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Prolactin-Secreting Pituitary Adenomas: Clinical Management

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Prolactin Disorders

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Hyperprolactinemia is frequently identified in individuals with galactorrhea, oligo-amenorrhea, infertility, or other manifestations of hypogonadism. Although prolactin-secreting pituitary adenomas may be managed expectantly in some asymptomatic patients, treatment is often indicated. This chapter reviews the clinical management of prolactinomas with a focus on pharmacologic, surgical, and radiation therapy, including emerging treatment options. Treatment efficacy, special patient populations, safety, and cost considerations are discussed.

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References

  1. Ciccarelli A, Daly AF, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3–6. PubMed PMID: 16411062.

    Article  PubMed  Google Scholar 

  2. Kunwar S, Wilson CB. Pediatric pituitary adenomas. J Clin Endocrinol Metab. 1999;84(12):4385–9. PubMed PMID: 10599692.

    Article  CAS  PubMed  Google Scholar 

  3. Kane LA, Leinung MC, Scheithauer BW, Bergstralh EJ, Laws ER Jr, Groover RV, et al. Pituitary adenomas in childhood and adolescence. J Clin Endocrinol Metab. 1994;79(4):1135–40. PubMed PMID: 7525627.

    CAS  PubMed  Google Scholar 

  4. Carter JN, Tyson JE, Warne GL, McNeilly AS, Faiman C, Friesen HG. Adrenocortical function in hyperprolactinemic women. J Clin Endocrinol Metab. 1977;45(5):973–80. PubMed PMID: 200633.

    Article  CAS  PubMed  Google Scholar 

  5. Lobo RA, Kletzky OA, Kaptein EM, Goebelsmann U. Prolactin modulation of dehydroepiandrosterone sulfate secretion. Am J Obstet Gynecol. 1980;138(6):632–6. PubMed PMID: 6449151.

    Article  CAS  PubMed  Google Scholar 

  6. Faje AT, Klibanski A. The treatment of hyperprolactinemia in postmenopausal women with prolactin-secreting microadenomas: cons. Endocrine. 2015;48(1):79–82. PubMed PMID: 24888765.

    Article  CAS  PubMed  Google Scholar 

  7. Caron MG, Beaulieu M, Raymond V, Gagne B, Drouin J, Lefkowitz RJ, et al. Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release. J Biol Chem. 1978;253(7):2244–53. PubMed PMID: 416027.

    CAS  PubMed  Google Scholar 

  8. Goldsmith PC, Cronin MJ, Weiner RI. Dopamine receptor sites in the anterior pituitary. J Histochem Cytochem. 1979;27(8):1205–7. PubMed PMID: 383827.

    Article  CAS  PubMed  Google Scholar 

  9. Turkington RW, Underwood LE, Van Wyk JJ. Elevated serum prolactin levels after pituitary-stalk section in man. N Engl J Med. 1971;285(13):707–10. PubMed PMID: 5106280.

    Article  CAS  PubMed  Google Scholar 

  10. Mori H, Mori S, Saitoh Y, Arita N, Aono T, Uozumi T, et al. Effects of bromocriptine on prolactin-secreting pituitary adenomas. Mechanism of reduction in tumor size evaluated by light and electron microscopic, immunohistochemical, and morphometric analysis. Cancer. 1985;56(2):230–8. PubMed PMID: 4005795.

    Article  CAS  PubMed  Google Scholar 

  11. Pascal-Vigneron V, Weryha G, Bosc M, Leclere J. Hyperprolactinemic amenorrhea: treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study. Presse Med. 1995;24(16):753–7. PubMed PMID: 7784413. Amenorrhee hyperprolactinemique: traitement par cabergoline versus bromocriptine. Resultats de l'etude nationale, multicentrique, randomisee, en double insu.

    CAS  PubMed  Google Scholar 

  12. Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med. 1994;331(14):904–9. PubMed PMID: 7915824.

    Article  CAS  PubMed  Google Scholar 

  13. dos Santos Nunes V, El Dib R, Boguszewski CL, Nogueira CR. Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis. Pituitary. 2011;14(3):259–65. PubMed PMID: 21221817.

    Article  PubMed  CAS  Google Scholar 

  14. Wang AT, Mullan RJ, Lane MA, Hazem A, Prasad C, Gathaiya NW, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012;1:33. PubMed PMID: 22828169. Pubmed Central PMCID: 3483691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, et al. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab. 2001;86(11):5256–61. PubMed PMID: 11701688.

    Article  PubMed  Google Scholar 

  16. Colao A, Di Sarno A, Sarnacchiaro F, Ferone D, Di Renzo G, Merola B, et al. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J Clin Endocrinol Metab. 1997;82(3):876–83. PubMed PMID: 9062500.

    Article  CAS  PubMed  Google Scholar 

  17. Cho KR, Jo KI, Shin HJ. Bromocriptine therapy for the treatment of invasive prolactinoma: the single institute experience. Brain Tumor Res Treat. 2013;1(2):71–7. PubMed PMID: 24904895. Pubmed Central PMCID: 4027106.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Delgrange E, Raverot G, Bex M, Burman P, Decoudier B, Devuyst F, et al. Giant prolactinomas in women. Eur J Endocrinol. 2014;170(1):31–8. PubMed PMID: 24088550.

    Article  CAS  PubMed  Google Scholar 

  19. Shimon I, Benbassat C, Hadani M. Effectiveness of long-term cabergoline treatment for giant prolactinoma: study of 12 men. Eur J Endocrinol. 2007;156(2):225–31. PubMed PMID: 17287412.

    Article  CAS  PubMed  Google Scholar 

  20. Clayton RN, Webb J, Heath DA, Dunn PJ, Rolfe EB, Hockley AD. Dramatic and rapid shrinkage of a massive invasive prolactinoma with bromocriptine: a case report. Clin Endocrinol. 1985;22(5):573–81. PubMed PMID: 4028456.

    Article  CAS  Google Scholar 

  21. Scarone P, Losa M, Mortini P, Giovanelli M. Obstructive hydrocephalus and intracranial hypertension caused by a giant macroprolactinoma. Prompt response to medical treatment. J Neuro-Oncol. 2006;76(1):51–4. PubMed PMID: 16205966.

    Article  CAS  Google Scholar 

  22. Woodhouse NJ, Khouqueer F, Sieck JO. Prolactinomas and optic nerve compression: disappearance of suprasellar extension and visual recovery after two weeks bromocriptine treatment. Horm Res. 1981;14(3):141–7. PubMed PMID: 7286886.

    Article  CAS  PubMed  Google Scholar 

  23. Colao A, Di Sarno A, Landi ML, Scavuzzo F, Cappabianca P, Pivonello R, 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(6):2247–52. PubMed PMID: 10852458.

    CAS  PubMed  Google Scholar 

  24. Cannavo S, Bartolone L, Blandino A, Spinella S, Galatioto S, Trimarchi F. Shrinkage of a PRL-secreting pituitary macroadenoma resistant to cabergoline. J Endocrinol Investig. 1999;22(4):306–9. PubMed PMID: 10342366.

    Article  CAS  Google Scholar 

  25. Jones SE, James RA, Hall K, Kendall-Taylor P. Optic chiasmal herniation – an under recognized complication of dopamine agonist therapy for macroprolactinoma. Clin Endocrinol. 2000;53(4):529–34. PubMed PMID: 11012580.

    Article  CAS  Google Scholar 

  26. Leong KS, Foy PM, Swift AC, Atkin SL, Hadden DR, MacFarlane IA. CSF rhinorrhoea following treatment with dopamine agonists for massive invasive prolactinomas. Clin Endocrinol. 2000;52(1):43–9. PubMed PMID: 10651752.

    Article  CAS  Google Scholar 

  27. Karavitaki N, Dobrescu R, Byrne JV, Grossman AB, Wass JA. Does hypopituitarism recover when macroprolactinomas are treated with cabergoline? Clin Endocrinol. 2013;79(2):217–23. PubMed PMID: 23215960.

    Article  CAS  Google Scholar 

  28. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–88. PubMed PMID: 21296991.

    Article  CAS  PubMed  Google Scholar 

  29. Molitch ME. Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma. Eur J Endocrinol. 2015;172(5):R205–13. PubMed PMID: 25805896.

    Article  CAS  PubMed  Google Scholar 

  30. Webster J. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Saf. 1996;14(4):228–38. PubMed PMID: 8713691.

    Article  CAS  PubMed  Google Scholar 

  31. Auriemma RS, Perone Y, Di Sarno A, Grasso LF, Guerra E, Gasperi M, et al. Results of a single-center observational 10-year survey study on recurrence of hyperprolactinemia after pregnancy and lactation. J Clin Endocrinol Metab. 2013;98(1):372–9. PubMed PMID: 23162092.

    Article  CAS  PubMed  Google Scholar 

  32. Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol. 2006;65(2):265–73. PubMed PMID: 16886971.

    Article  Google Scholar 

  33. Bahuleyan B, Menon G, Nair S, Rao BR, Easwer HV, Krishna K. Non-surgical management of cystic prolactinomas. J Clin Neurosci Off J Neurosurg Soc Australas. 2009;16(11):1421–4. PubMed PMID: 19699096.

    Google Scholar 

  34. Balarini Lima GA, Machado Ede O, Dos Santos Silva CM, Filho PN, Gadelha MR. Pituitary apoplexy during treatment of cystic macroprolactinomas with cabergoline. Pituitary. 2008;11(3):287–92. PubMed PMID: 17570067.

    Article  PubMed  Google Scholar 

  35. Delgrange E, Gustin T. Cystic macroprolactinoma: primary medical treatment? Intern Med J. 2005;35(11):687; author reply 8. PubMed PMID: 16248870.

    Article  CAS  PubMed  Google Scholar 

  36. Faje A, Chunharojrith P, Nency J, Biller BM, Swearingen B, Klibanski A. Dopamine agonists can reduce cystic prolactinomas. J Clin Endocrinol Metab. 2016;101(10):3709–15. PubMed PMID: 27459530.

    Article  CAS  PubMed  Google Scholar 

  37. Behan LA, Draman MS, Moran C, King T, Crowley RK, O'Sullivan EP, et al. Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review. Pituitary. 2011;14(4):362–6. PubMed PMID: 19191028.

    Article  CAS  PubMed  Google Scholar 

  38. Delgrange E, Daems T, Verhelst J, Abs R, Maiter D. Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients. Eur J Endocrinol. 2009;160(5):747–52. PubMed PMID: 19223454.

    Article  CAS  PubMed  Google Scholar 

  39. Ono M, Miki N, Kawamata T, Makino R, Amano K, Seki T, et al. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab. 2008;93(12):4721–7. PubMed PMID: 18812485.

    Article  CAS  PubMed  Google Scholar 

  40. Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, et al. Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol. 2012;167(5):651–62. PubMed PMID: 22918301.

    Article  CAS  PubMed  Google Scholar 

  41. Salenave S, Ancelle D, Bahougne T, Raverot G, Kamenicky P, Bouligand J, et al. Macroprolactinomas in children and adolescents: factors associated with the response to treatment in 77 patients. J Clin Endocrinol Metab. 2015;100(3):1177–86. PubMed PMID: 25532043.

    Article  CAS  PubMed  Google Scholar 

  42. Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J. Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab. 1997;82(7):2102–7. PubMed PMID: 9215279.

    CAS  PubMed  Google Scholar 

  43. Delgrange E, Vasiljevic A, Wierinckx A, Francois P, Jouanneau E, Raverot G, et al. Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. Eur J Endocrinol. 2015;172(6):791–801. PubMed PMID: 25792376.

    Article  CAS  PubMed  Google Scholar 

  44. Colao A, Sarno AD, Cappabianca P, Briganti F, Pivonello R, Somma CD, et al. Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol. 2003;148(3):325–31. PubMed PMID: 12611613.

    Article  CAS  PubMed  Google Scholar 

  45. Passos VQ, Fortes MA, Giannella-Neto D, Bronstein MD. Genes differentially expressed in prolactinomas responsive and resistant to dopamine agonists. Neuroendocrinology. 2009;89(2):163–70. PubMed PMID: 18791324.

    Article  CAS  PubMed  Google Scholar 

  46. Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak CP, et al. Resistance to bromocriptine in prolactinomas. J Clin Endocrinol Metab. 1989;69(3):500–9. PubMed PMID: 2760167.

    Article  CAS  PubMed  Google Scholar 

  47. Caccavelli L, Feron F, Morange I, Rouer E, Benarous R, Dewailly D, et al. Decreased expression of the two D2 dopamine receptor isoforms in bromocriptine-resistant prolactinomas. Neuroendocrinology. 1994;60(3):314–22. PubMed PMID: 7969790.

    Article  CAS  PubMed  Google Scholar 

  48. Peverelli E, Mantovani G, Vitali E, Elli FM, Olgiati L, Ferrero S, et al. Filamin-A is essential for dopamine d2 receptor expression and signaling in tumorous lactotrophs. J Clin Endocrinol Metab. 2012;97(3):967–77. PubMed PMID: 22259062.

    Article  CAS  PubMed  Google Scholar 

  49. Caccavelli L, Morange-Ramos I, Kordon C, Jaquet P, Enjalbert A. Alteration of G alpha subunits mRNA levels in bromocriptine resistant prolactinomas. J Neuroendocrinol. 1996;8(10):737–46. PubMed PMID: 8910802.

    Article  CAS  PubMed  Google Scholar 

  50. Filopanti M, Barbieri AM, Angioni AR, Colao A, Gasco V, Grottoli S, et al. Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas. Pharm J. 2008;8(5):357–63. PubMed PMID: 18332900.

    CAS  Google Scholar 

  51. Bueno C, Trarbach EB, Bronstein MD, Glezer A. Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment. Pituitary. 2017;20(3):295–300. PubMed PMID: 27848079.

    Article  CAS  PubMed  Google Scholar 

  52. Ilhan M, Kahraman OT, Turan S, Turgut S, Karaman O, Zeybek U, et al. Does DRD2 polymorphism influence the clinical characteristics of prolactinoma? Ann Endocrinol. 2015;76(5):614–9. PubMed PMID: 26514951.

    Article  Google Scholar 

  53. Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. 1999;84(7):2518–22. PubMed PMID: 10404830.

    Article  CAS  PubMed  Google Scholar 

  54. Morange I, Barlier A, Pellegrini I, Brue T, Enjalbert A, Jaquet P. Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy. Eur J Endocrinol. 1996;135(4):413–20. PubMed PMID: 8921822.

    Article  CAS  PubMed  Google Scholar 

  55. Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab. 2002;87(10):4447–51. PubMed PMID: 12364416.

    Article  CAS  PubMed  Google Scholar 

  56. Primeau V, Raftopoulos C, Maiter D. Outcomes of transsphenoidal surgery in prolactinomas: improvement of hormonal control in dopamine agonist-resistant patients. Eur J Endocrinol. 2012;166(5):779–86. PubMed PMID: 22301915.

    Article  CAS  PubMed  Google Scholar 

  57. Molitch ME. Management of medically refractory prolactinoma. J Neuro-Oncol. 2014;117(3):421–8. PubMed PMID: 24146188.

    Article  Google Scholar 

  58. Vallette S, Serri K, Rivera J, Santagata P, Delorme S, Garfield N, et al. Long-term cabergoline therapy is not associated with valvular heart disease in patients with prolactinomas. Pituitary. 2009;12(3):153–7. PubMed PMID: 18594989.

    Article  CAS  PubMed  Google Scholar 

  59. Klibanski A. Clinical practice. Prolactinomas. N Engl J Med. 2010;362(13):1219–26. PubMed PMID: 20357284.

    Article  CAS  PubMed  Google Scholar 

  60. Jean WC, Felbaum DR. Fertility, pregnancy, and prolactinoma: a survey of pituitary surgeons’ view and review of the literature. J Clin Neurosci. 2017;42:198–203. PubMed PMID: 28511976.

    Article  PubMed  Google Scholar 

  61. Donegan D, Atkinson JL, Jentoft M, Natt N, Nippoldt TB, Erickson B, et al. Surgical outcomes of prolactinomas in recent era: results of a heterogenous group. Endocr Pract. 2017;23(1):37–45. PubMed PMID: 27682355.

    Article  PubMed  Google Scholar 

  62. Kreutzer J, Buslei R, Wallaschofski H, Hofmann B, Nimsky C, Fahlbusch R, et al. Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. Eur J Endocrinol. 2008;158(1):11–8. PubMed PMID: 18166812.

    Article  CAS  PubMed  Google Scholar 

  63. Smith TR, Hulou MM, Huang KT, Gokoglu A, Cote DJ, Woodmansee WW, et al. Current indications for the surgical treatment of prolactinomas. J Clin Neurosci. 2015;22(11):1785–91. PubMed PMID: 26277642.

    Article  PubMed  Google Scholar 

  64. Ogiwara T, Horiuchi T, Nagm A, Goto T, Hongo K. Significance of surgical management for cystic prolactinoma. Pituitary. 2017;20(2):225–30. PubMed PMID: 27757801.

    Article  CAS  PubMed  Google Scholar 

  65. Andujar-Plata P, Villar-Taibo R, Ballesteros-Pomar MD, Vidal-Casariego A, Perez-Corral B, Cabezas-Agricola JM, et al. Long-term outcome of multimodal therapy for giant prolactinomas. Endocrine. 2017;55(1):231–8. PubMed PMID: 27704480.

    Article  CAS  PubMed  Google Scholar 

  66. Shimon I, Sosa E, Mendoza V, Greenman Y, Tirosh A, Espinosa E, et al. Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas. Pituitary. 2016;19(4):429–36. PubMed PMID: 27138902.

    Article  CAS  PubMed  Google Scholar 

  67. Yoo F, Kuan EC, Bergsneider M, Wang MB. Comparison of male and female prolactinoma patients requiring surgical intervention. J Neurosurg Skull Base. 2017;178(S01):S1–S156.

    Google Scholar 

  68. Ikeda H, Watanabe K, Tominaga T, Yoshimoto T. Transsphenoidal microsurgical results of female patients with prolactinomas. Clin Neurol Neurosurg. 2013;115(9):1621–5. PubMed PMID: 23498159.

    Article  PubMed  Google Scholar 

  69. Andereggen L, Frey J, Andres RH, El-Koussy M, Beck J, Seiler RW, et al. Long-term follow-up of primary medical versus surgical treatment of prolactinomas in men: effects on hyperprolactinemia, hypogonadism, and bone health. World Neurosurg. 2017;97:595–602. PubMed PMID: 27773859.

    Article  PubMed  Google Scholar 

  70. Andereggen L, Frey J, Andres RH, El-Koussy M, Beck J, Seiler RW, et al. 10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas. Endocrine. 2017;55(1):223–30. PubMed PMID: 27688009.

    Article  CAS  PubMed  Google Scholar 

  71. Menucci M, Quinones-Hinojosa A, Burger P, Salvatori R. Effect of dopaminergic drug treatment on surgical findings in prolactinomas. Pituitary. 2011;14(1):68–74. PubMed PMID: 20878243. Pubmed Central PMCID: 4612584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Jethwa PR, Patel TD, Hajart AF, Eloy JA, Couldwell WT, Liu JK. Cost-effectiveness analysis of microscopic and endoscopic transsphenoidal surgery versus medical therapy in the management of microprolactinoma in the United States. World Neurosurg. 2016;87:65–76. PubMed PMID: 26548828.

    Article  PubMed  Google Scholar 

  73. Zygourakis CC, Imber BS, Chen R, Han SJ, Blevins L, Molinaro A, et al. Cost-effectiveness analysis of surgical versus medical treatment of prolactinomas. J Neurol Surg Part B Skull Base. 2017;78(2):125–31. PubMed PMID: 28321375. Pubmed Central PMCID: 5357228.

    Google Scholar 

  74. Cohen-Inbar O, Xu Z, Schlesinger D, Vance ML, Sheehan JP. Gamma knife radiosurgery for medically and surgically refractory prolactinomas: long-term results. Pituitary. 2015;18(6):820–30. PubMed PMID: 25962347.

    Article  CAS  PubMed  Google Scholar 

  75. Landolt AM, Lomax N. Gamma knife radiosurgery for prolactinomas. J Neurosurg. 2000;93(Suppl 3):14–8. PubMed PMID: 11143231.

    Article  PubMed  Google Scholar 

  76. Pouratian N, Sheehan J, Jagannathan J, Laws ER Jr, Steiner L, Vance ML. Gamma knife radiosurgery for medically and surgically refractory prolactinomas. Neurosurgery. 2006;59(2):255–66; discussion -66. PubMed PMID: 16883166.

    Article  PubMed  Google Scholar 

  77. Kim W, Clelland C, Yang I, Pouratian N. Comprehensive review of stereotactic radiosurgery for medically and surgically refractory pituitary adenomas. Surg Neurol Int. 2012;3(Suppl 2):S79–89. PubMed PMID: 22826820. Pubmed Central PMCID: 3400491.

    PubMed  PubMed Central  Google Scholar 

  78. Sheplan Olsen LJ, Robles Irizarry L, Chao ST, Weil RJ, Hamrahian AH, Hatipoglu B, et al. Radiotherapy for prolactin-secreting pituitary tumors. Pituitary. 2012;15(2):135–45. PubMed PMID: 21948464.

    Article  PubMed  Google Scholar 

  79. Jaquet P, Ouafik L, Saveanu A, Gunz G, Fina F, Dufour H, et al. Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab. 1999;84(9):3268–76. PubMed PMID: 10487698.

    CAS  PubMed  Google Scholar 

  80. Bronstein MD, Knoepfelmacher M, Liberman B, Marino R Jr, Germek OA, Schally AV. Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia. Horm Metab Res Hormon Stoffwechselforschung Horm Metab. 1987;19(6):271–4. PubMed PMID: 2887502.

    Article  CAS  Google Scholar 

  81. Lamberts SW, Zweens M, Klijn JG, van Vroonhoven CC, Stefanko SZ, Del Pozo E. The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201-995 in patients with prolactinomas and acromegaly. Clin Endocrinol. 1986;25(2):201–12. PubMed PMID: 2878748.

    Article  CAS  Google Scholar 

  82. Del Gatto V, Bima C, Chiloiro S, Giampietro A, Bianchi A. Use of 111In-pentetreotide scintigraphy for diagnosis and management of resistant macroprolactinoma. Endocrine. 2018;60(3):532–4. PubMed PMID: 29214441.

    Google Scholar 

  83. Fusco A, Lugli F, Sacco E, Tilaro L, Bianchi A, Angelini F, et al. Efficacy of the combined cabergoline and octreotide treatment in a case of a dopamine-agonist resistant macroprolactinoma. Pituitary. 2011;14(4):351–7. PubMed PMID: 19152032.

    Article  PubMed  Google Scholar 

  84. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002;146(5):707–16. PubMed PMID: 11980628.

    Article  CAS  PubMed  Google Scholar 

  85. Hofland LJ, van der Hoek J, van Koetsveld PM, de Herder WW, Waaijers M, Sprij-Mooij D, et al. The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro. J Clin Endocrinol Metab. 2004;89(4):1577–85. PubMed PMID: 15070915.

    Article  CAS  PubMed  Google Scholar 

  86. Fusco A, Gunz G, Jaquet P, Dufour H, Germanetti AL, Culler MD, et al. Somatostatinergic ligands in dopamine-sensitive and -resistant prolactinomas. Eur J Endocrinol. 2008;158(5):595–603. PubMed PMID: 18426817.

    Article  CAS  PubMed  Google Scholar 

  87. Gruszka A, Ren SG, Dong J, Culler MD, Melmed S. Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules. Endocrinology. 2007;148(12):6107–14. PubMed PMID: 17656461.

    Article  CAS  PubMed  Google Scholar 

  88. Baldari S, Ferrau F, Alafaci C, Herberg A, Granata F, Militano V, et al. First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary. 2012;15(Suppl 1):S57–60. PubMed PMID: 22222543.

    Article  PubMed  Google Scholar 

  89. Maclean J, Aldridge M, Bomanji J, Short S, Fersht N. Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: variable clinical response in preliminary evaluation. Pituitary. 2014;17(6):530–8. PubMed PMID: 24323313.

    Article  CAS  PubMed  Google Scholar 

  90. Komor J, Reubi JC, Christ ER. Peptide receptor radionuclide therapy in a patient with disabling non-functioning pituitary adenoma. Pituitary. 2014;17(3):227–31. PubMed PMID: 23740146.

    Article  PubMed  Google Scholar 

  91. Fadul CE, Kominsky AL, Meyer LP, Kingman LS, Kinlaw WB, Rhodes CH, et al. Long-term response of pituitary carcinoma to temozolomide. Report of two cases. J Neurosurg. 2006;105(4):621–6. PubMed PMID: 17044568.

    Article  PubMed  Google Scholar 

  92. Lim S, Shahinian H, Maya MM, Yong W, Heaney AP. Temozolomide: a novel treatment for pituitary carcinoma. Lancet Oncol. 2006;7(6):518–20. PubMed PMID: 16750503.

    Article  PubMed  Google Scholar 

  93. Syro LV, Uribe H, Penagos LC, Ortiz LD, Fadul CE, Horvath E, et al. Antitumour effects of temozolomide in a man with a large, invasive prolactin-producing pituitary neoplasm. Clin Endocrinol. 2006;65(4):552–3. PubMed PMID: 16984254.

    Article  Google Scholar 

  94. Raverot G, Burman P, McCormack A, Heaney A, Petersenn S, Popovic V, et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018;178(1):G1–G24. PubMed PMID: 29046323.

    Article  CAS  PubMed  Google Scholar 

  95. Whitelaw BC, Dworakowska D, Thomas NW, Barazi S, Riordan-Eva P, King AP, et al. Temozolomide in the management of dopamine agonist-resistant prolactinomas. Clin Endocrinol. 2012;76(6):877–86. PubMed PMID: 22372583.

    Article  CAS  Google Scholar 

  96. Almalki MH, Aljoaib NN, Alotaibi MJ, Aldabas BS, Wahedi TS, Ahmad MH, et al. Temozolomide therapy for resistant prolactin-secreting pituitary adenomas and carcinomas: a systematic review. Hormones. 2017;16(2):139–49. PubMed PMID: 28742502.

    PubMed  Google Scholar 

  97. Bode H, Seiz M, Lammert A, Brockmann MA, Back W, Hammes HP, et al. SOM230 (pasireotide) and temozolomide achieve sustained control of tumour progression and ACTH secretion in pituitary carcinoma with widespread metastases. Exp Clin Endocrinol Diabetes. 2010;118(10):760–3. PubMed PMID: 20496311.

    Article  CAS  PubMed  Google Scholar 

  98. Thearle MS, Freda PU, Bruce JN, Isaacson SR, Lee Y, Fine RL. Temozolomide (Temodar(R)) and capecitabine (Xeloda(R)) treatment of an aggressive corticotroph pituitary tumor. Pituitary. 2011;14(4):418–24. PubMed PMID: 19960369. Pubmed Central PMCID: 2891584.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Touma W, Hoostal S, Peterson RA, Wiernik A, SantaCruz KS, Lou E. Successful treatment of pituitary carcinoma with concurrent radiation, temozolomide, and bevacizumab after resection. J Clin Neurosci. 2017;41:75–7. PubMed PMID: 28291643.

    Article  CAS  PubMed  Google Scholar 

  100. Bush ZM, Longtine JA, Cunningham T, Schiff D, Jane JA Jr, Vance ML, et al. Temozolomide treatment for aggressive pituitary tumors: correlation of clinical outcome with O(6)-methylguanine methyltransferase (MGMT) promoter methylation and expression. J Clin Endocrinol Metab. 2010;95(11):E280–90. PubMed PMID: 20668043. Pubmed Central PMCID: 5393383.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Bengtsson D, Schroder HD, Andersen M, Maiter D, Berinder K, Feldt Rasmussen U, et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab. 2015;100(4):1689–98. PubMed PMID: 25646794.

    Article  CAS  PubMed  Google Scholar 

  102. Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, et al. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab. 2010;95(10):4592–9. PubMed PMID: 20660056.

    Article  CAS  PubMed  Google Scholar 

  103. Asimakopoulou A, Tzanela M, Koletti A, Kontogeorgos G, Tsagarakis S. Long-term remission in an aggressive Crooke cell adenoma of the pituitary, 18 months after discontinuation of treatment with temozolomide. Clin Case Rep. 2014;2(1):1–3. PubMed PMID: 25356225. Pubmed Central PMCID: 4184761.

    Article  PubMed  Google Scholar 

  104. Hirohata T, Asano K, Ogawa Y, Takano S, Amano K, Isozaki O, et al. DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide: the national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors. J Clin Endocrinol Metab. 2013;98(3):1130–6. PubMed PMID: 23365123.

    Article  CAS  PubMed  Google Scholar 

  105. Raverot G, Castinetti F, Jouanneau E, Morange I, Figarella-Branger D, Dufour H, et al. Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment. Clin Endocrinol. 2012;76(6):769–75. PubMed PMID: 22404748.

    Article  CAS  Google Scholar 

  106. Nagasubramanian R, Dolan ME. Temozolomide: realizing the promise and potential. Curr Opin Oncol. 2003;15(6):412–8. PubMed PMID: 14624222.

    Article  CAS  PubMed  Google Scholar 

  107. Trinh VA, Patel SP, Hwu WJ. The safety of temozolomide in the treatment of malignancies. Expert Opin Drug Saf. 2009;8(4):493–9. PubMed PMID: 19435405.

    Article  CAS  PubMed  Google Scholar 

  108. Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, et al. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res. 2007;13(7):2038–45. PubMed PMID: 17404084. Pubmed Central PMCID: 2873832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003. PubMed PMID: 15758010.

    Article  CAS  PubMed  Google Scholar 

  110. Murakami M, Mizutani A, Asano S, Katakami H, Ozawa Y, Yamazaki K, et al. A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report. Neurosurgery. 2011;68(6):E1761–7; discussion E7. PubMed PMID: 21389894.

    Article  PubMed  Google Scholar 

  111. Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, et al. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res. 2006;66(8):3987–91. PubMed PMID: 16618716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Carlson BL, Grogan PT, Mladek AC, Schroeder MA, Kitange GJ, Decker PA, et al. Radiosensitizing effects of temozolomide observed in vivo only in a subset of O6-methylguanine-DNA methyltransferase methylated glioblastoma multiforme xenografts. Int J Radiat Oncol Biol Phys. 2009;75(1):212–9. PubMed PMID: 19695438. Pubmed Central PMCID: 2773462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Kil WJ, Cerna D, Burgan WE, Beam K, Carter D, Steeg PS, et al. In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin Cancer Res. 2008;14(3):931–8. PubMed PMID: 18245557.

    Article  CAS  PubMed  Google Scholar 

  114. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. PubMed PMID: 15758009.

    Article  CAS  PubMed  Google Scholar 

  115. Nakada M, Furuta T, Hayashi Y, Minamoto T, Hamada J. The strategy for enhancing temozolomide against malignant glioma. Front Oncol. 2012;2:98. PubMed PMID: 22912934. Pubmed Central PMCID: 3418701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Messaoudi K, Clavreul A, Lagarce F. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov Today. 2015;20(7):899–905. PubMed PMID: 25744176.

    Article  CAS  PubMed  Google Scholar 

  117. Jouanneau E, Wierinckx A, Ducray F, Favrel V, Borson-Chazot F, Honnorat J, et al. New targeted therapies in pituitary carcinoma resistant to temozolomide. Pituitary. 2012;15(1):37–43. PubMed PMID: 21858654.

    Article  CAS  PubMed  Google Scholar 

  118. Donovan LE, Arnal AV, Wang SH, Odia Y. Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy. CNS Oncol. 2016;5(4):203–9. PubMed PMID: 27615706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ortiz LD, Syro LV, Scheithauer BW, Ersen A, Uribe H, Fadul CE, et al. Anti-VEGF therapy in pituitary carcinoma. Pituitary. 2012;15(3):445–9. PubMed PMID: 21918831.

    Article  PubMed  Google Scholar 

  120. Moshkin O, Syro LV, Scheithauer BW, Ortiz LD, Fadul CE, Uribe H, et al. Aggressive silent corticotroph adenoma progressing to pituitary carcinoma: the role of temozolomide therapy. Hormones. 2011;10(2):162–7. PubMed PMID: 21724542.

    Article  PubMed  Google Scholar 

  121. Cooper O, Mamelak A, Bannykh S, Carmichael J, Bonert V, Lim S, et al. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors. Endocrine. 2014;46(2):318–27. PubMed PMID: 24287797. Pubmed Central PMCID: 4037394.

    Article  CAS  PubMed  Google Scholar 

  122. Agarwal N, Machiels JP, Suarez C, Lewis N, Higgins M, Wisinski K, et al. Phase I study of the prolactin receptor antagonist LFA102 in metastatic breast and castration-resistant prostate cancer. Oncologist. 2016;21(5):535–6. PubMed PMID: 27091421. Pubmed Central PMCID: 4861370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. March CM, Kletzky OA, Davajan V, Teal J, Weiss M, Apuzzo ML, et al. Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas. Am J Obstet Gynecol. 1981;139(7):835–44. PubMed PMID: 7193977.

    Article  CAS  PubMed  Google Scholar 

  124. Schlechte J, Dolan K, Sherman B, Chapler F, Luciano A. The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab. 1989;68(2):412–8. PubMed PMID: 2918052.

    Article  CAS  PubMed  Google Scholar 

  125. Weiss MH, Teal J, Gott P, Wycoff R, Yadley R, Apuzzo ML, et al. Natural history of microprolactinomas: six-year follow-up. Neurosurgery. 1983;12(2):180–3. PubMed PMID: 6682188.

    Article  CAS  PubMed  Google Scholar 

  126. Sisam DA, Sheehan JP, Sheeler LR. The natural history of untreated microprolactinomas. Fertil Steril. 1987;48(1):67–71. PubMed PMID: 3595916.

    Article  CAS  PubMed  Google Scholar 

  127. Dekkers OM, Lagro J, Burman P, Jorgensen JO, Romijn JA, Pereira AM. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95(1):43–51. PubMed PMID: 19880787.

    Article  CAS  PubMed  Google Scholar 

  128. Hu J, Zheng X, Zhang W, Yang H. Current drug withdrawal strategy in prolactinoma patients treated with cabergoline: a systematic review and meta-analysis. Pituitary. 2015;18(5):745–51. PubMed PMID: 25500765.

    Article  CAS  PubMed  Google Scholar 

  129. Xia MY, Lou XH, Lin SJ, Wu ZB. Optimal timing of dopamine agonist withdrawal in patients with hyperprolactinemia: a systematic review and meta-analysis. Endocrine. 2018;59(1):50–61. PubMed PMID: 29043560.

    Article  PubMed  CAS  Google Scholar 

  130. Kwancharoen R, Auriemma RS, Yenokyan G, Wand GS, Colao A, Salvatori R. Second attempt to withdraw cabergoline in prolactinomas: a pilot study. Pituitary. 2014;17(5):451–6. PubMed PMID: 24078319.

    Article  CAS  PubMed  Google Scholar 

  131. Vilar L, Albuquerque JL, Gadelha PS, Rangel Filho F, Siqueira AM, da Fonseca MM, et al. Second attempt of cabergoline withdrawal in patients with prolactinomas after a failed first attempt: is it worthwhile? Front Endocrinol. 2015;6:11. PubMed PMID: 25699020. Pubmed Central PMCID: 4316769.

    Article  Google Scholar 

  132. Kletzky OA, Vermesh M. Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia. Fertil Steril. 1989;51(2):269–72. PubMed PMID: 2912773.

    Article  CAS  PubMed  Google Scholar 

  133. Katz E, Schran HF, Adashi EY. Successful treatment of a prolactin-producing pituitary macroadenoma with intravaginal bromocriptine mesylate: a novel approach to intolerance of oral therapy. Obstet Gynecol. 1989;73(3 Pt 2):517–20. PubMed PMID: 2915884.

    CAS  PubMed  Google Scholar 

  134. Motta T, de Vincentiis S, Marchini M, Colombo N, D'Alberton A. Vaginal cabergoline in the treatment of hyperprolactinemic patients intolerant to oral dopaminergics. Fertil Steril. 1996;65(2):440–2. PubMed PMID: 8566276.

    Article  CAS  PubMed  Google Scholar 

  135. Darwish AM, Farah E, Gadallah WA, Mohammad II. Superiority of newly developed vaginal suppositories over vaginal use of commercial bromocriptine tablets: a randomized controlled clinical trial. Reprod Sci. 2007;14(3):280–5. PubMed PMID: 17636242.

    Article  CAS  PubMed  Google Scholar 

  136. Darwish AM, El-Sayed AM, El-Harras SA, Khaled KA, Ismail MA. Clinical efficacy of novel unidirectional buccoadhesive vs. vaginoadhesive bromocriptine mesylate discs for treating pathologic hyperprolactinemia. Fertil Steril. 2008;90(5):1864–8. PubMed PMID: 18462734.

    Article  PubMed  Google Scholar 

  137. Martinkova J, Trejbalova L, Sasikova M, Benetin J, Valkovic P. Impulse control disorders associated with dopaminergic medication in patients with pituitary adenomas. Clin Neuropharmacol. 2011;34(5):179–81. PubMed PMID: 21738024.

    Article  CAS  PubMed  Google Scholar 

  138. Turner TH, Cookson JC, Wass JA, Drury PL, Price PA, Besser GM. Psychotic reactions during treatment of pituitary tumours with dopamine agonists. Br Med J. 1984;289(6452):1101–3. PubMed PMID: 6435792. Pubmed Central PMCID: 1443261.

    Article  CAS  Google Scholar 

  139. Davie M. Pathological gambling associated with cabergoline therapy in a patient with a pituitary prolactinoma. J Neuropsychiatr Clin Neurosci. 2007;19(4):473–4. PubMed PMID: 18070857.

    Article  Google Scholar 

  140. Falhammar H, Yarker JY. Pathological gambling and hypersexuality in cabergoline-treated prolactinoma. Med J Aust. 2009;190(2):97. PubMed PMID: 19236300.

    PubMed  Google Scholar 

  141. Voon V, Fernagut PO, Wickens J, Baunez C, Rodriguez M, Pavon N, et al. Chronic dopaminergic stimulation in Parkinson’s disease: from dyskinesias to impulse control disorders. Lancet Neurol. 2009;8(12):1140–9. PubMed PMID: 19909912.

    Article  CAS  PubMed  Google Scholar 

  142. Voon V, Hassan K, Zurowski M, Duff-Canning S, de Souza M, Fox S, et al. Prospective prevalence of pathologic gambling and medication association in Parkinson disease. Neurology. 2006;66(11):1750–2. PubMed PMID: 16769956.

    Article  CAS  PubMed  Google Scholar 

  143. Dorevitch A, Aronzon R, Stark M. Psychotic exacerbation attributed to low-dose bromocriptine treatment of galactorrhea and hyperprolactinemia. Acta Obstet Gynecol Scand. 1991;70(4–5):375–6. PubMed PMID: 1746267.

    Article  CAS  PubMed  Google Scholar 

  144. Chang SC, Chen CH, Lu ML. Cabergoline-induced psychotic exacerbation in schizophrenic patients. Gen Hosp Psychiatry. 2008;30(4):378–80. PubMed PMID: 18585544.

    Article  PubMed  Google Scholar 

  145. de Bartolomeis A, Tomasetti C, Iasevoli F. Update on the mechanism of action of aripiprazole: translational insights into antipsychotic strategies beyond dopamine receptor antagonism. CNS Drugs. 2015;29(9):773–99. PubMed PMID: 26346901. Pubmed Central PMCID: 4602118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Bakker IC, Schubart CD, Zelissen PM. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole. Endocrinol Diabetes Metabol Case Rep. 2016;2016:160028. PubMed PMID: 27284453. Pubmed Central PMCID: 4898067.

    Google Scholar 

  147. Freeman B, Levy W, Gorman JM. Successful monotherapy treatment with aripiprazole in a patient with schizophrenia and prolactinoma. J Psychiatr Pract. 2007;13(2):120–4. PubMed PMID: 17414690.

    Article  PubMed  Google Scholar 

  148. Steinhagen CK. Normalization of prolactin with aripiprazole in a patient with psychotic depression and a comorbid pituitary microadenoma. Psychosomatics. 2007;48(4):350–1. PubMed PMID: 17600173.

    Article  PubMed  Google Scholar 

  149. Ranjbar F, Sadeghi-Bazargani H, Niari Khams P, Arfaie A, Salari A, Farahbakhsh M. Adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia. Neuropsychiatr Dis Treat. 2015;11:549–55. PubMed PMID: 25784810. Pubmed Central PMCID: 4356449.

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007;356(1):29–38. PubMed PMID: 17202453.

    Article  CAS  PubMed  Google Scholar 

  151. Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med. 2007;356(1):39–46. PubMed PMID: 17202454.

    Article  CAS  PubMed  Google Scholar 

  152. Tran T, Brophy JM, Suissa S, Renoux C. Risks of cardiac valve regurgitation and heart failure associated with ergot- and non-ergot-derived dopamine agonist use in patients with Parkinson’s disease: a systematic review of observational studies. CNS Drugs. 2015;29(12):985–98. PubMed PMID: 26585874.

    Article  CAS  PubMed  Google Scholar 

  153. Kvernmo T, Hartter S, Burger E. A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006;28(8):1065–78. PubMed PMID: 16982285.

    Article  CAS  PubMed  Google Scholar 

  154. Miyagi M, Itoh F, Taya F, Arai N, Isaji M, Kojima M, et al. Dopamine receptor affinities in vitro and stereotypic activities in vivo of cabergoline in rats. Biol Pharm Bull. 1996;19(9):1210–3. PubMed PMID: 8889042.

    Article  CAS  PubMed  Google Scholar 

  155. Hutcheson JD, Ryzhova LM, Setola V, Merryman WD. 5-HT(2B) antagonism arrests non-canonical TGF-beta1-induced valvular myofibroblast differentiation. J Mol Cell Cardiol. 2012;53(5):707–14. PubMed PMID: 22940605. Pubmed Central PMCID: 3472096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Hutcheson JD, Setola V, Roth BL, Merryman WD. Serotonin receptors and heart valve disease – it was meant 2B. Pharmacol Ther. 2011;132(2):146–57. PubMed PMID: 21440001. Pubmed Central PMCID: 3179857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Roth BL. Drugs and valvular heart disease. N Engl J Med. 2007;356(1):6–9. PubMed PMID: 17202450.

    Article  CAS  PubMed  Google Scholar 

  158. Colao A, Galderisi M, Di Sarno A, Pardo M, Gaccione M, D'Andrea M, et al. Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline. J Clin Endocrinol Metab. 2008;93(10):3777–84. PubMed PMID: 18682513.

    Article  CAS  PubMed  Google Scholar 

  159. Drake WM, Stiles CE, Bevan JS, Karavitaki N, Trainer PJ, Rees DA, et al. A follow-up study of the prevalence of valvular heart abnormalities in hyperprolactinemic patients treated with cabergoline. J Clin Endocrinol Metab. 2016;101(11):4189–94. PubMed PMID: 27571182.

    Article  CAS  PubMed  Google Scholar 

  160. Vroonen L, Lancellotti P, Garcia MT, Dulgheru R, Almanza M, Maiga I, et al. Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia. Endocrine. 2017;55(1):239–45. PubMed PMID: 27709470.

    Article  CAS  PubMed  Google Scholar 

  161. Auriemma RS, Pivonello R, Perone Y, Grasso LF, Ferreri L, Simeoli C, et al. Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas. Eur J Endocrinol. 2013;169(3):359–66. PubMed PMID: 23824978.

    Article  CAS  PubMed  Google Scholar 

  162. Delgado V, Biermasz NR, van Thiel SW, Ewe SH, Marsan NA, Holman ER, et al. Changes in heart valve structure and function in patients treated with dopamine agonists for prolactinomas, a 2-year follow-up study. Clin Endocrinol. 2012;77(1):99–105. PubMed PMID: 22211510.

    Article  CAS  Google Scholar 

  163. De Vecchis R, Esposito C, Ariano C. Cabergoline use and risk of fibrosis and insufficiency of cardiac valves. Meta-analysis of observational studies. Herz. 2013;38(8):868–80. PubMed PMID: 23743769.

    Article  PubMed  Google Scholar 

  164. Caputo C, Prior D, Inder WJ. The need for annual echocardiography to detect cabergoline-associated valvulopathy in patients with prolactinoma: a systematic review and additional clinical data. Lancet Diabetes Endocrinol. 2015;3(11):906–13. PubMed PMID: 25466526.

    Article  CAS  PubMed  Google Scholar 

  165. Samson SL, Ezzat S. AACE/ACE disease state clinical review: dopamine agonists for hyperprolactinemia and the risk of cardiac valve disease. Endocr Pract. 2014;20(6):608–16. PubMed PMID: 24969114.

    Article  PubMed  Google Scholar 

  166. Reuwer AQ, Nieuwland R, Fernandez I, Goffin V, van Tiel CM, Schaap MC, et al. Prolactin does not affect human platelet aggregation or secretion. Thromb Haemost. 2009;101(6):1119–27. PubMed PMID: 19492157.

    Article  CAS  PubMed  Google Scholar 

  167. Wallaschofski H, Donne M, Eigenthaler M, Hentschel B, Faber R, Stepan H, et al. PRL as a novel potent cofactor for platelet aggregation. J Clin Endocrinol Metab. 2001;86(12):5912–9. PubMed PMID: 11739463.

    Article  CAS  PubMed  Google Scholar 

  168. Mon SY, Alkabbani A, Hamrahian A, Thorton JN, Kennedy L, Weil R, et al. Risk of thromboembolic events in patients with prolactinomas compared with patients with nonfunctional pituitary adenomas. Pituitary. 2013;16(4):523–7. PubMed PMID: 23203499.

    Article  CAS  PubMed  Google Scholar 

  169. van Zaane B, Squizzato A, Reuwer AQ, van Zanten AP, Twickler MT, Dekkers OM, et al. Prolactin and venous thrombosis: indications for a novel risk factor? Arterioscler Thromb Vasc Biol. 2011;31(3):672–7. PubMed PMID: 21164080.

    Article  PubMed  CAS  Google Scholar 

  170. Shelly S, Boaz M, Orbach H. Prolactin and autoimmunity. Autoimmun Rev. 2012;11(6–7):A465–70. PubMed PMID: 22155203.

    Article  CAS  PubMed  Google Scholar 

  171. Savino W. Prolactin: an immunomodulator in health and disease. Front Horm Res. 2017;48:69–75. PubMed PMID: 28245452.

    Article  PubMed  Google Scholar 

  172. Fernandez I, Touraine P, Goffin V. Prolactin and human tumourogenesis. J Neuroendocrinol. 2010;22(7):771–7. PubMed PMID: 20456598.

    CAS  PubMed  Google Scholar 

  173. Goffin V, Touraine P. The prolactin receptor as a therapeutic target in human diseases: browsing new potential indications. Expert Opin Ther Targets. 2015;19(9):1229–44. PubMed PMID: 26063597.

    Article  CAS  PubMed  Google Scholar 

  174. Berinder K, Akre O, Granath F, Hulting AL. Cancer risk in hyperprolactinemia patients: a population-based cohort study. Eur J Endocrinol. 2011;165(2):209–15. PubMed PMID: 21602317.

    Article  CAS  PubMed  Google Scholar 

  175. Dekkers OM, Romijn JA, de Boer A, Vandenbroucke JP. The risk for breast cancer is not evidently increased in women with hyperprolactinemia. Pituitary. 2010;13(3):195–8. PubMed PMID: 20012697. Pubmed Central PMCID: 2913002.

    Article  CAS  PubMed  Google Scholar 

  176. Vonderhaar BK. Prolactin: the forgotten hormone of human breast cancer. Pharmacol Ther. 1998;79(2):169–78. PubMed PMID: 9749881.

    Article  CAS  PubMed  Google Scholar 

  177. Clevenger CV, Furth PA, Hankinson SE, Schuler LA. The role of prolactin in mammary carcinoma. Endocr Rev. 2003;24(1):1–27. PubMed PMID: 12588805. Pubmed Central PMCID: 1698952.

    Article  CAS  PubMed  Google Scholar 

  178. Marano RJ, Ben-Jonathan N. Minireview: extrapituitary prolactin: an update on the distribution, regulation, and functions. Mol Endocrinol. 2014;28(5):622–33. PubMed PMID: 24694306. Pubmed Central PMCID: 5414853.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Gellersen B, Kempf R, Telgmann R, DiMattia GE. Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma. Mol Endocrinol. 1994;8(3):356–73. PubMed PMID: 8015553.

    CAS  PubMed  Google Scholar 

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Faje, A., Zachariah, M.A., Swearingen, B. (2019). Prolactin-Secreting Pituitary Adenomas: Clinical Management. In: Tritos, N., Klibanski, A. (eds) Prolactin Disorders. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-030-11836-5_8

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