Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas

As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha-subunit-secreting adenomas, respectively. Six of the 7 patients with FSH-secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4±15.4 IU/I to a nadir of 20.3+11.9 IU/I (−17%, p<0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit-secreting adenomas. D-Trp6-GnRH administration to patients with FSH-secreting adenomas produced a sharp increase in FSH (+115%) and alpha-subunit levels on the second day after the injection, and high values persisted for two weeks. Serum LH and testosterone concentrations declined to hypogonadal values following the initial increase. We conclude that the combined use of these tests may be of value in determining the potential gonadotroph nature of adenomas. However the great heterogeneity observed in the individual responses limits the use of these provocative tests in a given patient suspected of harboring gonadotroph adenoma.