Hormonal imbalance and gut microbes related to cognitive deficits in patients with PitNETs

Pituitary neuroendocrine tumors (PitNETs) are sometimes related to visual impairment and endocrine abnormalities; Nevertheless, many patients also experience cognitive deficits, particularly in memory, attention and executive function, which significantly impact quality of life. Although this burden is increasingly recognized, the mechanisms underlying cognitive impairment remain unclear. Traditionally, cognitive changes have been attributed to tumor mass effects or direct compression of surrounding structures. Nevertheless, emerging evidence points to hormonal dysregulation and the gut-brain axis, suggesting that the gut microbiota may influence cognition through inflammatory, metabolic and endocrine pathways.

To fill this gap, researchers from Kunming Medical University led by Dr Gut microbiota Composition. The study was made available online and published in Volume 11, Issue 33 on December 30, 2025. Dr. Deng explained the motivation behind the study: “.”

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 after surgery. 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). Stool samples collected before treatment were subjected to 16S rRNA sequencing to characterize the composition of the gut microbiota. Statistical analyzes assessed group differences and correlations between cognitive scores, clinical variables, and microbial profiles.

The outcomes were remarkable. ” noted Dr. Deng. Cognitive impairment was particularly pronounced in patients with functional tumors, particularly those classified within the PIT1 lineage. Notably, tumor volume and invasiveness weren’t significantly related to cognitive outcomes, questioning the notion that structural mass effects are the first causes of neurocognitive decline. Importantly, cognitive scores improved three months after surgical tumor removal, accompanied by a discount in elevated hormone levels corresponding to growth hormone (GH), insulin-like growth factor 1 (IGF-1) and prolactin (PRL). These results support a possible endocrine mechanism underlying cognitive dysfunction and recovery.

Microbiome evaluation revealed significant changes within the composition of intestinal bacteria in PitNET patients. Reduced abundance of the butyrate-producing genus Agathobacter, known for its anti-inflammatory properties, was observed, together with increased levels of doubtless pro-inflammatory taxa corresponding to Alistipes indistinctus and UBA1819. These changes suggest that inflammatory and metabolic pathways related to changes in gut microbiota may interact with hormonal dysregulation to influence cognitive outcomes.

This study integrates clinical, endocrine, cognitive, and microbiome data inside a well-characterized cohort, reinforced by pre- and postoperative assessments and household-matched controls. By linking tumor lineage and microbiota alterations to cognitive impairment, it goes beyond traditional structural explanations and proposes a multifactorial model involving endocrine and gut-brain axis mechanisms. Nevertheless, the modest sample size and cross-sectional design of the microbiome make the outcomes exploratory. Larger longitudinal studies are needed to make clear causality and determine whether microbiota-targeted interventions alongside surgical operation can meaningfully improve cognitive outcomes.

In conclusion, cognitive impairment is common in patients with PitNETs, ​​particularly in patients with PIT1 lineage tumors. Cognitive dysfunction is more strongly related to hormonal dysregulation and changes in gut microbiota than with traditional indicators of tumor burden. Surgical procedures are related to measurable cognitive improvement, and modulation of the gut-brain axis may represent a promising future therapeutic avenue. Taken together, these results provide a comprehensive framework for understanding the multifactorial basis of neurocognitive dysfunction in PitNET patients and open recent avenues for integrated treatment strategies to enhance neurological function and quality of life.