Hypophysitis and Infiltrative Pituitary Disease
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Direct answer
Hypophysitis is inflammation of the pituitary gland, and its main types are lymphocytic, IgG4-related, granulomatous and checkpoint inhibitor-induced. Infiltrative lesions such as metastases, germinomas and histiocytosis can mimic it. Headache, visual symptoms and hypopituitarism are typical, and MRI showing gland and stalk enlargement points towards the diagnosis.
What you must remember
- Lymphocytic: the commonest type, affecting mainly women, often in late pregnancy or the early postpartum period.
- IgG4-related: part of systemic IgG4-related disease, with raised serum IgG4 and a thickened stalk; diabetes insipidus is relatively common.
- Granulomatous: caused by sarcoidosis, tuberculosis or granulomatosis with polyangiitis, so systemic evidence is sought.
- Checkpoint inhibitor: ipilimumab causes it more often than anti-PD-1 agents, and central hypoadrenalism is often the first deficit.
- Infiltrative mimics: metastases from breast or lung, germinoma and Langerhans cell histiocytosis; the last two often cause diabetes insipidus with a thick stalk.
- MRI pattern: diffuse gland and stalk enlargement with enhancement, which differs from the focal appearance of most adenomas.
- Treatment: glucocorticoids for mass effect or severe inflammation, plus lifelong replacement of any deficient axis.
Matching the type to the clinical picture
Several conditions cause a sellar mass with headache, hormone loss or diabetes insipidus. The clinical context and the MRI pattern usually narrow the list. The table below pairs each type with its typical clues and the feature that separates it on investigation.
| Type | Typical clues | Distinguishing feature |
|---|---|---|
| Lymphocytic | Women, late pregnancy or postpartum | Diffuse gland enlargement; diabetes insipidus is less consistent |
| IgG4-related | Middle-aged adults, often men | Raised serum IgG4; thick stalk; steroid responsive |
| Granulomatous | Known sarcoidosis, tuberculosis or vasculitis | Systemic disease or tissue diagnosis needed |
| Checkpoint inhibitor | Patient on ipilimumab or other immunotherapy | Central hypoadrenalism; headache |
| Germinoma or histiocytosis | Young patients with diabetes insipidus | Thick stalk; biopsy or germ cell markers |
| Metastasis | Known primary, often breast or lung | Stalk or posterior lobe infiltration |
Infiltrative mimics such as germinoma and histiocytosis must be excluded before inflammatory disease is assumed, because treatment and prognosis differ. Tuberculosis is also excluded before high-dose steroids are started.
Where students lose marks
These are the points most often tested.
- Trap: assuming every enlarged pituitary is an adenoma. Correct: inflammatory and infiltrative lesions can enlarge the gland and stalk in a similar way, so the history and MRI pattern matter.
- Trap: attributing diabetes insipidus in a young patient with a thick stalk to a non-functioning adenoma. Correct: Langerhans cell histiocytosis and germinoma commonly cause this picture, and biopsy or markers are needed.
- Trap: giving high-dose steroids for every pituitary inflammation without excluding infection. Correct: tuberculosis must be excluded first, since steroids can worsen untreated infection.
Frequently asked questions
What MRI features suggest hypophysitis rather than a pituitary adenoma?
Hypophysitis usually causes diffuse enlargement of the gland with thickening and enhancement of the pituitary stalk. A pituitary adenoma is typically a focal lesion with its own enhancement pattern. Stalk thickening is therefore a helpful clue, although biopsy may still be needed when the picture is unclear.
Which types of hypophysitis commonly cause diabetes insipidus?
IgG4-related hypophysitis and Langerhans cell histiocytosis commonly cause diabetes insipidus with a thickened stalk. Lymphocytic hypophysitis can also cause it, but less consistently. Diabetes insipidus in a young patient with stalk thickening should prompt a search for these causes.
Why is checkpoint inhibitor hypophysitis important in oncology patients?
Checkpoint inhibitor hypophysitis matters because it can cause permanent hormone deficiency that must be recognised early. Ipilimumab causes it more often than PD-1 inhibitors do. Central hypoadrenalism is often the first deficiency, so stress-dose steroid cover is needed during acute illness.
How is hypophysitis treated?
Hypophysitis is treated with glucocorticoids for mass effect or severe inflammation, along with replacement of any deficient pituitary axis. Lymphocytic disease may improve on its own, but many patients need long-term replacement. IgG4-related disease is managed with steroids and sometimes rituximab.