Abstract
Following presentation and diagnosis, microprolactinomas usually follow a benign course and rarely progress to macroprolactinomas. However, clinically significant enlargement of prolactinomas during pregnancy, presumably related to estrogen stimulation, has been reported. This report describes a patient with amenorrhea and hyperprolactinemia and a microadenoma by computed tomography scan who developed a macroprolactinoma within 10 months after being placed on estrogen therapy. We propose that exogenous estrogen administration in this patient most likely promoted growth from a microprolactinoma to a macroprolactinoma. This case emphasizes the primary role of dopaminergic agonist therapy in the management of pathological hyperprolactinemia and suggests that estrogen therapy should not be casually given to patients with known prolactinomas to avoid the possibility of promoting tumor growth. A correlate of this approach is that caution regarding estrogen therapy should also be exercised in patients with idiopathic hyperprolactinemia who might have an occult microprolactinoma which could grow following estrogen stimulation. If estrogen treatment is deemed necessary, dopaminergic agonist therapy should also be used prophylactically to prevent potential tumor growth due to estrogen. The patient should then be carefully monitored with periodic serum PRLs and for the development of clinical manifestations suggesting pituitary growth. An imaging study should be performed when there is a significant increase in serum PRL or the development of new clinical manifestations.
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Hardy J., Beauregard H., Robert F. Prolactin-secreting pituitary adenomas: transsphenoidal microsurgical treatment. In: Robyn C., Harter M. (Eds.), Progress in prolactin physiology and pathology. Elsevier/North-Holland Biomedical Press, Amsterdam, 1978, p. 361.
Sherman B.M., Harris C.E., Schlechte J., Duello T.M., Halmi N.S., Van Gilder J., Chapler F.K., Granner D.K. Pathogenesis of prolactin-secreting pituitary adenomas. Lancet 2: 1019, 1978.
Furth J., Clifton K. Experimental pituitary tumors. In: Harris G.W., Donovan B.T. (Eds.), The Pituitary Gland. Butterworth Inc., Washington, DC 1966, p. 460.
Pituitary adenoma study group. Pituitary adenomas and oral contraceptives: a multicenter case-control study. Fertil. Steril. 39: 753, 1983.
Shy K., McTiernan A., Daling J., Weiss N. Oral contraceptive use and the occurrence of pituitary prolactinoma. JAMA 249: 2204, 1983.
Wiklund J., Wertz N., Gorski J. A comparison of estrogen effects on uterine and pituitary growth and prolactin synthesis in F344 and Holtzman rats. Endocrinology 109: 1700, 1981.
Burgett R., Garris P., Ben-Jonathan N. Estradiol-induced prolactinomas: differential effects on dopamine in posterior pituitary and median eminence. Brain Res. 531: 143, 1990.
Schmeithauer B. Effects of estrogen on the human pituitary: a clinico-pathologic study. Mayo Clin. Proc. 64: 1077, 1989.
Gooren L., Harmen-Louman W., Van Kessel H. Follow-up of prolactin levels in long-term oestogentreated male-to-female transsexuals with regard to prolactinoma induction. Clin. Endocrinol. (Oxf.) 22: 201, 1985.
Peillon F., Vila-Porcile E., Oliver L., Racadot J. L’action des oestrogenes sur les adenomes hypophysares chez l’homme. Ann. Endocrinol. (Paris) 31: 259, 1984.
Gooren L., Assies J., Asscheman H., de Siegte R., van Kessel H. Estrogen-induced prolactinoma in a man. J. Clin. Endocrinol. Metab 66: 444, 1988.
Sisam D., Sheehan J., Sheeler L. The natural history of untreated microprolactinomas. Fertil. Steril. 48: 67, 1987.
Schlechte J., Dolan K., Sherman B., Chapler F., Luciano A. The natural history of untreated hyperprolactinemia: a prospective analysis. J. Clin. Endocrinol. Metab. 68: 412, 1989.
Weiss M., Teal J., Gott P., Wycoff R., Yadley. R., Appuzo M., Giannnnotta S., Kletzky O., March C. Natural history of microprolactinomas: six-year follow-up. Neurosurgery 12: 180, 1983.
Martin T., Kim M., Malarkey W. The natural history of idiopathic hyperprolactinemia. J. Clin. Endocrinol. Metab. 60: 855, 1985.
Dietemann J.L., Portha C., Cattin F., Mollet E., Bonneville J.F. CT follow-up of microprolactinomas during bromocriptine-induced pregnancy. Neuroradiology 25: 133, 1983.
Fujimoto M., Yoshino E., Mizukawa N., Hirakawa K. Spontaneous reduction in size of prolactin-producing adenoma after delivery. J. Neurosurg. 63: 973, 1985.
Gemzell C., Wang C. Outcome of pregnancy in women with pituitary adenoma. Fertil. Steril. 31: 363, 1979.
Molitch M. Pregnancy and the hyperprolactinemic woman. N. Engl. J. Med. 312: 1364, 1985.
Vician L., Shupnik M., Gorski J. Effects of estrogen on primary ovine pituitary cell cultures: stimulation of prolactin secretion, synthesis, and preprolactin messenger ribonucleic acid activity. Endocrinology 104: 736, 1979.
Canales E.S., Garcia I.C., Ruiz J.E., Zarate A. Bromocriptine as prophylactic therapy in prolactinoma during pregnancy. Fertil. Steril. 36: 524, 1981.
Vance M.L., Thorner M.O. Prolactinomas. Endocrinol. Metab. Clinics 16: 731, 1987.
Ruiz-Velascox V., Tolis G. Pregnancy in hyperprolactinemic women. Fertil. Steril. 41: 793, 1984.
Parkes D. Drug therapy: bromoergocriptine. N. Engl. J. Med. 301: 873, 1979.
Moult P.J.A., Dacie J.E., Rees L.H., Besser G.M. Oral contraception in patients with hyperprolactinemia. Br. Med. J. 284: 868, 1982.
Bevan J., Sussman J., Roberts A., Hourihan M., Peters J. Development of an invasive macroprolactinoma: a possible consequence of prolonged oestrogen replacement. Br. J. Obstet. Gynaecol. 96: 1440, 1989.
Prior J., Cox T., Fairholm D., Kostashuk E., Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J. Clin. Endocrinol. Metab. 64: 391, 1987.
Gerstman B.B., Piper J.M., Tomita D.K., Ferguson, W.J., Stadek B.V., Lundin F.E. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am. J. Epidemiol. 133: 32, 1991.
Lamberts S.W.J., Klijn J.G.M., deLange S.A., Singh R., Stefanko S.Z., Birkenhäger J.C. The incidence of complications during pregnancy after treatment of hyperprolactinemia with bromocriptine in patients with radiologically evident pituitary tumors. Fertil. Steril. 31: 614, 1979.
Divers A., Yen S. Prolactin-producing microadenomas in pregnancy. Obstet. Gynecol. 61: 425, 1983.
Woodhouse N.J.Y., Niles N., McDonald D., McCorkell S. Prolactin levels in pregnancy: comparison of normal subjects with patients having micro- or microadenomas after early bromocriptine withdrawal. Hormone Res. 21: 1, 1985.
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Garcia, M.M., Kapcala, L.P. Growth of a microprolactinoma to a macroprolactinoma during estrogen therapy. J Endocrinol Invest 18, 450–455 (1995). https://doi.org/10.1007/BF03349744
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DOI: https://doi.org/10.1007/BF03349744