Immune-Mediated Hypophysitis: An Updated Review

Background: Immune-mediated hypophysitis comprises a heterogeneous group of inflammatory pituitary disorders, including primary lymphocytic hypophysitis, immune checkpoint inhibitor (ICI)-induced hypophysitis, IgG4-related hypophysitis, and paraneoplastic autoimmune hypophysitis. Although these entities share immune-mediated mechanisms, they differ substantially in clinical presentation, imaging features, and therapeutic implications. Methods: This narrative review synthesizes current evidence on the pathophysiology, clinical manifestations, radiological characteristics, diagnostic approach, and management of immune-mediated hypophysitis, with particular emphasis on etiological heterogeneity. Results: Hypopituitarism—particularly ACTH deficiency—is the most frequent and clinically relevant manifestation, as secondary adrenal insufficiency may be life-threatening if not promptly recognized and treated. It is often accompanied by headache, arginine vasopressin deficiency, or mass effect depending on the subtype. Magnetic resonance imaging typically shows symmetrical pituitary enlargement and stalk thickening in inflammatory forms, although findings vary according to etiology and may be minimal in certain subtypes such as PD-1/PD-L1 inhibitor-associated hypophysitis. Distinct clinical phenotypes are observed across subtypes, particularly in ICI-induced hypophysitis and IgG4-related disease. Diagnosis relies on the integration of endocrine, radiological, and clinical features, supported by clinicoradiological scoring systems in selected cases. Management is primarily based on prompt hormone replacement, with selective use of glucocorticoids or immunosuppressive therapies depending on disease severity and underlying etiology. Conclusions: Immune-mediated hypophysitis represents a clinically relevant and increasingly recognized spectrum of disorders requiring a multidisciplinary and etiology-specific approach. Early recognition is essential to prevent life-threatening endocrine complications. Advances in the understanding of immunopathogenic mechanisms and the identification of reliable biomarkers may enable earlier diagnosis and more personalized therapeutic strategies.