Human pituitary gonadotroph adenomas: Relationship between gonadotropin immunoreactivity and clinicopathologic findings

Clinically nonfunctioning pituitary adenomas are generally seen in middle-aged and older patients, and most of them may be gonadotropin-immunoreactive adenomas, that is, gonadotroph adenomas. Our aim was to clarify the relationships between the gonadotropin immunoreactivity, patient age, sex, and microscopic features in 68 gonadotroph adenomas with special reference to either gonadotropin-immunonegative or intensively immunopositive adenomas. There were 68 patients with gonadotroph adenomas (mean age 54.7 yr) in the study, including 39 men (mean age, 52.8 yr) and 29 women (mean age, 57.4 yr). The adenomas were diagnosed on the basis of immunoreactivity for gonadotropins (β-subunit of follicle-stimulating hormone: β-FSH; β-subunit of luteinizing hormone: β-LH; and the α-subunit of the pituitary glycoprotein hormone: α-SU) by the avidin-biotin peroxidase complex (ABC) method or by the characteristic histological feature of a perivascular or pseudorosette pattern, that is, the cells aligned polarity directed toward the capillaries. Fifty-four adenomas (79%) were positive for one or more gonadotropin subunits and β-FSH was the most common subunit encountered (47/68, 69%). In men β-FSH immunoreactivity was similar among all age groups, whereas in women, it was significantly less frequent in patients who were 50 yr or older, compared to younger patients. Gonadotropin-immunonegative adenomas were seen in 4 men (mean age, 46.8 yr) and 10 women (mean age, 61.5 yr). Among the 22 women aged 50 or over, β-FSH was negative in 12 tumors (55%), whereas in men of the same age group, it was negative in 3 of 26 tumors (12%). The reason for this reduced frequency is not clear, but the postmenopausal state and associated changes in the systemic endocrine state may play a role. Adenomas that were intensively positive for β-FSH showed an unusual morphology other than the characteristic perivascular pattern, regardless of the patients' age and sex; the tumor cells had abundant vacuolated cytoplasms and were arranged in a sheet-like pattern. Electron microscopically, these cells with abundant cytoplasm had well-developed Golgi complexes, suggesting an enhanced activity of gonadotropin synthesis, and these adenomas seem to be endocrinologically, if not clinically, functioning. The results indicate that gonadotroph adenomas may vary from functioning adenomas with intense immunoreactivity and unusual histology to immunonegative and less functioning adenomas, which are more frequent in women 50 yr or older.