Cushing’s disease (CD) is caused by cortisol excess due to excess adrenocorticotrophin (ACTH) secretion, predominantly due to pituitary tumours. It is often associated with symptoms consistent with hyperandrogenism. However, such symptoms are insufficiently explained by serum androgen levels. 11-Oxygenated C19 (11oxC19) steroids are adrenally derived and stimulated by ACTH.

To investigate whether 11oxC19 steroids may explain the clinical hyperandrogenism observed in CD, Nowotny and colleagues undertook salivary day profiles in women with CD before (n =23) and after (n =13) successful transsphenoidal surgery, as well as in five women with CD treated with metyrapone and five treated with osilodrostat. In addition, 24-h urinary analysis was undertaken.

Pretreatment, women with CD had a significantly elevated AUC of salivary 11oxC19 steroids, including increased 11-hydroxyandrostenedione (11OHA4), compared with controls, as well as an increased AUC of salivary 11-ketotestosterone (11KT).

Testosterone, androstenedione and dehydroepiandrosterone sulfate levels were comparable with controls. After transsphenoidal surgery, 11OHA4 and 11KT and urinary 11-oxo-androsterone were all significantly reduced, compared with preoperative levels. Both osilodrostat and metyrapone blocked 11oxC19 synthesis.

These data suggest that the active androgens responsible for clinical hyperandrogenism in patients with CD are predominantly ACTH-mediated 11oxC19 steroids.

Read the full article in European Journal of Endocrinology.