Pituitary neuroendocrine tumors (PitNETs) are commonly associated with visual disturbances and endocrine abnormalities; however, many patients also experience cognitive deficits, particularly in memory, attention, and executive function, which significantly affect quality of life. Despite increasing recognition of this burden, the mechanisms underlying cognitive impairment remain unclear. Traditionally, cognitive changes have been attributed to tumor mass effects or direct compression of surrounding structures. Emerging evidence, however, implicates hormonal dysregulation and the gut–brain axis, suggesting that intestinal microbiota may influence cognition through inflammatory, metabolic, and endocrine pathways.
To bridge this gap, researchers from Kunming Medical University, led by Dr. Xingli Deng, conducted a prospective cross-sectional study to evaluate cognitive function in patients with PitNETs and examine associations among tumor lineage, hormonal abnormalities, and gut microbiota composition. The study made available online and published in Volume 11, Issue 33 of the Chinese Neurosurgical Journal on 30 December 2025 . Dr. Deng explained the motivation behind the study, "By integrating neurocognitive assessment with endocrine profiling and microbiome analysis, we aimed to move beyond traditional explanations centered solely on tumor size and mass effect, and instead explore a more comprehensive, biologically grounded model of cognitive dysfunction in PitNET patients."
This prospective cross-sectional study included 42 patients with PitNETs and 42 matched healthy controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) before surgery and again three months postoperatively. Tumor characteristics, including volume and invasiveness on MRI, and pituitary hormone levels, were recorded. Tumors were classified as functional or nonfunctional and grouped by molecular lineage (PIT1 and SF-1). Fecal samples collected before treatment underwent 16S rRNA sequencing to characterize gut microbiota composition. Statistical analyses evaluated group differences and correlations between cognitive scores, clinical variables, and microbial profiles.
The findings were remarkable. "Patients with PitNETs demonstrated significantly lower cognitive performance than healthy controls, particularly in attention, executive function, and memory, with impairments more pronounced in functional and PIT1-lineage tumors," noted Dr. Deng. Cognitive impairment was especially pronounced in patients with functional tumors, particularly those classified within the PIT1 lineage. Notably, tumor volume and invasiveness were not significantly associated with cognitive outcomes, challenging the assumption that structural mass effects are the primary drivers of neurocognitive decline. Importantly, cognitive scores improved three months after surgical tumor removal, accompanied by reductions in elevated hormone levels such as growth hormone (GH), insulin-like growth factor 1 (IGF-1), and prolactin (PRL). These findings support a potential endocrine mechanism underlying cognitive dysfunction and recovery.
Microbiome analysis revealed distinct alterations in gut bacterial composition among PitNET patients. Reduced abundance of the butyrate-producing genus Agathobacter, known for its anti-inflammatory properties, was observed, along with increased levels of potentially pro-inflammatory taxa such as Alistipes indistinctus and UBA1819. These changes suggest that inflammatory and metabolic pathways linked to gut microbiota alterations may interact with hormonal dysregulation to influence cognitive outcomes.
This study integrates clinical, endocrine, cognitive, and microbiome data within a well-characterized cohort, strengthened by pre- and postoperative assessments and household-matched controls. By linking tumor lineage and microbiota alterations to cognitive impairment, it moves beyond traditional structural explanations and proposes a multifactorial model involving endocrine and gut–brain axis mechanisms. However, the modest sample size and cross-sectional microbiome design render the findings exploratory. Larger longitudinal studies are needed to clarify causality and to determine whether microbiota-targeted interventions could meaningfully enhance cognitive outcomes alongside surgical management.
In conclusion, cognitive impairment appears to be common among patients with PitNETs, particularly those with PIT1-lineage tumors. Cognitive dysfunction is more strongly associated with hormonal dysregulation and gut microbiota alterations than with conventional indicators of tumor burden. Surgical intervention is associated with measurable cognitive improvement, and modulation of the gut–brain axis may represent a promising future therapeutic avenue. Collectively, these findings provide a comprehensive framework for understanding the multifactorial basis of neurocognitive dysfunction in PitNET patients and open new directions for integrated treatment strategies aimed at improving neurological function and quality of life.
