What is cortisol? What it does, how it is controlled and how it is measured

Cortisol is a steroid hormone made by your adrenal glands, which sit above the kidneys. It is the body's main glucocorticoid, one of a family of hormones that help control how you use energy, and it comes from a layer of the adrenal cortex called the zona fasciculata.¹ A chain of signals from the brain, the hypothalamic-pituitary-adrenal (HPA) axis, decides how much is made.¹ Cortisol is often called the stress hormone, but it is busy every hour of the day, helping to manage your blood sugar, immune system and blood pressure. Too much or too little over a long period causes real illness, which is why doctors measure it.

What cortisol does in your body

Cortisol acts on almost every tissue. Its main effects are on metabolism, immune activity, the heart and blood vessels, and the stress response.¹

• Making energy available. It raises the amount of glucose (sugar) available in the blood and releases fuel by breaking down protein and fat. The breakdown of fat is called lipolysis.¹
• Regulating inflammation. It changes inflammatory signalling and immune activity.¹
• Supporting blood pressure. It helps maintain cardiovascular tone, the background tension in the heart and blood vessels.¹
• Driving the stress response. It is the end product of the body's main hormonal stress system, described below.¹

Levels are never constant. In people who sleep at night, cortisol starts rising from about 4 am, peaks within three hours of waking and falls through the day to its lowest point around midnight. Smaller pulses arrive every one to two hours on top of that curve.² Stress, exercise, pregnancy, very hot or cold temperatures and some medicines, including birth control pills, can all change it.³ The cortisol daily rhythm guide covers the daily cycle in detail.

How your body controls cortisol: the HPA axis

The HPA axis links three places: the hypothalamus in the brain, the pituitary gland just beneath it, and the adrenal glands.¹ It works in four steps.

1. The hypothalamus sends the first signal. Nerve cells in a region called the paraventricular nucleus release corticotrophin-releasing hormone (CRH). During stress, this is driven mainly by nerve signals from other parts of the brain.⁴
2. The pituitary relays it. The pituitary gland makes adrenocorticotrophic hormone (ACTH), which travels in the blood to the adrenal glands and tells them how much cortisol to make.³
3. The adrenal glands respond. The adrenal cortex releases cortisol into the bloodstream.¹
4. Cortisol switches the system off. As levels rise, cortisol acts back on the brainstem, on parts of the brain's limbic system such as the hippocampus, and directly on the CRH-producing cells, turning the signal down. This is called negative feedback.⁴

Negative feedback is what normally ends a stress response. Long-running stress can change the system, though, and not always in the same way. In some people the HPA axis produces too much cortisol all the time. In others it reacts more strongly to each new stressor. Which pattern appears depends on how long, how intense and how frequent the stress is and what kind it is. It also depends on genes, early-life experience, environment, sex and age.⁴ Read more in cortisol and stress.

Free and bound cortisol

Most of the cortisol in your blood is not active. About 90 per cent is bound to a carrier protein called corticosteroid-binding globulin (CBG), about 4 to 6 per cent is bound to other proteins such as albumin, and only about 4 to 6 per cent circulates free.² The free fraction is the active part.

This matters for testing. A standard blood test measures total cortisol, bound and free together, so anything that changes CBG changes the result. Saliva and urine tests measure free cortisol and are not affected by changes in CBG.² Cortisol passes from blood into saliva in well under five minutes, and salivary cortisol is directly proportional to free cortisol in the blood.⁵

Two examples show how big the effect can be. Oral oestrogen, found in many contraceptive pills and some HRT, raises CBG, and so do the high oestrogen levels of pregnancy. The result is a falsely high total cortisol.² In one study, women taking oral oestrogen had 67 per cent higher total blood cortisol than women who were not (660.9 against 395.4 nmol/L), while their saliva cortisol was much the same.⁶ The opposite happens in critical illness with low albumin: total cortisol was lower (435 against 633 nmol/L), but the active free cortisol was almost identical (140 against 143 nmol/L).²

What happens when there is too much cortisol

Long-term excess cortisol causes Cushing's syndrome. Its typical effects are fat building up around the middle of the body, muscle wasting, high blood pressure and difficulty controlling blood sugar.¹ The NHS lists more fat on the neck, upper back, chest and tummy with thin-looking arms and legs, a red, round face, easy bruising and stretch marks, and weakness in the muscles at the top of the arms and legs. Mood changes, low sex drive and irregular periods are common too.⁷

Cushing's syndrome is rare, and much more common in women than in men. The most common cause is taking high-dose steroid medicine, such as prednisolone or hydrocortisone, for a long time. Less often, a growth in the pituitary gland is responsible, which is called Cushing's disease.⁷ Left untreated, it raises the risk of heart attack, stroke, type 2 diabetes, blood clots and osteoporosis.⁷ See high cortisol symptoms and how Cushing's is tested for.

What happens when there is too little cortisol

Too little cortisol is called adrenal insufficiency. In Addison's disease, the primary form, the adrenal cortex is destroyed, and in Western countries about 90 per cent of cases are autoimmune.⁸ Low cortisol causes fatigue, low blood pressure and weight loss, and in Addison's disease darkening of the skin.¹ The NHS also lists loss of appetite, tummy pain, feeling sick, salt craving, dizziness on standing, muscle weakness and cramps, and anxiety and depression.⁹

A more common route is long-term steroid treatment. At least 1 per cent of the population takes glucocorticoid medicines long term, and these people are at risk of their own adrenal glands not making enough cortisol.¹⁰ MedlinePlus lists long-term steroid use, or stopping it suddenly, as the most common cause of abnormal cortisol levels.³

Very low cortisol can lead to an adrenal crisis, which is a medical emergency. If someone with Addison's disease suddenly gets worse, with severe dizziness, vomiting, severe tummy pain, confusion, drowsiness or collapse, call 999.⁹ See low cortisol symptoms and testing for Addison's.

How cortisol is measured

Because cortisol changes from hour to hour, each type of test answers a different question. There are four main ones.

• Blood. Measures total cortisol at one moment. For suspected low cortisol, NICE advises a sample between 8 and 9 am, close to the daily peak.¹¹ Having blood taken can itself raise cortisol, in somewhere between about 30 and 47 per cent of people.¹² See the blood cortisol test.
• Saliva. Measures free cortisol at the moment you give the sample, and can be collected at home. A sample taken late at night, when cortisol should be at its lowest, is one of the first-line tests for Cushing's syndrome.¹³ See the saliva cortisol test.
• Urine. A 24-hour collection measures the free cortisol passed over one day. It smooths out the hours, but in people with Cushing's disease it still varied by about 52 per cent from one collection to the next.¹⁴ See the urine cortisol test.
• Hair. Hair grows about 1 cm a month and takes up cortisol as it grows, so the 3 cm nearest the scalp reflect roughly the last three months.¹⁵ See the hair cortisol test.

If your question is what your cortisol has been doing over the long term, hair answers it most directly. A hair test is the most accurate way to measure long-term cortisol from a single sample, and it is far more consistent from one test to the next. In one study, the same people's hair cortisol correlated at r = 0.84 from one month to the next, against 0.38 to 0.61 week to week for saliva and 0.59 to 0.68 for 24-hour urine.¹⁶ It does not vary with the time of day the sample is cut.¹⁷ A blood sample, by contrast, depends heavily on timing: in healthy people, blood cortisol peaks at around 8.30 am and falls to below 2 µg/dL around midnight.¹⁸

The tests are not interchangeable, and each has its place. Doctors diagnose Cushing's syndrome with late-night saliva, 24-hour urine and dexamethasone suppression tests.¹³ They diagnose adrenal insufficiency with blood tests, the standard being the short Synacthen test.¹⁹ Hair is not part of those guidelines. It measures your long-term level rather than diagnosing or ruling out a condition. To work out which test fits your question, see which cortisol test, cortisol tests compared and normal cortisol levels.