Prognostic value of PANOMEN-3 classification for hypopituitarism in surgically and nonoperatively managed pituitary adenomas

Background: The prognostic value of Pituitary Adenoma Nomenclature 3 (PANOMEN-3) for incident or persistent hypopituitarism remains uncertain. This study aimed to assess whether baseline PANOMEN-3 grade and its components predict secondary adrenal insufficiency or secondary hypothyroidism in surgically and nonoperatively managed patients. Methods: We conducted a retrospective cohort study of adults with newly diagnosed pituitary adenoma at Rambam Health Care Campus, a tertiary referral center in Haifa, Israel, between 2010 and 2023. Follow-up was censored on August 31, 2025. Patients were stratified by management (surgical or nonoperative). PANOMEN-3 grades were assigned at the index visit, defined as the initial endocrinology consultation. The primary outcome was the incidence of the composite of secondary adrenal insufficiency or secondary hypothyroidism at follow-up. Results: The study included 208 adults with pituitary adenomas: 118 underwent transsphenoidal surgery and 90 were managed nonoperatively. In the surgical group, the incidence of secondary adrenal insufficiency or secondary hypothyroidism at a median follow-up of 17.4 months (IQR: 5.0–47.7) was 32.2% and increased with higher baseline PANOMEN-3 grade (0% in grade 0 to 61.1% in grade 3; P = 0.01). In the nonoperative group, the incidence was 11.1% at a median follow-up of 15.5 months (IQR: 5.7–35.8) and was likewise associated with higher baseline grade (0% in grade 0 to 20.0% in grade 3; P = 0.02). Across both groups, baseline hypopituitarism and larger adenoma size were associated with secondary adrenal insufficiency or secondary hypothyroidism (surgical: P < 0.001 and P = 0.04; nonoperative: P < 0.001 and P = 0.03). Conclusion: PANOMEN-3 grading effectively stratifies the risk of secondary adrenal and thyroid dysfunction in both surgical and nonoperative settings.