Subtle Cognitive Impairments and Psychological Complaints in Patients With Prolactinoma Despite Biochemical Control

van Trigt, Victoria R; Andela, Cornelie D; Bakker, Leontine E H; Brama, Steffanie C M; Schmidt, Lotte E; Sneekes, Florian M; Zeelenberg, Margot W; Huisman, Sasja D; Bauduin, Stephanie E E C; Dekkers, Olaf M; Verstegen, Marco J T; van Furth, Wouter R; Pelsma, Iris C M; Biermasz, Nienke R · 2025 · OpenAlex-citations

DOI: 10.1210/clinem/dgaf355

archive: archived pipeline: cataloged verified

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Summary

This study investigates whether patients with prolactinoma experience residual cognitive and psychological deficits even after achieving biochemical control (normoprolactinemia). While prolactinoma treatments, such as dopamine agonists (DA) and transsphenoidal surgery (TSS), effectively normalize prolactin levels, previous research has been limited by small sample sizes, lack of control groups, or high bias. This research aimed to provide a rigorous assessment of cognitive functioning and psychological complaints in biochemically controlled patients compared to matched healthy controls, hypothesizing that subtle impairments would persist and potentially correlate with treatment modality or disease duration. The researchers conducted a cross-sectional study involving 60 patients with prolactinoma and 60 age-, gender-, and education-matched healthy controls. The patient cohort was evenly split between those controlled on stable DA doses (n=30) and those in surgical remission for at least six months (n=30). Strict exclusion criteria were applied to both groups to eliminate confounding factors, including psychiatric history, neurological conditions, and medication use affecting cognition. Participants underwent an extensive cognitive assessment comprising eight standardized tests evaluating memory, verbal fluency, processing speed, selective attention, and executive functioning. Additionally, all participants completed seven validated questionnaires measuring psychological complaints, including apathy, irritability, fatigue, anxiety, depression, irrational beliefs, and personality traits. Statistical analysis utilized generalized estimating equations to compare patient outcomes against matched controls, with secondary analyses examining differences between treatment groups and potential influencing factors. The results revealed that patients with biochemically controlled prolactinoma exhibited significant subtle cognitive impairments compared to healthy controls. Specifically, patients scored lower on tests of verbal memory (Verbal Learning Test of Rey), selective attention (Digit Deletion Test and Trail Making Test A), and processing speed (Digit-Symbol Substitution Test). However, no significant differences were found in executive functioning or task switching. Psychologically, patients reported significantly higher levels of apathy, irritability, fatigue, anxiety, and depressive symptoms. Notably, these impairments and complaints were present in both the DA-treated and surgically treated groups, with no significant differences observed between the two treatment modalities. Furthermore, multilinear regression analyses indicated that factors such as prolactin levels at diagnosis, hypopituitarism, and duration of biochemical control did not significantly predict the degree of cognitive impairment or psychological complaints. The study concludes that despite successful biochemical normalization, patients with prolactinoma suffer from persistent subtle cognitive deficits and increased psychological burden. These findings challenge the assumption that biochemical control equates to full clinical recovery regarding mental health and cognitive function. The authors emphasize that these impairments are independent of the treatment method (medical vs. surgical) and disease duration. Consequently, they recommend that clinicians remain aware of these residual issues and actively address them in patient care, suggesting that biochemical success alone is insufficient for ensuring optimal quality of life and cognitive health in this patient population.

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• cognitive impairment