Macroprolactinemia: a mini-review and update on clinical practice

Abstract

Hyperprolactinemia is common among infertile patients, with up to 15%–20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%–10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%–46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL. Hyperprolactinemia is common among infertile patients, with up to 15%–20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%–10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%–46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL. Prolactin (PRL) is secreted by the anterior pituitary and has 3 forms in circulation, demonstrated in Table 1 (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google Scholar, 2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). Monomeric PRL has a molecular weight (MW) of 23 kDa and accounts for 85% of total immunoreactive PRL, dimeric PRL has a MW of 48–56 kDa and comprises 5%–10%, and macro-PRL has a MW >150 kDa and is responsible for 5%–10% of circulating PRL in healthy patients (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google Scholar, 2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, 4Wallace I.R. Satti N. Courtney C.H. Leslie H. Bell P.M. Hunter S.J. et al.Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.J Clin Endocrinol Metab. 2010; 95: 3268-3271Crossref PubMed Scopus (39) Google Scholar). The predominant form of PRL in healthy individuals and patients with prolactinomas is monomeric PRL (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 5Vilar L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar, 6De Soárez P.C. De Arêa Leão Souza S.C. Vieira J.G.H. Ferraz M.B. The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.Value Heal. 2009; 12: 930-934Abstract Full Text PDF PubMed Scopus (0) Google Scholar). Dimeric PRL consists of glycosylated monomers that form aggregates and are clinically benign (7Samson S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 8Quynh N. Nguyen K. Langevin R.H. McPhaul M.J. Hashim I.A. Circulating macroprolactin molecular and is not Scopus Google Scholar). is of of monomeric PRL and (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, A. N. and Scopus Google Scholar, N. K. A. of the of macroprolactin by different Scopus (22) Google Scholar). of macro-PRL monomeric PRL with or glycosylated monomeric PRL, or and monomeric PRL (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar). PRL are to the 3 forms of circulating PRL (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google of circulating prolactin (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google Scholar, 2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google of in in a PRL Hyperprolactinemia with and L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, 5Vilar L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar, A. N. and Scopus Google Scholar). of hyperprolactinemia PRL pituitary and pituitary prolactin and macroprolactinemia (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, 5Vilar L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar, A. N. and Scopus Google Scholar). the predominant form of PRL in is monomeric PRL (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar). Among the of women and of have and among patients with hyperprolactinemia, 10%–46% have macroprolactinemia (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, 4Wallace I.R. Satti N. Courtney C.H. Leslie H. Bell P.M. Hunter S.J. et al.Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.J Clin Endocrinol Metab. 2010; 95: 3268-3271Crossref PubMed Scopus (39) Google Scholar, 5Vilar L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar, 6De Soárez P.C. De Arêa Leão Souza S.C. Vieira J.G.H. Ferraz M.B. The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.Value Heal. 2009; 12: 930-934Abstract Full Text PDF PubMed Scopus (0) Google Scholar, 8Quynh N. Nguyen K. Langevin R.H. McPhaul M.J. Hashim I.A. Circulating macroprolactin molecular and is not Scopus Google Scholar, A. N. and Scopus Google Scholar, N. K. A. of the of macroprolactin by different Scopus (22) Google Scholar, N. of PubMed Google Scholar, S. P.M. in women with a 2013; Google Scholar, S. et and in PubMed Scopus (20) Google Scholar, N. A. The of J PubMed Scopus (0) Google Scholar, A. M. and of 2019; Scopus Google Scholar). Patients should and for at serum PRL levels L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). Hyperprolactinemia is serum PRL levels the of on the on L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). elevated PRL should be at L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar). if PRL levels are elevated PRL be to hyperprolactinemia L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). consists of monomeric PRL with macro-PRL is of monomeric PRL with L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, A. N. and Scopus Google Scholar, S. A. of 2019; Scopus Google Scholar, H. et of a for Scopus (0) Google Scholar). of the A. N. and Scopus Google Scholar). is that a to of monomeric PRL, as and the of to the L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar). There is a and serum PRL a of macroprolactinemia A. N. and Scopus Google Scholar, N. of PubMed Google Scholar). macro-PRL has in a with the of N. of PubMed Google Scholar). The pituitary not normally in patients with macroprolactinemia. 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Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, N. of PubMed Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar). to serum levels of macro-PRL and hyperprolactinemia. The hyperprolactinemia macroprolactinemia is on of macro-PRL of PRL L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). The with monomeric or true hyperprolactinemia in women are and I.R. Satti N. Courtney C.H. Leslie H. Bell P.M. Hunter S.J. et al.Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.J Clin Endocrinol Metab. 2010; 95: 3268-3271Crossref PubMed Scopus (39) Google Scholar, M. H. S. Clinical of patients with macroprolactinemia and monomeric J PubMed Scopus Google Scholar). hyperprolactinemia is with and M. H. S. Clinical of patients with macroprolactinemia and monomeric J PubMed Scopus Google Scholar). the effect of PRL on the pulsatile of gonadotropin releasing hormone the via inhibition of PRL and the effect on (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar). by et (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google demonstrated that patients with macroprolactinemia are patients with true hyperprolactinemia to oligomenorrhea and vs and vs of in patients with with true hyperprolactinemia, have in I.R. Satti N. Courtney C.H. Leslie H. Bell P.M. Hunter S.J. et al.Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.J Clin Endocrinol Metab. 2010; 95: 3268-3271Crossref PubMed Scopus (39) Google Scholar, S. P.M. in women with a 2013; Google Scholar, A. M. and of 2019; Scopus Google among patients with true hyperprolactinemia and macroprolactinemia (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google Hyperprolactinemia in a The of patients with macroprolactinemia is on the of macro-PRL with monomeric PRL L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). PRL and PRL to on the PRL A. N. and Scopus Google Scholar). it has that PRL in patients with macroprolactinemia with PRL for the of PRL A. N. and Scopus Google Scholar). macro-PRL is to the by high MW and is to as the pituitary and (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, N. of PubMed Google Scholar, H. et of a for Scopus (0) Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar). is that the of oligomenorrhea and by patients with macroprolactinemia are because of of monomeric PRL and a in monomeric PRL (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar). patients with macroprolactinemia have serum PRL levels L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). PRL levels are to L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). The of PRL levels for hyperprolactinemia, and L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). by et A. M. and of 2019; Scopus Google in PRL levels patients with macroprolactinemia and true hyperprolactinemia vs Given the and PRL levels with true monomeric hyperprolactinemia and the diagnosis be on or (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, 6De Soárez P.C. De Arêa Leão Souza S.C. Vieira J.G.H. Ferraz M.B. The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.Value Heal. 2009; 12: 930-934Abstract Full Text PDF PubMed Scopus (0) Google Scholar, M. H. S. Clinical of patients with macroprolactinemia and monomeric J PubMed Scopus Google Scholar, S. et and in PubMed Scopus (20) Google Scholar). a of patients have macroprolactinemia in with of hyperprolactinemia (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar). Patients with macroprolactinemia or of should with pituitary imaging L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). to of patients with macroprolactinemia have are with elevated monomeric PRL N. of PubMed Google Scholar, S. et and treatment of endocrine clinical Metab. PubMed Scopus Google Scholar). identifying the etiology of hyperprolactinemia is because dopamine agonists are to hormone PRL levels in the of and of dopamine hyperprolactinemia in L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). agonists are the treatment for patients with hyperprolactinemia A. N. and Scopus Google Scholar). to patients with serum PRL A. N. and Scopus Google Scholar). macroprolactinemia not treatment (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 3Vilar L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar). The to macroprolactinemia is that monomeric PRL dimeric PRL, macro-PRL, or PRL (7Samson S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 8Quynh N. Nguyen K. Langevin R.H. McPhaul M.J. Hashim I.A. Circulating macroprolactin molecular and is not Scopus Google Scholar, N. K. A. of the of macroprolactin by different Scopus (22) Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar, L. L. total prolactin and monomeric prolactin by with and on common PubMed Scopus (0) Google Scholar). to diagnosis of hyperprolactinemia, unnecessary pituitary and of dopamine agonists (7Samson S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, H. et of a for Scopus (0) Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar, L. L. total prolactin and monomeric prolactin by with and on common PubMed Scopus (0) Google Scholar). elevated PRL, it is to for the presence of macro-PRL M. A. macroprolactin 2019; Scopus Google Scholar). of for PRL demonstrated PRL levels in patients with macroprolactinemia L. L. total prolactin and monomeric prolactin by with and on common PubMed Scopus (0) Google Scholar). of the to be the with macro-PRL with macro-PRL in of the patients with macroprolactinemia N. K. A. of the of macroprolactin by different Scopus (22) Google Scholar). that macro-PRL monomeric PRL. the to all patients with hyperprolactinemia for for macro-PRL has not S. et and treatment of endocrine clinical Metab. PubMed Scopus Google Scholar, L. L. total prolactin and monomeric prolactin by with and on common PubMed Scopus (0) Google Scholar). a by et S. A. of 2019; Scopus Google that of serum for PRL, elevated PRL and macro-PRL for the patients for macro-PRL with with macroprolactinemia S. A. of 2019; Scopus Google Scholar). that patients with hyperprolactinemia are screened for patients be diagnosed. of macro-PRL with is a and of for macro-PRL and is with the (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, A. N. and Scopus Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar). The and to M. of the macroprolactin Clin Endocrinol Metab. 2013; PubMed Scopus Google Scholar). When to to the of and levels of PRL in the L. Fleseriu M. Bronstein M.D. Challenges and pitfalls in the diagnosis of macroprolactinemia.Arq Bras Endocrinol Metabol. 2014; 58: 9-22Crossref PubMed Google Scholar, N. of PubMed Google Scholar, H. et of a for Scopus (0) Google Scholar). PRL with a serum is with and serum is with and to the total PRL A. N. and Scopus Google Scholar, N. of PubMed Google Scholar). The PRL in the is The PRL, macro-PRL, is as PRL A. N. and Scopus Google Scholar). When the of PRL is of monomeric PRL is macroprolactinemia is (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google Scholar, S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, A. N. and Scopus Google Scholar, M. H. S. Clinical of patients with macroprolactinemia and monomeric J PubMed Scopus Google Scholar, N. of PubMed Google Scholar, S. et and in PubMed Scopus (20) Google Scholar). The and of with for macroprolactinemia are and H. et of a for Scopus (0) Google Scholar). When of monomeric PRL is as a of patients are with with of patients a of is M. A. macroprolactin 2019; Scopus Google Scholar). with is a because it for macro-PRL (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar). of is that of monomeric PRL, to of monomeric PRL, in patients with macroprolactinemia and monomeric PRL (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, M. A. macroprolactin 2019; Scopus Google Scholar). should be monomeric PRL levels elevated with L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar). macroprolactinemia to be M. of the macroprolactin Clin Endocrinol Metab. 2013; PubMed Scopus Google Scholar). it has that with correctly macroprolactinemia in of L. Vilar C.F. Lyra R. Da Conceição Freitas M. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.Neuroendocrinology. 2019; 109: 7-19Crossref PubMed Scopus (62) Google Scholar). is the for it is and (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. 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N. and Scopus Google Scholar). of macroprolactinemia are and A. N. and Scopus Google Scholar). to the of the in the to the common in macro-PRL A. N. and Scopus Google Scholar). it is and the of macro-PRL A. N. and Scopus Google Scholar). a serum with with by A. N. and Scopus Google Scholar, N. of PubMed Google Scholar). The of the is and is to the presence of A. N. and Scopus Google Scholar). is to a of all macro-PRL A. N. and Scopus Google Scholar). is and to a A. N. and Scopus Google Scholar). et (1Thirunavakkarasu K. Dutta P. Sridhar S. Dhaliwal L. Prashad G.R.V. Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google demonstrated that patients with hyperprolactinemia, and macroprolactinemia. of patients with to have macroprolactinemia et of macroprolactinemia in women for 2014; Scopus Google Scholar). with macroprolactinemia healthy and treatment for hyperprolactinemia A. N. and Scopus Google Scholar, N. of PubMed Google Scholar). is to macroprolactinemia true hyperprolactinemia as to not with imaging and of dopamine in a has macroprolactinemia. follow-up have demonstrated that macroprolactinemia not (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, A. N. and Scopus Google Scholar, S. P.M. in women with a 2013; Google Scholar). cohort of 51 patients with macroprolactinemia for a of demonstrated macroprolactinemia at follow-up with in I.R. Satti N. Courtney C.H. Leslie H. Bell P.M. Hunter S.J. et al.Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.J Clin Endocrinol Metab. 2010; 95: 3268-3271Crossref PubMed Scopus (39) Google Scholar). patients follow-up I.R. Satti N. Courtney C.H. Leslie H. Bell P.M. 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Gainder S. et al.Macroprolactinemia in hyperprolactinemic infertile women.Endocrine. 2013; 4: 750-755Crossref Scopus (22) Google Scholar). is by the to for macroprolactinemia in patients with hyperprolactinemia S. et and treatment of endocrine clinical Metab. PubMed Scopus Google Scholar). When serum PRL is the should be in the state with for macro-PRL. for macro-PRL in all serum with elevated PRL levels should be all for macro-PRL. as a by et S. A. of 2019; Scopus Google demonstrated that of serum with PRL levels the for macro-PRL to the to the macro-PRL for macro-PRL has in in (7Samson S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar). macroprolactinemia is because patients as having hyperprolactinemia are to and imaging in to a of the in to treatment with a dopamine and unnecessary N. Nguyen K. Langevin R.H. McPhaul M.J. Hashim I.A. Circulating macroprolactin molecular and is not Scopus Google Scholar, N. of PubMed Google Scholar). for macro-PRL should be for all serum with PRL levels the of for the Patients with hyperprolactinemia and a of macro-PRL not pituitary imaging or treatment with a dopamine (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar). the monomeric PRL the of for the pituitary imaging to for a pituitary for macro-PRL of all women with hyperprolactinemia for macro-PRL is because it costs on imaging and treatment with dopamine agonists (2Kasum M. Orešković S. Čehić E. Šunj M. Lila A. Ejubović E. Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia.Taiwan J Obstet Gynecol. 2017; 56: 719-724Crossref PubMed Scopus (20) Google Scholar, 6De Soárez P.C. De Arêa Leão Souza S.C. Vieira J.G.H. Ferraz M.B. The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.Value Heal. 2009; 12: 930-934Abstract Full Text PDF PubMed Scopus (0) Google Scholar, S.L. Hamrahian A.H. Ezzat S. American Association of Clinical Endocrinologists, American College of Endocrinology disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia.Endocr Pract. 2015; 21: 1427-1435Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar). patients with elevated PRL of with true hyperprolactinemia, and with demonstrated that unnecessary in macroprolactinemia patients in and dopamine that and Soárez P.C. De Arêa Leão Souza S.C. Vieira J.G.H. Ferraz M.B. The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.Value Heal. 2009; 12: 930-934Abstract Full Text PDF PubMed Scopus (0) Google Scholar). patients with hyperprolactinemia should be screened for macroprolactinemia. for macro-PRL in patients with hyperprolactinemia on unnecessary and high levels of for patients and M. of the macroprolactin Clin Endocrinol Metab. 2013; PubMed Scopus Google Scholar). with the of and high and with is a for identifying patients with macroprolactinemia PRL is persistently elevated S. P.M. in women with a 2013; Google Scholar).

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