Impaired estrogen-induced negative feedback on gonadotropin secretion in patients with gonadotropin-secreting and nonfunctioning pituitary adenomas.
BACKGROUND
Several in vitro studies suggest that gonadotropin-secreting pituitary adenomas (Gn-omas) and non functioning pituitary adenomas (NFPA) originate from gonadotroph cells. Patients with Gn-oma and NFPA frequently show abnormal gonadotropin response to TRH. The aim of the study was to investigate whether the estrogen-induced negative feedback is operating in either patients with Gn-oma or NFPA.


METHODS
Serum gonadotropin levels were evaluated at 24 h after ethinylestradiol administration (1 mg per os; EE2 test) in seven patients with a diagnosis of Gn-oma, based on the presence of high follicle-stimulating hormone (FSH) and/or lutenising hormone (LH) levels with normal or high levels of sex steroids, in 22 patients with NFPA with normal or low levels of gonadotropin and sex steroids, and 30 sex- and age-matched healthy subjects. A normal response to EE2 test was arbitrarily defined as a serum LH and FSH decrease of at least 40 and 30% below basal levels.


RESULTS
Among patients with Gn-oma, only one had a normal FSH inhibition and another, a normal LH inhibition. Among the 22 patients with NFPA, the EE2 test caused a normal FSH or LH reduction in 10 and 15, respectively, while a normal reduction of both FSH and LH was observed in nine.


CONCLUSIONS
The study demonstrates that estrogen-induced negative feedback of gonadotropin secretion is disrupted in almost all patients with Gn-oma and in half of those with NFPA. This defective feedback is reminiscent of the resistance to thyroid hormones and glucocorticoids observed in patients with thyroid-stimulating hormone- (TSH-) and adrenocorticotropic hormone- (ACTH-)secreting adenomas, respectively.
Lania
A
A
University of Milan, Ospedale Maggiore IRCCS, San Raffaele IRCCS, Milan, Italy.
Gangi
E
E
Romoli
R
R
Losa
M
M
Travaglini
P
P
Meringolo
D
D
Ambrosi
B
B
Faglia
G
G
Beck-Peccoz
P
P
Spada
A
A
D000236:Adenoma / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D045166:Estradiol Congeners / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D025461:Feedback, Physiological / Q000187:drug effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009934:Organization and Administration; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage*
D045166:Estradiol Congeners; D006065:Gonadotropins, Pituitary; D004997:Ethinyl Estradiol; D013973:Thyrotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone