How do the adrenal glands work?

The adrenal glands are responsible for the hormones that govern your stress response – fight or flight. We look at them in more detail, including why your doctor may be unlikely to diagnose you with adrenal fatigue.

• What are the adrenal glands and what do they do?
• What can go wrong with the adrenal glands?
• Cushing’s disease
• Addison’s disease
• What is adrenal fatigue?

What are the adrenal glands and what do they do?

The adrenal glands are two triangular-shaped glands that sit on top of the kidneys [1]. They are best known for producing the hormones that govern our stress response, but they also have an important role to play in metabolism, immune function, and regulation of blood pressure.

The adrenal glands are made up of two parts, the cortex and the medulla, and each is responsible for producing different hormones.

• The adrenal cortex is the outer part of the adrenal glands and is responsible for producing hormones that are vital for life including cortisol and aldosterone (that helps regulate blood pressure and salt levels).

• The adrenal medulla is the inner part of the adrenal glands and is responsible for producing catecholamines, the hormones that are released in our “fight or flight” response.

What hormones are produced in the adrenal glands?

Hormones produced in the adrenal cortex:

1. Cortisol (a glucocorticoid) is the best-known hormone of the adrenal cortex.

Cortisol has a role in:

• Metabolism, signalling the body when to convert fat, proteins, and carbohydrates into glucose for energy. 
• The body’s stress response, releasing glucose to provide an energy boost in an emergency and shuts down non-essential bodily functions (digestion, immune function, reproduction) to preserve energy.

2. Aldosterone (a mineralocorticoid) helps the body regulate blood pressure and regulate the level of electrolytes (sodium and potassium) in the blood.
3. Androgens, like DHEA, are also produced by the adrenal cortex. These are weak hormones that are converted to male hormones in the testes and female hormones in the ovaries.

Hormones produced in the adrenal medulla:

1. Adrenaline (epinephrine) is a neurotransmitter and hormone that is released into the bloodstream when a person is under stress or in danger. It aims to make them physically more able to deal with the threat. Once the perceived threat has gone, adrenaline levels go back to normal.

Adrenaline is responsible for:

• Increasing blood sugar for energy
• Causing the heart muscle to contract faster and harder to get more blood to the muscles and the brain
• Relaxing the airways to get more oxygen to the lungs.

2. Noradrenaline (norepinephrine) is very similar to adrenaline but also acts to constrict blood vessels to increase blood pressure in times of stress.

What can go wrong with the adrenal glands?

Adrenal disorders are usually caused by the over or under-production of adrenal hormones, which can be caused by adrenal or pituitary problems.

Adrenal disorders include Cushing’s disease and Addison’s disease.

Cushing’s disease

Cushing’s disease or Cushing’s syndrome is caused when the body produces too much cortisol [2].

This can be caused by a pituitary disorder (often a tumour) which causes too much ACTH to be produced which overstimulates the adrenal glands to produce cortisol, or by a tumour on the adrenal glands themselves.

Cushing’s can also be caused by taking steroid medication, or by an ACTH-producing tumour elsewhere in the body. Cushing’s is rare, and mostly affects women between the ages of 30 and 40.

What are the symptoms of Cushing’s disease?

Cushing’s disease causes many symptoms, including [2]:

• A fatty “hump” on the back of the neck and shoulders
• Weight gain around the torso (but not arms and legs)
• A round, red puffy face
• Purple stretch marks
• Acne
• High blood sugar/diabetes
• Irregular periods
• Loss of libido
• Infertility
• Excessive hair growth on the face and body (women)
• Mood swings and depression
• Low bone density

How is Cushing’s disease diagnosed?

Cushing’s disease can be difficult to diagnose, especially as some of the symptoms are common with other conditions.

Typically, a diagnosis will be made with a series of tests to measure cortisol production over a day (urine, saliva, or blood tests), a physical examination or scans to detect whether there is pituitary or adrenal tumour.

Sometimes, a cortisol-mimicking drug will be given, which in someone without Cushing’s would cause a reduction in cortisol. In people with Cushing’s disease, this has little to no effect.

How is Cushing’s disease treated?

Treatment will depend on what is causing the production of excessive cortisol.

This can mean surgery to remove a pituitary or adrenal tumour, or even removal of the adrenal glands themselves. If a steroid treatment has caused the problem, treatment may include a gradual reduction of the treatment.

Medication can also be prescribed which suppresses cortisol production, although this is normally a short-term solution.

Addison’s disease

Addison’s disease is also known as adrenal insufficiency and occurs when your adrenal glands don’t produce enough hormones [3].

In primary adrenal insufficiency, the problem is caused by damage to the adrenal cortex, usually because of an autoimmune disease where the body starts attacking its tissues.

Primary adrenal insufficiency affects the production of both cortisol and aldosterone and causes wide-ranging symptoms including:

• Weight loss
• Areas of dark skin
• Low blood pressure

Secondary adrenal insufficiency is normally caused by a pituitary problem (usually a tumour) which results in a reduced production of ACTH which then fails to stimulate the adrenal glands to produce cortisol and androgens (aldosterone is unaffected).

Taking steroid medication (e.g. for asthma or rheumatoid arthritis) can also affect adrenal function. The pituitary gland, which normally regulates the output of adrenal hormones, senses that there are normal levels of steroid hormones in the blood (due to the medication) and stops sending signals to the adrenal glands to make more. This doesn’t usually cause problems until a time of severe stress (when insufficient hormones are released to manage the stress response), or if steroid medication is stopped too quickly.

Addison’s disease can develop slowly and in its early stages can be mistaken for other conditions. However, when more advanced, or if symptoms deteriorate sharply (adrenal crisis), Addison’s disease can be life-threatening.

What are the symptoms of Addison’s disease?

• Unintended weight loss
• Loss of appetite
• Hyperpigmentation (darkening of the skin)
• Low blood sugar
• Low blood pressure
• Fatigue
• Salt cravings
• Increased thirst
• Irritability and depression
• Muscle weakness and aches and pains
• Nausea and gastrointestinal problems
• Irregular menstrual periods and loss of pubic and underarm hair

How is Addison’s disease diagnosed?

Addison’s disease is normally diagnosed through a combination of a physical examination, including a blood pressure test to check for low blood pressure, and tests (blood, urine, or saliva) to measure levels of adrenal and pituitary hormones.

Tests for cortisol, ACTH, aldosterone, and DHEA, may all be used to make a diagnosis. Tests for sodium, potassium and glucose can help to distinguish between primary and secondary adrenal insufficiency.

For confirmation, a synacthen test is performed. Synacthen is a synthetic form of ACTH and should stimulate the adrenal glands to make cortisol. If, after an injection of synacthen adrenal hormones remain low, then adrenal insufficiency is confirmed. An adrenal antibody test can confirm whether an autoimmune disorder is causing the adrenal glands to fail.

How is Addison’s disease treated?

Addison’s disease or primary adrenal insufficiency is normally treated by replacing the adrenal hormones that are missing [3].

Hydrocortisone is a synthetic hormone that is used to replace cortisol. If aldosterone is also affected then a replacement (fludrocortisone) is prescribed alongside a recommendation to increase salt in the diet if needed.

What is adrenal fatigue?

Adrenal fatigue is a theory suggesting that, when overloaded, your adrenal glands fail to produce the right amount of cortisol for the demands of the body at the right time of day. It’s thought to occur if you suffer from an acutely stressful event, or suffer from prolonged, chronic stress, meaning the glands become ineffective.

Normally, cortisol levels are highest in the morning on waking, and decline naturally through the day until their lowest level, just before bed. We wake with energy and vitality to take on the day ahead and fall asleep in an easy and relaxed state at bedtime. If the cortisol cycle is broken, this can lead to you feeling exhausted on waking and alert when you’re supposed to be going to sleep.

What symptoms are attributed to adrenal fatigue?

The symptoms that are attributed to adrenal fatigue are very general and can be experienced with other conditions [4].

• Craving salt and sugar
• Retaining fat around your middle
• Low mood and depression
• Brain fog
• Fatigue
• Weight gain
• Body aches

What is the controversy around adrenal fatigue?

Adrenal fatigue would not normally be diagnosed by a conventionally trained doctor. The Society of Endocrinologists has stated that there is no evidence that this condition exists and it is not a recognised medical condition. 

While there are conditions that do affect the adrenal glands, like Addison’s Disease (primary adrenal insufficiency) and Cushing’s Syndrome (caused by the over-production of cortisol), there is no medical evidence that overloading the adrenal glands through stress causes any functional problems which could lead to adrenal insufficiency.

Most endocrinologists suggest that when the body experiences stress, the adrenal glands increase their production of cortisol rather than reduce it.

How is adrenal fatigue diagnosed?

There is no test that can tell whether you have adrenal fatigue. Instead, adrenal fatigue is much more likely to be diagnosed by an alternative or natural health practitioner than by a GP or endocrinologist. 

A 24-hour salivary adrenal test has been used to check the adrenal glands’ function. However, many doctors (including adrenal gland specialists) do not consider the test to be appropriate to measure the function of the glands.

In most cases, they will treat it by natural methods such as nutrition and lifestyle, rather than a course of drugs or hormone replacement. They will typically use non-invasive saliva testing to assess cortisol rhythm. Cortisol levels that remain flat all day or even rise at bedtime would signal to them that the adrenal glands are impaired.

What are the risks of being diagnosed with adrenal fatigue?

Problems can arise if symptoms, which are general and non-specific, are attributed to adrenal fatigue when in fact they are early signs of something more serious or another treatable condition.

Conditions that may be attributed to adrenal fatigue because of similar symptoms include anaemia and thyroid problems. Please remember it is also always important to talk to your GP and rule out any more serious conditions before seeking an alternative diagnosis.

Most alternative practitioners will treat adrenal fatigue through lifestyle changes aimed at:

• Reducing stress
• Establishing a good bedtime routine
• Getting a full night’s sleep
• Eating an unprocessed diet rich in vegetables and whole grains
• Taking time in the day to meditate and re-charge batteries
• Taking regular moderate exercise

This is sensible advice for anyone who is looking to improve their lifestyle. As it advocates many healthy habits, this advice can also improve symptoms associated with chronic stress.

In some cases, practitioners will recommend the use of supplements containing dried adrenal cortex. This contains the hormone hydrocortisone and can cause symptoms that resemble Cushing’s disease if excessive amounts are taken.

Where next?

Learn more about other glands and their role in hormone health:

1. The hypothalamus

2. The pituitary gland 

3. The gonads

4. The thyroid and parathyroid glands

5. The pancreas, pineal and thymus

6. Hormone blood test buying guide

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References

1. Hopkinsmedicine.org. 2022. Adrenal Glands. [online] Available at: <https://www.hopkinsmedicine.org/health/conditions-and-diseases/adrenal-glands#:~:text=Adrenal%20glands%2C%20also%20known%20as,stress%20and%20other%20essential%20functions.> [Accessed 12 July 2022].
2. nhs.uk. 2022. Cushing's syndrome. [online] Available at: <https://www.nhs.uk/conditions/cushings-syndrome/#:~:text=Cushing's%20syndrome%20is%20a%20condition,serious%20if%20it's%20not%20treated.> [Accessed 12 July 2022].
3. nhs.uk. 2022. Addison's disease. [online] Available at: <https://www.nhs.uk/conditions/addisons-disease/> [Accessed 12 July 2022].
4. Willacy, D., 2022. Adrenal Fatigue | Health. [online] Patient.info. Available at: <https://patient.info/hormones/adrenal-fatigue> [Accessed 12 July 2022].