A diagnostic pitfall in IgG4-related hypophysitis: infiltration of IgG4-positive cells in the pituitary of granulomatosis with polyangiitis

Abstract

Introduction: Immunoglobulin (Ig) G4-related hypophysitis is an emerging clinical entity, which is characterized by an elevated serum IgG4 concentration and infiltration of IgG4-positive plasma cells in the pituitary. Although some criteria for its diagnosis have been proposed, they have not been fully established. In particular, differential diagnosis from secondary chronic inflammation including granulomatosis with polyangiitis (GPA) is difficult in some cases. We describe central diabetes insipidus with pituitary swelling exhibiting infiltration of IgG4-positive cells.

Patient: A 43-year-old woman in the remission stage of GPA presented with sudden-onset polyuria and polydipsia. Pituitary magnetic resonance imaging revealed swelling of the anterior and posterior pituitary and stalk, with heterogeneous gadolinium enhancement and disappearance of the high signal intensity of the posterior pituitary. Evaluation of biochemical markers for GPA suggested that the disease activity was well-controlled. Endocrinological examination revealed the presence of central diabetes insipidus and growth hormone deficiency. Pituitary biopsy specimen showed IgG4-positive cells, with a 43% IgG4(+)/IgG(+) ratio, which met the criteria for IgG4-related hypophysitis. However, substantial infiltration of polymorphonuclear neutrophils with giant cells was also noted, resulting in a final diagnosis of pituitary involvement of GPA.

Conclusion: These results suggest that pituitary involvement of GPA should be taken into account for the differential diagnosis of IgG4-related hypophysitis.