Changes overtime in primary and secondary empty sella: a comparative real-world study

Purpose: Primary (PES) and Secondary (SES) Empty Sella (ES) show similar radiological appearances, but they may be associated with variable degrees of pituitary dysfunction. Long-term comparative data are limited. This study aimed to compare baseline and longitudinal endocrine outcomes of PES and SES in a large single-center cohort. Methods: We conducted a retrospective, longitudinal study including adults with ES followed at a tertiary endocrinology center between 2007 and 2025. ES was classified as PES or SES based on clinical history. Clinical and neuroradiological features, comorbidities, and pituitary hormonal assessments were collected at baseline and during follow-up. Results: A total of 258 participants were included (64.3% women; median age 51.5 years; median follow-up 58.5 months). PES was more prevalent than SES (61.6% vs. 38.4%). At baseline, 41.1% of patients had at least one pituitary hormone deficiency, significantly more frequent in SES than PES (62.6% vs. 27.7%), with gonadotropic deficiency the most common alteration. During follow-up, pituitary function remained stable in most PES patients (83.3%), with a very low incidence of new deficiencies. In contrast, SES showed a significantly higher risk of developing new corticotropic, thyrotropic, and gonadotropic deficiencies. Arginine vasopressin deficiency occurred exclusively in SES. Conclusion: In this large longitudinal cohort, PES and SES showed distinct clinical and endocrine evolution. While PES was generally stable course over time, SES was associated with a higher risk of progressive pituitary dysfunction. These findings support systematic baseline endocrine evaluation in all ES patients and a tailored follow-up strategy, with closer surveillance for SES.