Fetal gonadotrope cell origin of FSH‐secreting pituitary adenoma – insight into human pituitary tumour pathogenesis

Abstract

We propose that this pituitary adenoma represents an indolent tumour of monohormonal fetal gonadotrope cells that originated early in gestation. Pituitary tumours may therefore arise from abnormal persistence of fetal cell types, with extremely slow growth over many years until reaching a size threshold to generate an endocrine syndrome. Understanding fetal pituitary architecture and function may be more informative for new insights into pituitary tumour pathogenesis than classical theories of cancer biology that invoke unrestrained cell proliferation.

Spontaneous Ovarian Hyperstimulation Syndrome Caused by a Follicle-Stimulating Hormone-Secreting Pituitary Macroadenoma in an Early Pubertal Girl

“…Rarely, however, these tumors may first appear with alteration of the menstrual cycle and ovarian hyperstimulation without neurological signs and symptoms, as it was initially the case in our patient. The effects in the ovary that lead to the formation of multiple cysts and a clinical OHSS could be the result of marginal but sustained FSH secretion together with absence of LH pulses [12]. The fast growth of the pituitary tumor when our patient abandoned the hospital is a noticeable finding.…”

“…It would be unlikely to suspect an FSH-secreting adenoma even in the presence of that finding. Fifteen cases of FSH-secreting adenomas presenting as OHSS were reported in adults [2,3,4,5,6,7,8,9,10,11,12,13] and 2 in the pubertal age. The youngest girl, aged 10.9 years, was admitted to Kumamoto University Hospital with nausea, abdominal distention, and pain.…”

“…The pathogenesis of human pituitary adenomas remains unclear. Davis et al [12] propose that these adenomas represent the proliferation of monohormonal FSH fetal gonadotroph cells originated early in gestation. Pituitary tumors may therefore arise from abnormal persistence of fetal cell types with extremely slow growth over many years, until reaching a size threshold to generate an endocrine syndrome.…”

“…To date a total of 17 cases (2 in children) of OHSS have been published in association with follicle-stimulating hormone (FSH) or α-subunit-producing adenomas [2,3,4,5,6,7,8,9,10,11,12,13,14,15]. In those series, diagnosis of the pituitary tumor was made in most patients only after confirming benign follicular cysts at the ovarian biopsy (10/17).…”

A pituitary adenoma secreting follicle-stimulating hormone with ovarian hyperstimulation: treatment using a gonadotropin-releasing hormone antagonist

“…Inhibin A acts on the normal gonadotrope to reduce FSH secretion. So decreased inhibin responsiveness of the tumor is a possible basis of the persistence of FSH secretion despite ovarian hyperstimulation (20).…”