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Technology Insight: measuring prolactin in clinical samples

Abstract

Measurement of prolactin is one of the most commonly undertaken hormonal investigations in evaluating patients with reproductive disorders. Hyperprolactinemia is found in up to 17% of such cases. Diagnostic evaluation of hyperprolactinemia is difficult but is facilitated by a logical approach where a thorough patient history is obtained, secondary causes of hyperprolactinemia are excluded, and the limitations of current prolactin assays are appreciated. Once hyperprolactinemia has been confirmed, attempts to establish the underlying cause can start. Given current workloads, laboratories rely on automated platforms to measure prolactin, most of which employ two-site immunoassay sandwich methods. Although generally robust and reliable, such immunoassays are susceptible to interference, and good collaboration between clinicians and the laboratory helps to minimize problems. A major challenge facing laboratories is correct differentiation of patients with true hyperprolactinemia from those with macroprolactinemia. Macroprolactin is a high-molecular-mass, biologically inactive form of prolactin that is detected to varying degrees by all prolactin immunoassays. Conservative estimates suggest that the presence of macroprolactin leads to misdiagnosis in as many as 10% of all reported instances of biochemical hyperprolactinemia. In the absence of specific testing, macroprolactin represents a diagnostic pitfall that results in the misdiagnosis and mismanagement of large numbers of patients.

Key Points

  • Prolactin levels are invariably measured in patients presenting with infertility

  • Although the etiology of hyperprolactinemia is complex, correct diagnosis is facilitated by a logical and systematic investigative approach

  • Immunoassay interference together with physiologic, pharmacologic, and secondary causes of hyperprolactinemia should be ruled out before embarking on pituitary imaging

  • The introduction of screening for macroprolactin has significantly reduced the extent of misdiagnosis and mismanagement of patients

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Figure 1: Known causes of hyperprolactinemia
Figure 2: Schematic illustrating the principle of a two-site immunometric assay for prolactin
Figure 3: Diagnostic algorithm for the investigation of hyperprolactinemia
Figure 4: Schematic illustrating potential sources of interference in immunometric assays for prolactin
Figure 5: Mean serum prolactin levels reported by nine different immunoanalyzer user groups in specimens collected from 10 subjects who had macroprolactinemia
Figure 6: Schematic illustration of a theoretical model to explain the variability in macroprolactin detection observed between different prolactin immunoassays

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Smith, T., Kavanagh, L., Healy, ML. et al. Technology Insight: measuring prolactin in clinical samples. Nat Rev Endocrinol 3, 279–289 (2007). https://doi.org/10.1038/ncpendmet0447

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