Abstract
Cabergoline (CAB) treatment is an effective, safe and well tolerated approach for hyperprolactinemia. We investigated the efficacy of 24-month treatment with CAB in 37 patients with previously untreated PRL-secreting pituitary adenoma and evaluated the hormonal and neuroradiological changes after the discontinuation of long-term therapy. Eleven patients with macroprolactinoma (1M/10F) and 26 with microprolactinoma (4M/22F) started treatment taking 0.25 mg CAB twice a week for 4 weeks. The dose was increased stepwise in 0.5 mg increments until reaching lowest maximally effective and tolerated dose. CAB was withdrawn before the end of the study in 6 women who became pregnant and in one patient who showed a slight increase of the macroadenoma at MRI. During treatment, PRL levels decreased significantly in macro (11.1±1.1 vs 407.8±98.3 μg/l, p<0.001) and microprolactinomas (11.1±1.6 vs 193.8±23.4 μg/l, p<0.05) and normalized in all macro and in 23/26 microprolactinomas. In 3 cases PRL levels decreased but did not normalize because the appearance of side effects, such as nausea or hypotension, prevented the increase of the dose of CAB. The effective dose of drug correlated significantly with basal serum PRL levels (p<0.05) and with the pituitary tumor size (p<0.05). A significant decrease of the mean adenoma size was evident for macro (6.9±1.8 vs 16.0±1.8 mm, p<0.001) and microprolactinomas (3.0±0.5 vs 6.5±0.4 mm, p<0.001) at MRI. The tumor disappeared in 4 macroadenomas and in 11 microadenomas after 12 months of treatment. CAB withdrawal was followed by serum PRL increase in 13 cases after 3 months, in 6 after 6 months, in 2 after 9 months, and in one patient at the 12th month. Five patients showed normo-prolactinemia with negative MRI after one year. Regular menses were restored in 7/10 macro-prolactinomas and in all oligo-amenorrhoic patients with microadenoma; serum testosterone levels normalized in 2/3 hypogonadic men. Five out of 6 women become pregnant and had uneventful pregnancies which resulted in deliveries of normal babies. In conclusion, this study confirms the effectiveness and safety of CAB for patients with PRL-secreting pituitary adenoma and suggests that it can be considered a first choice treatment.
Similar content being viewed by others
References
Bevan J.S., Webster J., Burke C.W., Scanlon M.F. Dopamine agonists and pituitary tumor shrinkage. Endocr. Rev. 1992, 13: 220.
Crosignani P.G., Ferrari C., Liuzzi A., Benco R., Mattei A., Rampini P., Dellabonzana D., Scarduelli C., Spelta B. Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline and lisuride. Fertil. Steril. 1982, 37: 61.
Franks S., Horrocks P.M., Lynch S.S., Butt W.R., London D.R. Effectiveness of pergolide mesylate in long-term treatment of hyperprolactinaemia. Br. Med. J. 1983, 286: 1177,.
Ferrari C., Barbieri C., Caldara R., Mucci M., Codecasa F., Paracchi A., Romano C., Boghen M., Dubini A. Long-lasting prolactin lowering effect of cabergoline, a new dopamine agonist, in hyperprolactinemic patients. J. Clin. Endocrinol. Metab. 1986, 63: 941.
Dallabonzana D., Liuzzi A., Opizzi G., Cozzi R., Verde G., Chiodini P.G., Rainer E., Dorow R., Horowski R. Chronic treatment of pathological hyperprolactine-mia and acromegaly with the new ergot derivative terguride. J. Clin. Endocrinol. Metab. 1986, 63: 1002.
Rasmussen C., Bergh T., Wide L., Brownell J. CV 205–502: a new long-acting drug for inhibition of prolactin hypersecretion. Clin. Endocrinol.(Oxf.) 1987, 26: 321.
Benker G., Gieshoff B., Freundlieb O., Windeck R., Schute H.M., Lancranjan I., Reinwein D. Parenteral bromocriptine in the treatment of hor-monally active pituitary tumours. Clin. Endocrinol. (Oxf.) 1986, 24: 505.
Kletzky O.A., Vermesh M. Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia. Fertil. Steril. 1989, 51: 269.
Ferrari C., Mattei A., Melis G.B., Paracchi A., Muratori M., Faglia G., Sghedoni D., Crosignani P.G. Cabergoline: long-acting oral treatment of hyper-prolactinemic disorders. J. Clin. Endocrinol. Metab. 1989, 68: 1201.
Ciccarelli E., Giusti M., Miola C., Potenzoni F., Sghedoni D., Camanni F., Giordano G. Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hypeprolactinemic patients. J. Clin. Endocrinol. Metab. 1989, 69: 725.
Ferrari C., Paracchi A., Mattei A., de Vincentiis S., D’Alberton A., Crosignani P.G. Cabergoline in the long-term therapy of hyperpro-lactinemic disorders. Acta Endocrinol. (Copenh.) 1992, 126: 489.
Pellegrini I., Rasolonjanahary R., Gunz G., Bertrand P., Delivet S., Jedynak C.P., Kordon C., Peillon F., Jaquet P., Enjalbert A. Resistance to bromocriptine in prolactinomas. J. Clin. Endocrinol. Metab. 1989, 69: 500.
Colao A., Di Sarno A., Sarnacchiaro F., Ferone D., Di Renzo G., Merola B., Annunziato L., Lombardi G. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J. Clin. Endocrinol. Metab. 1997, 82: 876.
Delgrange E., Maiter D., Donckier J. Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. Eur. J. Endocrinol. 1996, 134: 456.
Biller B.M.K., Molitch M.E., Vance M.L., Cannistraro K.B., Davis K.R., Simons J.A., Schoenfelder J.R., Klibanski A. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J. Clin. Endocrinol. Metab. 1996, 81: 2338.
Ferrari C.I., Abs R., Bevan J.S., Brabant G., Ciccarelli E., Motta T., Mucci M., Muratori M., Musatti L., Verbessem G., Scanlon M.F. Treatment of macroprolactinoma with cabergoline: a study of 85 patients. Clin. Endocrinol. (Oxf.), 1997, 46: 409.
Webster J., Piscitelli G., Polli A., Ferrari C.I., Ismail I., Scanlon M.F. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N. Engl. J. Med. 1994, 331: 904.
Webster J., Piscitelli G., Polli A., D’Alberon A., Falsetti L., Ferrari C., Fioretti P., Giordano G., L’Hermite M., Ciccarelli E., Crosignani P.G, De Cecco L., Fadini R., Faglia G., Flamigni C., Tamburrano G., Ismail I., Scanlon M.F. (European Multicentre Cabergoline Study Group). The efficacy and tolerability of long-term cabergo-line therapy in hyperprolactinaemic disorders: an open, uncontrolled, multicentre study. Clin. Endocrinol. (Oxf.), 1993, 39: 323.
Mattei A.M., Ferrari C., Baroldi P., Cavioni V., Paracchi A., Galparoli C., Romano C., Spellecchia D., Gerevini G., Crosignani P.G. Prolactin-lowering effect of acute and once weekly repetitive oral administration of cabergoline at two dose levels in hypeprolactinemic patients. J. Clin. Endocrinol. Metab. 1988, 66: 193.
Molitch M.E. Pregnancy and the hyperprolactinemic woman. N. Engl. J. Med. 1985, 312: 1364.
Robert E., Musatti L., Piscitelli G., Ferrari C.I. Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod. Toxicol. 1996, 10: 333.
Ciccarelli E., Grottoli S., Razzore P., Gaia D., Bertagna A., Cirillo S., Cammarota T., Camanni M., Camanni F. Long-term treatment with cabergoline, a new long-lasting ergoline derivate, in idiopathic or tumorous hyperprolactinaemia and outcome of drug-induced pregnancy. J. Endocrinol. Invest. 1997, 20: 547.
Colao A., Di Sarno A., Landi M.L. Cirillo S., Sarnachiaro F., Faccioli G., Pivonello R., Cataldi M., Merola B., Annunziato L., Lombardi G. Long-term and low-dose treatment with cabergoline induces macroprolactinomas shrinkage. J. Clin. Endocrinol. Metab. 1997, 82: 3574.
Chiodini P., Liuzzi A., Cozzi R., Verde G., Opizzi G., Dallabonzana D., Spelta B., Silvestrini F., Borghi G., Lucarelli G., Rainer E., Horowski R. Size reduction of macroprolactinomas by bromocrip-tine or lisuride treatment. J. Clin. Endocrinol. Metab. 1981, 53: 737.
Melis G.B., Gambacciani M., Paoletti A.M., Mais V., Sghedoni D., Fioretti P. Reduction in the size of prolactin-producing pituitary tumor after cabergoline administration. Fertil. Steril. 1989, 52: 412.
Muratori M., Arosio M., Gambino G., Romano C., Biella O., Faglia G. Use of cabergoline in the long-term treatment of hy-perprolactinemic and acromegalic patients. J. Endocrinol. Invest. 1997, 20: 537.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cannavò, S., Curtò, L., Squadrito, S. et al. Cabergoline: A first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenoma. J Endocrinol Invest 22, 354–359 (1999). https://doi.org/10.1007/BF03343573
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03343573