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Should macroprolactin be measured in all hyperprolactinaemic sera?
1Department of Endocrinology and Diabetes Mellitus, Saint Vincent's University Hospital, Elm Park, Dublin 4, Dublin, Ireland. mckennatj@gmail.com
Abstract:
Macroprolactin is a nonbioactive prolactin isoform usually composed of a monomer of prolactin and a IgG molecule which has a prolonged clearance rate similar to that of the immunoglobulins. Macroprolactinaemia, hyperprolactinaemia entirely accounted for by the presence of macroprolactin, is estimated to account for approximately 10% of all hyperprolactinaemia coming to clinical attention in the United Kingdom and the United States. Failure to recognize that macroprolactinaemia can explain hyperprolactinaemia, leads to unnecessary investigation, incorrect diagnosis and inappropriate treatment. Screening of hyperprolactinaemic sera for the presence of misleading concentrations of macroprolactin is readily performed in biochemistry laboratories although the procedures have not been automated. The most widely employed method is to treat the hyperprolactinaemic sera with polyethylene glycol which precipitates out high-molecular weight constituents including immunoglobulins. Re-assay of the sera for prolactin will then identify those sera which yield values within the relevant normal range indicative of macroprolactinaemia and not true hyperprolactinaemia. The case for the routine screening of all hyperprolactinaemic sera for macroprolactin is compelling. The consequences of failure to recognize macroprolactinaemia are significant, the problem is frequently encountered, the means of addressing it are immediately available and it is cost effective.
Insights
Macroprolactin, a large prolactin variant, causes most cases of hyperprolactinaemia. Recognizing macroprolactinaemia prevents unnecessary tests and misdiagnosis.
Area of Science:
- Clinical Biochemistry
- Endocrinology
- Reproductive Medicine
Background:
- Macroprolactin is a nonbioactive prolactin isoform comprising prolactin and IgG.
- Macroprolactinaemia accounts for approximately 10% of clinical hyperprolactinaemia cases in the UK and US.
- Failure to identify macroprolactinaemia leads to unnecessary investigations and inappropriate treatment.
Purpose of the Study:
- To highlight the clinical significance of macroprolactinaemia.
- To advocate for routine screening of hyperprolactinaemic sera for macroprolactin.
- To emphasize the cost-effectiveness and availability of screening methods.
Main Methods:
- Polyethylene glycol (PEG) precipitation assay is the primary method.
- PEG precipitates high-molecular-weight constituents, including macroprolactin.
- Re-assaying prolactin levels after PEG treatment identifies macroprolactinaemia.
Main Results:
- Macroprolactin is a common cause of elevated prolactin levels.
- Screening readily identifies macroprolactinaemia in biochemistry laboratories.
- The PEG precipitation method effectively distinguishes macroprolactin from bioactive prolactin.
Conclusions:
- Routine screening for macroprolactin in hyperprolactinaemic patients is strongly recommended.
- Early recognition of macroprolactinaemia improves diagnostic accuracy and patient management.
- Available screening methods are effective, accessible, and cost-efficient.
