IgG4-related hypophysitis: a new addition to the hypophysitis spectrum

Abstract

Context: Hypophysitis is a chronic inflammation of the pituitary gland that comprises an increasingly complex clinicopathological spectrum. Within this spectrum, lymphocytic and granulomatous hypophysitis are the most common forms, but newer variants have recently been reported.

Objective: The aims of the study were to describe a new patient with IgG4-related hypophysitis, review the published literature, and provide diagnostic criteria.

Setting: A 75-yr-old man presented with a 1-yr history of frontal headache. Initial studies revealed panhypopituitarism and a mass in both the sella turcica and the sphenoidal sinus. The patient underwent transphenoidal surgery, initiated high-dose prednisone followed by hormone replacement therapy, and was closely monitored for 3 yr.

Results: Symptoms improved after prednisone, along with shrinkage of the pituitary and sphenoidal masses, but recurred when prednisone dose was lowered. Histopathology showed a marked mononuclear infiltrate in both the pituitary and sphenoidal specimens, mainly characterized by increased numbers of plasma cells. Many of the infiltrating plasma cells (>10 per high-power field) were IgG4-positive. Review of the literature identified 11 cases of IgG4-related hypophysitis (two diagnosed based on pituitary histopathology).

Conclusions: We describe the first Caucasian patient with biopsy-proven IgG4-related hypophysitis and provide classification criteria for this disease.

Fig. 1.

Pituitary MRI and histopathology, highlighting a marked lymphoplasmacytic infiltration, rich in IgG4-producing cells, and serum IgG4 levels. A, Baseline (January 2008) T1-weighted magnetic resonance image showing enlargement of the pituitary gland, thickening of the stalk, with a depressed and eroded floor of the sella, and a mass in the sphenoidal sinus. B, Pituitary hematoxylin and eosin, 40×. C, MRI performed approximately 2.5 yr after the second surgery (July 2010) showing persistence of the pituitary inflammation. D, Pituitary CD138 (a marker for plasma cells), 40×. E, ELISA to detect serum IgG4 at multiple time points. The numbers on the x-axis correspond to the date IDs reported in Supplemental Table 1. F, Pituitary IgG4, 64×.