There are other diseases that can result in similar groups of symptoms in women, most importantly Polycystic Ovarian Syndrome (PCOS, multiple benign cysts of the ovary associated with increased androgen levels) and Congenital Adrenal Hyperplasia (CAH, see section on CAH). Diagnosis aims to exclude these biochemical non-surgical causes from tumour causes that may require surgical intervention.
The main principles are:
Testosterone Testosterone is one of the main androgens produced at the end of the steroid synthesis pathway in the adrenal gland and gonadal tissue (see section on congenital adrenal hyperplasia for a diagram of this pathway). Testosterone is raised in all androgen-secreting tumours, with malignant tumours generally producing the highest concentrations. It is normally over twice the upper limit of the normal concentration, higher than the raised testosterone in PCOS.
Other androgens Other androgens from the steroid pathway such as androstenedione and dehydroepiandrosterone sulphate (DHEAS) are also raised in ASTs. It is these androgens that help distinguish between ASTs and congenital adrenal hyperplasia (CAH). The earlier androgen precursors from the sex steroid pathway (e.g. 17-hydroxy-progesterone, 17-OHP) are raised more in CAH than in ASTs and increase more after stimulation with ACTH.
Examination of pituitary-adrenal axis As explained in the physiology section, the pituitary releases ACTH to stimulate the adrenal cortex to produce cortisol. To a much more limited extent, the ACTH also stimulates aldosterone and androgen production. Therefore one would expect that in gradual suppression of the pituitary-adrenal axis with dexamethasone (a glucocorticoid - see physiology section and section on Cushing's syndrome), the cortisol levels would drop first, and then the androgen levels. In the presence of an AST which is still responsive to pituitary ACTH, i.e. a benign adrenal tumour, this suppression of the already elevated levels should be slight but still there. In the case of an AST which is autonomous having lost its sensitivity to pituitary ACTH, i.e. a malignant tumour, there should be no suppression at all.
This helps distinguish more advanced tumours from more benign ones but does not distinguish between adrenal and ovarian ASTs.
CT and MRI After these less expensive studies have identified a likely cause, the expensive imaging techniques of CT and MRI can be employed to more precisely localise a tumour. For those tumours of greater than 2cm diameter accuracy is 95%.
Ultrasound Transvaginal ultrasound (where the probe examines the pelvis from within the vagina) can examine and localise ovarian tumours well.
Venous sampling In the absence of unequivocal results from these studies, specific and more invasive sampling of blood in veins directly draining the ovaries or adrenal glands can be done to precisely localise the source of androgens. Tubes are passed through the femoral veins in the leg into the adrenal veins and ovarian veins and blood samples taken. This is difficult to do and more risky for the patient and so is not an initial diagnostic tool.