Macroprolactin: an overlooked reason of hyperprolactinemia

Abstract

Background Immunoassays show variability in the detection of macroprolactin. The aim of this study was to detect the frequency of macroprolactinemia in hyperprolactinemic patients and the problems encountered in routine clinical practice. Methods The screening of macroprolactinemia was performed by precipitation with polyethylene glycol (PEG) in 900 patient samples with hyperprolactinemia over a period of approximately 6 months. Recovery values of less than 40% and greater than 60% were considered as macroprolactinemia and predominantly monomeric prolactin (PRL), respectively. Results A total of 900 (17.9%) of the 5007 PRL results were out of reference range. Thirty-one (3.4%) of the patients had less than 40% recovery after screening of all patients with hyperprolactinemia. However, the macroprolactin test was requested by clinics from only 171 patients and seven of these patients had less than 40% recovery. We also detected predominantly macroprolactin in 24 samples, overlooked in routine practice. The patients with PRL above 100 ng/mL had no macroprolactinemia. Conclusions The screening for macroprolactinemia of hyperprolactinemic patients who have <100 ng/mL and also with unexplained hyperprolactinemia should be the first approach before any further research or treatment is initiated. Thus, unnecessary test repetition, investigation and inappropriate treatment can be avoided. Each laboratory should inform clinicians about the frequency of macroprolactinemia.

Global Prevalence of Macroprolactinemia among Patients with Hyperprolactinemia: A Systematic Review and Meta-Analysis

“…This could be due to a higher number of female patients being investigated for infertility and menstrual disturbance than men who are only being investigated for sexual dysfunction [69,90]. Subgroup analysis also did not show any difference in prevalence estimate based on age group, similar to other previous studies [49,88]. However, several other studies reported that the prevalence of mPRL tends to increase with advancing age [36,86].…”

“…A lower prevalence estimate was observed among studies involving both sexes than studies involving only female participants. Findings from previous studies regarding the matter are inconclusive, with some studies reporting no difference in the prevalence of mPRL between sex [77,[86][87][88]. In contrast, some other studies reported a higher prevalence of mPRL among females than males [35,36,51,89].…”

Macroprolactinemia: a mini-review and update on clinical practice

“…Macro-PRL consists of monomeric PRL complexed with immunoglobulins. Most macro-PRL (87%) is composed of monomeric PRL complexed with IgG ( 3 , 9 , 17 , 18 ). Within this category of PRL-IgG complexes, the majority (67%) involve anti-PRL autoantibodies ( Fig.…”

“…In fact, a recent study by Muhtaroglu et al. ( 17 ) found that of 5,007 consecutive serum samples evaluated for PRL, 900/5,007 (17.9%) had elevated PRL levels, and providers requested macro-PRL screening for only 171/900 (19.0%) samples. Of the 171 patients who underwent screening for macro-PRL with polyethylene glycol (PEG), 31 were diagnosed with macroprolactinemia ( 17 ).…”

“…( 17 ) found that of 5,007 consecutive serum samples evaluated for PRL, 900/5,007 (17.9%) had elevated PRL levels, and providers requested macro-PRL screening for only 171/900 (19.0%) samples. Of the 171 patients who underwent screening for macro-PRL with polyethylene glycol (PEG), 31 were diagnosed with macroprolactinemia ( 17 ). This study demonstrates that unless patients with hyperprolactinemia are screened for macroprolactinemia, many patients will be incorrectly diagnosed.…”