Abstract
ContextAndrogen excess in women is predominantly due to underlying polycystic ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and severity of androgen excess that should be considered predictive of non-PCOS pathology.ObjectiveWe examined the diagnostic utility of simultaneous measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone (T) to delineate biochemical signatures and cutoffs predictive of non-PCOS disorders in women with androgen excess.DesignRetrospective review of all women undergoing serum androgen measurement at a large tertiary referral center between 2012 and 2016. Serum A4 and T were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased serum androgen underwent phenotyping by clinical notes review.ResultsIn 1205 women, DHEAS, A4, and T were measured simultaneously. PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n = 15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4 (59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS (80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were caused by ACC and severe T excess equally by ACC and OHT.ConclusionsPattern and severity of androgen excess are important predictors of non-PCOS pathology and may be used to guide further investigations as appropriate.
Highlights
MethodsSubjects and clinical protocol We included all women who had undergone measurements of serum dehydroepiandrosterone sulfate (DHEAS), A4, and T as part of routine clinical care at the University Hospital Birmingham NHS Foundation Trust between 1 January 2012 and 31 December 2016
Context: Androgen excess in women is predominantly due to underlying polycystic ovary syndrome (PCOS)
We examined the diagnostic utility of simultaneous measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone (T) to delineate biochemical signatures and cutoffs predictive of non-PCOS disorders in women with androgen excess
Summary
Subjects and clinical protocol We included all women who had undergone measurements of serum DHEAS, A4, and T as part of routine clinical care at the University Hospital Birmingham NHS Foundation Trust between 1 January 2012 and 31 December 2016. From the cohort of patients with simultaneous measurement of serum DHEAS, A4, and T, we identified a patient subset defined by at least one of the three serum androgens increased above the respective local normative reference range. This group underwent further clinical phenotyping by retrospective electronic case note review for age, menopausal status, body mass index, ethnicity, clinical presentation, and the underlying cause of androgen excess. The diagnosis of PCOS was established according to Rotterdam criteria [1]
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