Journal of Endocrinological Investigation

, Volume 5, Issue 6, pp 409–415 | Cite as

Bromocriptine treatment of macroprolactinomas: studies on the time course of tumor shrinkage and morphology

  • M. Nissim
  • B. Ambrosi
  • V. Bernasconi
  • G. Giannattasio
  • M. A. Giovanelli
  • M. Bassetti
  • U. Vaccari
  • P. Moriondo
  • A. Spada
  • P. Travaglini
  • G. Faglia


The effects of Bromocriptine (Brc) (7.5 2 - 15 mg/day for 45 days) on serum PRL levels and tumor size and morphology were investigated in 7 patients with macroprolactinomas (mean PRL ± SE = 4957 ± 920 ng/ml). Serial controls of serum PRL levels, CAT scan and visual field examination were carried out at the 5th, 10th, 20th and 45th day of Brc treatment. A rapid lowering in PRL concentrations (mean PRL ± SE = 23.1 ± 5.8 ng/ml) and a dramatic shrinkage of tumor mass were observed in 4 cases already at the 5th day of therapy. In 3 patients Brc was then withdrawn and a rapid rise of serum PRL concentration (mean PRL ± SE = 2618 ± 683 ng/ml) along with a reexpansion of the adenomas was documented within 15 days. These patients were then restarted on Brc and tumor regression was noticed again. In the remaining 3 cases no CAT scan variations occurred, though 2 of them had serum PRL in the normal range. Transsphenoidal adenomectomy was then performed in 4 patients upon Brc (1 with a marked reduction of the adenoma size and 3 with unmodified tumor mass) and tumor tissue examined. The histological picture of the 4 Brc-treated tumors was homogeneous and no relevant changes were seen in comparison with fragments of prolactinomas obtained from patients never treated with Brc. Though PRL cells appeared somewhat more closely associated, neither the tissue architecture, not the distribution of necrotic and hemorragic areas, nor the mitosis rate appeared modified by the treatment. At electron microscopy all the Brc-treated adenomas showed an increase of PRL secretory granules and a decrease of RER and Golgi apparatus. The morphometric analysis revealed in all cases a marked reduction of the cell size in comparison with the untreated tumors (73.56 μm2 ± 6.90 SE vs 148.41 μm2 ± 11.29 SE in untreated patients; p < 0.0001). In conclusion: i) the prolactinoma regression induced by Brc occurred only in patients whose serum PRL levels were markedly suppressed; however the PRL normalization was not constantly associated with tumor shrinkage; ii) all the Brc-treated adenomas showed a marked reduction in cell size and a decrease of the cytoplasmic structures responsible for PRL production; iii) cell size reduction was observed also in 3 patients who did not reduce their tumor size. This suggests that additional mechanisms should have been operating in the Brc-induced tumor shrinkage.


Prolactinoma shrinkage morphology bromocriptine CAT light microscopy electron microscopy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Del Pozo E., Varga L., Wyss H., Tolis G., Friesen H., Wenner R., Vetter L., Vettwiler A. Clinical and hormonal response to bromocriptine (CB 154) in te galactorrhoea syndromes. J. Clin. Endocrinol. Metab. 39: 18, 1974.PubMedCrossRefGoogle Scholar
  2. 2.
    Franks S., Jacobs H.S., Hull M.G.R., Steele S.J., Nabarro J.D.N. Management of hyperprolactinemic amenorrhea. Br. J. Obstet. Gynaecol. 84: 241, 1977.PubMedCrossRefGoogle Scholar
  3. 3.
    Bergh T., Nillius S.J., Wide L. Bromocriptine treatment of 42 hyperprolactinemic women with secondary amenorrhea. Acta Endocrinol. (Kbh.) 88: 435, 1978.Google Scholar
  4. 4.
    Von Werder K., Fahlbusch R., Landgrat R., Pickardt C.R., Rjosk H.K., Scriba P.C. Treatment of patients with prolactinomas. J. Endocrinol. Invest. 1: 47, 1978.PubMedCrossRefGoogle Scholar
  5. 5.
    Thorner M.O., Besser G.M. Bromocriptine treatment of hyperprolactinemic hypogonadism. Acta Endocrinol. (Kbh.) 88 (Suppl. 216): 131, 1978.Google Scholar
  6. 6.
    Corenblum B. Bromocriptine in pituitary tumors. Lancet 2: 786, 1978.PubMedCrossRefGoogle Scholar
  7. 7.
    Wass J.A.H., Moult P.J.A., Thorner M.O., Dacie J.E., Charlesworth M., Jones A.E., Besser G.M. Reduction of pituitary-tumor size in patients with prolactinomas and acromegaly treated with bromocriptine with ot without radiotherapy. Lancet 2: 66, 1979.PubMedCrossRefGoogle Scholar
  8. 8.
    McGregor A.M., Scanlon M.F., Hall R., Hall K. Effects of bromocriptine on pituitary tumor size. Br. Med. J. 2: 700, 1979.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Landolt A.M., Wutrick R., Fellmann H. Regression of pituitary prolactinoma after treatment with bromocriptine. Lancet 1: 1082, 1979.PubMedCrossRefGoogle Scholar
  10. 10.
    Thorner M.O., Martin W.H., Rogol A.D., Morris J.L., Perryman R.L., Conway B.P., Howards S.S., Wolfman M.G., MacLeod R.M. Rapid regression on pituitary prolactinomas during bromocriptine treatment. J. Clin. Endocrinol. Metab. 51: 438, 1980.PubMedCrossRefGoogle Scholar
  11. 11.
    Chiodini P., Liuzzi A., Cozzi R., Verde G., Oppizzi G., Dallabonzana D., Spelta B., Silvestrini F., Borghi G., Lucarelli G., Rainer E., Horowsky R. Size reduction of macroprolactinomas by bromocriptine or lisuride treatment. J. Clin. Endocrinol. Metab. 53: 737, 1981.PubMedCrossRefGoogle Scholar
  12. 12.
    Sobrinho L.G., Nunes M.C., Calhaz-Jorge C., Mauricio J.C., Santos A.M. Effect of treatment with bromocriptine on the size and activity of prolactin producing pituitary tumors. Acta Endocrinol. (Kbh.) 96: 24, 1981.Google Scholar
  13. 13.
    Wass J.A.H., Williams J., Charlesworth M., Kingsley D.P.E., Halliday A.M., Doniach I., Rees L.H., McDonald W.I., Besser G.M. Bromocriptine in management of large pituitary tumors. Br. Med. J. 284:1908, 1982.CrossRefGoogle Scholar
  14. 14.
    Corenblum B., Webster B.R., Mortimer C.B. Possible anti-tumor effect of 2-bromo-ergocryptine in two patients with large prolactin-secreting pituitary adenomas. Clin. Res. 23: 614, 1975 (Abstract).Google Scholar
  15. 15.
    Vaidya R.A., Aloorkar S.D., Rege N.R., Maskati B.T., Jahangir R.P., Sheth A.R., Pandya S.K. Normalization of visual fields following bromocriptine treatment in hyperprolactinemic patients with visual field constriction. Fertil. Steril. 29: 632, 1978.PubMedGoogle Scholar
  16. 16.
    Wollesen F., Andersen T., Karle A. Size reduction of extrasellar pituitary tumors during bromocriptine treatment. Quantitation of effect on different types of tumors. Ann. Intern. Med. 96: 281, 1982.PubMedCrossRefGoogle Scholar
  17. 17.
    Ambrosi B., Travaglini P., Moriondo P., Nissim M., Nava C., Bochicchio D., Faglia G. Effects of bromocriptine and metergoline in the treatment of hyperprolactinemic states. Acta Endocrinol. (Kbh) 100: 10, 1982.Google Scholar
  18. 18.
    Spark R.F., Baker R., Bienfang D.C., Bergland R. Bromocriptine reduces pituitary tumor size and hypersecretion. Requiem for pituitary surgery? J. Am. Med. Assoc. 247: 311, 1982.CrossRefGoogle Scholar
  19. 19.
    Quadri S.K., Lu K.H., Meites J. Ergot-induced inhibition of pituitary tumor growth in rats. Science 176: 417, 1972.PubMedCrossRefGoogle Scholar
  20. 20.
    Lloyd H.M., Meares J.D., Jacobi J. Effects of oestrogen and bromocriptine on in vivo secretion and mitosis in prolactin cells. Nature: 255: 497, 1975.PubMedCrossRefGoogle Scholar
  21. 21.
    Woodhouse N.J.Y., Khouqueer F., Sieck J.O. Prolactinomas and optic nerve compression: disappearance of a suprasellar extension and visual recovery after two weeks bromocriptine treatment. Horm. Res. 14: 141, 1981.PubMedCrossRefGoogle Scholar
  22. 22.
    Thorner M.O., Perryman R.L., Rogol A.D., Convay B.P., MacLeod R.M., Login I.S., Morris J.L. Rapid changes of prolactinoma volume after withdrawal and reinstitution of bromocriptine. J. Clin. Endocrinol. Metab. 153: 480, 1981.CrossRefGoogle Scholar
  23. 23.
    Vezina J.L. Prolactin-secreting pituitary adenomas: radiologic diagnosis. In: Robin C., Harter M. (Eds.), Progress in prolactin physiology and pathology. Elsevier North Holland Biomedical Press, 1978, p. 351.Google Scholar
  24. 24.
    Roth J., Bendayan M., Orci L. Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. J. Histochem. Cytochem. 26: 1074, 1978.PubMedCrossRefGoogle Scholar
  25. 25.
    Genze H.J., Slot J.W., Van der Ley P.A., Scheffer R.C.T., Griffith J.M. Use of colloidal gold-particles in double-labeling immunoelectron microscopy of ultrathin frozen tissue sections. J. Cell Biol. 89: 653, 1981.CrossRefGoogle Scholar
  26. 26.
    Werbel E.R. Stereological principles for morphometry in electron microscopic citology. Int. Rev. Cytol. 26: 235, 1969.CrossRefGoogle Scholar
  27. 27.
    Peilion F., Racadot J., Olivier L., Vila-Porcile E. Microadenomas, structure and function. In: Faglia G., Giovanelli M.A., MacLeod R.M. (Eds.), Pituitary microadenomas. Academic Press, London, 1980, p. 91.Google Scholar
  28. 28.
    George S.R., Burrow G.N., Zinman B., Ezrin C. Regression of pituitary tumors, a possible effect of bromoergocryptine. Am. J. Med. 66: 697, 1979.PubMedCrossRefGoogle Scholar
  29. 29.
    Eversmann T., Fahlbusch R., Ryosk H.K., VonWerder K. Persisting suppression of prolactin secretion after long-term treatment with bromocriptine in patients with prolactinomas. Acta Endocrinol. (Kbh.) 92: 413, 1979.Google Scholar
  30. 30.
    Lamberts S.J.W., MacLeod R.M. The inability of bromocriptine to inhibit prolactin secretion by transplantable rat pituitary tumors: observations on the mechanism and dynamics of the autofeedback regulation of prolactin secretion. Endocrinology 104: 65, 1979.PubMedCrossRefGoogle Scholar
  31. 31.
    Mc Comb D.J., Kovacs K., Croxford R., Milligan J.V. Bromocriptine suppression of dispersed pituitary lactotrophs from estrogen-pretreated rats: a quantitative electron microscopic study. Can. J. Physiol. Pharmacol. 60: 154, 1982.CrossRefGoogle Scholar
  32. 32.
    Thorner M.O., Tindall G.T., Kovacs K., Horvath E. Human prolactinomas and bromocriptine: a histologic, immunocytochemical, ultrastructural and morphometric study. The Endocrine Society 64th Annual Meeting — San Francisco, June 16–18, 1982, p. 149 (Abstract 277).Google Scholar
  33. 33.
    Rengachary S.S., Tomita T., Jefferies B.F., Watanabe I. Structural changes in human pituitary tumor after bromocriptine treatment. Neurosurgery 10: 242, 1982.PubMedCrossRefGoogle Scholar
  34. 34.
    Brismar K., Siden A., Werner S. Effects of bromocriptine on CSF proteins and amines in patients with empty sella syndrome, acromegaly and prolactin producing pituitary adenomas. J. Endocrinol. Invest. 4: 393, 1981.PubMedCrossRefGoogle Scholar
  35. 35.
    Johnston D.G., McGregor A., Ross W.M., Hall R. Bromocriptine therapy for “non functioning” pituitary tumors. Am. J. Med. 71: 1059, 1981.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1982

Authors and Affiliations

  • M. Nissim
    • 1
  • B. Ambrosi
    • 2
  • V. Bernasconi
    • 3
  • G. Giannattasio
    • 4
  • M. A. Giovanelli
    • 3
  • M. Bassetti
    • 4
  • U. Vaccari
    • 3
  • P. Moriondo
    • 1
  • A. Spada
    • 1
  • P. Travaglini
    • 2
  • G. Faglia
    • 1
  1. 1.Cattedra di Endocrinologia e Medicina CostituzionaleUniversità di MilanoMilanoItalia
  2. 2.Clinica Medica IIUniversità di MilanoMilanoItalia
  3. 3.Istituto di NeurochirurgiaUniversità di MilanoMilanoItalia
  4. 4.Centro CNR per lo Studio della Farmacologia delle Infrastrutture Cellulari — Istituto di FarmacologiaUniversità di MilanoMilanoItalia

Personalised recommendations