Prevalence of Macroprolactinaemia by Polyethylene Glycol Precipitation Method: A Cross-sectional Study

Abstract

Introduction: Macroprolactin, an immunoreactive molecule resulting from association of monomeric Prolactin (mPRL) and immunoglobulin G is a significant cause of misdiagnosis, unnecessary radiological investigation and treatment for hyperprolactinaemia. Data on its prevalence and clinical manifestation varies regionally. Case presentation can vary with assymptomatic cases to those with galactorrhea and irregular menses. Aim: To find the prevalence and clinical features associated with macroprolactin in cases of hyperprolactinaemia in hospital patients. Materials and Methods: A cross-sectional study was conducted in the Department of Biochemistry, Institute of Postgraduate Medical Education and Research and SSKM hospital, Kolkata, India, from November 2018 to April 2019. Serum samples were assayed for serum PRL levels in 1400 subjects by Chemiluminescence immunoassay (Immulite 1000 siemens) based on presenting symptoms of galactorrhoea, amenorrhoea and infertility. Serum PRL samples (n=240) above the manufacturer’s reference cut-off level (PRL ≥30 ng/ mL) were obtained from patients with or without symptoms of hyperprolactinaemia. Retesting for PRL levels were done following precipitation of macroprolactin using Polyethylene Glycol (PEG, MW: 6000). Fourty cases with physiological causes of PRL excess, hypothyroidism, polycystic ovary syndrome, antidopaminergic drug intake, hepatorenal diseases and chest wall disorders were excluded. The results were expressed in terms of Mean±Standard Deviation (SD) and compared using student t-test. Results: Prevalence of macroprolactin was 16 (13.3%) out of 120 among true hyperprolactaemic cases (male=2; female, n=14) based on percentage recovery of PRL in post-PEG cases (Recovery Rate (RR) <40%). The mean pre-PEG and post-PEG values were 52.5 ng/mL and 19.2 ng/mL (RR: 36.5%; p-value <0.05), respectively. The mean pre PEG, PRL values were significantly lower in macroprolactaemic cases than those with true hyperprolactinaemia (52.5 ng/mL versus 74.57 ng/ mL; p-value 0.038). Some of the Macro-PRL cases reported with complaints of galactorrhoea, menstrual irregularities and infertility. Conclusion: The results revealed a prevalence rate similar to those reported in other studies worldwide. Clinical features alone are an unreliable tool to distinguish between cases with true high PRL levels and macroprolactinaemia. Macro-PRL cases once diagnosed requires no extended endocrine review and long term management. Hence, in cases with high PRL levels discordant with clinical symptoms/radiological data routine PEG precipitation test is an inexpensive assay for initial screening for presence of macroprolactin and also monitoring of patients already started on dopamine agonists for hyperprolactinaemia of unknown aetiology.

Keywords

• prolactin
• galactorrhoea
• hyperprolactinaemia