Natural history and predictors of growth in conservatively managed non-functioning pituitary macroadenomas: A volumetric study of 232 tumors.

Background: Although patients with clinically non-functioning pituitary macroadenomas (NFPMAs) are typically monitored without immediate therapeutic intervention, their natural course remains unclear. This study aimed to characterize growth dynamics in conservatively managed NFPMAs and identify clinical predictors of tumor progression using volumetric MRI analysis.

Methods: We retrospectively analyzed 232 patients with NFPMAs who underwent at least two high-resolution MRI scans over a minimum follow-up of 12 months without therapeutic intervention. Tumor volumes were assessed using semi-automated segmentation. Progression was defined as a ≥ 20 % increase in volume. Clinical and radiological variables were evaluated to identify predictors of growth.

Results: Over a median follow-up of 37 months, 110 tumors (47.4 %) demonstrated significant growth. The median initial tumor volume was 1.9 cm³ , with median absolute and relative annual growth rates of 0.13 cm³ /year and 5.47 %/year, respectively. Multivariate Cox regression identified larger initial tumor volume (HR 1.140, 95 % CI 1.005-1.081; p = 0.027) and female sex (HR 1.594, 95 % CI 1.076-2.361; p = 0.020) as independent predictors. A tumor volume threshold of 2.5 cm³ was associated with increased growth risk. Among age-matched groups, females exhibited greater volumetric growth than males.

Conclusions: Approximately half of NFPMAs exhibit slow but measurable growth over time. Tumor volume at diagnosis and female sex are significant predictors of progression. These findings underscore the importance of individualized surveillance strategies, particularly for female patients with larger baseline tumors, and provide clinically relevant data to inform long-term management of NFPMAs.