FSH-producing pituitary neuroendocrine tumor as a cause of ovarian hyperstimulation syndrome

Takuya Kitamura; Kazutaka Nanba; Kento Doi; Naoya Kishimoto; Kaoru Abiko; Ryo Kuwahara; Koki Moriyoshi; Naoko Inoshita; Tetsuya Tagami

doi:10.1530/EDM-23-0119

FSH-producing pituitary neuroendocrine tumor as a cause of ovarian hyperstimulation syndrome

Endocrinol Diabetes Metab Case Rep. 2024 Feb 28;2024(1):23-0119. doi: 10.1530/EDM-23-0119. Print 2024 Jan 1.

Authors

Takuya Kitamura^{1

2}, Kazutaka Nanba^{1

2}, Kento Doi³, Naoya Kishimoto⁴, Kaoru Abiko⁴, Ryo Kuwahara⁵, Koki Moriyoshi⁶, Naoko Inoshita⁷, Tetsuya Tagami^{1

2}

Affiliations

¹ Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
² Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
³ Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
⁴ Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
⁵ Department of Radiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
⁶ Department of Diagnostic Pathology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
⁷ Department of Pathology, Moriyama Memorial Hospital, Tokyo, Japan.

Abstract

Summary: Functioning gonadotroph tumors are rare neoplasms that can cause ovarian hyperstimulation syndrome (OHSS) in women of reproductive age. Here, we present a case of a follicle-stimulating hormone (FSH)-producing pituitary neuroendocrine tumor (PitNET) with irregular menstrual cycles and OHSS in a Japanese woman. A 34-year-old woman with bilateral multi-cystic ovarian mass was referred to our hospital for ovarian surgery. The imaging feature of magnetic resonance imaging (MRI) of the ovary and elevated estradiol levels with normal FSH and low luteinizing hormone (LH) levels led us to suspect the presence of a functioning gonadotroph PitNET. MRI revealed a 19-mm pituitary tumor, and increased tracer uptake was observed in the pituitary lesion on 111In-pentetreotide scintigraphy. Transsphenoidal tumor resection resulted in the resolution of the ovarian enlargement, normalization of her menstrual cycles, and spontaneous pregnancy. Immunohistochemistry (IHC) of the resected tumor for pituitary transcription factors, including steroidogenesis factor 1 (SF1) and estrogen receptor alpha, demonstrated positive immunoreactivity, whereas IHC for pituitary-specific positive transcription factor 1 was negative, suggesting that the tumor belonged to the SF1 lineage of PitNETs (gonadotroph tumor). The tumor cells showed positive expression of FSHβ, while LHβ was mostly negative. Consistent with the high pituitary tumor uptake observed on 111In-pentetreotide scintigraphy, the pituitary tumor showed positive expression of somatostatin receptor 2A. Detailed clinical and histological evaluations will provide useful information to understand these rare functioning gonadotroph tumors better.

Learning points: Functioning gonadotroph tumors are very rare neuroendocrine tumors of pituitary origin. Women of reproductive age presenting with bilateral multi-cystic ovarian enlargement, irregular menstrual cycles, and hyperestrogenemia under unsuppressed follicle-stimulating hormone (FSH) levels should be evaluated for FSH-producing tumor. Raising awareness of OHSS due to functioning gonadotroph tumors is crucial to prevent unnecessary ovarian surgery. Comprehensive histological analysis may provide useful information to better understand the characteristics of functioning gonadotroph tumors.