Luteinizing Hormone- and α-Subunit-Secreting Pituitary Tumor: Positive Feedback of Estrogen*

Abstract

Gonadotropin-secreting pituitary tumors have rarely been reported in eugonadal patients. A 30-yr-old man, sexually potent, with normal-sized testes, but azoospermic, presented with a pituitary tumor documented by an enlarged sella turcica and an intrasellar mass by pneumoencephalography and computerized tomography. Testicular biopsy demonstrated marked Leydig cell hyperplasia and decreased spermatocyte maturation. The plasma LH level was elevated at 207 mlU/ml (normal, 6–26 mlU/ml), but the FSH level was low at 2 mlU/ml (normal, 5–25 mlU/ml). Plasma testosterone was elevated at 1500 ng/dl (normal, 300–1000 ng/dl); othergonadal steroids were also increased in the circulation, i.e. 5α-dihydrotestosterone, androstenedione, estradiol, and 17α-hydroxyprogesterone. The α-subunit was markedly elevated at 72 ng/ml plasma (normal, <0.5 to 2.5 ng/ml). The molar plasma α-subunit to LH ratio was 2.8, whereas normal or hypogonadal subjects have ratios less than 1. After 100 μg LRH iv, there was an increase of plasma LH to 444 mlU/ml (114% increment) and of α-subunit to 88 ng/ml (22% increment), both lower increments than those seen in hypogonadal patients. The plasma GH and cortisol reserves were impaired; basal plasma PRL and TSH and their responses to 500 μg TRH iv were evaluated. The peak plasma α-subunitlevel of 88 ng/ml after TRH was identical to that seen after LRH. Furthermore, there was an increase of plasma LH to 249 mlU/ml after TRH. After a transsphenoidal pituitary adenomectomy and the removal of a chromophobe adenoma, plasma LH and α-subunit levels decreased but remained elevated. Gonadal steroids also remained elevated. Tumor cells in culture for 15 days secreted LH and α-subunit, but little FSH or TSH. Five months postoperatively, dexamethasone caused no decrease in plasma LH or α-subunit or in their percent increments after LRH. However, 3 mgestradiol orally daily for 5 days increased basal plasma LH to 127 mlU/ml and α-subunitto 34 ng/ml; after the infusionof LRH, peak plasma LH and α-subunit also increased. LH hypersecretion by a pituitary tumor may occur in the absence of FSH secretion. Hypersecretion of α-subunit, with elevated molar ratios of α-subunit to compete glycoprotein hormone, occurs in LH-secreting as well as TSH-secreting pituitary tumors. Gonadotropin-secreting pituitary tumors may not be completely autonomous, as evidenced by partial responsiveness to LRH and paradoxical responses to TRH and estrogen.