Endocrine Abstracts

Background: Neuroendocrine tumors (NET) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations.

Methods: A clinical workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Ovarian tissue was collected after oophorectomy, cultured ex vivo and incubated with anti-hormonal and antitumoral drugs. Electronic medical records were screened for postmenopausal patients with ovarian NET localizations and similar symptoms that presented in our center between 1991 and 2023.

Results: In the index patients, clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells, although a link with gonadotrophins was observed in one case. A retrospective analysis revealed that 21% (14/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Estradiol and gonadotrophin levels were available in 7 of these patients and were compatible with aberrant estradiol production in postmenopausal women.

Conclusions: Together, these findings support the presence of a novel NET-associated hormonal syndrome, which is presumably caused by paracrine effects of infiltrating NET cells on ovarian steroidogenesis.