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Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients

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Abstract

Cabergoline (Cab), a very potent and long-lasting dopaminergic compound, was administered to 26 women with pituitary microprolactinoma [mean serum PRL levels: 124.8±11.3 µg/l (±SE), range 62–300 µg/l] and 3 patients with GH-secreting pituitary adenoma (2 with associated PRL hypersecretion) for 12 and 24 months, respectively. In microprolactinomas, a stable normoprolactinemia was achieved in 96.1% of cases: in 13 women (50%) with the lowest dose of the drug (0.5 mg/week), and in other 12 patients (46.1%) with increasing doses up to 3 mg/week. All the oligomenorrheic/amenorrheic women, except one, restored regular and ovulatory menses. Two patients became pregnant. Pituitary abnormalities at high resolution-CT (HR-CT) scan disappeared in 13 of 19 patients (68.4%) after 12 months of therapy and this feature persisted in 8/13 cases (61.5%) 12 months after drug withdrawal. During Cab discontinuation (range: 3–60 months), mean serum PRL levels remained significantly lower than the basal ones. Six of 25 women are still without therapy. In 2 patients, normoprolactinemia persisted up to 38 and 60 months, respectively. Cab treatment was re-instituted in 13 patients because of the recurrence of hyperprolactinemia. Five patients were lost at follow up. In all the acromegalic patients, Cab (1–3 mg/week) normalized serum GH, IGF-I and PRL levels. A clear improvement in clinical symptoms was observed in all patients, but neuroradiological improvement in only one. Cab therapy was very well tolerated, as only seven patients complained of mild and transient side-effects and none had to stop treatment. In conclusion, Cab is an effective, safe, and well tolerated dopaminergic compound for the treatment of hyperprolactinemic disorders and the control of the clinical and hormonal features of dopamine-sensitive acromegalic patients.

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References

  1. Besser G.M., Parke L., Edwards C.R.W., Forsyth I.A., McNeilly A.S. Galactorrhea: successful treatment with reduction of plasma prolactin levels by bromoergocryptine. Br. Med. J. 3: 669, 1972.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Robbins R.J. Medical management of prolactinomas. In: Olefsky J.M., Robbins R.J. (Eds.), Prolactinomas. Churchill Livingstone, New York, 1986, p. 97.

    Google Scholar 

  3. Bevan J.S., Webster J., Burke C.W., Scanion M.F. Dopamine agonists and pituitary tumor shrinkage. Endocr. Rev. 13: 220, 1992.

    Article  PubMed  CAS  Google Scholar 

  4. Spark R.F., Baker R., Bienfang D.C., Bergland R. Bromocriptine reduces pituitary tumor size and hypersecretion. Requiem for pituitary surgery? J.A.M.A. 247: 311, 1982.

    Article  PubMed  CAS  Google Scholar 

  5. Thorner M.O., Schran H.F., Evans W.S., Rogol A.D., Morris J.L., MacLeod R.M. A broad spectrum of prolactin suppression by bromocriptine in hyperprolactinemic women: a study of serum prolactin and bromocriptine levels after acute and chronic administration of bromocriptine. J. Clin. Endocrinol. Metab. 50: 1026, 1980.

    Article  PubMed  CAS  Google Scholar 

  6. Moriondo P., Travaglini P., Nissim M., Conti A., Faglia G. Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal. J. Clin. Endocrinol. Metab. 60: 764, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. Pellegrini I., Rosolonjanahary 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. 69: 500, 1989.

    Article  PubMed  CAS  Google Scholar 

  8. Crosignani P.G., Mattei A., Ferrari C., Giovanelli M.A. Enlargement of a prolactin-secreting pituitary microadenoma during bromocriptine treatment. Br. J. Obstet. Gynecol. 89: 169, 1982.

    Article  CAS  Google Scholar 

  9. Dallabonzana D., Spelta B., Oppizzi G., Tonon C., Luccarelli G., Chiodini P.G., Liuzzi A. Re-enlargement of macroprolactinomas during bromocriptine treatment: report of two cases. J. Endocrinol. Invest. 6: 47, 1983.

    Article  PubMed  CAS  Google Scholar 

  10. Faglia G. Should dopamine agonist treatment for prolactinomas be lifelong? Clin. Endocrinol. (Oxf) 34: 173, 1991.

    Article  CAS  Google Scholar 

  11. Parkes D. Drug therapy. Bromocriptine. N. Engl. J. Med. 301: 873, 1978.

    Google Scholar 

  12. Mattei A.M., Ferrari C., Baroldi P., Cavioni V., Paracchi A., Galparoli G., 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 hyperprolactinemic patients. J. Clin. Endocrinol. Metab. 66: 193, 1988.

    Article  PubMed  CAS  Google Scholar 

  13. Ferrari C., Mattei A.M., Melis G.B., Paracchi A., Muratori M., Faglia G., Sghedoni D., Crosignani P.G. Cabergoline: long-acting oral treatment of hyperprolactinemic disorders. J. Clin. Endocrinol. Metab. 68: 1201, 1989.

    Article  PubMed  CAS  Google Scholar 

  14. Webster J., Piscitelli G., Polli A., Ferrari C., Ismail I., Scanion M.F. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N. Engl. J. Med. 331: 904, 1994.

    Article  PubMed  CAS  Google Scholar 

  15. Thorner M.O., Chait A., Aitken M., Benker G., Bloom S.R., Mortimer C.H., Sanders P., Stuart Mason A., Besser G.M. Bromocriptine treatment of acromegaly. Br. Med. J. 1: 299, 1975.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Liuzzi A., Chiodini P.G., Botalla L., Cremascoli G., Muller E.E., Silvestrini F. Decreased plasma growth hormone (GH) levels in acromegalics following CB 154 (2-Br-alpha-ergocryptine) administration. J. Clin. Endocrinol. Metab. 38: 910, 1974.

    Article  PubMed  CAS  Google Scholar 

  17. Chiodini P.G., Cozzi R., Dallabonzana D., Oppizzi G., Verde G., Petroncini M., Liuzzi A., Del Pozo E. Medical treatment of acromegaly with SMS 201–995, a somatostatin analog: A comparison with bromocriptine. J. Clin. Endocrinol. Metab. 64: 447, 1987.

    Article  PubMed  CAS  Google Scholar 

  18. Scanion M.F. Dopamine agonists in the treatment of acromegaly. In: Wass J.A.H. (Ed.), Treating Acromegaly. Journal of Endocrinology Ltd, Bristol, 1994, p. 139.

    Google Scholar 

  19. Bression D., Brandi A.M., Martres M.P., Nousbaum A., Cesselin F., Racadot J., Peilion F. Dopaminergic receptors in human prolactin-secreting adenomas: a quantitative study. J. Clin. Endocrinol. Metab. 51: 1037, 1980.

    Article  PubMed  CAS  Google Scholar 

  20. Caccavelli L., Feron F., Dewailly D., Jaquet P., Kordon C., Enjalbert A. Dopaminergic D2 receptor and G protein expression in bromocriptine resistant prolactinomas. VI International Prolactin Congress, Paris, 1993, Abstract 15.

  21. Cronin M.J., Valdenegro C.A., Perkins S.N., MacLeod R.M. The 7315a pituitary tumor is refractory to dopamine inhibition of prolactin release but contains dopamine receptors. Endocrinology 109: 2160, 1981.

    Article  PubMed  CAS  Google Scholar 

  22. Collu R., Bouvier C., Lagacé G., Unson C.G., Milligan G., Goldsmith P., Spiegel A.M. Selective deficiency of guanine nucleotide-binding protein G0 in two dopamine resistant pituitary tumors. Endocrinology 122: 1176, 1988.

    Article  PubMed  CAS  Google Scholar 

  23. Gen M., Uozumi T., Ohta M., Ito A., Kajiwara H., Mori S. Necrotic changes in prolactinomas after long term administration of bromocriptine. J. Clin. Endocrinol. Metab. 59: 463, 1984.

    Article  PubMed  CAS  Google Scholar 

  24. Hassoun J., Jaquet P., Devictor B., Andonian C., Grisoli F., Gunz G., Toga M. Bromocriptine effects on cultured human prolactin-producing pituitary adenomas: in vivo ultrastructural, morphometric and immunoelectron microscopic studies. J. Clin. Endocrinol. Metab. 61: 686, 1985.

    Article  PubMed  CAS  Google Scholar 

  25. Ferrari C., Paracchi A., Romano C., Gerevini G., Boghen M., Barreca A., Fortini P., Dubini A. Long-lasting lowering of serum growth hormone and prolactin levels by single and repetitive cabergoline administration in dopamine-responsive acromegalic patients. Clin. Endocrinol. (Oxf) 29: 467, 1988.

    Article  CAS  Google Scholar 

  26. Colao A.M., Ferone D., Marzullo P., Di Sarno A., Cerbone G., Sarnacchiaro F., Cirillo S., Merola B., Lombardi G. Effect of different dopaminergic agents in the treatment of acromegaly. J. CIin. Endocrinol. Metab. 82: 518, 1997.

    Article  CAS  Google Scholar 

  27. Jackson S.N.J., Fowler J., Howlett T.A. Cabergoline treatment of acromegaly: a preliminary dose finding study. Clin. Endocrinol. (Oxf) 46: 745, 1997.

    Article  CAS  Google Scholar 

  28. Bassetti M., Arosio M., Spada A., Brina M., Bazzoni N., Faglia G., Giannattasio G. Growth hormone and prolactin secretion in acromegaly: correlations between hormonal dynamics and immunocytochemical findings. J. Clin. Endocrinol. Metab. 67: 1195, 1988.

    Article  PubMed  CAS  Google Scholar 

  29. Spada A., Bassetti M., Reza-Elahi F., Arosio M., Gil del Alamo P., Vallar L. Differential transduction of dopamine-signal in different subtypes of human GH-secreting adenomas. J. Clin. Endocrinol. Metab. 78: 411, 1994.

    PubMed  CAS  Google Scholar 

  30. Wachtel H., Dorow R. Dual action on central dopamine function of transdihydrolisuride, a 9, 10-dihydrogenate analogue of the ergot dopamine agonist lisuride. Life Sci. 32: 421, 1983.

    Article  PubMed  CAS  Google Scholar 

  31. MacKenzie F.J., James M.D., Wilson C.A. The effect of selective D1 and D2 agonists and antagonists injected into the zona incerta on ovulation and LH release. In: Muller E.E., MacLeod R.M. (Eds.), Neuroendocrine Perspectives. Elsevier, Amsterdam, 1986, p. 277.

    Google Scholar 

  32. Knobil E. The neuroendocrine control of the menstrual cycle. Recent. Prog. Horm. Res. 36: 53, 1980.

    PubMed  CAS  Google Scholar 

  33. Ferrari C., Paracchi A., Mattei A.M., De Vincentiis S., D’Alberton A., Crosignani P.G. Cabergoline in the long-term therapy of hyperprolactinemic disorders. Acta Endocrinol. (Copenh.) 126: 489, 1992

    CAS  Google Scholar 

  34. Johnston D.G., Hall K., Kendal-Taylor P., Patrick D., Watson M., Cook D.B. Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Lancet 8: 187, 1984.

    Article  Google Scholar 

  35. van’t Verlaat J.W., Croughs R.J.M. Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size. Clin. Endocrinol. (Oxf) 34: 175, 1991.

    Article  Google Scholar 

  36. Liuzzi A., Dallabonzana D., Oppizzi G., Verde G.G., Cozzi R., Chiodini P.G., Luccarelli G. Low doses of dopamine agonists in the long-term treatment of macroprolactinomas. N. Engl. J.Med. 313: 656, 1985.

    Article  PubMed  CAS  Google Scholar 

  37. Di Salle E., Ornati G., Briatico G. FCE 21336, a new derivative with a potent and long-acting lowering effect on prolactin secretion in rats. J. Endocrinol. Invest. 5(Suppl. 1): 45, 1982.

    Google Scholar 

  38. Yeo T., Thorner M.O., Jones A., Lowry P.J., Besser G.M. The effect of dopamine, bromocriptine, lergotrile, and metoclopramide on prolactin release from continuously perfused columns of isolated rat pituitary cells. Clin. Endocrinol. (Oxf) 10: 123, 1979.

    Article  CAS  Google Scholar 

  39. Ferrari C., Di Salle E., Persiani S., Piscitelli G., Strolin Benedetti M. Cabergoline (DostinexR), a long-acting prolactin lowering drug: a review of preclinical and clinical studies. Drugs of Today 31: 569, 1995.

    CAS  Google Scholar 

  40. Brambilla E., Di Salle E., Briatico G., Mantegani S., Temperilli A. Synthesis and nidation inhibitory activity of a new class of ergoline derivatives. Eur. J. Med. Chem. 24: 421, 1989.

    Article  CAS  Google Scholar 

  41. Di Salle E., Giudici D., Ornati G. Are cabergoline metabolites involved in its long-lasting prolactin lowering effect in rats? 8th Intl. Cong. Endocrinol., Kyoto, Japan, 1988, Abstract 05-19-031.

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Muratori, M., Arosio, M., Gambino, G. et al. Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients. J Endocrinol Invest 20, 537–546 (1997). https://doi.org/10.1007/BF03348016

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