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Cross-reactivity in assays for prolactin and optimum screening policy for macroprolactinaemia
Thomas P Smith1, Sinead Kelly1, Michael N Fahie-Wilson2
1Department of Investigative Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.
Objectives:
Macroprolactin cross-reacts in immunoassays for prolactin causing apparent hyperprolactinaemia (macroprolactinaemia) and consequent misdiagnosis and mismanagement of patients.
Methods:
We determined the prevalence of macroprolactinaemia using prolactin immunoassays with reported "high" (Tosoh) or "low" cross-reactivity (Roche) with macroprolactin. We additionally modelled the effects of increasing the screening threshold on workload and sensitivity in the detection of macroprolactinaemia.
Results:
A review of routine requests for prolactin received in a 12 month period identified 670 sera with hyperprolactinaemia (Tosoh assay). Treatment with polyethylene glycol (PEG) precipitation demonstrated normal levels of monomeric prolactin in 165 sera (24.6%) indicating macroprolactinaemia. In the macroprolactinaemic cohort, total prolactin levels were lower with the Roche assay (473 ± 132 mU/L; mean ± SD) compared to the Tosoh assay (683 ± 217 mU/L), p < 0.005. The prevalence of macroprolactinaemia was also lower with the Roche assay (6.2%). The number of samples that required screening for macroprolactinaemia fell by 14% when Roche gender specific total prolactin reference limits were applied. Use of a higher screening threshold (700 mU/L) reduced the screening workload considerably (Roche by 45%, Tosoh by 37%) however, the sensitivity of detection of macroprolactinaemia decreased markedly (Roche 90%, Tosoh 59%).
Conclusions:
Macroprolactin interferes in both Tosoh and Roche prolactin immunoassays. Use of an assay with a relatively low cross reactivity with macroprolactin, e.g. Roche, will lead to a modest reduction in the screening workload. Increasing the screening threshold above the upper limit of the assay reference interval will also reduce the screening workload but leads to disproportionate increases in the number of cases of macroprolactinaemia which are missed.
Insights
Macroprolactin, a common cause of false hyperprolactinemia, affects immunoassay results. Using assays with lower macroprolactin cross-reactivity can reduce screening workload but may miss cases.
Area of Science:
- Clinical Chemistry
- Endocrinology
Background:
- Macroprolactin causes apparent hyperprolactinemia in immunoassays, leading to misdiagnosis.
- This interference can result in inappropriate patient management.
Purpose of the Study:
- To determine the prevalence of macroprolactinemia using two different prolactin immunoassays.
- To model the impact of adjusting screening thresholds on workload and detection sensitivity.
Main Methods:
- Reviewed 670 sera with hyperprolactinemia (Tosoh assay) over 12 months.
- Assessed macroprolactinemia prevalence using Tosoh and Roche assays with varying cross-reactivity.
- Modeled effects of increased screening thresholds on workload and sensitivity.
Main Results:
- Macroprolactinemia was identified in 24.6% of hyperprolactinemic sera.
- The Roche assay showed lower total prolactin levels and a lower prevalence (6.2%) of macroprolactinemia compared to Tosoh.
- Increasing the screening threshold reduced workload but decreased macroprolactinemia detection sensitivity.
Conclusions:
- Macroprolactin interferes with both Tosoh and Roche prolactin immunoassays.
- Low cross-reactivity assays (e.g., Roche) modestly reduce screening workload.
- Higher screening thresholds decrease workload but significantly increase missed macroprolactinemia cases.
