Infiltrative and inflammatory systemic disorders involving the pituitary gland

The hypothalamic-pituitary region can be affected by a wide and heterogeneous group of infiltrative and inflammatory disorders, including granulomatous, histiocytic, storage, infectious, non-pituitary neoplastic, and autoimmune or inflammatory conditions collectively grouped as hypophysitis. Although individually rare, these disorders are increasingly recognized due to growing awareness, wider use of pituitary imaging, and the emergence of immune checkpoint inhibitor-induced hypophysitis. They typically present with hypopituitarism (often including arginine vasopressin deficiency, which, particularly when accompanied by pituitary stalk thickening, is highly suggestive of a non-adenomatous lesion) together with mass effect symptoms and, in many cases, systemic manifestations reflecting extrapituitary organ involvement. Neuroimaging findings, while rarely pathognomonic, can narrow the differential diagnosis, particularly when pituitary stalk involvement is present: symmetric stalk/gland enlargement with homogeneous enhancement suggests lymphocytic, IgG4-related, or granulomatous hypophysitis, whereas rim enhancement, necrosis, or bone-destructive lesions point toward infectious or neoplastic causes. A structured diagnostic work-up, combining clinical history, hormonal evaluation, targeted laboratory testing, pituitary and systemic imaging, and, when necessary, histopathological confirmation, is essential to establish an accurate diagnosis before committing patients to long-term immunosuppression or unnecessary pituitary surgery. Management requires two parallel strategies: prompt hormone replacement therapy, with urgent attention to corticotroph deficiency, and disease-specific treatment tailored to the underlying etiology, ranging from glucocorticoids and immunosuppressants to antimicrobial therapy, targeted oncologic agents, or surgery. Because pituitary deficits are frequently irreversible and several of these disorders follow a relapsing course, long-term multidisciplinary follow-up is warranted. This review summarizes the pathophysiology, clinical presentation, diagnostic approach and neuroimaging features, for infiltrative and inflammatory hypothalamic-pituitary disorders, aiming to facilitate their timely recognition and appropriate management.