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Hyperprolactinemia

Pathophysiology and Management

  • Therapy in Practice
  • Published:
Treatments in Endocrinology

Abstract

Hyperprolactinemia is commonly found in both female and male patients with abnormal sexual and/or reproductive function or with galactorrhea. If serum prolactin levels are above 200 Hμ/L, a prolactin-secreting pituitary adenoma (prolactinoma) is the underlying cause, but if levels are lower, differential diagnoses include the intake of various drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia. When a pituitary tumor is present, patients often have pressure symptoms in addition to endocrine dysfunction, such as headaches, visual field defects, or cranial nerve deficits.

The large majority of patients with prolactinomas, both micro-and macroprolactinomas, can be successfully treated with dopaminergic drugs as first-line treatment, with normalization of prolactin secretion and gonadal function, and with significant tumor shrinkage in a high percentage of cases. Surgical resection of the prolactinoma is the option for patients who may refuse or do not respond to long-term pharmacological therapy. Radiotherapy and/or estrogens are also reasonable choices if surgery fails. In patients with asymptomatic microprolactinoma no treatment needs to be given and a regular follow-up with serial prolactin measurements and pituitary imaging should be organized.

Currently, the most commonly used dopamine agonists are bromocriptine, pergolide, quinagolide and cabergoline. When comparing the plasma half-life, efficacy and tolerability of these drugs, cabergoline seems to have the most favorable profile, followed by quinagolide. If prolactin levels are well controlled with dopamine agonist therapy, gradual tapering of the dose to the lowest effective amount is recommended, and in a number of cases medication can be stopped after several years.

Evidence to date suggests that cabergoline and quinagolide appear to have a good safety profile for women who wish to conceive, but hard evidence proving that dopamine agonists do not provoke congenital malformations when taken during early pregnancy is currently only available for bromocriptine. Once pregnant, dopamine agonist therapy should be immediately stopped, unless growth of a macroprolactinoma is likely or pressure symptoms occur.

At our institution patients with symptomatic prolactinomas, both micro- and macroadenomas, are treated with cabergoline as the first-line aproach. In the small group of patients who do not respond to this treatment, or who refuse long-term therapy, surgery is offered. Radiotherapy is given if both pharmacologic therapy and surgery fail.

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References

  1. Tyson JE, Hwang P, Guyda H, et al. Studies of prolactin secretion in human pregnancy. Am J Obstet Gynecol 1972 May 1; 113(1): 14–20

    PubMed  CAS  Google Scholar 

  2. Molitch ME. Disorders of prolactin secretion. Endocrinol Metab Clin North Am 2001; 30: 585–610

    Article  PubMed  CAS  Google Scholar 

  3. Delgrange E, Trouillas J, Maiter D, et al. Sex-related difference in the growth of prolactinomas: a clinical and prolifertion marker study. J Clin Endocrinol Metab 1997 Jul; 82(7): 2102–7

    Article  PubMed  CAS  Google Scholar 

  4. Popadic A, Witzmann A, Buchfelder M, et al. Malignant prolactinoma: case report and review of the literature. Surg Neurol 1999; 51: 47–54; discussion 54-5

    Article  PubMed  CAS  Google Scholar 

  5. Marken PA, Haykal RF, Fisher JN. Management of psychotropic-induced hyperprolactinemia. Clin Pharm 1992; 11: 851–6

    PubMed  CAS  Google Scholar 

  6. Wernze H, Schmitz E. Plama prolactin and prolactin release in liver cirhosis. Acta Hepatogastroenterol (Stuttg) 1997 Apr; 24(2): 97–101

    Google Scholar 

  7. Kelver ME, Nagamani M. Hyperprolactinemia in primary adrenocortical insufficiency. Fertil Steril 1985 Sep; 44(3): 423–5

    PubMed  CAS  Google Scholar 

  8. Ozarda AT. Prolactin-secreting tumors. J Surg Oncol 1983 Jan; 22(1): 9–10

    Article  PubMed  CAS  Google Scholar 

  9. Stanisic TH, Donovan J. Prolactin secreting renal cell carcinoma. J Urol 1986 Jul; 136(1): 85–6

    PubMed  CAS  Google Scholar 

  10. Milewicz A. Prolactin levels in the polycystic ovary syndrome. J Reprod Med 1984 Mar; 29(3): 193–6

    PubMed  CAS  Google Scholar 

  11. Sluijmer AV, Lappohn RE. Clinical history and outcome of 59 patients with idiopathic hyperprolactinemia. Fertil Steril 1992 Jul; 58(1): 72–7

    PubMed  CAS  Google Scholar 

  12. Schlechte J, Dolan K, Sherman B, et al. The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab 1989; 68: 412–8

    Article  PubMed  CAS  Google Scholar 

  13. Greenman Y, Tordjman K, Stern N. Increase in body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol 1998; 48: 547–53

    Article  CAS  Google Scholar 

  14. Vartej P, Poiana C, Vartej I. Effects of hyperprolactinemia on osteoporotic fracture risk in premenopausal women. Gynecol Endocrinol 2001; 15: 43–7

    PubMed  CAS  Google Scholar 

  15. Walsh JP, Pullan PT. Hyperprolactinemia in males: a heterogeneous disorder. Aust NZJ Med 1997; 27: 385–90

    Article  CAS  Google Scholar 

  16. Valette-Kasic S, Morange-Ramos I, Selim A, et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002; 87: 581–8

    Article  Google Scholar 

  17. St Jean E, Blain F, Comtois R. High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas. Clin Endocrinol 1996; 44: 305–9

    Article  Google Scholar 

  18. Wieck A, Haddad P. Hyperprolactinemia caused by antipsychotic drugs. BMJ 2002; 324: 250–2

    Article  PubMed  Google Scholar 

  19. McDonald WM, Sibley DR, Kilpatrick BF, et al. Dopaminergic inhibition of adenylate cyclase correlates with high affinity agonist binding to anterior pituitary D2-dopamine receptors. Mol Cell Endocrinol 1984; 36: 201–9

    Article  PubMed  CAS  Google Scholar 

  20. Vance ML, Evans WS, Thorner MO. Bromocriptine. Ann Intern Med 1984; 100: 78–91

    PubMed  CAS  Google Scholar 

  21. Webster J, Piscitelli G, Polli A, et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 1994; 331: 904–9

    Article  PubMed  CAS  Google Scholar 

  22. Di Sarno A, Landi ML, Cappabianca P, et al. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol 2001; 86: 5256–61

    Article  Google Scholar 

  23. Bevan JS, Webster J, Burke CW, et al. Dopamine agonists and pituitary tumor shrinkage. Endocr Rev 1992; 13: 220–40

    PubMed  CAS  Google Scholar 

  24. Lamberts S, Quik R. A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia. J Clin Endocrinol Metab 1991; 72: 635–8

    Article  PubMed  CAS  Google Scholar 

  25. Krupp P, Monka C. Bromocriptine in pregnancy: safety aspects. Klin Wochenschr 1987; 65: 823–7

    Article  PubMed  CAS  Google Scholar 

  26. Molitch ME. Management of prolactinomas during pregnancy. J Reproduct Med 1999; 44: 1121–6

    CAS  Google Scholar 

  27. Orrego JJ, Chandler WF, Barkan AL. Pergolide a primary therapy for macroprolactinomas. Pituitary 2000; 3: 251–6

    Article  PubMed  CAS  Google Scholar 

  28. Franks S, Hoorocks PM, Lynch SS, et al. Effectiveness of pergolide mesylate in the long-term treatment of hyperprolactinemia. BMJ 1983; 286: 1177–9

    Article  PubMed  CAS  Google Scholar 

  29. Freda PU, Andreadadis CI, Khandji AG, et al. Long-term treatment of prolactinsecreting macroadenomas with pergolide. J Clin Endocrinol Metab 2000; 85: 8–13

    Article  PubMed  CAS  Google Scholar 

  30. Van der Heijden PFM, De Wit W, Brownell J, et al. CV205-502, a new dopamine agonist, versus bromocriptine in the treatment of hyperprolactinemia. Eur J Obstet Gynecol Reprod Biol 1991;40: 111–8

    Article  PubMed  Google Scholar 

  31. Schultz PN, Ginsberg L, McCutcheon IE, et al. Quinagolide in the management of prolactinoma. Pituitary 2000; 3: 239–49

    Article  PubMed  CAS  Google Scholar 

  32. 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 2000; 53: 53–60

    Article  Google Scholar 

  33. Morange I, Barlier A, Pellegrini I, et al. Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy. Eur J Endocrinol 1996; 135: 413–20

    Article  PubMed  CAS  Google Scholar 

  34. 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: 2518–22

    Article  PubMed  CAS  Google Scholar 

  35. Biller_BMK, Molitch ME, Vance ML, et al. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J Clin Endocrinol Metab 1996; 81: 2338–43

    Article  Google Scholar 

  36. 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: 3574–9

    Article  PubMed  CAS  Google Scholar 

  37. Ferrari C, Abs R, Bevan J, et al. Treatment of macroprolactinoma with cabergoline: a study of 85 patients. Clin Endocrinol 1997; 46: 409–13

    Article  CAS  Google Scholar 

  38. Colao A, Di Sarno A, Landi ML, et al. Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab 2000; 85: 2247–52

    Article  PubMed  CAS  Google Scholar 

  39. Berwaerts J, Verhelst J, Abs R, et al. A giant prolactinoma presenting with exophtalmus: effect of cabergoline and review of the literature. J Endocrinol Invest 2000; 23: 393–8

    PubMed  CAS  Google Scholar 

  40. Ciccarelli E, Grottoli S, Razzore P, et al. Long-term treatment with cabergoline a new long-lasting ergoline derivative in idiopathic or tumorous hyperprolactinemia and outcome of drug-induced pregnancy. J Endocrinol Invest 1997; 20: 547–51

    PubMed  CAS  Google Scholar 

  41. Colao A, Di Sarno A, Sarnacchiaro F, et al. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J Clin Endocrinol Metab 1997; 82: 876–83

    Article  PubMed  CAS  Google Scholar 

  42. Katz E, Schran HF, Adashi EY. Successful treatment of a prolactin-producing pituitary macroadenoma with intravaginal bromcriptine meslate: a novel approach to intolerance of oral therapy. Obstet Gynecol 1989 Mar; 73 (3 Pt 2): 517–20

    PubMed  CAS  Google Scholar 

  43. Van’t Verlaat JW, Croughs RJ. Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size. Clin Endocrinol 1991; 34: 175–8

    Article  Google Scholar 

  44. Lemberger L, Crabtree RE. Pharmacologic effects in man of a potent, long-acting dopamine receptor agonist. Science 1979 Sep 14; 205(4411): 1151–3

    Article  PubMed  CAS  Google Scholar 

  45. Nordmann R, Fluckiger EW, Petcher TJ, et al. Endocrine actions of the potent dopamine D2-agonist CV 205–502 and related octrahydrobenzo(g)quinolines. Drugs Future 1998; 13: 951–9

    Google Scholar 

  46. Newman CB, Hurley AM, Kleinberg Dl, et al. Effect of CV 205–502 in hyperprolactinemic patients intolerant to bromocriptine. Clin Endocrinol 1989; 31:391–400

    Article  CAS  Google Scholar 

  47. Brae T, Pellegrini J, Gunz G, et al. Effects of dopamine agonist CV 205–502 in human prolactinomas resistant to bromocriptine. J Clin Endocrinol Metab 1992; 74: 577–84

    Article  Google Scholar 

  48. Rohmer V, Frenau E, Morange I, et al. Efficacy of quinagolide in resistance to dopamine agonists: results of a multicenter study. Ann Endocrinol (Paris) 2000; 61:411–7

    CAS  Google Scholar 

  49. Vilar L, Burke CW. Quinagolide efficacy and tolerability in hyperprolactinemic patients who are resistant to or intolerant of bromocriptine. Clin Endocrinol 1994; 41: 821–6

    Article  CAS  Google Scholar 

  50. Merola B, Sarnacchiaro F, Colao A, et al. Positive response to compound CV 205–502 in hyperprolactinemic patients resistant to or intolerant of bromocriptine. Gynecol Endocrinol 1994; 8: 1–7

    Article  Google Scholar 

  51. Ferrari C, Barbieri C, Caldara R, et al. Long-lasting prolactin lowering effect of cabergoline, a new dopamine agonist, in hyperprolactinemic patients. J Clin Endocrinol Metab 1986; 63: 941–5

    Article  PubMed  CAS  Google Scholar 

  52. Cocchiara G, Strolin Benedetti M. Excretion balance and urinary metabolic pattern of 3[H] cabergoline in man. Drag Metab Drug Interact 1992; 10: 199–211

    CAS  Google Scholar 

  53. Biller BMK, Baum HBA, Rosenthal DL, et al. Progressive trabecular osteopenia in women with hyperprolactinemic amenorrhea. J Clin Endocrinol Metab 1992; 75: 692–7

    Article  PubMed  CAS  Google Scholar 

  54. Ciric I, Ragin A, Baumgartner C, et al. Complications of transsphenoidal surgery: results of a national survey, review of the literature and personal experience. Neurosurgery 1997; 40: 225–37

    Article  PubMed  CAS  Google Scholar 

  55. Laws ER, Thapar K. Pituitary surgery. Endocrinol Metab Clin North Am 1999; 28: 119–31

    Article  PubMed  Google Scholar 

  56. Schlechte JA, Sherman BM, Chapler FK, et al. Long-term follow-up of women with surgically treated prolactin-secreting pituitary tumours. J Clin Endocrinol Metab 1986; 62: 1296–301

    Article  PubMed  CAS  Google Scholar 

  57. Cappabianca P, Lodrini S, Felisati G, et al. Cabergoline-induced CSF-rhinorrhea in patients with macroprolactinoma: report of three cases. J Endocrinol Invest 2001; 24: 183–7

    PubMed  CAS  Google Scholar 

  58. Tsagarakis S, Grossman A, Plowman PN, et al. Megavoltage pituitary irradiation in the management of prolactinomas: long-term follow-up. Clin Endocrinol 1991; 34: 399–406

    Article  CAS  Google Scholar 

  59. Tsang RW, Brierley JD, Panzarella T, et al. Role of radiation therapy in clinical hormonally active pituitary adenomas. Radiother Oncol 1996; 41: 45–53

    Article  PubMed  CAS  Google Scholar 

  60. Plowman PN. Radiotherapy for pituitary tumors. Bailliere’s Clin Endocrinol Metab 1995; 9: 407–20

    Article  CAS  Google Scholar 

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  1. Department of Endocrinology, Algemeen Ziekenhuis Middelheim, Middelheim Hospital and University, Lindendreef 1, 2020, Antwerp, Belgium

    Johan Verhelst & Roger Abs

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  1. Johan Verhelst
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Correspondence to Johan Verhelst.

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Verhelst, J., Abs, R. Hyperprolactinemia. Mol Diag Ther 2, 23–32 (2003). https://doi.org/10.2165/00024677-200302010-00003

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