Pathogenesis, diagnosis and current treatment of prolactinoma: a review of the literature
DOI:
https://doi.org/10.12775/QS.2024.18.53224Keywords
prolactinoma pathogenesis, prolactinoma treatment, dopamine agonists, cabergoline, bromocriptine, temozolomideAbstract
ABSTRACT:
Prolactinoma is a benign tumor of the pituitary gland that leads to the overproduction of prolactin. It is the most common type of pituitary adenoma, accounting for approximately 50% of all pituitary tumors. The clinical presentation of prolactinoma varies depending on the level of prolactin elevation and the size of the tumor. In women, common symptoms include galactorrhea, amenorrhea, and infertility. Men may present with hypogonadism, decreased libido, erectile dysfunction, and gynecomastia. Large prolactinomas, known as macroadenomas, can cause mass effects such as headaches, visual disturbances due to compression of the optic chiasm, and hypopituitarism due to pressure on surrounding pituitary tissue. Understanding the pathogenesis of prolactinoma is crucial for developing effective treatments and improving patient outcomes. The development of prolactinomas involves a complex interplay of genetic, hormonal, and cellular factors. Treatment of prolactinoma aims to normalize prolactin levels, reduce tumor size, and alleviate symptoms. The first-line therapy is dopamine agonists, such as cabergoline and bromocriptine, with surgery and radiotherapy reserved for refractory cases. Furthermore, chemotherapeutic agent - temozolomide may be a treatment of choice in aggressive or malignant prolactinomas. By understanding the underlying mechanisms and different treatment methods, healthcare providers can optimize the management and outcomes for patients with prolactinoma.
References
Auriemma RS, Pirchio R, Pivonello C, Garifalos F, Colao A, Pivonello R. Approach to the Patient With Prolactinoma. J Clin Endocrinol Metab. 2023 Aug 18;108(9):2400-2423. doi: 10.1210/clinem/dgad174. PMID: 36974474; PMCID: PMC10438891.
De Sousa SMC. Dopamine agonist therapy for prolactinomas: do we need to rethink the place of surgery in prolactinoma management? Endocr Oncol. 2022 Apr 21;2(1):R31-R50. doi: 10.1530/EO-21-0038. PMID: 37435462; PMCID: PMC10259306.
Adrian F. Daly, Maria A. Tichomirowa, Albert Beckers, The epidemiology and genetics of pituitary adenomas, Best Practice & Research Clinical Endocrinology & Metabolism, Volume 23, Issue 5, 2009, Pages 543-554, ISSN 1521-690X, https://doi.org/10.1016/j.beem.2009.05.008.
Mark E. Molitch, Pituitary incidentalomas, Best Practice & Research Clinical Endocrinology & Metabolism, Volume 23, Issue 5, 2009, Pages 667-675, ISSN 1521-690X, https://doi.org/10.1016/j.beem.2009.05.001.
Chanson P, Maiter D. Prolactinoma. In: Melmed S, editor. The pituitary. 4th ed. London, UK: Elsevier; 2017. p. 467e514.
Kars M, Souverein PC, Herings RM, et al. Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia. J Clin Endocrinol Metab 2009; 94:2729e34.
Schlechte JA. Clinical practice. Prolactinoma N Engl J Med 2003; 349:2035e41.
Soto-Pedre E, Newey PJ, Bevan JS, et al. The epidemiology of hyperprolactinaemia over 20 years in the tayside region of scotland: the prolactin epidemiology, audit and research study (PROLEARS). Clinical Endocrinology 2017; 86:60e7
Irfan H, Shafiq W, Siddiqi AI, Ashfaq S, Attaullah S, Munir Alvi A, Khan SA, Abu Bakar M, Azmat U. Prolactinoma: Clinical Characteristics, Management and Outcome. Cureus. 2022 Oct 2;14(10):e29822. doi: 10.7759/cureus.29822. PMID: 36337795; PMCID: PMC9626374.
Chanson P, Maiter D. The epidemiology, diagnosis and treatment of Prolactinomas: The old and the new. Best Pract Res Clin Endocrinol Metab. 2019 Apr;33(2):101290. doi: 10.1016/j.beem.2019.101290. Epub 2019 Jul 10. PMID: 31326373.
Yatavelli RKR, Bhusal K. Prolactinoma. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459347
Raappana A, Koivukangas J, Ebeling T, et al. Incidence of pituitary adenomas in Northern Finland in 1992-2007. J Clin Endocrinol Metab 2010; 95:4268e75.
Gruppetta M, Mercieca C, Vassallo J. Prevalence and incidence of pituitary adenomas: a population based study in Malta. Pituitary 2013; 16:545e53.
Agustsson TT, Baldvinsdottir T, Jonasson JG, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol 2015; 173:655e64.
Day PF, Loto MG, Glerean M, et al. Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina. Arch Endocrinol Metab 2016;60: 554e61.
Daly AF, Rixhon M, Adam C, et al. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006;91:4769e75.
Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 2010;72:377e82.
Fontana E, Gaillard R. Epidemiology of pituitary adenoma: results of the first Swiss study. Rev Med Suisse 2009;5: 2172e4.
Tjornstrand A, Gunnarsson K, Evert M, et al. The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011. Eur J Endocrinol 2014;171:519e26.
Agustsson TT, Baldvinsdottir T, Jonasson JG, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol 2015;173:655e64.
Day PF, Loto MG, Glerean M, et al. Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina. Arch Endocrinol Metab 2016;60: 554e61.
Molitch ME, Drummond J, Korbonits M. Prolactinoma Management. [Updated 2022 Jan 6]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279174/
Guo J, Li C, Fang Q, Liu Y, Wang D, Chen Y, Xie W, Zhang Y. The SF3B1R625H mutation promotes prolactinoma tumor progression through aberrant splicing of DLG1. J Exp Clin Cancer Res. 2022 Jan 17;41(1):26. doi: 10.1186/s13046-022-02245-0. PMID: 35039052; PMCID: PMC8762886.
Fukuhara N, Nishiyama M, Iwasaki Y. Update in Pathogenesis, Diagnosis, and Therapy of Prolactinoma. Cancers (Basel). 2022 Jul 24;14(15):3604. doi: 10.3390/cancers14153604. PMID: 35892862; PMCID: PMC9331865.
Karavitaki N, Thanabalasingham G, Shore HC, Trifanescu R, Ansorge O, Meston N, Turner HE, Wass JA. Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf). 2006 Oct;65(4):524-9. doi: 10.1111/j.1365-2265.2006.02627.x. PMID: 16984247.
Maiter D. Current Challenges in the Management of Prolactinomas. Eur Endocrinol. 2015 Apr;11(1):39-40. doi: 10.17925/EE.2015.11.01.39. Epub 2015 Apr 11. PMID: 29632566; PMCID: PMC5819061.
Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev. 2006 Aug;27(5):485-534. doi: 10.1210/er.2005-9998. Epub 2006 May 26. PMID: 16705142.
Maiter D, Delgrange E. Therapy of endocrine disease: the challenges in managing giant prolactinomas. Eur J Endocrinol. 2014 Jun;170(6):R213-27. doi: 10.1530/EJE-14-0013. Epub 2014 Feb 17. PMID: 24536090.
Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA; Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-88. doi: 10.1210/jc.2010-1692. PMID: 21296991.
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(2):265-273.
Inder WJ, Jang C. Treatment of Prolactinoma. Medicina (Kaunas). 2022 Aug 13;58(8):1095. doi: 10.3390/medicina58081095. PMID: 36013562; PMCID: PMC9413135.
Melis GB, Gambacciani M, Paoletti AM, Mais V, Sghedoni D, Fioretti P. Reduction in the size of prolactin-producing pituitary tumor after Cabergoline administration. Fertil Steril. 1989 Sep;52(3):412-5. doi: 10.1016/s0015-0282(16)60909-3. PMID: 2570719.
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 Oct 6;331(14):904-9. doi: 10.1056/NEJM199410063311403. PMID: 7915824.
Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, Mockel J, Lamberigts G, Petrossians P, Coremans P, Mahler C, Stevenaert A, Verlooy J, Raftopoulos C, Beckers A. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. 1999 Jul;84(7):2518-22. doi: 10.1210/jcem.84.7.5810. PMID: 10404830.
Colao A, Di Sarno A, Landi ML, Scavuzzo F, Cappabianca P, Pivonello R, Volpe R, Di Salle F, Cirillo S, Annunziato L, Lombardi G. 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 Jun;85(6):2247-52. doi: 10.1210/jcem.85.6.6657. PMID: 10852458.
Colao A, Di Sarno A, Landi ML, Cirillo S, Sarnacchiaro F, Facciolli G, Pivonello R, Cataldi M, Merola B, Annunziato L, Lombardi G. Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab. 1997 Nov;82(11):3574-9. doi: 10.1210/jcem.82.11.4368. PMID: 9360509.
De Rosa M, Colao A, Di Sarno A, Ferone D, Landi ML, Zarrilli S, Paesano L, Merola B, Lombardi G. Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol. 1998 Mar;138(3):286-93. doi: 10.1530/eje.0.1380286. PMID: 9539303.
Glezer A, Bronstein MD. Prolactinomas in pregnancy: considerations before conception and during pregnancy. Pituitary. 2020 Feb;23(1):65-69. doi: 10.1007/s11102-019-01010-5. PMID: 31792668.
Maiter D. Management of Dopamine Agonist-Resistant Prolactinoma. Neuroendocrinology. 2019;109(1):42-50. doi: 10.1159/000495775. Epub 2019 Mar 18. PMID: 30481756.
Brownell J. Quinagolide in hyperprolactinemia. Rev Contemp Pharmacother 1998;9:1e75.
Barlier A, Jaquet P. Quinagolide–a valuable treatment option for hyperprolactinaemia. Eur J Endocrinol 2006;154: 187e95.
Webster J. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Saf 1996;14:228e38.
Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38. doi: 10.1056/NEJMoa062222. PMID: 17202453.
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 Jan 4;356(1):39-46. doi: 10.1056/NEJMoa054830. PMID: 17202454.
Dogansen SC, Cikrikcili U, Oruk G, Kutbay NO, Tanrikulu S, Hekimsoy Z, Hadzalic A, Gorar S, Omma T, Mert M, Akbaba G, Yalin GY, Bayram F, Ozkan M, Yarman S. Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2527-2534. doi: 10.1210/jc.2018-02202. PMID: 30848825.
De Sousa SMC, Baranoff J, Rushworth RL, Butler J, Sorbello J, Vorster J, Thompson T, McCormack AI, Inder WJ, Torpy DJ. Impulse Control Disorders in Dopamine Agonist-Treated Hyperprolactinemia: Prevalence and Risk Factors. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz076. doi: 10.1210/clinem/dgz076. PMID: 31580439.
Honegger J, Nasi-Kordhishti I, Aboutaha N, Giese S. Surgery for prolactinomas: a better choice? Pituitary. 2020 Feb;23(1):45-51. doi: 10.1007/s11102-019-01016-z. PMID: 31853793.
Zamanipoor Najafabadi AH, Zandbergen IM, de Vries F, Broersen LHA, van den Akker-van Marle ME, Pereira AM, Peul WC, Dekkers OM, van Furth WR, Biermasz NR. Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e32–41. doi: 10.1210/clinem/dgz144. PMID: 31665485; PMCID: PMC7112976.
Bloomgarden E, Molitch ME. Surgical treatment of prolactinomas: cons. Endocrine. 2014 Dec;47(3):730-3. doi: 10.1007/s12020-014-0369-9. Epub 2014 Aug 12. PMID: 25112227.
Lasolle H, Ilie MD, Raverot G. Aggressive prolactinomas: how to manage? Pituitary. 2020 Feb;23(1):70-77. doi: 10.1007/s11102-019-01000-7. PMID: 31617128.
O'Reilly SM, Newlands ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P, et al. Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur J Cancer. 1993;29A(7):940-2. doi: 10.1016/s0959-8049(05)80198-4. Erratum in: Eur J Cancer 1993;29A(10):1500. PMID: 8499146.
Lim S, Shahinian H, Maya MM, Yong W, Heaney AP. Temozolomide: a novel treatment for pituitary carcinoma. Lancet Oncol. 2006 Jun;7(6):518-20. doi: 10.1016/S1470-2045(06)70728-8. PMID: 16750503.
Lasolle H, Cortet C, Castinetti F, Cloix L, Caron P, Delemer B, Desailloud R, Jublanc C, Lebrun-Frenay C, Sadoul JL, Taillandier L, Batisse-Lignier M, Bonnet F, Bourcigaux N, Bresson D, Chabre O, Chanson P, Garcia C, Haissaguerre M, Reznik Y, Borot S, Villa C, Vasiljevic A, Gaillard S, Jouanneau E, Assié G, Raverot G. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol. 2017 Jun;176(6):769-777. doi: 10.1530/EJE-16-0979. PMID: 28432119.
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