Amenorrhoea and failure to virilize in a patient with a testosterone secreting granulosa cell tumour.

A 39-year-old woman presented with secondary amenorrhoea in the absence of galactorrhoea, hirsutism or virilization. Investigation revealed a strikingly elevated serum testosterone, dihydrotesterone, free testosterone and LH level. At laparotomy a large granulosa cell tumour was encountered and totally removed. Analysis of the tumour revealed 127 ng of testosterone/mg of tumour tissue. The testosterone was localized immunocytochemically to the granulosa cells, which demonstrated typical ultrastructural characteristics of oestrogen rather than androgen secreting tissue. A study of androgen binding and metabolism prior to tumour resection revealed a normal androgen receptor as evidenced by normal maximum binding, dissociation constant and nuclear uptake. Removal of the tumour resulted in a return to normal of all abnormalities. We conclude that granulosa cell tumours may rarely secret large amounts of testosterone and that in this situation their ultrastructure is unchanged. Furthermore, absence of LH suppression or hirsutism in an amenorrhoeic patient does not dismiss the possibility of a significant androgen-secreting tumour. In this situation, the failure to virilize may be due to a post-nuclear translocational defect.