EFFECTS OF LONG-TERM TREATMENT WITH THE GONADOTROPIN-RELEASING-HORMONE ANALOG NAFARELIN IN PATIENTS WITH NONFUNCTIONING PITUITARY-ADENOMAS

The supposed origin of non-functioning pituitary adenomas (NEPA) from gonadotrophs prompted us to investigate the effects of the gonadotropi n-releasing hormone (GnRH) analog nafarelin on hormonal and tumoral pa rameters in eight patients with NFPA, previously unsuccessfully operat ed and all hypogonadal. Nafarelin was administered intranasally for 1 year to all patients. Four patients received a dose of 1200 mu g/day; the remaining four received 800 mu g/day for 3 months, which was subse quently increased to 1200 mu g/day. Basal gonadotropin and alpha-subun it (alpha SU) levels were low-normal. In four patients (nos. 1,2,3,5) nafarelin significantly lowered luteinizing hormone (LH) levels, and a lso follicle-stimulating hormone (FSH) in three of them (nos. 1,2,3). Persistent FSH stimulation occurred in three patients (nos. 6,7,8), wi th a transient slight LH increase only in patient no. 8. In one patien t (no. 7), alpha SU levels were persistently stimulated. Hormonal resp onses to an acute GnRH test during nafarelin administration were gener ally blunted when compared to the pretreatment responses. Immunofluore scence results, obtained before treatment in five adenomas (nos. 2,3,4 ,6,7), had been as follows: positive for FSH-beta in all: negative for LH-beta in all, except a few positive cells in case no. 4; positive f or alpha SU in three (nos. 2,3,7). No changes of visual field and tumo r size occurred in any patient during treatment. However, one patient who showed a persistent increase in FSH levels exhibited left palpebra l ptosis after 12 months of therapy and underwent a second transspheno idal surgery. In conclusion: NFPA behave heterogeneously in terms of h ormonal responses to GnRH analog therapy; long-term nafarelin treatmen t was unsuccessful in reducing the size of NFPA; and stimulation rathe r than inhibition of gonadotropin levels may suggest discontinuance of GnRH analog therapy in NFPA.