11-oxygenated androgens and their relation to hypothalamus-pituitary-gonadal-axis disturbances in adults with congenital adrenal hyperplasia

Auer, Matthias; Paizoni, Luisa; Neuner, Meike; Lottspeich, Christian; Schmidt, Heinrich; Bidlingmaier, Martin; Hawley, James; Keevil, Brian; Reisch, Nicole

doi:10.1016/j.jsbmb.2021.105921

Cited by 16 publications

(5 citation statements)

References 37 publications

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“…In a recent publication that measured all seven of them using a validated mass spectrometry (MS) assay ( 21 ), 11-oxygenated androgens were associated with poor prognosis in a cohort of 1793 men with localized prostate cancer undergoing prostatectomy ( 25 ). Other studies using either non validated and validated assays (discussed in reference 21 ), reported few of these non-canonical 11-oxygenated androgens in a number of other clinical conditions, including androgen excess conditions, Cushing’s syndrome and congenital adrenal hyperplasia, all using validated MS methods ( 24 , 26 – 29 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer

Dahmani

Caron

Simonyan³

et al. 2023

Front. Endocrinol.

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ContextRecent evidence support that androgens play an important role in the etiology of endometrial cancer (EC). Adrenal-derived 11-oxygenated androgens are highly potent agonists of the androgen receptor (AR), comparable to testosterone (T) and dihydrotestosterone (DHT) that have not been studied in the context of EC.MethodologyWe studied a cohort of 272 newly diagnosed postmenopausal EC cases undergoing surgical treatment. Circulating concentrations of seven 11-oxygenated androgens including precursors, potent androgens and their metabolites were established in serum samples collected before and 1 month after surgery using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). Free (unconjugated) and total (free + sulfate and glucuronide conjugates following enzymatic hydrolysis) were analyzed in relation to clinicopathological features, recurrence and disease-free survival (DFS).ResultsLevels of 11-oxygenated androgens were weakly correlated to those of canonical androgens such as testosterone (T) and dihydrotestosterone (DHT), with no evidence of their association with clinicopathological features. Levels of 11-oxygenated androgens declined after surgery but remained higher in overweight and obese compared to normal weight cases. Higher levels of preoperative free 11-ketoandrosterone (11KAST) were associated with an increased risk of recurrence (Hazard ratio (HR) of 2.99 (95%CI=1.09-8.18); P=0.03). Postoperative free 11β-hydroxyandrosterone (11OHAST) levels were adversely associated with recurrence and DFS (HR = 3.23 (1.11-9.40); P=0.03 and 3.27 (1.34-8.00); P=0.009, respectively).Conclusion11-oxygenated androgen metabolites emerge as potential prognostic markers of EC.

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Section: Introductionmentioning

confidence: 99%

Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer

Dahmani

Caron

Simonyan³

et al. 2023

Front. Endocrinol.

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“…There are other potential biomarkers than the traditional serum 17OHP levels that may be used for screening of CAH in the clinical management of AIs. The steroids 11-deoxycortisol, 11-ketotestosterone, 21-dexycortisol, and 11-hydroxytestosterone may be more sensitive biomarkers than the traditional serum 17OHP levels, with the potential to facilitate diagnostics of NC CAH ( 31 , 35 – 38 ).…”

Section: Discussionmentioning

confidence: 99%

Congenital adrenal hyperplasia is a very rare cause of adrenal incidentalomas in Sweden

2022

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BackgroundUndiagnosed congenital adrenal hyperplasia (CAH) can cause adrenal incidentalomas, but the frequency is unclear.ObjectivesThis study aimed to investigate the prevalence of CAH in a population with adrenal incidentalomas and report the clinical characterization.Material and methodsThis was a prospective study performed at a regional hospital from 2016 to 2021. Patients with adrenal incidentalomas were investigated with an adrenocorticotropic hormone (ACTH)-stimulation test in addition to hormonal workup. Serum cortisol and 17-hydroxyprogesterone (17OHP) were analyzed. Individuals with a basal or stimulated 17OHP ≥30 nmol/L were classified as suspicious non-classic CAH, and a CYP21A2-gene analysis was performed in these subjects.ResultsIn total, 320 individuals with adrenal incidentalomas were referred to the center, and of these individuals, an ACTH-stimulation test was performed in 222 (median age, 67 (24–87) years; 58.6% women; and 11.7% with bilateral lesions). None of the individuals presented a basal 17OHP ≥30 nmol/L, but there were 8 (3.6%) who did after ACTH stimulation. Four of these subjects (50%) presented bilateral lesions, and the tumor size was larger compared to that of the individuals with a stimulated 17OHP <30 nmol/L (median, 38 (19–66) vs. 19 (11–85) mm, p=0.001). A CYP21A2 variation (p.Val282Leu) was detected in one of the eight subjects with a stimulated 17OHP ≥30 nmol/L, i.e., the patient was a heterozygotic carrier. None of the eight subjects presented with cortisol insufficiency or clinical signs of hyperandrogenism.ConclusionsThe prevalence of non-classic CAH in an adrenal incidentaloma cohort was 3.6% based on stimulated 17OHP and 0% based on gene analysis. CAH should be considered in AI management in selected cases and confirmed by genetic analysis.

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“…40 They are associated with androgen excess disorders, for example PCOS 41 or congenital adrenal hyperplasia. 42,43 Our finding that these androgens dominated in all forms of CS might be a reason, why symptoms of androgen excess such as menstrual disorders, acne and hirsutism are both prominent in patients with ACTH-dependent and ACTH-independent CS-although the classical androgens are suppressed in patients with ACTHindependent CS. It is known, that the 11-oxygenated androgens are nearly as potent as the classical androgens.…”

Section: The 11-oxygenated Androgensmentioning

confidence: 91%

Delineating endogenous Cushing’s syndrome by GC-MS urinary steroid metabotyping

Braun,

Osswald,

Zopp

et al. 2024

eBioMedicine

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11-oxygenated androgens and their relation to hypothalamus-pituitary-gonadal-axis disturbances in adults with congenital adrenal hyperplasia

Cited by 16 publications

References 37 publications

Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer

Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer

Congenital adrenal hyperplasia is a very rare cause of adrenal incidentalomas in Sweden

Delineating endogenous Cushing’s syndrome by GC-MS urinary steroid metabotyping

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