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Effects of long-term treatment with the gonadotropin-releasing hormone analog nafarelin in patients with non-functioning pituitary adenomas

Colombo P, Ambrosi B, Saccomanno K, Bassetti M, Cortelazzi D, Faglia G. Effects of long-term treatment with the gonadotropin-releasing hormone analog nafarelin in patients with non-functioning pituitary adenomas. Eur J Endocrinol 1994;130:339–45. ISSN 0804–4643

The supposed origin of non-functioning pituitary adenomas (NFPA) from gonadotrophs prompted us to investigate the effects of the gonadotropin-releasing hormone (GnRH) analog nafarelin on hormonal and tumoral parameters in eight patients with NFPA, previously unsuccessfully operated and all hypogonadal. Nafarelin was administered intranasally for 1 year to all patients. Four patients received a dose of 1200 µg/day; the remaining four received 800 µg/day for 3 months, which was subsequently increased to 1200 µg/day. Basal gonadotropin and -subunit (SU) levels were low–normal. In four patients (nos. 1,2,3,5) nafarelin significantly lowered luteinizing hormone (LH) levels, and also folliclestimulating hormone (FSH) in three of them (nos. 1,2,3). Persistent FSH stimulation occurred in three patients (nos. 6,7,8), with a transient slight LH increase only in patient no. 8. In one patient (no. 7), SU levels were persistently stimulated. Hormonal responses to an acute GnRH test during nafarelin administration were generally blunted when compared to the pretreatment responses. Immunofluorescence results, obtained before treatment in five adenomas (nos. 2,3,4,6,7), had been as follows: positive for FSH-β in all; negative for LH-β in all, except a few positive cells in case no. 4; positive for SU in three (nos. 2,3,7). No changes of visual field and tumor size occurred in any patient during treatment. However, one patient who showed a persistent increase in FSH levels exhibited left palpebral ptosis after 12 months of therapy and underwent a second transsphenoidal surgery. In conclusion: NFPA behave heterogeneously in terms of hormonal responses to GnRH analog therapy; long-term nafarelin treatment was unsuccessful in reducing the size of NFPA; and stimulation rather than inhibition of gonadotropin levels may suggest discontinuance of GnRH analog therapy in NFPA.

Paolo Colombo, Istituto di Scienze Endocrine, Ospedale Maggiore IRCCS-Pad, Granelli, via F. Sforza 35, 20122 Milano, Italy

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