The usefulness of cannulated prolactin test in mild hyperprolactinemia: case series and systematic review of the literature

Purpose Mild hyperprolactinemia can occur due to venipuncture-related stress leading to unnecessary diagnostic investigations/treatment. We aimed to assess the cannulated prolactin testing (CPT) usefulness in the investigation of mild hyperprolactinemia by evaluating our case series and conducting a literature review. Methods We conducted a retrospective study including hyperprolactinemia patients on an initial measurement (referral prolactin (rPRL)), who underwent a CPT between 2018–2025. During CPT a catheter was inserted and samples for prolactin were drawn at baseline (PRL0’), 30 min and 60 min. Prolactin normalization was defined as a PRL0’ or nadir PRL within the normal range. For the literature review, we included articles published until 1 October 2025 identified through PubMed and Scopus search. Results We included 105 patients (82% females) with a mean rPRL of 59.5±43.2ng/mL. Sixty-two of 105 patients (59%) had normal prolactin during the CPT, 47 (75.8%) had normal PRL0’ while 15 cases normalized prolactin at 30 min (n=10) or 60 min (n=5). PRL0’ predicted normalization with good accuracy (AUC 0.905, 95%CI 0.850–0.960), and optimal cut-off was 30.1ng/mL. Among the 1700 patients from 12 series we analysed, 913 (53.7%) normalized prolactin during the CPT, and 75.3% of these were already normal at timepoint 0’. Conclusions CPT is useful in excluding hyperprolactinemia in more than 50% of mild hyperprolactinemia patients, avoiding unnecessary imaging, overdiagnosis and treatment. More than three-quarters of patients who normalize prolactin during CPT have normal PRL0’. These data support a stepwise approach in which prolactin is first repeated under stress-free conditions reserving full CPT for those with persistent hyperprolactinemia.