DOI: https://doi.org/10.18370/2309-4117.2019.49.35-42

Contemporary approaches to the diagnosis of hyperprolactinemia

О. А. Бурка, Т. М. Тутченко

Abstract


Hyperprolactinemia (HP) is a persistent prolactin increase in serum. HP is a common endocrinopathy that impairs reproductive function, long term HP may lead to the metabolic disorders and a decrease in bone mineral density.

Prolactin increase may be result of many physiological and pathological conditions, the diagnosis of which directly affects treatment approaches.

Evaluation of prolactin is not only the basis for the HP diagnosis but also an indirect indicator of its cause. For this reason it is important to recognize the possible difficulties in the

HP diagnosis associated with the following factors: pulsate nature of prolactin secretion; sensitivity to various exogenous and endogenous factors; presence of various molecular prolactin forms (macroprolactinemia) and rare laboratory artifacts (hook effect). Laboratory studies are also used to evaluate other endocrinopathies that can be the primary HP cause (hypothyroidism) or coexisting conditions (mixed pituitary adenomas, polycystic ovary syndrome). Stress-induced HP has to be differentiated from physiological HP via repeated prolactin tests is gaining increasing clinical importance.

The article provides an overview of modern research and relevant clinical guidelines for the diagnosis of various HP causes and offers an algorithmic approach for this clinical problem, the main principles are: to exclude iatrogenic causes, pregnancy and hypothyroidism at the initial stage of diagnosis; in the absence of neuroophthalmic symptoms and prolactin levels under 50–80 ng/ml repeated prolactin testing may be necessary to exclude physiological HP; screening for macroprolactinemia in all cases of prolactin level under of 200 ng/ml allows diagnosing macroprolactinemia or non-functioning pituitary adenoma; if MRT shows on macroprolactinoma and/or there are neuroophthalmic symptoms in combination with a normal or slightly elevated prolactin level it is necessary to exclude possible hook effect; in order to exclude mixed pituitary adenomas based on clinical features it is necessary to evaluate growth hormone, insulin-like growth factor 1, adrenocorticotrophic and thyroid-stimulating hormones in addition to prolactin

Keywords


hyperprolactinemia; prolactinoma; hormone-secreting pituitary adenomas; macroprolactin; stress; hypothyroidism

References


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Melmed, S., Casanueva, F.F., Hoffman, A.R., et al. “Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline.” J Clin Endocrinol Metab 96 (2011): 273–88. doi:10.1210/jc.2010-1692

Chiloiro, S., Giampietro, A., Bianchi, A., De Marinis, L. “Prolactinoma and Bone.” Curr Opin Endocr Metab Res 3 (2018): 21–4. doi:10.1016/J.COEMR.2018.02.006

Ben-Jonathan, N., Hugo, E.R., Brandebourg, T.D., LaPensee, C.R. “Focus on prolactin as a metabolic hormone.” Trends Endocrinol Metab 17 (2006): 110–6. doi:10.1016/J.TEM.2006.02.005

Vilar, L., Abucham, J., Albuquerque, J.L., et al. “Controversial issues in the management of hyperprolactinemia and prolactinomas – An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism.” Arch Endocrinol Metab 62 (2018): 236–63. doi:10.20945/2359-3997000000032

Tirosh, A., Shimon, I. “Management of macroprolactinomas.” Clin Diabetes Endocrinol 1 (2015): 5. doi:10.1186/s40842-015-0006-4

Pekić, S., Medic Stojanoska, M., Popovic, V. “Hyperprolactinemia/Prolactinomas in the Postmenopausal Period: Challenges in Diagnosis and Management.” Neuroendocrinology 109 (2019): 28–33. doi:10.1159/000494725

Matalliotakis, M., Koliarakis, I., Matalliotaki, C., et al. “Clinical manifestations, evaluation and management of hyperprolactinemia in adolescent and young girls: a brief review.” Acta Biomed 90 (2019): 149–57. doi:10.23750/abm.v90i1.8142

Hughes, E.G., Garner, P.R. “Primary amenorrhea associated with hyperprolactinemia:

four cases with normal sellar architecture and absence of galactorrhea.” Fertil Steril 47 (1987): 1031–2. doi:10.1016/s0015-0282(16)59241-3

Coulam, C.B., Laws, E.R., Abboud, C.F., Randall, R.V. “Primary amenorrhea and pituitary adenomas.” Fertil Steril 35 (1981): 615–9. doi:10.1016/S0015-0282(16)45551-2

Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G.“Prolactin: Structure, Function, and Regulation of Secretion.” Physiol Rev 80 (2000): 1523–1631. doi:10.1152/physrev.2000.80.4.1523

Grattan, D.R., Kokay, I.C. “Prolactin: A Pleiotropic Neuroendocrine Hormone.” J Neuroendocrinol 20 (2008): 752–63. doi:10.1111/j.1365-2826.2008.01736.x

Tritos, N.A., Klibanski, A. “Prolactin and Its Role in Human Reproduction.” Yen Jaffe’s Reprod Endocrinol (2019): 58–74.e8. doi:10.1016/B978-0-323-47912-7.00003-2

Mancini, T., Casanueva, F.F., Giustina, A. “Hyperprolactinemia and Prolactinomas.” Endocrinol Metab Clin North Am 37 (2008): 67–99. doi:10.1016/j.ecl.2007.10.013

Ciccarelli, A., Daly, A.F., Beckers, A. “The Epidemiology of Prolactinomas.” Pituitary 8 (2005): 3–6. doi:10.1007/s11102-005-5079-0

Pivonello, R., Salzano, C., Galdiero, M., Colao, A. “Male Hypogonadism Due to Disorders of the Pituitary and Suprasellar Region.” In: Male Hypogonadism. Springer International Publishing. Cham (2017): 169–86. doi:10.1007/978-3-319-53298-1_8

Corona, G., Mannucci, E., Fisher, A.D., et al. “Effect of Hyperprolactinemia in Male Patients Consulting for Sexual Dysfunction.” J Sex Med 4 (2007): 1485–93. doi:10.1111/j.1743-6109.2007.00569.x

Molitch, M.E. “Diagnosis and Treatment of Pituitary Adenomas.” JAMA 317 (2017): 516. doi:10.1001/jama.2016.19699

Voogt, J.L., Lee, Y., Yang, S., Arbogast, L. “Chapter 12. Regulation of prolactin secretion during pregnancy and lactation.” Prog Brain Res 133 (2001): 173–85. doi:10.1016/S0079-6123(01)33013-3

Glezer, A., Bronstein, M.D. “The Pituitary Gland in Pregnancy.” Pituitary (2017): 397–411. doi:10.1016/B978-0-12-804169-7.00013-1.

Levine, S., Muneyyirci-Delale, O. “Stress-Induced Hyperprolactinemia: Pathophysiology and Clinical Approach.” Obstet Gynecol Int 2018 (2018): 9253083. doi:10.1155/2018/9253083

La Torre, D., Falorni, A. “Pharmacological causes of hyperprolactinemia.” Ther Clin Risk Manag 3 (2007): 929–51. Available from: [ http://www.ncbi.nlm.nih.gov/pubmed/18473017], last accessed Oct 17, 2019.

Molitch, M.E. “Drugs and prolactin.” Pituitary 11 (2008): 209–18. doi:10.1007/s11102-008-0106-6

Vilar, L., Vilar, C.F., Lyra, R., et al. “Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.” Neuroendocrinology 109 (2019): 7–19. doi:10.1159/000499694

Ajmal, A., Joffe, H., Nachtigall, L.B. “Psychotropic-Induced Hyperprolactinemia: A Clinical Review.” Psychosomatics 55 (2014): 29–36. doi:10.1016/J. PSYM.2013.08.008

Falkai, P., Wobrock, T., Lieberman, J., et al. “Guidelines for Biological Treatment of Schizophrenia, Part 1: Acute treatment of schizophrenia.” World J Biol Psychiatry 6 (2005): 132–91. doi:10.1080/15622970510030090

Reeves, K.W., Okereke, O.I., Qian, J., et al. “Antidepressant use and circulating prolactin levels.” Cancer Causes Control 27 (2016): 853–61. doi:10.1007/s10552-016-0758-x

Petrikis, P., Tigas, S., Tzallas, A.T., et al. “Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders.” Int J Psychiatry Clin Pract 20 (2016): 165–9. doi:10.1080/13651501.2016.1197274

Praharaj, S.K. “Euprolactinemic Galactorrhea With Escitalopram.” J Neuropsychiatry Clin Neurosci 26 (2014): E25–E26. doi:10.1176/appi.neuropsych.13070147

Nebhinani, N. “Sertraline-induced galactorrhea: case report and review of cases reported with other SSRIs.” Gen Hosp Psychiatry 35 (2013): 576. e3-576.e5. doi:10.1016/J.GENHOSPPSYCH.2012.10.010

Montejo, Á.L., Arango, C., Bernardo, M., et al. “Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics.” Front Neuroendocrinol 45 (2017): 25–34. doi:10.1016/J. YFRNE.2017.02.003

Jabbar, A., Khan, R., Farrukh, S.N. “Hyperprolactinaemia induced by proton pump inhibitor.” J Pak Med Assoc 60 (2010): 689–90. Available from: [http://www.ncbi. nlm.nih.gov/pubmed/20726208], last accessed Oct 16, 2019.

Romeo, J.H., Dombrowski, R., Kwak, Y.S., et al. “Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men.” Clin Endocrinol (Oxf) 45 (1996): 571–5. doi:10.1046/j.1365-2265.1996.00859.x

Kelley, S.R., Kamal, T.J., Molitch, M.E. “Mechanism of verapamil calcium channel blockade-induced hyperprolactinemia.” Am J Physiol 270 (1996): E96–100. doi:10.1152/ajpendo.1996.270.1.E96

Baldini, M., Cornelli, U., Molinari, M., Cantalamessa, L. “Effect of methyldopa on prolactin serum concentration.” Eur J Clin Pharmacol 34 (1988): 513–5. doi:10.1007/BF01046712

Murai, L., Ben-Jonathan, N. “Acute Stimulation of Prolactin Release by Estradiol: Mediation by the Posterior Pituitary.” Endocrinology 126 (1990): 3179–84. doi:10.1210/endo-126-6-3179

Luciano, A.A., Sherman, B.M., Chapler, F.K., et al. “Hyperprolactinemia and contraception: a prospective study.” Obstet Gynecol 65 (1985): 506–10. Available from: [http://www. ncbi.nlm.nih.gov/pubmed/3982724], last accessed Oct 17, 2019.

Davis, J.R.E., Selby, C., Jeffcoate, W.J. “Oral contraceptive agents do not affect serum prolactin in normal women.” Clin Endocrinol (Oxf) 20 (1984): 427–34. doi:10.1111/j.1365-2265.1984.tb03438.x

Foth, D., Römer, T. “Prolactin Serum Levels in Postmenopausal Women Receiving Long-Term Hormone Replacement Therapy.” Gynecol Obstet Invest 44 (1997): 124–6. doi:10.1159/000291502

Schlegel, W., Petersdorf, L.I., Junker, R., et al. “The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women.” Clin Endocrinol (Oxf) 51 (1999): 643–51. doi:10.1046/j.1365-2265.1999.00857.x

Cicero, T.J. “Neuroendocrinological Effects of Alcohol.” Annu Rev Med 32 (1981): 123–42. doi:10.1146/annurev.me.32.020181.001011

Vilar, L., Freitas, M.C., Naves, L.A., et al. “Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients.” J Endocrinol Invest 31 (2008): 436–44. doi:10.1007/BF03346388

Cocks Eschler, D., Javanmard, P., Cox, K., Geer, E.B. “Prolactinoma through the female life cycle.” Endocrine 59 (2018): 16–29. doi:10.1007/s12020-017-1438-7

Chanson, P., Maiter, D. “Prolactinoma.” Pituitary (2017): 467–514. doi:10.1016/B978-0-12-804169-7.00016-7

Morselli, L.L., Schlechte, J.A. “Prolactin-Secreting Pituitary Adenomas: Epidemiology

and Natural History.” In: Humana. Cham (2019): 111–126. doi:10.1007/978-3-030-11836-5_6

Tjörnstrand, A., Gunnarsson, K., Evert, M., et al. “The incidence rate of pituitary adenomas in western Sweden for the period 2001–2011.” Eur J Endocrinol 171 (2014): 519–26. doi:10.1530/EJE-14-0144

Raappana, A., Koivukangas, J., Ebeling, T., Pirilä, T. “Incidence of Pituitary Adenomas in Northern Finland in 1992–2007.” J Clin Endocrinol Metab 95 (2010): 4268–75. doi:10.1210/jc.2010-0537

Agustsson, T.T., Baldvinsdottir, T., Jonasson, J.G., et al. “The epidemiology of pituitary adenomas in Iceland, 1955–2012: a nationwide population-based study.” Eur J Endocrinol 173 (2015): 655–64. doi:10.1530/EJE-15-0189

Haddad, R.A., Giacherio, D., Barkan, A.L. “Interpretation of common endocrine laboratory tests: technical pitfalls, their mechanisms and practical considerations.” Clin Diabetes Endocrinol 5 (2019): 12. doi:10.1186/s40842-019-0086-7

Krysiak, R., Kowalska, B., Szkróbka, W., Okopień, B. “The effect of oral contraception on macroprolactin levels in women with macroprolactinemia: A pilot study.” Pharmacol Reports 67 (2015): 854–7. doi:10.1016/J.PHAREP.2015.02.001

Kalsi, A.K., Halder, A., Jain, M., et al. “Prevalence and reproductive manifestations of macroprolactinemia.” Endocrine 63 (2019): 332–40. doi:10.1007/s12020-018-1770-6

Dellal, F.D., Ozdemir, D., Aydin, C., et al. “Gigantomastia and Macroprolactinemia Responding to Cabergoline Treatment: A Case Report and Minireview of the Literature.” Case Rep Endocrinol 2016 (2016): 3576024. doi:10.1155/2016/3576024

Krysiak, R., Marek, B., Okopień, B. “Cardiometabolic risk factors in young women with macroprolactinaemia.” Endokrynol Pol 70 (2019): 336–41. doi:10.5603/EP.a2019.0013


GOST Style Citations


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2.         Melmed, S., Casanueva, F.F., Hoffman, A.R., et al. “Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline.”  J Clin Endocrinol Metab 96 (2011): 273–88. doi:10.1210/jc.2010-1692

3.         Chiloiro, S., Giampietro, A., Bianchi, A., De Marinis, L. “Prolactinoma and Bone.”  Curr Opin Endocr Metab Res 3 (2018): 21–4. doi:10.1016/J.COEMR.2018.02.006

4.         Ben-Jonathan, N., Hugo, E.R., Brandebourg, T.D., LaPensee, C.R. “Focus on prolactin as a metabolic hormone.”  Trends Endocrinol Metab 17 (2006): 110–6. doi:10.1016/J.TEM.2006.02.005

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6.         Tirosh, A., Shimon, I. “Management of macroprolactinomas.”  Clin Diabetes Endocrinol 1 (2015): 5. doi:10.1186/s40842-015-0006-4

7.         Pekić, S., Medic Stojanoska, M., Popovic, V. “Hyperprolactinemia/Prolactinomas in the Postmenopausal Period: Challenges in Diagnosis and Management.” Neuroendocrinology 109 (2019): 28–33. doi:10.1159/000494725

8.         Matalliotakis, M., Koliarakis, I., Matalliotaki, C., et al. “Clinical manifestations, evaluation and management of hyperprolactinemia in adolescent and young girls: a brief review.” Acta Biomed 90 (2019): 149–57. doi:10.23750/abm.v90i1.8142

9.         Hughes, E.G.,  Garner, P.R. “Primary amenorrhea associated with hyperprolactinemia:

four cases with normal sellar architecture and absence of galactorrhea.”  Fertil Steril 47 (1987): 1031–2. doi:10.1016/s0015-0282(16)59241-3

10.       Coulam, C.B., Laws, E.R., Abboud, C.F., Randall, R.V. “Primary amenorrhea and pituitary adenomas.”  Fertil Steril 35 (1981): 615–9. doi:10.1016/S0015-0282(16)45551-2

11.       Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G.“Prolactin: Structure, Function, and Regulation of Secretion.” Physiol Rev 80 (2000): 1523–1631. doi:10.1152/physrev.2000.80.4.1523

12.       Grattan, D.R., Kokay, I.C. “Prolactin: A Pleiotropic Neuroendocrine Hormone.”  J Neuroendocrinol 20 (2008): 752–63. doi:10.1111/j.1365-2826.2008.01736.x

13.       Tritos, N.A., Klibanski, A. “Prolactin and Its Role in Human Reproduction.”  Yen Jaffe’s Reprod Endocrinol (2019): 58–74.e8. doi:10.1016/B978-0-323-47912-7.00003-2

14.       Mancini, T., Casanueva, F.F., Giustina, A. “Hyperprolactinemia and Prolactinomas.”  Endocrinol Metab Clin North Am 37 (2008): 67–99. doi:10.1016/j.ecl.2007.10.013

15.       Ciccarelli, A., Daly, A.F., Beckers, A. “The Epidemiology of Prolactinomas.”  Pituitary 8 (2005): 3–6. doi:10.1007/s11102-005-5079-0

16.       Pivonello, R., Salzano, C., Galdiero, M., Colao, A. “Male Hypogonadism Due to Disorders of the Pituitary and Suprasellar Region.”  In: Male Hypogonadism. Springer International Publishing. Cham (2017): 169–86. doi:10.1007/978-3-319-53298-1_8

17.       Corona, G., Mannucci, E., Fisher, A.D., et al. “Effect of Hyperprolactinemia in Male Patients Consulting for Sexual Dysfunction.”  J Sex Med 4 (2007): 1485–93. doi:10.1111/j.1743-6109.2007.00569.x

18.       Molitch, M.E. “Diagnosis and Treatment of Pituitary Adenomas.”  JAMA 317 (2017): 516. doi:10.1001/jama.2016.19699

19.       Voogt, J.L., Lee, Y., Yang, S., Arbogast, L. “Chapter 12. Regulation of prolactin secretion during pregnancy and lactation.”  Prog Brain Res 133 (2001): 173–85. doi:10.1016/S0079-6123(01)33013-3

20.       Glezer, A., Bronstein, M.D. “The Pituitary Gland in Pregnancy.”  Pituitary (2017): 397–411. doi:10.1016/B978-0-12-804169-7.00013-1.

21.       Levine, S., Muneyyirci-Delale, O. “Stress-Induced Hyperprolactinemia: Pathophysiology and Clinical Approach.”  Obstet Gynecol Int 2018 (2018): 9253083. doi:10.1155/2018/9253083

22.       La Torre, D., Falorni, A. “Pharmacological causes of hyperprolactinemia.” Ther Clin Risk Manag 3 (2007): 929–51. Available from: [ http://www.ncbi.nlm.nih.gov/pubmed/18473017], last accessed Oct 17, 2019.

23.       Molitch, M.E. “Drugs and prolactin.”  Pituitary 11 (2008): 209–18. doi:10.1007/s11102-008-0106-6

24.       Vilar, L., Vilar, C.F., Lyra, R., et al. “Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.” Neuroendocrinology 109 (2019): 7–19. doi:10.1159/000499694

25.       Ajmal, A., Joffe, H., Nachtigall, L.B. “Psychotropic-Induced Hyperprolactinemia: A Clinical Review.”  Psychosomatics 55 (2014): 29–36. doi:10.1016/J. PSYM.2013.08.008

26.       Falkai, P., Wobrock, T., Lieberman, J., et al. “Guidelines for Biological Treatment of Schizophrenia, Part 1: Acute treatment of schizophrenia.”  World J Biol Psychiatry 6 (2005): 132–91. doi:10.1080/15622970510030090

27.       Reeves, K.W., Okereke, O.I., Qian, J., et al. “Antidepressant use and circulating prolactin levels.”  Cancer Causes Control 27 (2016): 853–61. doi:10.1007/s10552-016-0758-x

28.       Petrikis, P., Tigas, S., Tzallas, A.T., et al. “Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders.”  Int J Psychiatry Clin Pract 20 (2016): 165–9. doi:10.1080/13651501.2016.1197274

29.       Praharaj, S.K. “Euprolactinemic Galactorrhea With Escitalopram.”  J Neuropsychiatry Clin Neurosci 26 (2014): E25–E26. doi:10.1176/appi.neuropsych.13070147

30.       Nebhinani, N. “Sertraline-induced galactorrhea: case report and review of cases reported with other SSRIs.”  Gen Hosp Psychiatry 35 (2013): 576. e3-576.e5. doi:10.1016/J.GENHOSPPSYCH.2012.10.010

31.       Montejo, Á.L., Arango, C., Bernardo, M., et al. “Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics.” Front Neuroendocrinol 45 (2017): 25–34. doi:10.1016/J. YFRNE.2017.02.003

32.       Jabbar, A., Khan, R., Farrukh, S.N. “Hyperprolactinaemia induced by proton pump inhibitor.”  J Pak Med Assoc 60 (2010): 689–90. Available from: [http://www.ncbi. nlm.nih.gov/pubmed/20726208], last accessed Oct 16, 2019.

33.       Romeo, J.H., Dombrowski, R., Kwak, Y.S., et al. “Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men.”  Clin Endocrinol (Oxf) 45 (1996): 571–5. doi:10.1046/j.1365-2265.1996.00859.x

34.       Kelley, S.R., Kamal, T.J., Molitch, M.E. “Mechanism of verapamil calcium channel blockade-induced hyperprolactinemia.”  Am J Physiol 270 (1996): E96–100. doi:10.1152/ajpendo.1996.270.1.E96

35.       Baldini, M., Cornelli, U., Molinari, M., Cantalamessa, L. “Effect of methyldopa on prolactin serum concentration.”  Eur J Clin Pharmacol 34 (1988): 513–5. doi:10.1007/BF01046712

36.       Murai, L., Ben-Jonathan, N. “Acute Stimulation of Prolactin Release by Estradiol: Mediation by the Posterior Pituitary.”  Endocrinology 126 (1990): 3179–84. doi:10.1210/endo-126-6-3179

37.       Luciano, A.A., Sherman, B.M., Chapler, F.K., et al. “Hyperprolactinemia and contraception: a prospective study.” Obstet Gynecol 65 (1985): 506–10. Available from: [http://www. ncbi.nlm.nih.gov/pubmed/3982724], last accessed Oct 17, 2019.

38.       Davis, J.R.E., Selby, C., Jeffcoate, W.J. “Oral contraceptive agents do not affect serum prolactin in normal women.”  Clin Endocrinol (Oxf) 20 (1984): 427–34. doi:10.1111/j.1365-2265.1984.tb03438.x

39.       Foth, D., Römer, T. “Prolactin Serum Levels in Postmenopausal Women Receiving Long-Term Hormone Replacement Therapy.”  Gynecol Obstet Invest 44 (1997): 124–6. doi:10.1159/000291502

40.       Schlegel, W., Petersdorf, L.I., Junker, R., et al. “The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women.”  Clin Endocrinol (Oxf) 51 (1999): 643–51. doi:10.1046/j.1365-2265.1999.00857.x

41.       Cicero, T.J. “Neuroendocrinological Effects of Alcohol.”  Annu Rev Med 32 (1981): 123–42. doi:10.1146/annurev.me.32.020181.001011

42.       Vilar, L., Freitas, M.C., Naves, L.A., et al. “Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients.”  J Endocrinol Invest 31 (2008): 436–44. doi:10.1007/BF03346388

43.       Cocks Eschler, D., Javanmard, P., Cox, K., Geer, E.B. “Prolactinoma through the female life cycle.”  Endocrine 59 (2018): 16–29. doi:10.1007/s12020-017-1438-7

44.       Chanson, P., Maiter, D. “Prolactinoma.”  Pituitary (2017): 467–514. doi:10.1016/B978-0-12-804169-7.00016-7

45.       Morselli, L.L., Schlechte, J.A. “Prolactin-Secreting Pituitary Adenomas: Epidemiology

and Natural History.”  In: Humana. Cham (2019): 111–126. doi:10.1007/978-3-030-11836-5_6

46.       Tjörnstrand, A., Gunnarsson, K., Evert, M., et al. “The incidence rate of pituitary adenomas in western Sweden for the period 2001–2011.”  Eur J Endocrinol 171 (2014): 519–26. doi:10.1530/EJE-14-0144

47.       Raappana, A., Koivukangas, J., Ebeling, T., Pirilä, T. “Incidence of Pituitary Adenomas in Northern Finland in 1992–2007.”  J Clin Endocrinol Metab 95 (2010): 4268–75. doi:10.1210/jc.2010-0537

48.       Agustsson, T.T., Baldvinsdottir, T., Jonasson, J.G., et al. “The epidemiology of pituitary adenomas in Iceland, 1955–2012: a nationwide population-based study.”  Eur J Endocrinol 173 (2015): 655–64. doi:10.1530/EJE-15-0189

49.       Haddad, R.A., Giacherio, D., Barkan, A.L. “Interpretation of common endocrine laboratory tests: technical pitfalls, their mechanisms and practical considerations.” Clin Diabetes Endocrinol 5 (2019): 12. doi:10.1186/s40842-019-0086-7

50.       Krysiak, R., Kowalska, B., Szkróbka, W., Okopień, B. “The effect of oral contraception on macroprolactin levels in women with macroprolactinemia: A pilot study.”  Pharmacol Reports 67 (2015): 854–7. doi:10.1016/J.PHAREP.2015.02.001

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52.       Dellal, F.D., Ozdemir, D., Aydin, C., et al. “Gigantomastia and Macroprolactinemia Responding to Cabergoline Treatment: A Case Report and Minireview of the Literature.”  Case Rep Endocrinol 2016 (2016): 3576024. doi:10.1155/2016/3576024

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