steroid MoMs can serve alone as predictors of 21OHD and 11OHD. Finally, MoM transformation offers substantial enhancement of routine and scientific steroid hormone data exchange due to improved comparability.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocortical Carcinoma; Age Factors; Child; Child, Preschool; Chromatography, Liquid; Cortodoxone; Female; Humans; Infant; Infant, Newborn; Male; Mass Spectrometry; Obesity; Sex Factors

To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men.. Cross-sectional study.. Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts.. We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (-0.34 nmol/L, P = 0.045), cortisol (-87 nmol/L, P = 0.045-0.002) and corticosterone (-10.1 nmol/L, P = 0.048-0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively.. Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.

Topics: 17-alpha-Hydroxyprogesterone; Age Factors; Androstenedione; Body Mass Index; Body Weight; Chromatography, Liquid; Corticosterone; Cortodoxone; Cross-Sectional Studies; Dehydroepiandrosterone; Dihydrotestosterone; Humans; Hydrocortisone; Male; Multivariate Analysis; Obesity; Overweight; Risk Factors; Tandem Mass Spectrometry

Women with normogonadotrophic normo-estrogenic oligomenorrhoea often disclose a variety of clinical symptoms. Many of these individuals are obese with features of pseudo-hypercortisolism. In the current study, 11-deoxycortisol and cortisol concentrations were determined in this group and compared with ovulatory controls.. Twenty-six women with clomiphene citrate-resistant infertility, 12 lean and 11 obese ovulatory controls were studied. Women with infertility had the highest 11-deoxycortisol concentrations (mean +/- SD: 4.1 +/- 1.5 ng/ml) compared with obese and lean controls (3.1 +/- 1.4 and 2.4 +/- 0.9 ng/ml) (P < 0.01), but similar morning cortisol concentrations (0.47 +/- 0.15, 0.45 +/- 0.16 and 0.47 +/- 0.18 nmol/l). Baseline 11-deoxycortisol/cortisol ratios (>90th percentile of ovulatory controls) were elevated in 23/26 infertile women (88%), and in 3/26 women (12%) after adrenocorticotrophic hormone (ACTH) stimulation. Three out of six lean infertile women had elevated baseline 11-deoxycortisol/cortisol ratios, but none of these women had elevated ratios after ACTH stimulation. Stepwise regression analysis, after exclusion of testosterone, revealed significant correlations between the groups (lean controls, obese controls, infertility) and ACTH-stimulated 11-deoxycortisol/cortisol ratio (P < 0.05), but not with fasting glucose, insulin, cortisol, 11-deoxycortisol and baseline 11-deoxycortisol/cortisol ratios.. Congenital adrenal hyperplasia was not observed in the majority of infertile women. The data indicate that extra-adrenal factors were involved in most of the infertility syndromes that were studied.

Topics: Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Case-Control Studies; Cortodoxone; Estrogens; Female; Gonadotropins; Humans; Hydrocortisone; Incidence; Infertility, Female; Obesity; Osmolar Concentration

Certain differences in regional fat distribution might be explicable by subtle hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. We examined prospectively PA function relative to abdominal obesity defined by waist-to-hip circumference ratio (WHR) in 71 normotensive men aged 30-55 years. Basal PA activity was assessed by measurements of serum cortisol and plasma corticotropin (ACTH) concentrations during the oral glucose tolerance test (OGTT). Functional activity was examined by dexamethasone suppression and ACTH stimulation tests; responses of 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol, dehydroepiandrosterone (DHEA), and androstenedione were determined. When the subjects were divided into tertiles for the WHR, the ratio of mean ACTH to mean cortisol during the OGTT was increased (p < 0.05), and the ratio of urinary cortisol to body-mass index was decreased (p < 0.01), whilst the net increments of cortisol (p < 0.05) and 17-OHP (p < 0.05) from 0 to 60 min, as well as the ratio of 17-OHP to S increments (p < 0.05) after ACTH were elevated in the highest vs lowest WHR tertile. The ratio of mean ACTH to mean cortisol (r = 0.495; p < 0.001) during the OGTT, the ratio of net 17-OHP to S increments (r = 0.404; p < 0.001), and the net DHEA (r = 0.276; p = 0.020) and 17-OHP (r = 0.336; p = 0.005) responses to ACTH at 60 min correlated with WHR. In multivariate analyses the ratio of mean ACTH to cortisol, cortisol response to ACTH, and the ratio of net 17-OHP to S increments were all significant predictors of WHR independent of smoking, physical activity, and BMI explaining 49.0% of the variance in WHR. Thus, abdominal obesity may be associated with decreased activity of adrenal 21-hydroxylase. Either obesity-related functional alteration of 21-hydroxylase activity or the high carrier prevalence of genetic defects of this enzyme may explain these findings.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Adult; Androstenedione; Body Constitution; Cortodoxone; Dehydroepiandrosterone; Dexamethasone; Glucose Tolerance Test; Humans; Hydrocortisone; Hydroxyprogesterones; Male; Middle Aged; Obesity; Pituitary-Adrenal System; Prospective Studies; Regression Analysis; Smoking; Steroid 21-Hydroxylase