Amenorrhoea and Failure to Virilize in a Patient With a Testosterone Secreting Granulosa Cell Tumour

Abstract

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.

Granulosa cell tumor associated with secondary amenorrhea and serum luteinizing hormone elevation

“…2 There have been only two reported cases of GCT associated with high LH levels. 2,5 In the present report, the patient presented with secondary amenorrhea and serum LH elevation at the time of the initial treatment and at recurrence. In the present patient, the inappropriate elevation of LH was thought to have interfered with normal follicular development and ovulation.…”

Androgenic adult granulosa cell tumor in a teenager: a case report and review of the literature

“…The most common gross appearance in virilizing granulosa cell tumor was a solid mass in approximately 14 patients (3,4,12,13–18,21–23) , a cystic mass in 10 patients (9,11,17,19,20) , a mixed solid/cystic mass in 4 patients (4,8,17,24) , and a multiloculated cyst in 2 patients (6,7) . The tumor in our case was also a thin‐walled, multilocular cyst.…”

“…The most common clinical symptoms were hirsutism, amenorrhea, abdominal mass, and deepening of the voice. In more than half of the cases, elevated serum or plasma levels of testosterone were reported (7,9,11–15,18–24) . After tumor removal, the androgenic clinical findings usually disappeared and plasma testosterone levels returned to normal limits (11–14,17,19–24) .…”

“…Granulosa cell tumors are usually associated with manifestation of hyperestrogenism and are rarely associated with virilization. Considering all age groups, less than 35 cases of virilizing adult‐type granulosa cell tumors have been reported in the literature (3–24) . So far, only two such cases have been reported in patients under 15 years of age (20,23) .…”

Changing pattern of gonadotropins in a patient with an adrenal-androgen secreting tumor

“…Additionally, mean basal LH levels and LH pulse number and amplitude were lower in patients with ovarian tumors than compared to those with PCOS or normal women,10 suggesting different mechanisms of hypothalamic or pituitary feedback. In the same way, gonadotropin levels in patients with adrenal androgen‐secreting tumors have also been reported as normal or suppressed, and significantly lower than in patients with non‐tumors forms of hyperandrogenism 5. …”