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Immunotherapy Side Effects · Hormone & Endocrine Reactions
Adrenal Insufficiency — The Immune Effect That Can Be Fatal
Extreme tiredness, nausea, or dizziness during immunotherapy are usually put down to treatment fatigue — but they can be the first signs of adrenal insufficiency, a reduction in the adrenal glands' ability to make the hormones the body needs under stress, caused by an immune reaction to checkpoint-inhibitor immunotherapy. Left unrecognised, it can progress to an adrenal crisis, a genuine medical emergency. NCCN and ESMO guidance on immune-related adverse events lists adrenal insufficiency among the endocrine irAEs that need active screening, not a wait-and-watch approach.
Medically reviewed by Dr. Bharati Devi Gorantla, Medical Oncologist, MBBS · MD · DM (Adyar, Chennai) · ECMO · MRCP SCE (UK) · Last reviewed August 2026
- Vague symptoms are the danger — extreme tiredness, nausea, or dizziness on immunotherapy are easy to write off, until they progress to a crisis.
- Know the crisis signs — severe vomiting, fainting, or collapse during immunotherapy needs emergency care immediately.
- Report early symptoms — persistent tiredness or low blood pressure caught early is treated before it becomes an emergency.
- Carry emergency identification — a steroid card, and an injection kit if your team has prescribed one, can be lifesaving in a crisis.
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Emergency first
What Is an Adrenal Crisis, and How Urgent Is It?
An adrenal crisis is a medical emergency in which the body cannot produce enough of the hormone it needs to cope with physical stress, causing severe vomiting, profound weakness, severe dizziness or fainting, and dangerously low blood pressure — it can be fatal within hours without emergency treatment. If you or a family member on immunotherapy have these signs, call an ambulance or get to the nearest emergency room immediately; do not wait to see if it passes.
Go to the ER now, or call an ambulance, if you have any of these:
- Severe vomiting or diarrhoea, or being unable to keep fluids down
- Severe dizziness, fainting, or collapse
- Sudden severe abdominal, back, or leg pain
- Confusion, extreme drowsiness, or unresponsiveness
- A known diagnosis of adrenal insufficiency plus fever, injury, surgery, or another physical stress
For persistent tiredness, nausea, or dizziness that isn't one of the above, call the CION helpline the same day:
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Know the difference
What Are the Warning Signs of Adrenal Insufficiency on Immunotherapy?
The warning signs are easy to miss because they mimic ordinary treatment fatigue: persistent tiredness that doesn't improve with rest, low appetite, nausea, unexplained weight loss, salt craving, and dizziness or fainting when standing up. Because these build gradually, they are often dismissed for weeks — which is exactly why any combination of them during immunotherapy should be reported rather than watched.
| Feature | Everyday tiredness (treatment fatigue, poor sleep) | Possible adrenal insufficiency — needs review |
|---|---|---|
| Energy pattern | Improves somewhat with rest or a good night's sleep | Persistent, doesn't lift with rest, worsens over weeks |
| Appetite | Normal or mildly reduced | Noticeably low, often with weight loss |
| Standing up | No change or a brief head-rush | Marked dizziness or near-fainting on standing |
| Salt or savoury cravings | Absent | Can be present and unusual for the person |
| Nausea | Occasional, tied to meals or medicines | Persistent, sometimes with vomiting |
Timing matters
When Does Adrenal Insufficiency Typically Start After Immunotherapy?
Adrenal insufficiency related to immunotherapy has one of the most unpredictable timelines among immune reactions — it can appear a few weeks into treatment, many months in, or even after immunotherapy has already finished. This delayed, insidious pattern is a major reason it goes unrecognised until symptoms become severe or a crisis is triggered.
| Stage | What's typically happening |
|---|---|
| Typically starts | Can begin anywhere from a few weeks after starting immunotherapy to many months in — and, less commonly, even after treatment has ended. |
| Early phase | Vague tiredness, low appetite, mild nausea, sometimes weight loss — often mistaken for general treatment fatigue or low mood. |
| If unreported | Can progress to an adrenal crisis, often triggered by an infection, dehydration, surgery, or another physical stress the body can no longer cope with. |
This slow, easy-to-miss build-up is why adrenal insufficiency is treated as a harm-prevention priority even though the day-to-day symptoms feel unremarkable. There is no safe home-management step for persistent tiredness, nausea, or dizziness on immunotherapy — the correct response is always to get it checked, or go to the ER for the emergency signs above.
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What Must Be Carried at All Times if You Have Adrenal Insufficiency?
Carry a steroid emergency card or medical alert bracelet stating you have adrenal insufficiency and need urgent steroid treatment if unwell or unconscious, along with written sick-day instructions from your endocrinologist. If your team has prescribed an emergency injection kit, keep it with you and make sure someone travelling with you knows how to use it.
- 1
A steroid emergency card
States your diagnosis and that you need urgent steroid treatment in an emergency, even if you can't speak for yourself.
- 2
A medical alert bracelet or pendant
Visible to paramedics and emergency room staff at a glance, especially useful if you're unconscious or confused.
- 3
An emergency injection kit, if prescribed
Not every patient is prescribed one — follow your endocrinologist's guidance on whether you need it and who else should know how to give it.
- 4
Written sick-day dose rules
Your endocrinologist's instructions for adjusting your dose during fever, vomiting, infection, or before any procedure or surgery.
- 5
Your oncology and endocrine team's contact numbers
Saved in your phone and known to whoever travels with you, so they can be reached quickly if you're unwell.
A clinician-directed decision
Will Hormone Replacement Be Needed for Life?
For some patients, adrenal insufficiency caused by immunotherapy does not fully resolve and needs ongoing steroid replacement — but whether that's the case, and for how long, is decided by your endocrinologist and oncology team together, based on repeat hormone tests over time. It is never something to decide, start, or stop on your own. Our companion page, Will I Need Hormone Tablets for Life After Immunotherapy?, walks through how that decision is actually made.
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Common questions
Adrenal Insufficiency on Immunotherapy: Your Questions Answered
What are the warning signs of adrenal insufficiency on immunotherapy?
The warning signs are easy to miss because they look like ordinary treatment fatigue: persistent tiredness that doesn't improve with rest, low appetite, nausea, unexplained weight loss, salt craving, and dizziness or fainting on standing up. Low blood pressure and low blood sugar can also occur. Because these symptoms build gradually, they are frequently dismissed until they become severe — which is why any combination of them during immunotherapy should be reported to your oncology team rather than watched for a few weeks.
What is an adrenal crisis?
An adrenal crisis is a medical emergency in which the body cannot produce enough of the hormone it needs to cope with physical stress, causing severe vomiting or diarrhoea, profound weakness, severe dizziness or fainting, and dangerously low blood pressure. It can be fatal within hours if not treated immediately. If you or a family member on immunotherapy have these signs, call an ambulance or get to the nearest emergency room immediately — do not wait to see if it passes on its own.
What must I carry at all times if I have adrenal insufficiency?
Carry a steroid emergency card or medical alert bracelet stating you have adrenal insufficiency and need urgent steroid treatment if you're unwell or unconscious, along with written sick-day dose instructions from your endocrinologist. If your team has prescribed an emergency injection kit, carry it with you and make sure a family member knows how and when to use it. Keep your oncology and endocrine team's contact numbers saved and accessible to whoever travels with you.
How is adrenal insufficiency on immunotherapy diagnosed?
Diagnosis usually starts with a blood test measuring morning cortisol and, in some cases, other pituitary hormone levels, alongside checks on sodium, potassium, and blood sugar. Your team may also arrange a stimulation test or pituitary imaging if a related hormone gland is suspected to be affected. Because symptoms overlap with general treatment fatigue, blood tests are the only reliable way to confirm the diagnosis — a clinical impression alone isn't enough.
Will I need hormone replacement for life after immunotherapy?
For some patients, adrenal insufficiency caused by immunotherapy does not fully resolve and needs ongoing steroid replacement, but this is an individual decision your endocrinologist and oncology team make together, based on repeat hormone tests over time — it is never something to decide or stop on your own. Our companion page, Will I Need Hormone Tablets for Life After Immunotherapy?, walks through how that decision is actually made.
Can adrenal insufficiency develop after immunotherapy has already ended?
Yes. Unlike some immune reactions that appear early, adrenal insufficiency can develop months into treatment or even after immunotherapy has finished, because the underlying immune effect on the hormone-producing glands can be slow and insidious. This is why persistent tiredness, nausea, or dizziness should be reported to your care team even well after your last dose, rather than assumed to be unrelated to treatment.