Pituitary function in primary and secondary empty sella: a comparative study on a large cohort of patients.

Background: Empty Sella (ES) is an anatomical condition characterized by partial or complete filling of the sella turcica with cerebrospinal fluid, resulting in flattening of the pituitary gland. It is classified into a primary form, caused by a congenital defect of the sellar diaphragm and often associated with idiopathic intracranial hypertension, and a secondary form, resulting from surgical, radiotherapeutic, and/or pharmacological treatment of pituitary and brain tumors, as well as from pituitary apoplexy, infections, inflammation of the pituitary gland, or head trauma. Pituitary function can range from normal to varying degrees of hypopituitarism, with reported prevalence in the literature between 19% and 40% for the primary form. Materials and Methods: A retrospective analysis was conducted on a cohort of 246 patients diagnosed with ES and followed at the Endocrinology Unit of the University of Modena and Reggio Emilia. Of these, 155 had the primary form and 91 had the secondary form. Data were collected for each patient on pituitary function, anthropometric, radiological, and clinical parameters. Statistical analyses were performed to compare the cohorts with primary and secondary ES, focusing on the prevalence of hormonal deficiencies (ACTH, TSH, LH/FSH, GH) and diabetes insipidus, as well as clinical-demographic characteristics and the predominant diagnostic modality (incidental vs. clinical). Results: Patients with primary ES were younger (p=0.045) than those with secondary ES and showed a higher prevalence of female sex (71%). Moreover, they more frequently received an incidental diagnosis compared to patients with secondary ES (p<0.001). The latter was more often associated with previous neurosurgical interventions for pituitary adenomas (71.5%). The prevalence of hypopituitarism was significantly higher in secondary ES, with more frequent deficiencies in ACTH (p<0.001), TSH (p<0.001), GH (p<0.001), and LH (p<0.001). Diabetes insipidus was present only in a minority of cases, predominantly in secondary ES. Additionally, 59% of patients with secondary ES presented with at least one pituitary deficiency, compared to 38.5% of patients with primary ES. Conclusions: Primary and secondary ES differ significantly in terms of pituitary functional profiles. The risk of hypopituitarism is higher in patients with secondary ES, suggesting the need for systematic hormonal screening in these individuals. However, the frequent incidental diagnosis of primary ES raises questions about the need for routine endocrinological follow-up in this group. Future studies should aim to define monitoring criteria for patients with primary ES, assessing the potential risk of progression toward pituitary dysfunction over time.