Specificity and clinical utility of methods for the detection of macroprolactin
TP Smith1, J Gibney1, L Kavanagh1, MN Fahie-Wilson2 & TJ McKenna1
Where screening for macroprolactin takes place, laboratories routinely rely on treatment of sera with polyethylene glycol (PEG) to distinguish macroprolactinaemia from true hyperprolactinaemia. However, PEG causes significant interference in some immunoassays and furthermore leads to co-precipitation of a variable amount of monomeric prolactin in addition to macroprolactin in treated sera. The aim of this study was to assess the specificity and clinical utility of alternative methods for removing bio-inactive prolactin IgG complexes such as macroprolactin from serum prior to immunoassay.
Sera from 19 female patients with macroprolactinaemia were subjected to gel filtration chromatography (GFC) with quantitation of monomeric prolactin levels by Delfia. Residual serum monomeric prolactin levels were also measured following removal of prolactin-IgG complexes by pre-treatment of serum with PEG or adsorption with protein G, protein A or anti-human IgG.
Total prolactin in the 19 sera examined ranged from 750-5,723milliUnits per litre with monomeric levels ranging from 126-421milliUnits per litre. Of the four methods examined PEG correlated best with GFC (r = 0.92) followed by protein G (r = 0.79), protein A (r = 0.65) and anti-human IgG (r = 0.62). However, PEG treatment resulted in significantly lower residual prolactin levels (mean 67%) compared to GFC. In contrast, sera pre-treated with protein G, protein A or anti-human IgG exhibited mean residual prolactin levels of 137%, 159% and 186% respectively relative to monomer levels obtained with GFC.
None of the methods examined yielded results similar to the GFC reference method. PEG and protein G pre-treatment yielded results that were closest to the target level. The PEG procedure is cheap, technically easy to perform and is the first alternative choice to GFC. In instances where the use of PEG is not possible, pre-treatment with protein G appears to be a useful though slightly more expensive alternative.