# Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card

Source: https://onco.cc/protocols/irae-hypophysitis-adrenal/  
OnCo record `irae-hypophysitis-adrenal` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Immunotherapy can damage the pituitary or adrenal glands so the body stops making cortisol, a hormone needed to survive illness. Anyone on immunotherapy who becomes very unwell should be treated for low cortisol at once while tests are done. Most then need hydrocortisone tablets for life, a steroid emergency card, and to know how to double the dose when ill. Immunotherapy can usually carry on.

## Summary

Hypophysitis affects up to 17% of people on checkpoint inhibitors, mostly with CTLA-4 blockade (70% of published cases) and at ipilimumab doses above 3 mg/kg; ACTH deficiency is present in about 95% of anti-CTLA-4 cases (ESE 2022). Primary adrenal insufficiency is rare. Both usually cause permanent hormone loss.

The emergency (Society for Endocrinology 2018; ESE 2022): any severely unwell patient on a checkpoint inhibitor is assumed to have cortisol deficiency until proven otherwise. Take blood for cortisol (and ACTH) and give hydrocortisone 100 mg intravenously or intramuscularly, then 50 mg every 6 hours, with fluids; check glucose. A pre-treatment cortisol above 450 nmol/L excludes deficiency. Methylprednisolone does not replace cortisol and is kept for pituitary compression (visual loss, cranial nerve palsy, severe headache); ESE recommends against high-dose steroids for hypophysitis otherwise. Never start levothyroxine until cortisol deficiency is excluded or treated.

Maintenance: hydrocortisone 15 to 25 mg a day in two or three doses (ESE) or 10, 5 and 5 mg (Society for Endocrinology), fludrocortisone for primary adrenal insufficiency only, a steroid emergency card, sick day rules and an injection kit, and no abrupt stop. A controlled endocrinopathy is not a reason to stop the checkpoint inhibitor (ESE, ASCO). SITC 2021 differs in advising interruption of immunotherapy and corticosteroids for acute hypophysitis.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: immune checkpoint inhibitor hypophysitis; ICI adrenal insufficiency; adrenal crisis on immunotherapy; cortisol deficiency immunotherapy; steroid sick day rules immunotherapy; ipilimumab hypophysitis
- Tags: protocol; irae; acute-oncology; endocrine

## Connected records

- protocols: [Baseline tests and monitoring before and during checkpoint inhibitor treatment](https://onco.cc/protocols/checkpoint-inhibitor-baseline-and-monitoring/), [Eye side effects of checkpoint inhibitors: dry eye, uveitis and optic neuritis](https://onco.cc/protocols/irae-ocular/), [Hyponatraemia and SIADH in cancer: emergency hypertonic saline, safe correction and treating the cause](https://onco.cc/protocols/hyponatraemia-siadh/), [Immune-related diarrhoea and colitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-colitis/), [Immune-related pneumonitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-pneumonitis/), [Immune-related type 1 diabetes and diabetic ketoacidosis from checkpoint inhibitors](https://onco.cc/protocols/irae-diabetes/), [Neurological side effects of checkpoint inhibitors: myasthenia gravis, Guillain-Barré syndrome, meningitis and encephalitis](https://onco.cc/protocols/irae-neurological/), [Steroid taper after immunotherapy side effects, with Pneumocystis prophylaxis and adrenal checks](https://onco.cc/protocols/irae-steroid-taper-and-pjp/), [Thyroid inflammation and underactive thyroid from checkpoint inhibitors](https://onco.cc/protocols/irae-thyroid/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Avelumab](https://onco.cc/drugs/avelumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Hydrocortisone](https://onco.cc/drugs/hydrocortisone/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/), [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Immune-related endocrinopathies (thyroiditis, hypophysitis)](https://onco.cc/terms/immune-endocrinopathy/)
- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/)

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