Introduction
Immunotherapy has transformed how many cancers are treated. It is used in the “adjuvant” setting after surgery for some people, and also used to control the disease when it has spread to other sites in the body. ‘Adjuvant’ is an additional treatment to eliminate any remaining cancer cells to reduce the risk of it returning at a future date.
Increasingly, it is being used in the 'neoadjuvant setting' – which means before surgery. Immunotherapy is now used to treat many types of cancers. While it can be highly effective, it can also affect the body, including the adrenal glands, in unexpected ways.
This guide explains what immunotherapy is, why it can lead to adrenal insufficiency, and what that means for you. It also answers common questions patients have when they are navigating both cancer treatment and hormone (or “endocrine”) health.
What is immunotherapy?
Immunotherapy (IO) is a type of treatment that helps your immune system recognise and attack disease, most commonly cancer. Instead of directly targeting tumours (like chemotherapy does), it “switches on” your immune system so it can do the job itself. We sometimes describe it as “taking the brakes off” the immune system, which is why the drugs are also known as “checkpoint inhibitors”. This activation of the immune system explains why it can cause a range of ‘inflammation-type’ side effects.
It is used to treat a wide range of conditions, including:
- Melanoma
- Lung cancer
- Kidney cancer
- Upper gastrointestinal cancer
- Some blood cancers
- Increasingly, many other tumour types and subgroups of cancer e.g. those affected by Lynch Syndrome
What are the advantages of immunotherapy?
- It can produce long-lasting responses.
- It is often better tolerated than chemotherapy.
- In some cases, it can lead to durable remission.
- Some of the drugs are now available as subcutaneous (meaning 'under the skin') injections that take only a matter of minutes to give every 4 or 6 weeks; a regimen that is much easier to manage than some other treatment options.
Further optional reading about Immunotherapy: 'It's incredible, like science fiction': How a new wave of immunotherapy is eliminating cancers - BBC Future(Apr 2026, Jamie Ducharme)
Why can immunotherapy cause adrenal insufficiency?
IO works by boosting the immune system, but sometimes this boost goes too far. The immune system may begin to cause inflammation of healthy tissues, including hormone-producing glands.
When this affects the adrenal glands that sit above the kidneys (or the pituitary gland in the brain that controls them), it can lead to adrenal insufficiency. This is a condition where your body does not produce enough cortisol and other steroid hormones that are essential for life.
If the IO affects the pituitary gland, then it will be the levels of adrenocorticotropic hormone (ACTH) that are affected. This is known as hypopituitarism.
Adrenal insufficiency caused by the immune system attacking the adrenal glands is called Primary Adrenal Insufficiency. Adrenal insufficiency caused by a lack of ACTH from the pituitary gland is called Secondary Adrenal Insufficiency.
What are the symptoms of adrenal insufficiency?
Fatigue that doesn't improve with rest- Dizziness or feeling faint
- Nausea or loss of appetite
- Weight loss
- Low blood pressure - which can cause dizziness, light-headedness or fainting
- Muscle weakness
How do I know if my symptoms are from adrenal insufficiency?
Adrenal insufficiency symptoms can overlap with cancer treatment side effects or even other life changes (like menopause).
As the common symptoms (shown above) are non-specific, blood tests are usually needed to confirm the cause. However, we are trying to raise awareness with immunotherapy patients that if they develop any of these vague symptoms and are fatigued, it is very important to get it checked and to continue to monitor the situation if things are not improving. Adrenal insufficiency from IO can even occur after the immunotherapy treatment has finished, so raising awareness is key.
Scientists who have reviewed cases of IO adrenal insufficiency describe fatigue, anorexia/loss of appetite, headache, nausea/vomiting, weakness, and drowsiness/lethargy as the most prevalent symptoms, while less common symptoms included abdominal pain, syncope (fainting) and insomnia.
As most cancer centres have a 24-hour helpline and a Same Day Emergency Care clinic, if you have these symptoms and they are not going away, it is recommended to access the urgent helpline and not to wait: low cortisol symptoms quickly improve once you start treatment.
How is adrenal insufficiency diagnosed?
Blood tests are needed to confirm adrenal insufficiency and its cause. These will be taken by your oncology team or wider health care team members.
These may include:
- Blood cortisol levels are taken at 9 am, due to the “diurnal” or daily rhythm of cortisol levels that typically peaks at 9 am. I often think of this as "we are getting ready for the day".
- Adrenocorticotropic hormone (ACTH) levels; a hormone that controls cortisol
- A Short Synacthen Test, which checks adrenal function and that the adrenal glands can still respond to a synthetic stimulus from ACTH.
How is adrenal insufficiency treated?
Adrenal insufficiency can be effectively treated with daily replacement steroid medication (a glucocorticoid), taken at set times each day.
It is a time-critical medication, which means it is one that you need to take promptly to avoid symptoms of low cortisol. Usually, this medication will be hydrocortisone (chemically identical to cortisol in the body) taken twice or three times a day. Sometimes prednisolone (similar chemically, but longer acting than natural cortisol in the body), is prescribed and will usually be taken once a day.
Inherent with adrenal insufficiency is a risk of adrenal crisis: a life-threatening but treatable condition, when the body experiences very low cortisol. Emergency treatment is with a hydrocortisone injection into the muscle or intravenously, followed by fluids and monitoring.
Explore adrenal insufficiency medication, adrenal crisis and emergency hydrocortisone injections in more detail below.
At certain times, the body needs more cortisol than at others. This is particularly during times of physical stress (e.g. illness or injury) or extreme psychological stress (e.g. bereavement). At these times, the usual replacement glucocorticoid (steroid) medication you take is not enough, so you need to increase your dose (known as 'updosing', 'stress dosing' or 'sick day dosing').
Yes, when you are diagnosed with adrenal insufficiency, you are given:
A huge thank you to Professor Helen Winter, Clinical Director for the Somerset, Wiltshire, Avon and Gloucestershire (SWAG) Cancer Alliance, hosted by Bristol NHS Foundation Trust, for authoring this article and to Dr Georgina Russell, Consultant Endocrinologist at Bristol NHS Foundation Trust, for her collaboration.
