Cannulated Prolactin Testing in Mild Hyperprolactinemia: Clinical Utility, Evidence, and Future Directions

Abstract Hyperprolactinemia is a common finding in endocrine practice. An underappreciated cause of mild prolactin elevation is venipuncture-induced stress, which may lead to false-positive diagnoses and unnecessary downstream investigations. Cannulated prolactin testing (CPT) was developed to minimize procedural stress and exploit prolactin's short half-life to unmask true basal secretion. This narrative review examines the physiological rationale, clinical evidence, and practical application of CPT in the evaluation of suspected venipuncture-induced mild hyperprolactinemia. Across predominantly retrospective cohorts, CPT results in prolactin normalization in approximately 25 to 70% of patients with mild hyperprolactinemia, indicating that many mild elevations are transient and nonpathological. Failure to normalize during CPT is consistently associated with a higher prevalence of pituitary abnormalities on magnetic resonance imaging (MRI), supporting its role as a gatekeeper to imaging. Available data suggest that the diagnostic yield of CPT is greatest when referral prolactin concentrations are below approximately two to three times the upper limit of normal, although there is no universally agreed exact threshold. Despite its clinical relevance, CPT remains variably implemented and methodologically heterogeneous across studies. Prospective, standardized studies are needed to define optimal protocols and identify the highest-yield clinical indications.