Immune Checkpoint Inhibitor Hypophysitis: Delayed Resolution on Low Dose Glucocorticoid Therapy

Document Type

Conference Proceeding

Publication Date

10-22-2025

Publication Title

J Endocr Soc

Keywords

glucocorticoid, hydrocortisone, immune checkpoint inhibitor, ipilimumab, nivolumab, prednisone, adrenal insufficiency, adult, adverse drug reaction, case report, clinical article, clinical outcome, conference abstract, diagnosis, diplopia, disease course, drug combination, drug dose, drug dose reduction, drug megadose, drug therapy, drug withdrawal, emergency ward, female, follow up, headache, human, human tissue, hypophysitis, low drug dose, maintenance drug dose, metastasis in breast, metastatic melanoma, MRI scanner, nuclear magnetic resonance imaging, optic chiasm, polyendocrinopathy, secondary hypothyroidism, side effect, therapy, unexpected outcome of drug treatment, visual field

Abstract

Background: Hypophysitis is a known adverse effect of immune checkpoint inhibitors (ICIs) that can present with a variable clinical course. Here we present a case of metastatic melanoma on immunotherapy who presented with acute pituitary enlargement and delayed but complete resolution on systemic glucocorticoid (GC) therapy. Case: A 48-year-old female with past medical history of stage IV melanoma with metastasis to the breast, treated with ipilimumab and nivolumab, presented to the emergency department with intractable headache after receiving two cycles of immunotherapy. Magnetic resonance imaging (MRI) showed pituitary enlargement with suprasellar extension abutting optic chiasm. Visual field testing was normal. Initial biochemical testing was unremarkable. High dose GCs were avoided initially as it may interfere with efficacy of ICI therapy and worsen outcome. However, due to progressive headache despite analgesics, the patient was started on prednisone 40mg daily, tapered over 1 month, and ICIs were held. MRI pituitary 1 month following initiation of GC revealed interval increase in pituitary size. The lack of response was concerning for potential metastatic lesion but based on available literature, longer period of GC therapy may be required for resolution of hypophysitis. The patient continued prednisone 5mg daily for a further 2 months and ICIs was resumed. Repeat MRI pituitary 3 months later showed resolution of pituitary enlargement. Baseline biochemical testing after GCs were held for 24 hours revealed secondary hypothyroidism and adrenal insufficiency. She transitioned from prednisone to maintenance dose hydrocortisone daily. Serial follow up imaging 18 months following initial diagnosis continue to demonstrate normal pituitary gland, but persistent central hormone deficiencies. Discussion: ICIs are associated with various immune-related adverse effects, including hypophysitis, which occurs in 1-10% of patients on ICIs. Both symptomology and management of hypophysitis are highly variable due to the array of effects, from mass effect due to pituitary enlargement to multiple endocrinopathies. High dose GCs are not typically needed to manage hypophysitis and have been associated with worse clinical outcomes. There are no established guidelines on indication and optimal duration of systemic GC therapy in severe ICI-related hypophysitis. A short course (1 week) of high dose systemic GC therapy can be considered for a patient who presents with compressive symptoms (headache, double vision). In our case, given persistent pituitary enlargement, longer duration of low dose of prednisone was administered alongside immunotherapy, which led to resolution of symptoms and clinical presentation. Management of hypophysitis should be tailored to each patient with close monitoring of hormone levels and pituitary imaging.

Volume

9

First Page

A858

Last Page

A859

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