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Objective: Patients with congenital adrenal hyperplasia (CAH) in developing countries have limited access to appropriate laboratory facilities for diagnosis and follow‐up. The aim of this study is to evaluate steroid measurement in hair as a diagnostic tool to identify and monitor CAH in these patients. Design: A method was developed to measure steroids in hair, the stability of steroids in hair was assessed, and the concentration range in healthy volunteers was determined. Hair samples of patients, before and after starting therapy, were transported at ambient temperature to The Netherlands for analysis. Patients: Twenty‐two Indonesian CAH patients and 84 healthy volunteers participated. Measurements: Cortisol, 17‐hydroxyprogesterone (17OHP), androstenedione, and testosterone in hair were measured by liquid chromatography with tandem mass spectrometry. Results: Steroids in hair could be measured and remained stable (<4.9% deviation) for at least 3 weeks at 4°C and 30°C. In each of the untreated patients, hair concentrations of 17OHP (9.43–1135 pmol/g), androstenedione (36.1–432 pmol/g), and testosterone (2.85–69.2 pmol/g) were all above the upper limit of the corresponding range in healthy volunteers; 5.5 pmol/g, 13 pmol/g, and 1.8 pmol/g, respectively. After starting glucocorticoid treatment, the steroid concentrations in the hair of CAH patients decreased significantly for androstenedione (73%) and testosterone (59%) after 6 months. Conclusions: CAH could be confirmed in Indonesian patients based on the concentration of 17OHP, androstenedione, and testosterone in hair, and a treatment effect was observed. These findings open up opportunities to diagnose and/or monitor CAH in developing countries with a simple noninvasive technique. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17‐hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH). Methods: A nonlinear mixed‐effect modelling approach was used to analyse cortisol, 17‐hydroxyprogesterone and androstenedione concentrations obtained over 6 hours from children with CAH (n = 50). A circadian rhythm was evident and the model leveraged literature information on circadian rhythm in untreated children with CAH. Indirect response models were applied in which cortisol inhibited the production rate of all three compounds using an Imax model. Results: Cortisol was characterized by a one‐compartment model with apparent clearance and volume of distribution estimated at 22.9 L/h/70 kg and 41.1 L/70 kg, respectively. The IC50 values of cortisol concentrations for cortisol, 17‐hydroxyprogesterone and androstenedione were estimated to be 1.36, 0.45 and 0.75 μg/dL, respectively. The inhibitory effect was found to be more potent on 17OHP than D4A, and the IC50 values were higher in salt‐wasting subjects than simple virilizers. Production rates of cortisol, 17‐hydroxyprogesterone and androstenedione were higher in simple‐virilizer subjects. Half‐lives of cortisol, 17‐hydroxyprogesterone and androstenedione were 60, 47 and 77 minutes, respectively. Conclusion: Rapidly changing biomarker responses to cortisol concentrations highlight that single measurements provide volatile information about a child's disease control. Our model closely captured observed cortisol, 17‐hydroxyprogesterone and androstenedione concentrations. It can be used to predict concentrations over 24 hours and allows many novel exposure metrics to be calculated, e.g., AUC, AUC‐above‐threshold, time‐within‐range, etc. Our long‐range goal is to uncover dose–exposure–outcome relationships that clinicians can use in adjusting hydrocortisone dose and timing. [ABSTRACT FROM AUTHOR]

Objective: Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) in four Turkish cities in 2017, and in 2018 extended the program, with a slight change in screening strategy, to fourteen cities. To evaluate the performance of the extended study and update previously reported outcomes. Methods: Retrospective, descriptive study. Neonates of =32 gestational weeks and =1500 gr birth weight from fourteen cities, born between May-December 2018, were included. Screening protocol included one sample, two-tier testing as applied in the previous pilot study. In the first step, 17a-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. Cases with positive initial screening underwent second tier testing by steroid profiling in DBS using liquid chromatographytandem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione. The babies with a steroid ratio (21-S+17-OHP)/F of =0.7 (increased from =0.5 in the earlier pilot study) were referred to pediatric endocrinology clinics for diagnostic assessment. Results: In the evaluated period, 241,083 newborns were screened. 12,321 (5.11%) required second-tier testing and 880 (0.36%) were referred for clinical assessment, twenty of whom were diagnosed with CAH (10 females, 10 males). Sixteen were diagnosed as classical 21-hydroxylase deficiency (21-OHD) CAH (12 with salt-wasting and four with simple virilising CAH), and four cases were identified with 11ß-OHD CAH. No case of salt-wasting CAH was missed by neonatal screening (sensitivity was 100%). The incidence of classical 21-OHD and 11ß-OHD in the screened population was 1:15,067 and 1:60,270, respectively. Conclusion: Turkish neonatal CAH screening effectively led to earlier diagnosis of 21-OHD and 11ß-OHD, using steroid profiling as a second-tier test. This will result in improved care of these patients in the future. [ABSTRACT FROM AUTHOR]

Background Glucocorticoid replacement therapy in congenital adrenal hyperplasia ( CAH) is challenging, especially in children, because both over- and under-dosing may have profound and long-lasting adverse effects. Clinical follow-up parameters are largely nonspecific and slow to develop. Steroid concentrations in scalp hair may be a useful monitoring tool, as it provides information on both long-term steroid precursor and glucocorticoid exposure. Aim We aimed to evaluate scalp hair steroid precursor concentrations as a monitoring tool for treatment follow-up in children with CAH. Methods Scalp hair 17-hydroxyprogesterone (17- OHP) and androstenedione concentrations, measured by LC- MS/ MS, of children with CAH ( N = 26) were correlated with concentrations in serum and saliva, and compared to scalp hair concentrations in patient controls with adrenal insufficiency ( AI) ( N = 12) and healthy controls ( N = 293). Results Hair cortisol concentrations were higher in children with CAH, compared to both healthy controls ( P < 0·001) and patient controls ( P = 0·05), and did not differ significantly between patient controls with AI and healthy controls. Concentrations of androstenedione in scalp hair were strongly correlated with concentrations in serum (ρ = 0·72, P < 0·001) and saliva (ρ = 0·82, P = 0·002). This was also seen for 17- OHP in hair with serum (ρ = 0·94, P < 0·001) and saliva (ρ = 0·69, P = 0·009). Both hair 17- OHP and androstenedione were higher in CAH patients (mean concentration 17- OHP 2·9 pg/mg; androstenedione 1·3 pg/mg), when compared to healthy controls (17- OHP 0·44 pg/mg; androstenedione 0·65 pg/mg) and when compared to patients with AI (17- OHP 0·12 pg/mg; androstenedione 0·32 pg/mg). Conclusion This study shows that scalp hair 17-hydroxyprogesterone and androstenedione concentrations seem to be a promising parameter for treatment monitoring in patients with CAH. [ABSTRACT FROM AUTHOR]

Background/Aim: Periodic measurement of plasma concentrations of cortisol precursors on a clinic visit may be of limited value in patients with congenital adrenal hyperplasia because it does not reflect a patient's circadian patterns of adrenal steroid secretion. Steroid profiling in dried blood spots (DBS) may allow for more frequent and sensitive monitoring. Methods: We compared the agreement between 17α-hydroxyprogesterone (17-OHP) and androstenedione (D4A) levels determined from DBS samples and concurrently collected serum samples. Blood was drawn from 9 congenital adrenal hyperplasia patients every 4 h over a 24-hour period. Serum and DBS steroid levels were measured by liquid chromatography tandem mass spectrometry. Results: DBS determinations of 17-OHP overestimated corresponding serum levels (mean difference 1.67 ng/ml), and underestimated D4A serum levels (mean difference 0.84 ng/ml). However, the DBS assay yielded excellent agreement (97%) with serum 17-OHP, but did considerably poorer for D4A (31%). Conclusions: Our results indicate an excellent agreement between DBS and serum 17-OHP measurements to identify the peaks and troughs associated with an individual's circadian pattern. Larger-scale studies are required to evaluate the utility of DBS for home monitoring and to determine if more frequent monitoring leads to improved clinical outcomes. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Salivary concentrations of unconjugated steroids reflect those for free steroids in serum although concentrations may differ because of salivary gland metabolism. Samples for salivary steroid analysis are stable for up to 7 days at room temperature, one month or more at 4°C and three months or more at —20°C. When assessed against strict criteria, the evidence shows that salivary cortisol in evening samples or following dexamethasone suppression provides a reliable and effective screen for Cushing's syndrome. Sequential salivary cortisol measurements are also extremely helpful for the investigation of suspected cyclical Cushing's syndrome. There is potential for the identification of adrenal insufficiency when used with Synacthen stimulation. Salivary 17-hydroxyprogesterone and androstenedione assays are valued as non-invasive tests for the homemonitoring of hydrocortisone replacement therapy in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The diagnostic value of salivary oestradiol, progesterone, testosterone, dehydroepiandrosterone and aldosterone testing is compromised by rapid fluctuations in salivary concentrations of these steroids. Multiple samples are required to obtain reliable information, and at present the introduction of these assays into routine laboratory testing is not justified. [ABSTRACT FROM AUTHOR]

A 16-year-old person, reared as female presented with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters, but without short stature and Turner's stigmata. She was taking steroids after being misdiagnosed as congenital adrenal hyperplasia (CAH). Karyotype analysis revealed 46XY karyotype. There was no evidence of hypocortisolemia (cortisol 9.08 µg/dl, adrenocorticotropic hormone [ACTH] 82.5 pg/ml) or elevated level of 17-OH-progesterone (0.16 ng/ml). Pooled luteinizing hormone (LH) was 11.79 mIU/ml and follicle-stimulating hormone (FSH) was 66.37 mIU/ml. Serum estradiol level was 25 pg/ml (21-251). Basal and 72 h post beta-human chorionic gonadotropin (hCG) levels of androstenedione and testosterone levels were done (basal testosterone of 652 ng/dl and basal androstenedione of 1.17 ng/ml; 72 h post hCG testosterone of 896 ng/dl and androstenedione of 1.34 ng/ml). Magnetic resonance imaging (MRI) pelvis (with ultrasonogrphy [USG] correlation) revealed uterus didelphys with obstructed right moiety and bilateral ovarian-like structures. Right sided gonads and adjacent tubal structures were visualized laparoscopically and removed. Left sided gonads were not visualized and Mullerian remnants were adhered to sigmoid colon. Histopathological examination revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of Leydig cells. No ovarian tissue was seen. Based on these results a diagnosis of 46XY mixed gonadal dysgenesis (MGD) was made, which is rare and is difficult to distinguish from 46XY ovotesticular disorder of sexual differentiation (OT-DSD). The patient was managed with a multidisciplinary approach and fertility issues discussed with the patient's caregivers. [ABSTRACT FROM AUTHOR]