Pituitary and Stalk Lesions (Infundibulo-hypophysitis) Associated with Immunoglobulin G4-related Systemic Disease: an Emerging Clinical Entity

Inflammatory lesions of the pituitary gland are rarely encountered. Recently, the concept of immunoglobulin G4 (IgG4)-related systemic disease was proposed in Japan, and more than 20 cases have been reported as possibly associated with infundibulo-hypophysitis since 2000. We herein review such case reports in the published literature and in the abstracts of scientific meetings. Almost all cases involved middle-aged to elderly men presenting with various degrees of hypopituitarism and diabetes insipidus and demonstrating a thickened pituitary stalk and/or pituitary mass. These structures shrank remarkably in response to glucocorticoid therapy, even in a lower dose range similar to that prescribed as a replacement for adrenocortical insufficiency. Some of the anterior pituitary insufficiencies were also resolved by glucocorticoid administration. The presence of IgG4-related systemic disease and an elevated serum IgG4 level before glucocorticoid therapy were the main clues to a correct diagnosis of IgG4-related infundibulo-hypophysitis. Autoimmunity is suggested but not yet established to play a role in the pathogenesis for IgG4-related systemic disease. The fact that hypertrophic pachymeningitis and para-sinusitis accompanied some cases suggested that both sellar and parasellar structures are involved in the chronic inflammation. We therefore classify this disorder not as a variant form of primary autoimmune hypophysitis but as a secondary form of infundibulo-hypophysitis associated with IgG4-related systemic disease.