Background: Premature adrenarche (PA) is defined as the appearance of pubic and/or axillary hair in girls younger than 8 years old and caused by the rise in adrenal androgen production including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (A4). DHEAS≥40 µg/dL is accepted as the biochemical marker of adrenarche. However, adrenals also produce 11-oxygenated C19 androgens such as 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT). The aim of our study was to investigate the relation of 11-oxygenated C19 androgens with the clinical and biochemical characteristics of PA.
Subjects and Methods: A cross-sectional study was conducted to quantitate plasma DHEA, DHEAS, A4, androsterone, 17OH-pregnenolone, 11OHA4 and 11OHT using tandem mass spectrometry (LCMS/MS) in 53 girls with idiopathic PA aged between 3.6-8.5 years. Age-matched 35 girls without PA were defined as the control group. Anthropometric data were collected. Advanced bone age was defined as chronological age/bone age (CA/BA) ratio <1.1. DHEAS >1300 µg/l was defined as exaggerated PA.
Results: Fourty-nine patients had Tanner 2, four had Tanner 3 pubic hair, and all had Tanner 1 breast development. The height and BMI-SDS were higher in the patients compared to controls (P < 0.001). Mean CA and BA of the patients were 6.8±1.1 and 7.6±1.4 years, respectively. Median concentrations of DHEA, DHEAS, A4, androsterone, 17OH-pregnenolone, 11OHA4 and 11OHT were 1.099, 559.3, 0.275, 0.677, 0.4685, 6.64 and 0.0465 µg/l, respectively. While DHEA, DHEAS, A4, androsterone and 17OH-pregnenolone concentrations were higher (P < 0.0001), no difference in 11OHA4 and 11OHT concentrations were noted in patients compared to controls. In patient group, a positive correlation between 11OHA4 and DHEA, DHEAS, A4 and 17OH-pregnenolone (P < 0.0001, 0.03, 0.004 and <0.0001, respectively) were observed, while no correlation existed between 11OHT and others. Patients with advanced BA had higher 11OHA4 (P = 0.01) and DHEA (P = 0.04) than the ones without advanced BA. CA/BA ratio was negatively correlated with 11OHA4, DHEA and 17OH-pregnenolone (P = 0.003, 0.008, 0.001). There was no difference in 11OHA4 levels between patients with exaggerated PA and the others (P = 0.410). In the patient group, 11OHA4 concentrations were similar in overweight/obese patients and patients with normal BMI. Plasma DHEAS, DHEA and A4 showed higher sensitivity to segregate PA patients than 11OHA4 (area under curve: 0.87, 0.80, 0.79 and 0.62 for DHEAS, DHEA, A4 and 11OHA4, respectively).
Conclusion: Although 11OHA4 correlated with adrenal androgens and associated with advanced bone age, our findings do not ascribe a significant role of 11-oxygenated androgens in the pathophysiology of premature adrenarche in girls.
22 Sep 2021 - 26 Sep 2021