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Objective To study the impact of the quality of therapeutic control on fertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adrenal hyperplasia (CAH). Design Combined cross-sectional and retrospective clinical study. Methods Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis. The quality of therapeutic control was categorized as ‘poor’, ‘moderate’ or ‘medium’. Evaluation of current control was based on concentrations of 17-hydroxy-progesterone and androstenedione in serum and 3 cm hair; previous control was categorized based on serum 17-hydroxy-progesterone concentrations during childhood and puberty, anthropometric and puberty data, bone age data and adrenal sizes. Results Semen quality was similar in males with CAH and controls (P = 0.066), however patients with ‘poor’ past control and large TART, or with ‘poor’ current CAH control had low sperm counts. Follicle-stimulating hormone was decreased, if current CAH control was ‘poor’ (1.8 ± 0.9 U/L; ‘good’: 3.9 ± 2.2 U/L); P = 0.015); luteinizing hormone was decreased if it was ‘poor’ (1.8 ± 0.9 U/L; P = 0.041) or ‘moderate’ (1.9 ± 0.6 U/L; ‘good’: 3.0 ± 1.3 U/L; P = 0.025). None of the males with ‘good’ past CAH control, 50% of those with ‘moderate’ past control and 80% with ‘poor past control had bilateral TART. The prevalence of TART in males with severe (class null or A) CYP21A2 mutations was 53% and 25% and 0% in those with milder class B and C mutations, respectively. Conclusions TART development is favoured by inadequate long-term hormonal control in CAH. Reduced semen quality may be associated with large TART. Gonadotropin suppression by adrenal androgen excess during the latest spermatogenic cycle may contribute to impairment of spermatogenesis.

Background Stress-related alterations in the regulation of several endocrine systems, including the hypothalamus-pituitary-adrenal (HPA) and -gonadal (HPG) axes and the endocannabinoid system are proposed to be involved in the etiology of major depressive disorder (MDD). Therefore, this study examines whether altered concentrations of glucocorticoids, testosterone, endocannabinoids, and related N-acylethanolamines accumulated in hair are present in MDD. Methods Female participants (range: 19–59, Mdn = 30.5 years) were recruited, including n = 21 with a current MDD episode and n = 27 nondepressed controls without any current mental disorder. Weight-standardized samples of 3 cm hair segments were analyzed which equals to three months of retrospectively assessed biomarkers in hair. Concentrations of cortisol, cortisone, testosterone, endocannabinoids (i.e., anandamide [AEA], 2-arachidonylglycerol [2-AG]), and selected N-acylethanolamines (i.e., stearoylethanolamide [SEA], oleoylethanolamide [OEA], palmitoylethanolamide [PEA]) were measured using mass spectrometry. Results Female MDD patients exhibited lower cortisol and cortisone levels in hair than nondepressed controls, whereas the hair concentrations of endocannabinoids, N-acylethanolamines, and testosterone did not differ between the groups. Conclusions Our results add to the heterogeneous body of findings on alterations in hair-stored glucocorticoids and endocannabinoids in MDD. As in previous studies, there was no evidence of altered testosterone concentrations in the hair of MDD patients. Larger and longitudinal studies are needed to comprehensively explore the overall picture of endocrine alterations in MDD.

Introduction: To evaluate scalp hair steroid concentrations as a monitoring tool for androgen control and metabolic outcomes in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Methods: 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, cortisol, cortisone, progesterone, prednisolone, and prednisone concentrations were measured in scalp hair by means of LC-MS/MS in 27 women and 15 men with CAH and controls (37 women, 42 men). Results: In CAH men and women, 17-OHP levels in hair showed a significant positive correlation with corresponding levels in serum (ρ = 0.654; p = 0.01; ρ = 0.553, p = 0.003 respectively), while total testosterone levels were only significantly correlated in CAH men (ρ = 0.543; p = 0.036). Androstenedione levels did not show a significant correlation. Receiver-operating characteristic (ROC) curve analysis indicated that a cutoff value of 21.7 pg/mg for 17-OHP in hair provided a sensitivity of 100% and a specificity of 88.9% for identifying men with elevated serum androstenedione. Hair 17-OHP in women showed a poorer performance in terms of identifying those with elevated androstenedione serum levels. However, when applying a cutoff value of 5.5 for the free androgen index as a marker of significant hyperandrogenism in CAH women, 17-OHP >27.6 pg/mg in hair provided a sensitivity of 100% and a specificity of 95.8% (AUC 0.986, 95% CI 0.945–1.000; p < 0.001). Neither hair cortisol nor markers of adrenal androgen control in hair showed significant associations with cardiometabolic outcome or bone health. Conclusion: This study shows that scalp hair 17-OHP concentrations may be a promising noninvasive long-term parameter for treatment monitoring in adult patients with CAH.

The endocannabinoid system has been implicated in the regulation of the stress response, fear memory formation, and inflammatory processes. Posttraumatic stress disorder (PTSD) can result from exposure to extreme stress and is characterized by strong, associative memories for the traumatic events experienced. Furthermore, an elevated physical disease risk has been observed in PTSD, likely to be mediated by inflammatory processes. Therefore, altered endocannabinoid regulation can be expected in individuals with PTSD. However, attempts to assess PTSD-associated differences in the endocannabinoid system from human blood samples have provided inconsistent results, possibly due to fluctuating levels of endocannabinoids. In hair, these neuromodulators are accumulated over time and thus give access to a more stable and reliable assessment. We therefore investigated PTSD-associated differences in hair concentrations of endocannabinoids (N-acyl-ethanolamides palmitoylethanolamide [PEA], oleoylethanolamide [OEA] and stearoylethanolamide [SEA]) in 38 rebel war survivors from Northern Uganda suffering from PTSD and N=38 healthy rebel war survivors without current and lifetime PTSD. PTSD diagnosis and symptom severity were assessed in structured clinical interviews employing the Posttraumatic Diagnostic Scale (PDS). A significant group difference was observed for OEA, with PTSD patients showing reduced hair concentrations. Regression analyses further revealed strong negative relationships between all investigated N-acyl-ethanolamides and symptom severity of PTSD. The observed reductions in endocannabinoids might account for the increased inflammatory state as well as for the failure to extinguish fear memories observed in PTSD. Our findings add to the accumulating evidence suggesting the endocannabinoid system as a target for pharmacological enhancement of exposure-based psychotherapy for PTSD. published

Background:Endogenous corticosteroids and endocannabinoids are both known to be involved in stress adaption and anti-inflammatory and immuneregulatory effects. The application of hair as retrospective specimen for long-term recording of corticosteroids and its association with stress-induced biochemical alterations was intensively examined.Methods:To evaluate the stability and correlation of various parameters of the endocannabinoid and corticosteroid systems, a prospective study was carried out. Hair samples were collected monthly over a pregnancy cycle (sixth week of pregnancy to 9 weeks postpartum). By comparison of hair concentrations in particular segments (ie, grown in the same time span but collected at different times), an examination of analyte stability in hair was achieved. Additionally, the comparison of proximal segments provided on biochemical information that is independent of alteration due to physical instability. The detection limits of a validated procedure using solid-phase extraction cleanup and liquid chromatography-mass spectrometry proved to be suitable to identify the endogenous levels of cortisol (limits of detection = 1.6 pg/mg), cortisone (2.1 pg/mg), anandamide (AEA, 0.3 pg/mg), and 2-arachidonoylglycerol (15 pg/mg).Results:Corticosteroid concentrations in corresponding hair segments were found to be reduced with increasing hair age; an average decline of cortisol and cortisone by 50% in 4 months was estimated. Independently, an increase of cortisol and cortisone in proximal segments collected during pregnancy was confirmed, which is assumed to be stress related. Endocannabinoids proved to be by far more stable, as demonstrated by subsequent monthly collection of corresponding segments and there was hardly any washout of AEA detectable. Elevated hair concentrations of AEA and 2-arachidonoylglycerol were detected in the first-second trimester of pregnancy, which corresponds to negative correlations between AEA, cortisol, and cortisone.

Prenatal steroids have an undisputed positive effect of decreasing neonatal morbidity and mortality by improving fetal lung maturation. Some concerns have been raised on long-term consequences on the hypothalamic-pituitary-adrenal axis and cognition, but there are no studies addressing effects on the immune system. The thymus is an essential organ for the development and selection of T cells, and thymocytes are extremely sensitive to steroids. Using a mouse model for prenatal steroid administration, we show here that betamethasone treatment to the mother has a profound effect on the thymus of the offspring. We find the thymus volume reduced, affecting mostly the developing CD4+ CD8+ double-positive thymocytes and a compensatory accelerated transition of the earlier stages to replenish the depleted compartment. This effect lasts for at least 3 days, which correspond to a very relevant period for the selection of the T cell repertoire. Moreover, we show that low doses of betamethasone have similar effects on human thymocytes in vitro. Therefore, further studies are needed to analyze possible long-term consequences of this treatment on the immune system of the offspring.Betamethasone administered to the mother before birth reaches the fetal thymus. Prenatal betamethasone results in massive loss of developing thymocytes. The effects of betamethasone on thymus development are visible for several days. Human thymocytes are also sensitive to low doses of betamethasone. Altered thymocyte development around birth may have an effect on the immune system.