Pituitary Hormone Deficiencies in Prolactinomas: Prevalence, Predictors, and Functional Recovery

Antonio Prinzi^1,2Ginevra Fava²Ignazio Bacchi³Federica Spitali²Antonio Galvano¹Giorgio Arnaldi³Francesco Frasca²Valentina Guarnotta^3*Pasqualino Malandrino²

• ¹Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy, Palermo, Italy
• ²Universita degli Studi di Catania Dipartimento di Medicina Clinica e Sperimentale, Catania, Italy
• ³Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Università degli studi di Palermo, Palermo, Italy

Introduction. To evaluate the prevalence of pituitary hormone deficiencies in patients with prolactinomas, identify clinical and radiological predictors of non-gonadal hypopituitarism at diagnosis, and evaluate the potential for pituitary function recovery over long-term follow-up. Methods. We conducted a retrospective multicentre study including 145 patients with prolactinomas diagnosed between 2000 and 2024 at two tertiary centers. All anterior pituitary axes were evaluated at diagnosis and during follow-up. Results. At diagnosis, 54 of 145 patients (37.2%) had at least one pituitary hormone deficiency. Hypogonadism was the most common deficit (34.5%), followed by non-gonadal hypopituitarism in 14.5%, including secondary adrenal insufficiency: 8.3%, central hypothyroidism: 7.6%, growth hormone deficiency (GHD): 6.9%. Macroadenomas were significantly more prevalent than microadenomas (25.8% vs. 2.7%, p<0.001). Tumor size was the only independent predictor of non-gonadal hypopituitarism at diagnosis (OR: 1.1, 95%CI: 1.03–1.20; p=0.007). ROC analysis identified 17 mm as the optimal cut-off to predict non-gonadal pituitary hormone deficiencies at diagnosis (sensitivity 84%, specificity 77%, AUC=0.836). During follow-up (median 70 months), 66.7% of patients recovered at least one pituitary axis, with higher recovery in microadenomas (100% vs. 63.0%, p=0.038). Tumor size remained the strongest predictor of recovery (OR: 0.56, 95%CI: 0.34– 0.94; p=0.029). Conclusions. Non-gonadal hypopituitarism is common in prolactinomas, especially larger tumors. Tumor size was the strongest predictor of both the presence and recovery of hormonal deficits, with an optimal cut-off of 17 mm. Long-term follow-up is essential, as many patients, especially those with smaller tumors, recover pituitary function after treatment, with gonadal and adrenal axes showing the highest likelihood.