Search

Objective Classic androgens such as dehydroepiandrosterone, androstenedione, and testosterone are generally measured for diagnosis and treatment monitoring in children and adolescents with hyperandrogenism, as can occur in congenital adrenal hyperplasia, premature pubarche, or polycystic ovarian syndrome. However, adrenally-derived 11-oxygenated androgens also contribute to the androgen pool and should therefore be considered in clinical management. Nevertheless, paediatric reference intervals are lacking. Therefore, we developed a serum assay to establish reference intervals for four 11-oxygenated androgens in addition to four classic androgens. Design Reference interval study for serum 11-oxygenated androgens in children. Methods We developed and validated a sensitive liquid chromatography-tandem mass spectrometry assay and quantified eight serum androgens, including four 11-oxygenated androgens, in serum of 256 healthy children (aged 0-17 years old). An age-dependency for all androgens was observed, and therefore we divided the cohort based on age (prepubertal [ n = 133; 94 boys, 39 girls] and pubertal [ n = 123; 52 boys, 71 girls]) to compute reference intervals (2.5th-97.5th percentiles). Results In the prepubertal group, there was no significant sex-difference for any of the measured androgens. In the pubertal group, androstenedione, testosterone, and dihydrotestosterone showed a significant difference between boys and girls. In contrast, adrenal androgens dehydroepiandrosterone, 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone did not. Conclusions We developed and validated an assay for 11-oxygenated androgens, in addition to four classic androgens and established reference intervals. This enables a comprehensive evaluation of serum androgen status in children with clinical symptoms of hyperandrogenism. [ABSTRACT FROM AUTHOR]

Objective: Treatment of congenital adrenal hyperplasia (CAH) patients with glucocorticoids is often challenging since there is a delicate balance between over‐ and undertreatment. Treatment can be monitored noninvasively by measuring salivary androstenedione (A4) and 17‐hydroxyprogesterone (17‐OHP). Optimal treatment monitoring requires the establishment of reference values in saliva. Design: A descriptive study. Patients: For this study saliva of 255 healthy paediatric and adult volunteers with an age range of 4–75 years old was used. Measurements: We developed a sensitive liquid chromatography‐tandem mass spectrometry method, assessed salivary A4 and 17‐OHP stability, and measured A4 and 17‐OHP concentrations in saliva collected in the morning, afternoon, and evening. Results: We quantified A4 and 17‐OHP concentrations in the morning, afternoon, and evening and demonstrated that there is a significant rhythm with the highest levels in the morning and decreasing levels over the day. A4 and 17‐OHP concentrations display an age‐dependent pattern. These steroids remain stable in saliva at ambient temperature for up to 5 days. Conclusions: Good stability of the steroids in saliva enables saliva collection by the patient at home. Since salivary A4 and 17‐OHP display a diurnal rhythm and age‐dependent pattern, we established reference values for both children and adults at three time points during the day. These reference values support treatment monitoring of children and adults with CAH. [ABSTRACT FROM AUTHOR]

Context: Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done. Objective: We aimed to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART. Methods: Using liquid chromatography-tandem mass spectrometry, steroids were measured in left (n = 7) and right (n = 4) spermatic vein and simultaneously drawn peripheral blood (n = 7) samples from 7 men with 21OHD and TART. For comparison, we also measured the peripheral steroid concentrations in 5 adrenalectomized patients and 12 age- and BMI-matched controls. Additionally, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation. Results: Compared with peripheral blood from 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11ß-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11ß-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone and lower levels of A4 and 11OHA4 after ACTH stimulation compared with adrenal cells, indicating ACTH-induced production of testosterone in TART. Conclusion: In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vs peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive. [ABSTRACT FROM AUTHOR]