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Adrenal Insufficiency

What is adrenal insufficiency?

Addison’s disease (also known as primary adrenal insufficiency or hypoadrenalism) is an endocrine (hormonal) disorder that occurs when the adrenal glands do not produce enough of their hormones. It can affect people of any sex or age although it is most common between the ages of 30 and 50 and, as in thyroid disease, it is more common in women than men.1

What part do the adrenal glands play in the body?

The adrenal glands sit on top of the kidneys and have two areas – the cortex (the outer layer) which is responsible for producing cortisol, aldosterone, DHEA and androgens and the medulla (the centre) which produces the stress hormones adrenaline and noradrenaline.2,3

The whole process starts with the hypothalamus, which is in the brain. The hypothalamus sends corticotrophin-releasing hormone (CRH) to the pituitary, a small gland at the base of the brain, which then stimulates the secretion of adrenocorticotropic hormone (ACTH) into the bloodstream.  The adrenal glands then detect this and produce cortisol. This process is called the hypothalamic-pituitary–adrenal (HPA) axis.  All three glands are constantly in touch with each other deciding whether or not the body needs more hormones or fewer hormones. This is called a negative feedback loop.4

Cortisol mainly helps the body respond to stress but it also helps maintain blood pressure and cardiovascular function; slow down the immune system’s inflammatory response; balance the effects of insulin in breaking down sugar for energy and regulates the metabolism of proteins, carbohydrates and fats.  Cortisol is essential for maintaining metabolism.5

Aldosterone is also essential – it keeps your levels of salt and water in the bloodstream normal to maintain blood pressure. 5

What are the causes of adrenal insufficiency?

There are two causes of adrenal insufficiency – primary adrenal insufficiency where the adrenal glands do not produce enough cortisol or secondary adrenal insufficiency where the pituitary gland does not produce enough ACTH.1,2

Primary adrenal insufficiency

The main cause of primary adrenal insufficiency (70-90%) is autoimmune where antibodies attack the cortex and slowly destroy it.1  There are other causes too which I won’t go into here.  According to the Pituitary Foundation, adrenal insufficiency occurs when at least 90% of the adrenal cortex has been destroyed causing the adrenal hormones to be very lacking.6

Patients with primary adrenal insufficiency have around 40-50% chance of developing other autoimmune conditions such as Hashimoto’s disease and Type 1 diabetes.7

Secondary adrenal insufficiency

Secondary adrenal insufficiency can be caused by a lack of ACTH, which can cause the adrenal glands to shrink. Lack of ACTH can be caused by long term steroid treatment such as prednisone (used to treat things such as rheumatoid arthritis, asthma etc).

It can also be caused by the removal of a tumour or when the pituitary gland either decreases in size or stops producing ACTH for reasons such as tumours or infections in the area, loss of blood flow to the pituitary, radiation treatment of pituitary tumours, removal of parts of the hypothalamus or the pituitary gland or damage to the pituitary gland such as a brain injury caused by a car accident or a fall causing damage to the brain.  Sheehan’s syndrome caused by massive haemorrhage during or after delivery of a baby can also cause secondary adrenal insufficiency.8,9

A brain injury can cause secondary adrenal insufficiency immediately after the injury or weeks, months or even years afterwards.10

What are the symptoms?

The main symptoms are weight loss, muscle weakness, fatigue, low blood pressure, loss of appetite and (in primary hypoadrenalism only) darkening of the skin.1

Other symptoms of adrenal insufficiency can include nausea, vomiting, diarrhoea, low blood pressure that drops further when a person stands up, causing dizziness or fainting, irritability and depression, craving salty foods, hypoglycaemia (low blood sugar), headache, sweating, irregular or absent menstrual periods.2

Because the symptoms of adrenal insufficiency can progress slowly, it can often be ignored until a stressful event such as surgery, a severe injury or infection, or pregnancy causes a sudden severe worsening of symptoms which is called an adrenal (or Addisonian) crisis. If not treated urgently it could prove fatal.11

How is it diagnosed?

Diagnosing either of these conditions can be difficult especially in the early stages.  Your doctor will take your medical history and possibly check your blood pressure whilst you first lie down and then stand up again to see if you have postural hypotension (low blood pressure when you change position).  If your doctor is concerned, he will then organise a cortisol blood test along with sodium and potassium tests.

If cortisol levels are low, you will usually be referred to an endocrinologist who will do further blood tests, and if primary adrenal insufficiency is being considered, this may include measuring aldosterone, ACTH, glucose and adrenal antibodies and an ACTH stimulation test (see below).  If these tests show lack of cortisol secretion from the adrenal glands and if antibodies to the adrenal are negative then it will usually be necessary to have a CT or MRI scan of your adrenal glands to check for other causes.12

What is an ACTH stimulation (synacthen) test?

There are two different types of ACTH test.  The short synacthen test (SST) and the long synacthen test (LST) although it’s rare that the LST is used now.

If you have the SST, the first thing that will happen is that a blood cortisol test is taken.  You will then be given an intravenous (IV) injection of a synthetic form of ACTH (synacthen).  30 minutes later another cortisol blood test is taken. The results of these tests will determine whether you have adrenal insufficiency.

If the LST is done, more cortisol tests are done at intervals after the ACTH is given.13

The ACTH test can also differ in the amount of synacthen used – the 1mcg synacthen test and the 250mcg synacthen test. Research shows that there is not much difference between them in respect of results but there are limitations in respect of the 1mcg dose so it is rarely used now.14

The normal response to synacthen is a rise in cortisol levels in the blood.2  However, patients with primary adrenal insufficiency will have a high ACTH but low cortisol and aldosterone levels.

Patients with secondary adrenal insufficiency usually have either a low normal or low level of ACTH in the blood, but low cortisol and normal aldosterone levels.15

Some patients with secondary adrenal insufficiency may ‘pass’ a synacthen test, and is important that any test result is considered in the context of the clinical situation. The consensus of the Pituitary Foundation Medical Committee members which includes adult consultant endocrinologists and a paediatric consultant endocrinologist is, “We use the SST for the vast majority of patients, but consider its limitations on an individualised basis, as we do for every test in clinical endocrinology. Any test results need to be considered in the context of clinical assessment.”

The Pituitary Foundation states on their website, “Please note: for patients with symptoms that may suggest cortisol deficiency, a ‘pass’ on a SST, may not always mean that cortisol deficiency is excluded and that with persisting symptoms, referral to an endocrinologist is recommended, where testing may be carried out with alternatives such as the glucagon test or insulin stress test. Choosing the correct test and then interpreting it correctly and considering alternatives is why endocrinology cannot be simply ‘a protocol’. No test is perfect and that consideration for further opinion is always an important option.”16

The glucagon and insulin stress tests are part of a collection of tests called “dynamic function tests” (as is the ACTH test) because they stimulate another hormone in the body.17

If the ACTH test concludes that you don’t have adrenal insufficiency and you are concerned about the result, discuss having further stimulation tests with your clinician.

There will be a doctor present to monitor you throughout the test, and the test will be stopped if your doctor has any concerns.18


The usual treatment for adrenal insufficiency is hydrocortisone to replace the cortisol. Alternatively, you may be given prednisolone or dexamethasone, although these are less commonly used.  If you have low aldosterone this is replaced with fludrocortisone.2,19

In stressful situations such as infections or an accident you will need to take extra medication (possibly by injection) to avoid an adrenal crisis.19

You can lead a normal life once on treatment although you should always remember to take your medication.   Your endocrinologist will monitor you, usually every 6-12 months.

It’s always a good idea to have something on your person alerting others of your condition such as a medical alert bracelet or a Medipal card.

For more support check out our online community:



  1. NHS Overview – Addison’s disease
  2. You and Your Hormones – Addison’s disease
  3. You and Your Hormones – Dehydroepiandrosterone
  4. You and Your Hormones – Hypothalamus
  5. You and Your Hormones – Adrenal glands
  6. NHS – Causes – Addison’s disease
  7. info – Adrenal Insufficiency and Addison’s disease
  8. Pituitary Network Association – Adrenal Insufficiency (Addison’s disease)
  9. Society for Endocrinology – Adrenal Insufficiency – Patient Booklet
  10. A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity?
    J Neurotrauma. 2013 Aug 15;30(16):1426-33
    Tanriverdi F, De Bellis A, Ulutabanca H, Bizzarro A, Sinisi AA, Bellastella G, Amoresano Paglionico V, Dalla Mora L, Selcuklu A, Unluhizarci K, Casanueva FF, Kelestimur F.
  11. Addison’s disease
    BMJ 2009;339:b2385
  12. NHS – Diagnosis – Addison’s disease
  13. info – Synacthen Test
  14. CTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis
    The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 2, 1 February 2016, Pages 427–434
    Naykky Singh Ospina Alaa Al Nofal Irina Bancos Asma Javed Khalid BenkhadraEkta Kapoor Aida N. Lteif Neena Natt M. Hassan Murad
  15. Labcorp
    ACTH Stimulation Test (Cosyntropin)
  16. The Pituitary Foundation – Patient Stories – Jill Mizen’s journey to diagnosis,-diagnosis-and-tests/tests/
  17. Brighton and Sussex Pathology
    Dynamic Function Tests
  18. University Hospital Southampton NHS Foundation Trust Patient Information Factsheet – Insulin Stress Test
  19. NHS – Treatment – Addison’s disease

Date updated: 15.04.21 (V1.4)
Review date: 14.02.22

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