UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Management of hyperprolactinemia

Author
Peter J Snyder, MD
Section Editor
David S Cooper, MD
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Lactotroph adenomas (prolactinomas) are more amenable to pharmacologic treatment than any other kind of pituitary adenoma because of the availability of dopamine agonists, which usually decrease both the secretion and size of these tumors. For the minority of lactotroph adenomas that do not respond to dopamine agonists, other treatments must be used. Hyperprolactinemia due to nonadenoma causes should also be treated if it causes hypogonadism.

This topic will review the major issues concerning the therapy of hyperprolactinemia due to lactotroph adenomas and other causes, with the exception of treatment during pregnancy, which is discussed separately. The causes, clinical manifestations, and diagnosis of hyperprolactinemia are also discussed elsewhere. (See "Management of lactotroph adenoma (prolactinoma) during pregnancy" and "Causes of hyperprolactinemia" and "Clinical manifestations and evaluation of hyperprolactinemia".)

INDICATIONS FOR TREATMENT

There are two principal reasons why patients with hyperprolactinemia may need to be treated: existing or impending neurologic symptoms due to the large size of a lactotroph adenoma, and hypogonadism or other symptoms due to hyperprolactinemia, such as galactorrhea [1,2].

A third indication is in women with mild hyperprolactinemia and normal cycles who are trying to conceive as they may have subtle luteal phase dysfunction (see "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Menstrual cycle dysfunction'). Our approach to management is similar to that suggested by the Endocrine Society Guidelines [2].

Adenoma size — A lactotroph adenoma (prolactinoma) 1 cm or more in size is a macroadenoma. Treatment is usually essential when the tumor is large enough to cause neurologic symptoms, such as visual impairment or headache (see "Causes, presentation, and evaluation of sellar masses", section on 'Clinical manifestations'). Treatment is usually desirable when the adenoma extends outside of the sella and abuts or elevates the optic chiasm, or invades the cavernous or sphenoid sinuses or the clivus; lesions of this size are likely to continue to grow and eventually cause neurologic symptoms.

                                   

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Oct 24 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 2006; 65:265.
  2. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96:273.
  3. Schlechte J, Dolan K, Sherman B, et al. The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab 1989; 68:412.
  4. Sisam DA, Sheehan JP, Sheeler LR. The natural history of untreated microprolactinomas. Fertil Steril 1987; 48:67.
  5. Carter JN, Tyson JE, Tolis G, et al. Prolactin-screening tumors and hypogonadism in 22 men. N Engl J Med 1978; 299:847.
  6. Buvat J, Lemaire A, Buvat-Herbaut M, et al. Hyperprolactinemia and sexual function in men. Horm Res 1985; 22:196.
  7. Buvat J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res 2003; 15:373.
  8. Vance ML, Evans WS, Thorner MO. Drugs five years later. Bromocriptine. Ann Intern Med 1984; 100:78.
  9. Wang AT, Mullan RJ, Lane MA, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev 2012; 1:33.
  10. Webster J, Piscitelli G, Polli A, et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med 1994; 331:904.
  11. Biller BM, Molitch ME, Vance ML, et al. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J Clin Endocrinol Metab 1996; 81:2338.
  12. Verhelst J, Abs R, Maiter D, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 1999; 84:2518.
  13. Schade R, Andersohn F, Suissa S, et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007; 356:29.
  14. Zanettini R, Antonini A, Gatto G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med 2007; 356:39.
  15. Kleinberg DL, Boyd AE 3rd, Wardlaw S, et al. Pergolide for the treatment of pituitary tumors secreting prolactin or growth hormone. N Engl J Med 1983; 309:704.
  16. US Food and Drug Administration. FDA announces voluntary withdrawal of pergolide products (March 29, 2007). http://www.fda.gov/newsevents/newsroom/pressannouncements/2007/ucm108877.htm (Accessed on August 01, 2012).
  17. Vance ML, Lipper M, Klibanski A, et al. Treatment of prolactin-secreting pituitary macroadenomas with the long-acting non-ergot dopamine agonist CV 205-502. Ann Intern Med 1990; 112:668.
  18. Di Sarno A, Landi ML, Marzullo P, et al. The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas. Clin Endocrinol (Oxf) 2000; 53:53.
  19. Schultz PN, Ginsberg L, McCutcheon IE, et al. Quinagolide in the management of prolactinoma. Pituitary 2000; 3:239.
  20. Tindall GT, Kovacs K, Horvath E, Thorner MO. Human prolactin-producing adenomas and bromocriptine: a histological, immunocytochemical, ultrastructural, and morphometric study. J Clin Endocrinol Metab 1982; 55:1178.
  21. Molitch ME, Elton RL, Blackwell RE, et al. Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study. J Clin Endocrinol Metab 1985; 60:698.
  22. van der Lely AJ, Brownell J, Lamberts SW. The efficacy and tolerability of CV 205-502 (a nonergot dopaminergic drug) in macroprolactinoma patients and in prolactinoma patients intolerant to bromocriptine. J Clin Endocrinol Metab 1991; 72:1136.
  23. Moster ML, Savino PJ, Schatz NJ, et al. Visual function in prolactinoma patients treated with bromocriptine. Ophthalmology 1985; 92:1332.
  24. Colao A, Di Sarno A, Landi ML, et al. Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 1997; 82:3574.
  25. De Rosa M, Colao A, Di Sarno A, et al. Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol 1998; 138:286.
  26. De Rosa M, Zarrilli S, Vitale G, et al. Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence. J Clin Endocrinol Metab 2004; 89:621.
  27. Colao A, Vitale G, Cappabianca P, et al. Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J Clin Endocrinol Metab 2004; 89:1704.
  28. Warfield A, Finkel DM, Schatz NJ, et al. Bromocriptine treatment of prolactin-secreting pituitary adenomas may restore pituitary function. Ann Intern Med 1984; 101:783.
  29. Kletzky OA, Vermesh M. Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia. Fertil Steril 1989; 51:269.
  30. Leong KS, Foy PM, Swift AC, et al. CSF rhinorrhoea following treatment with dopamine agonists for massive invasive prolactinomas. Clin Endocrinol (Oxf) 2000; 52:43.
  31. Davis JR, Sheppard MC, Heath DA. Giant invasive prolactinoma: a case report and review of nine further cases. Q J Med 1990; 74:227.
  32. Valassi E, Klibanski A, Biller BM. Clinical Review#: Potential cardiac valve effects of dopamine agonists in hyperprolactinemia. J Clin Endocrinol Metab 2010; 95:1025.
  33. Kars M, Delgado V, Holman ER, et al. Aortic valve calcification and mild tricuspid regurgitation but no clinical heart disease after 8 years of dopamine agonist therapy for prolactinoma. J Clin Endocrinol Metab 2008; 93:3348.
  34. Colao A, Galderisi M, Di Sarno A, et al. Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline. J Clin Endocrinol Metab 2008; 93:3777.
  35. Wakil A, Rigby AS, Clark AL, et al. Low dose cabergoline for hyperprolactinaemia is not associated with clinically significant valvular heart disease. Eur J Endocrinol 2008; 159:R11.
  36. Vallette S, Serri K, Rivera J, et al. Long-term cabergoline therapy is not associated with valvular heart disease in patients with prolactinomas. Pituitary 2009; 12:153.
  37. Herring N, Szmigielski C, Becher H, et al. Valvular heart disease and the use of cabergoline for the treatment of prolactinoma. Clin Endocrinol (Oxf) 2009; 70:104.
  38. Devin JK, Lakhani VT, Byrd BF 3rd, Blevins LS Jr. Prevalence of valvular heart disease in a cohort of patients taking cabergoline for management of hyperprolactinemia. Endocr Pract 2008; 14:672.
  39. Lafeber M, Stades AM, Valk GD, et al. Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline. Eur J Endocrinol 2010; 162:667.
  40. Tan T, Cabrita IZ, Hensman D, et al. Assessment of cardiac valve dysfunction in patients receiving cabergoline treatment for hyperprolactinaemia. Clin Endocrinol (Oxf) 2010; 73:369.
  41. Drake WM, Stiles CE, Howlett TA, et al. A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists. J Clin Endocrinol Metab 2014; 99:90.
  42. Auriemma RS, Pivonello R, Perone Y, et al. Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas. Eur J Endocrinol 2013; 169:359.
  43. Turkalj I, Braun P, Krupp P. Surveillance of bromocriptine in pregnancy. JAMA 1982; 247:1589.
  44. Robert E, Musatti L, Piscitelli G, Ferrari CI. Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod Toxicol 1996; 10:333.
  45. Ricci E, Parazzini F, Motta T, et al. Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 2002; 16:791.
  46. Ono M, Miki N, Kawamata T, et al. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab 2008; 93:4721.
  47. Motta T, de Vincentiis S, Marchini M, et al. Vaginal cabergoline in the treatment of hyperprolactinemic patients intolerant to oral dopaminergics. Fertil Steril 1996; 65:440.
  48. Colao A, Di Sarno A, Cappabianca P, et al. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003; 349:2023.
  49. Passos VQ, Souza JJ, Musolino NR, Bronstein MD. Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab 2002; 87:3578.
  50. Biswas M, Smith J, Jadon D, et al. Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol (Oxf) 2005; 63:26.
  51. Colao A, Di Sarno A, Guerra E, et al. Predictors of remission of hyperprolactinaemia after long-term withdrawal of cabergoline therapy. Clin Endocrinol (Oxf) 2007; 67:426.
  52. Kharlip J, Salvatori R, Yenokyan G, Wand GS. Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy. J Clin Endocrinol Metab 2009; 94:2428.
  53. Dekkers OM, Lagro J, Burman P, et al. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab 2010; 95:43.
  54. Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev 2006; 27:485.
  55. Thorner MO, Perryman RL, Rogol AD, et al. Rapid changes of prolactinoma volume after withdrawal and reinstitution of bromocriptine. J Clin Endocrinol Metab 1981; 53:480.
  56. van 't Verlaat JW, Croughs RJ. Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size. Clin Endocrinol (Oxf) 1991; 34:175.
  57. Faje A, Chunharojrith P, Nency J, et al. Dopamine Agonists Can Reduce Cystic Prolactinomas. J Clin Endocrinol Metab 2016; 101:3709.
  58. Liuzzi A, Dallabonzana D, Oppizzi G, et al. Low doses of dopamine agonists in the long-term treatment of macroprolactinomas. N Engl J Med 1985; 313:656.
  59. Feigenbaum SL, Downey DE, Wilson CB, Jaffe RB. Transsphenoidal pituitary resection for preoperative diagnosis of prolactin-secreting pituitary adenoma in women: long term follow-up. J Clin Endocrinol Metab 1996; 81:1711.
  60. Randall RV, Laws ER Jr, Abboud CF, et al. Transsphenoidal microsurgical treatment of prolactin-producing pituitary adenomas. Results in 100 patients. Mayo Clin Proc 1983; 58:108.
  61. Serri O, Rasio E, Beauregard H, et al. Recurrence of hyperprolactinemia after selective transsphenoidal adenomectomy in women with prolactinoma. N Engl J Med 1983; 309:280.
  62. Schlechte JA, Sherman BM, Chapler FK, VanGilder J. Long term follow-up of women with surgically treated prolactin-secreting pituitary tumors. J Clin Endocrinol Metab 1986; 62:1296.
  63. Ciric I, Ragin A, Baumgartner C, Pierce D. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 1997; 40:225.
  64. Snyder PJ, Fowble BF, Schatz NJ, et al. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 1986; 81:457.
  65. Byerly MJ, Marcus RN, Tran QV, et al. Effects of aripiprazole on prolactin levels in subjects with schizophrenia during cross-titration with risperidone or olanzapine: analysis of a randomized, open-label study. Schizophr Res 2009; 107:218.