Rising Burden of PRL-PitNETs: Patterns Across Tumour Sizes and Incidentalomas

Abstract Objective Epidemiology of prolactin-secreting pituitary neuroendocrine tumours (PRL-PitNETs) remains scarce and inconsistent. It is a heterogeneous disease regarding age at onset, sex, and tumour characteristics. We aimed to assess temporal epidemiological trends in PRL-PitNETs. Design Cohort study, systematic review and meta-analysis. Methods The cohort study was comprised of all PRL-PitNET patients in the North Denmark Region (2017–2022; N=594,634), identified via ICD-10 coding (E22.1) or dopamine agonist treatment. Data included sex, age at diagnosis, adenoma size and prolactin levels. For the systematic review, PubMed and Embase were searched (May 2025) for studies reporting ≥20 PRL-PitNETs. Extracted data comprised prevalence, incidence, age and sex distributions. A random-effects meta-analysis was applied. Results The cohort included 245 patients: 167 microprolactinomas, 78 macroprolactinomas, and 20 incidentalomas. From 2017–2022, prevalence increased by 41% (95%CI: 25-60%, +61 cases) overall, 42% (95%CI: 19-68%, +39 cases) for microprolactinomas, 41% (95%CI: 19-67%, +22 cases) for macroprolactinomas, and 57% (95%CI: 6-132%, +7 cases) for incidentalomas. Overall incidence was 2.8 (95%CI: 2.2-3.5) per 100,000 person-years. The systematic review and meta-analysis (15 studies, 16,000 PRL-PitNET cases) showed an increasing PRL-PitNET prevalence and incidence, reaching 41 (95%PI: 12-89) per 100,000 persons and 2.3 (95%PI: 1.2-4.3) per 100,000 person-years, respectively; with a phenotypical shift towards more men (from 10-20% to 20-30%), macroprolactinomas (∼25 to ∼30%) and incidentalomas (∼6% to ∼10%) over the last two decades. Conclusion PRL-PitNETs are increasingly prevalent, partly driven by a rising incidence of men and incidentalomas, suggesting a phenotypic shift and associated increase in clinical and healthcare burden.