INHIBIN AND FOLLICLE-STIMULATING-HORMONE LEVELS IN GONADOTROPH ADENOMAS - EVIDENCE OF A POSITIVE CORRELATION WITH TUMOR VOLUME IN MEN

OBJECTIVE Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (iINH) levels correlated with FSH hypersecretion and whether iINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas. PATIENTS Forty-five patients (30 men, 15 women) were retrospectively selected on the basis of immunostaining technique using specific antibodies raised against FSH-beta, LH-beta and glycoprotein alpha-subunit. MEASUREMENTS Immunoreactive inhibin (iINH) was measured by radioimmunoassay using antiserum 1989 raised to bovine inhibin. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography. RESULTS in men (age 21-61 years), iINH levels were positively correlated with FSH levels (Spearman's r = 0.67, P < 0.001), and both IINH and FSH levels were significantly correlated with tumour volume index (Spearman's r = 0.38, P < 0.05 and r = 0.39, P < 0.05 respectively). In the subgroup of men with normal FSH levels (n=17), the correlation of FSH with tumour volume index was high: Spearman's r=0.56, P<0.05. In the post-menopausal women (n = 8, age > 55 years), IINH levels were undetectable or below the follicular phase range regardless of FSH values. In the premenopausal women (n = 7, age 2249 years, follicular phase or amenorrhoea) iINH levels were above follicular phase range in three women including one who had very high FSH levels. CONCLUSIONS These data show that in men with gonadotroph adenoma FSH levels are related to tumour mass and suggest that a significant part of circulating FSH in patients with normal FSH levels arises from the tumour. The significant correlation between iINH and FSH levels demonstrates that tumoral FSH is bioactive and that high iINH levels do not exert any feedback control on tumoral FSH secretion. Therefore the coexistence of high FSH levels with high iINH levels is strongly suggestive of a gonadotroph adenoma. Gonadotroph adenomas seem to represent a unique model of long-term FSH stimulation of inhibin-producing cells, in some way analogous to that created by repetitive administration of exogenous FSH.