Prolactin immunoassay: does the high-dose hook effect still exist?

Veronique Raverot (1, 2, 3) , Pauline Perrin (1, 2, 3) , Philippe Chanson (4, 5, 6) , Emmanuel Jouanneau (7) , Thierry Brue (8, 9, 10, 11) , Gerald Raverot (7, 11, 12)

1 HCL - Hospices Civils de Lyon
2 LBMMS - Laboratoire de Biologie Médicale MultiSites [Bron]
3 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
4 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
5 Université Paris-Saclay
6 PHYSENDO - Physiologie et physiopathologie endocriniennes
7 GHE - Groupement Hospitalier Lyon-Est
8 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
9 MarMaRa - Institut Marseille Maladies Rares
10 Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM]
11 HYPO - Centre de référence des maladies rares de l'hypophyse
12 UCBL - Université Claude Bernard Lyon 1

Purpose: Measurement of prolactin in clinical laboratories is an important component in the management of patients with pituitary adenoma. Prolactin measurement is known to be sensitive to the high-dose hook effect, in the presence of extremely high prolactin concentrations. This interference is referred to in most recent articles discussing prolactin assays and the management of prolactin-secreting pituitary adenomas. The objective of our study was to evaluate if the high-dose hook effect remains relevant in current practice, when using currently available assays. Methods: Serum from a patient with a giant macroprolactinoma was assayed using all of the available prolactin assays in France in 2020, using native serum and after dilution. Technical inserts from assays were reviewed to assess the information on analytical principles, numbers of steps, and any reference to high dose hook effect. Results: Fourteen assay kits were studied by 16 laboratories; all were two-site immunometric assays, mostly using one step (11/14). Results obtained after dilution varied from 17,900 µg/L to 86,900 µg/L depending on the assay used. One tested assay was sensitive to the high-dose hook effect leading to a falsely lower prolactin concentration when measuring native serum (150 µg/L compared to 17,900 µg/L after dilution). Conclusion: The high-dose hook effect still exists in a very small minority of prolactin assays. The evolution of assay methods may lead to new assays that remain sensitive to this effect in the future. We therefore advise that the hook effect should still be mentioned in prolactin assay recommendations.

Mots clés: Hook-effect; Immunoassay; Macroprolactinoma; Prolactin; Prolactinoma

Domaines: Génétique

Veronique Raverot, Pauline Perrin, Philippe Chanson, Emmanuel Jouanneau, Thierry Brue, et al.. Prolactin immunoassay: does the high-dose hook effect still exist?. Pituitary, 2022, 25 (4), pp.653-657. ⟨10.1007/s11102-022-01246-8⟩. ⟨hal-03780369⟩