Natural history of non-functioning pituitary neuroendocrine tumours: impact of baseline characteristics and gender-specific clinical presentations

Non-functioning pituitary neuroendocrine tumours (NF-PitNETs) are the most common pituitary macroadenomas, with highly variable clinical behaviour. Although tumor growth and functional impairment are key considerations, the impact of patient sex on presentation and outcomes remains incompletely characterized. To investigate clinical, radiological and histopathological predictors of long-term outcomes in NF-PitNETs managed conservatively or surgically and to evaluate gender impact on initial presentation and tumour natural history. We retrospectively analyzed 170 patients with NF-PitNETs, including those under active surveillance and those treated surgically, with or without adjuvant therapies. Long-term clinical, endocrine and radiological follow-up was performed. Compared with female patients, males exhibited larger tumour dimensions and a higher prevalence of both visual field defects and endocrine dysfunction. Women, particularly in the surveillance cohort, had smaller tumours, often detected earlier, likely due to reproductive-age clinical monitoring. Despite these baseline differences, progression rates were similar between genders. In patients under surveillance, five-year tumour growth risk was higher for macroadenomas than microadenomas (45.7% vs. 22.5%, p = 0.030), and baseline tumour volume and visual impairment predicted progression. In the surgical cohort, residual tumour increased progression risk, while a > 40% volume reduction was associated with visual improvement. The Trouillas clinicopathological classification was not predictive of outcomes. Adjuvant therapies, including stereotactic radiosurgery and temozolomide, stabilized disease in most treated cases. Gender significantly influences NF-PitNETs presentation, with males harbouring larger, more symptomatic tumours whereas females tended to have an earlier detection. However, long-term progression seems to be independent of gender. These findings pinpoint the importance of individualized approach combining anatomical, volumetric, and functional assessments to optimize outcomes.