Table 2.
Salient features of common forms of hypophysitis.
| 1. Lymphocytic hypophysitis |
| • Most common form of hypophysitis (68% of PHy). |
| • Common in females (female:male = 4:1 for LADHy, 1.9:1 for LINHy, and 1:1 for LPHy). |
| • Mean age of presentation: females: 35 years, men: 49 years for LAHy. For LINHy, 39 years and for LPHy, 43 years in both sexes. |
| • Association with pregnancy and post-partum period. |
| • Histopathology: lymphocytic infiltration in the interstitium and in the pituitary acini. Lymphoid follicles with germinal centers can be observed. |
| 2. Granulomatous hypophysitis |
| • Second most common form (20% of PHy). |
| • Common in females (female:male = 2.6:1). |
| • Mean age of presentation: 44 years. |
| • Histopathology: arranged in the form of granulomas, along with lymphocytes, multinucleated giant cells, and areas of fibrosis. |
| • Might represent a later stage in the course of natural history of lymphocytic hypophysitis. |
| 3. IgG4 hypophysitis |
| • Prevalence of 4% among PHy (although some cohorts suggest as high as 41%). |
| • Often part of a systemic disease known as IgG4 disease. |
| • More common in males in cases of systemic involvement (female:male = 3:1), but isolated hypophysitis is more common in females (female:male = 2:1) |
| • Mean age of presentation is earlier in females (females: 56.4 years; males: 67.5 years). |
| • More common in eastern countries such as Japan. |
| • Histopathology: mononuclear infiltration with ≥10 IgG4 positive plasma cells per high power field, storiform fibrosis, rarely lymphoid follicles and eosinophils. |
| • Highly responsive to glucocorticoid therapy. |
| • Diagnosis can be established based on the following criteria: 1. Histopathological evidence on pituitary biopsy, 2. Hypophysitis on MRI, 3. Biopsy-proven systemic involvement, 4. Serum IgG4 levels >140 mg/dl, and 5. Excellent response to glucocorticoid therapy. Criterion 1 alone, or criteria 2 + 3, or criteria 2 + 4 + 5 establish the diagnosis. |
| 4. Xanthomatous hypophysitis |
| • Prevalence of about 3% among PHy. |
| • More common in females (female:male = 3:1). |
| • Commonly presents in the 4th decade. |
| • Usually causes adenohypophysitis. Central DI is uncommon. |
| • Histopathology: infiltration with CD68 positive foamy macrophages. Xanthogranulomatous sub-type can contain cholesterol clefts and hemosiderin deposits. |
| • MRI can show cystic areas of liquefaction. |
| • Visual symptoms are uncommon in this type of hypophysitis. |
| • Precise aetiology unclear: likely an inflammatory reaction to a ruptured Rathke’s cleft cyst. |
| 5. Necrotizing hypophysitis: |
| • Rarest histopathological form (0.6% of PHy). |
| • Can also occur in association with CTLA4 inhibitor therapy. |
| • Common in females (female:male = 3:1). |
| • More likely to present with acute onset of symptoms with mass effects. |
| • Histopathology: extensive areas of necrosis with infiltration of lymphocytes, plasmacytes, and a few eosinophils. Fibrosis can result from chronic inflammation. |
| 6. Immune checkpoint therapy induced hypophysitis: |
| • Most common form of secondary hypophysitis. |
| • Common in males (female:male = 1:4) |
| • Mean age of presentation: 59 ± 13 years |
| • Aetiology: combination of a type II and type IV hypersensitivity reaction, along with humoral immune response. |
| • More common with CTLA4 inhibitors (13.6%) as compared to PD1/PDL1 inhibitors (0.5%). |
| • Headaches are more common but visual disturbances are less on presentation when compared to PHy. |
| • Central DI is uncommon, and occurs in about 1% of patients. |
| • Isolated ACTH deficiency with hyponatraemia and a normal pituitary MRI is more common with PD1/PDL1 inhibitor therapy. |
| • Relatively refractory to glucocorticoid treatment. |
PHy: primary hypophysitis; LADHy: lymphocytic adenohypophysitis; LINHy: lymphocytic infundibuloneurohypophysitis; LPAHy: lymphocytic panhypophysitis; DI: diabetes insipidus; ACTH: adrenocorticotrophic hormone; MRI: magnetic resonance imaging.