Gonadotropin andα-Subunit Responses to Chronic Gonadotropin-Releasing Hormone Analog Administration in Patients With Glycoprotein Hormone- Secreting Pituitary Tumors*

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Abstract
Pituitary tumors secreting intact glycoprotein hormones (LH, FSH, and TSH) and/or α-subunit are being increasingly recognized. Because chronic administration of GnRH analogs decreases gonadotropin secretion in normal subjects, we investigated gonadotropin and α-subunit responses to chronic GnRH analog administration in five men with glycoprotein hormone-secreting pituitary tumors. Two patients (patients A and B) received the GnRH agonist analog (D-Trp6-Pro9-NEt- LHRH) for 4 weeks as a daily sc dose (8 μg/kg·day). In both, secretion of LH and/or α-subunit increased markedly. Subsequently, three patients received a higher analog dose (32 μg/kg·day) for a longer duration (8 weeks). One patient with a LHand FSH-secreting tumor (patient C) had a highly significant (P < 0.001) fall in serum LH and FSH concentrations; however, α-subunit secretion increased. During a subsequent study, when this patient received a lower dose (8 μg/kg·day) for 8 weeks, gonadotropin suppression also occurred. In two additional patients who received this dose (32 μg/kg·day), it had a persistentagonist effect on FSHβ (patient D) and α-subunit secretion (patient E). A marked increase in a-subunit secretion occurred in all five patients, regardless of whether basal serum α-subunit concentrations were elevated. These patients received the GnRH analog at doses 2–8 times greater than those that suppress gonadotropin secretion in normal men. Serum LH and FSH concentrations decreased in onlyone patient with a gonadotropin- secreting adenoma. The serum LH and FSH responses to acute GnRH stimulation did not predict the gonadotropin responses to chronic GnRH analog administration. Thus, gonadotropin and α-subunit production by most pituitary adenomas is augmentedduring chronic GnRH analog administration, consistent with defective GnRH desensitization in the adenomatous tissue. Despite the heterogeneous gonadotropin responses to the GnRH analog in these patients, serum α-subunit levels increased in all patients, indicating dissociation in the secretion of intact gonadotropins and α-subunit.

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