The present study describes the effect on plasma prolactin values and tumour size of bromocriptine withdrawal in 12 patients who had been treated for macroprolactinomas for a period of 3.5-7 (mean 4.9) years. Pretreatment plasma prolactin values ranged from 12,000 to 210,000 (mean: 66,000) mU/l. Immediately before bromocriptine withdrawal plasma prolactin values were in the normal range (less than 350 mU/l for men; less than 450 mU/l for women). Bromocriptine treatment was associated with tumour reduction in all cases. The following observations were made upon withdrawal of bromocriptine: (1) In 11 patients hyperprolactinaemia redeveloped although plasma prolactin levels remained below 600 mU/l in two of these patients during a follow-up period of 1 year. In the other nine patients bromocriptine treatment was reinstituted after 4-12 weeks. (2) Hyperprolactinaemia was associated with tumour reexpansion in one case and increased density of the tumour in two cases. (3) In one patient plasma prolactin remained undetectable during a follow-up period of 1 year and no tumour re-expansion was found. It is concluded that tumour regrowth is uncommon and of small extent after cessation of long-term bromocriptine treatment for macroprolactinomas.

We have studied seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary macroadenoma, four of whom received long term, high dose octreotide treatment. We have attempted to correlate the presence of somatostatin receptors (SS-R) in the adenomas and the outcome of octreotide treatment, as measured by tumor size, improvements in visual field defects, and hormonal response. The presence of SS-R in the pituitary adenomas was demonstrated in vivo using [111indium]octreotide scintigraphy and in vitro by autoradiography of tissue fragments obtained after transsphenoidal surgery. Adenomas from six of the seven subjects were SS-R positive. High dose (1200 micrograms, sc, daily) octreotide treatment was given to four subjects, three of whom were SS-R positive. Improvement of the visual field defects was observed in three of four patients (including the SS-R-negative subject), although no computed tomographic scan-assessed tumor size reduction was found. Two of four patients showed small but significant reductions in serum FSH concentrations (to 83% and 93% of initial values) with treatment. These in vivo responses to high dose octreotide treatment could not be predicted by pretreatment responses to 200 micrograms TRH or 100 micrograms octreotide. Tissue fragments for cell culture were obtained from six patients, and in vitro release of gonadotropins and/or alpha-subunit could be demonstrated in five cultures. In vitro, octreotide (10 nmol/L) significantly decreased gonadotropiin or subunit release in three of five cultures, whereas bromocriptine (10 nmol/L) significantly reduced the release in four of five cultures and to a significantly greater extent than octreotide. In conclusion, in six of seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary adenoma, SS-R were demonstrated in the tumor. In vitro incubation of adenoma cells with octreotide resulted in mild inhibition of gonadotropin or alpha-subunit release. Although in vivo long term treatment with high doses of octreotide did not result in substantial tumor size reduction, improvement of visual field defects was observed in three of four subjects.

Nineteen patients, seven women and twelve men, with macroprolactinomas characterized by extrasellar extension and basal prolactin levels above 6 U/l were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 3.4 years (range 1.5-5.5 years). Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in sixteen patients. Tumor size was reduced by more than 75% in seventeen patients and by 50-75% in two patients. Tumor reduction was associated with the development of a partial empty sella in fourteen cases. In seventeen cases the pituitary became visible. Diminished visual acuity (six patients), bitemporal hemianopia (nine patients), unilateral and bilateral central scotomas (three patients) and oculomotor palsy (two patients) improved or normalized in all cases. Hypogonadism (all patients), hypothyroidism (nine patients) and hypocorticism (four patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumor size. The good results in this study may be related to the continued use of a fixed dose regimen of bromocriptine regardless of the plasma prolactin lowering effect. RESUME: Resultats du traitement primaire par la bromocriptine des prolactinomes avec extension extrasellaire Dix-neuf patients, septs et douze hommes, porteurs de macroprolactinomes caracteris£s par une extension extrasellaire et des taux de prolactine plasmatique de base superieurs a 6 U/L ont ete traites avec 10-20 mg de Bromocriptine par jour en quatre doses separees pendant une duree moyenne de 3.4 ann£es (ecart de 1.5 a 5.5 annees). Les taux de prolactine plasmatique ont baisse de facon marquee chez tous les patients et des valeurs proches de la normale basse ont 6te" obtenues chez 16 patients. La taille de la tumeur etait reduite de plus de 75% chez dix-sept patients et de 50-75% chez deux patients. La reduction du volume tumoral etait associee avec I'apparition d'une selle partiellement vide dans quatorze cas. Dans dix-sept cas, l'hypophyse normale devenait visible. L'acuite visuelle abaissee (6 patients), PheVnianopsie bitemporale (9 patients), des scotomes centraux uni ou bilateraux (3 patients) et les paralysies oculo-motrices (2 patients) furent ameliores ou se normaliseront dans tous les cas. L'hypogonadisme (tous les patients), l'hypothyroi'die (9 patients) et l'hypocorticisme (4 patients) se sont ameliores ou normalises dans la plupart des cas. Les auteurs concluent que dans le traitement medical des macroprolactinomes, 10-20 mg de de bromocriptine en quatre doses s6parees reduit efficacement et la taille tumorale et le taux plasmatique de prolactine. Les bons rdsultats observes dans cette etude pourraient etre relies a l'utilisation continue d'une zone predeterminee de bromocriptine, quel que soit son effet r6ducteur du taux de prolactine serique.

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