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Published on: January 13, 2023
Specificity and clinical utility of methods for the detection of macroprolactin
Lucille Kavanagh1, T Joseph McKenna, Michael N Fahie-Wilson
1Department of Investigative Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.
Background:
Increased serum concentrations of macroprolactin are a relatively common cause of misdiagnosis and mismanagement of hyperprolactinemic patients.
Methods:
We studied sera from a cohort of 42 patients whose biochemical hyperprolactinemia was explained entirely by macroprolactin. Using 5 pretreatments, polyethylene glycol (PEG), protein A (PA), protein G (PG), anti-human IgG (anti-hIgG), and ultrafiltration (UF), to deplete macroprolactin from sera before immunoassay, we compared residual prolactin concentrations with monomer concentrations obtained by gel-filtration chromatography (GFC). A monomeric prolactin standard was used to assess recovery and specificity of the pretreatment procedures.
Results:
Residual prolactin concentrations in all pretreated sera differed significantly (P < 0.001) from monomeric concentrations obtained after GFC. PEG underestimated (mean, 75%), whereas PA, PG, anti-hIgG, and UF overestimated (means, 178%, 151%, 178%, and 112%, respectively) the amount of monomer present. Of the 5 methods examined, PEG correlated best with GFC (r = 0.80) followed by PG (r = 0.78), PA (r = 0.72), anti-hIgG (r = 0.70), and UF (r = 0.61). After UF or pretreatment with anti-hIgG or PEG, recovery of monomeric prolactin standard was low: 60%, 85%, and 77% respectively. In contrast, pretreatment with PA or PG gave almost quantitative recovery.
Conclusions:
None of the methods examined yielded results identical to the GFC method. PEG pretreatment yielded results that correlated best and is recommended as the first-choice alternative to GFC.
Insights
Macroprolactin can cause hyperprolactinemia misdiagnosis. Polyethylene glycol (PEG) pretreatment best correlated with gel-filtration chromatography (GFC) for measuring monomeric prolactin, making it a recommended alternative method.
Area of Science:
- Clinical Biochemistry
- Endocrinology
Background:
- Macroprolactin is a common cause of biochemical hyperprolactinemia.
- This can lead to misdiagnosis and inappropriate patient management.
Purpose of the Study:
- To evaluate five different pretreatment methods for macroprolactin depletion.
- To compare their accuracy against gel-filtration chromatography (GFC) for monomeric prolactin measurement.
Main Methods:
- Sera from 42 hyperprolactinemic patients were pretreated using polyethylene glycol (PEG), protein A (PA), protein G (PG), anti-human IgG (anti-hIgG), and ultrafiltration (UF).
- Residual prolactin concentrations were compared to monomer concentrations determined by GFC.
- Monomeric prolactin standard recovery and specificity were assessed.
Main Results:
- All pretreatment methods showed significant differences compared to GFC (P < 0.001).
- PEG underestimated monomeric prolactin, while PA, PG, anti-hIgG, and UF overestimated it.
- PEG demonstrated the highest correlation with GFC (r = 0.80), followed by PG (r = 0.78).
- PA and PG offered near-quantitative recovery of the monomeric prolactin standard.
Conclusions:
- No single method perfectly matched GFC results for macroprolactin assessment.
- Polyethylene glycol (PEG) pretreatment is recommended as the most suitable alternative to GFC due to its best correlation and practical applicability.