Diurnal salivary androstenedione and 17‐hydroxyprogesterone levels in healthy volunteers for monitoring treatment efficacy of patients with congenital adrenal hyperplasia

Adriaansen, Bas P. H.; Kamphuis, Johannes S.; Schröder, Mariska A M; Olthaar, André J.; Bock, Carina; Brandt, André; Stikkelbroeck, Nike M. M. L.; Lentjes, Eef G.W.M.; Span, P.N.; Sweep, Fred C.G.J.; Grinten, Hedi L Claahsen–van der; Herwaarden, Antonius E. van

doi:10.1111/cen.14690

Cited by 11 publications

(4 citation statements)

References 35 publications

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“…Diurnal variation in sample concentrations was also noted in testosterone (T), 17α-hydroxyprogesterone (17aOH-P4), dehydroepiandrosterone (DHEA), progesterone (P4) and androstenedione (A4). This circadian variation is well described in the literature for all four of these steroids, although studies do suggest a loss of this rhythm with increasing age [ 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 58%

Using LC-MS/MS to Determine Salivary Steroid Reference Intervals in a European Older Adult Population

et al. 2023

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A number of steroids, including glucocorticoids and sex hormones, have been associated with neurodegenerative and cardiovascular conditions common in aging populations. The application of liquid chromatography tandem mass spectrometry (LC-MS/MS) steroid analysis offers an opportunity to conduct simultaneous multiplex steroid analysis within a given sample. In this paper, we describe the application of an LC-MS/MS steroid analysis method for the assessment of reference ranges of steroids in human saliva samples (200 µL) collected from older adults (age 50 years and above) enrolled in a European cohort investigating the risk for Alzheimer’s dementia. Saliva samples were prepared using supported liquid extraction (SLE) along with a calibration curve and analysed using a Waters I-Class UPLC (Ultra Performance Liquid Chromatography) and a Sciex QTrap 6500+ mass spectrometer. Mass spectrometry parameters of steroids were optimised for each steroid and a method for the chromatographic separation of 19 steroids was developed. Lower limits of quantitation (LLOQs), linearity and other method criteria were assessed. In total, data from 125 participants (500 samples) were analysed and assessed for reference ranges (64 male, 61 female). A total of 19 steroids were detected in saliva within the range of the method. There were clear diurnal patterns in most of the steroid hormones detected. Sex differences were observed for androstenedione (A4), testosterone (T), cortisone (E) and aldosterone (Aldo). In the first sample of the day, dehydroepiandrosterone (DHEA) was significantly higher in healthy volunteers compared to those with Alzheimer’s disease biomarkers. This LC-MS/MS method is suitable for the analysis of 19 steroids in saliva in adults.

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Section: Discussionmentioning

confidence: 58%

Using LC-MS/MS to Determine Salivary Steroid Reference Intervals in a European Older Adult Population

et al. 2023

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“…For example, Javier et al 33 found that androstenedione can predict the progression of Frailty Syndrome in patients with localized breast cancer treated with aromatase inhibitors. Adriaansen et al 34 reported that diurnal salivary androstenedione levels in healthy volunteers for monitoring treatment efficacy of patients with congenital adrenal hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Identifies and Validates Serum Androstenedione as Novel Biomarker for Diagnosing Primary Angle Closure Glaucoma and Predicting the Visual Field Progression

Ren

Qiu

et al. 2023

Preprint

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Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness worldwide, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. we aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Methods: Here, we used a 5-phases (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui central hospital), cross-sectional, prospective cohort study design to perform widely-targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-Nearest neighbor, and Gaussian NB) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, areas under the receiver operating characteristic curve [AUC] =1.0 [95%CI, 1.00-1.00]; discovery set, AUC=0.85 [95%CI, 0.80-0.90]) and validation phases (internal validation, AUC=0.86 [95%CI, 0.81-0.91]; external validation, AUC=0.87 [95%CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, P=0.038) and significantly (P=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio=2.71 [95% CI: 1.199-6.104], P=0.017) were associated with faster visual field progression. Conclusion: Our study demonstrates serum androstenedione as a novel biomarker that can be used to diagnose PACG and predict visual field progression.

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“…When compared with saliva samples collected only before 11:00 h, the difference in age-matched testosterone concentrations with previous studies was reduced emphasizing the importance of specimen collection time. Salivary androgens exhibit diurnal rhythms ( 5 , 8 , 16 , 34 , 35 ) and the magnitude of the fall in testosterone across the day depends on the age and stage of pubertal development ( 11 , 34 , 36 , 37 ). The current study found that, in boys, salivary testosterone concentration showed a very high correlation with salivary A4.…”

Section: Discussionmentioning

confidence: 99%

Salivary androgens in adolescence and their value as a marker of puberty: results from the SCAMP cohort

Patjamontri,

Spiers,

Smith

et al. 2023

Endocrine Connections

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Context: Salivary androgens represent non-invasive biomarkers of puberty that may have utility in clinical and population studies. Objective: To understand normal age-related variation in salivary sex steroids and demonstrate their correlation to pubertal development in young adolescents. Design, Setting, and participants: School-based cohort study of 1,495 adolescents at two time points for collecting saliva samples approximately two years apart. Outcome measures: The saliva samples were analyzed for five androgens (testosterone, androstenedione (A4), 17-hydroxyprogesterone (17-OHP), 11-ketotestosterone (11-KT) and 11β-hydroxyandrostenedione (11-OHA4)) using LC-MS/MS; in addition, salivary dehydroepiandrosterone (DHEA) and oestradiol (OE2) were analyzed by ELISA. Pubertal staging was self-reported using the pubertal development scale (PDS). Results: In 1,236 saliva samples from 903 boys aged between 11-16 years, salivary androgens except DHEA exhibited an increasing trend with an advancing age (ANOVA, p<0.001), with salivary testosterone and A4 concentration showing the strongest correlation (r=0.55, p<0.001 and r=0.48, p<0.001, respectively). In a subgroup analysis of 155 and 63 saliva samples in boys and girls, respectively morning salivary testosterone concentrations showed the highest correlation with composite PDS scores and voice-breaking category from PDS self-report in boys (r=0.75, r=0.67, respectively). In girls, salivary DHEA and OE2 had negligible correlations with age or composite PDS scores. Conclusion: In boys aged 11-16 years, increase in salivary testosterone and A4 is associated with self-reported pubertal progress and represent valid non-invasive biomarkers of puberty in boys.

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Diurnal salivary androstenedione and 17‐hydroxyprogesterone levels in healthy volunteers for monitoring treatment efficacy of patients with congenital adrenal hyperplasia

Cited by 11 publications

References 35 publications

Using LC-MS/MS to Determine Salivary Steroid Reference Intervals in a European Older Adult Population

Using LC-MS/MS to Determine Salivary Steroid Reference Intervals in a European Older Adult Population

Metabolomics Identifies and Validates Serum Androstenedione as Novel Biomarker for Diagnosing Primary Angle Closure Glaucoma and Predicting the Visual Field Progression

Salivary androgens in adolescence and their value as a marker of puberty: results from the SCAMP cohort

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