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What is it?

Adrenal insufficiency is a disorder characterised by underactive adrenal glands and an insufficient production of the hormones cortisol and, sometimes, aldosterone. The adrenal glands are small organs located on top of each kidney. They consist of an inner layer called the medulla and an outer layer called the adrenal cortex. In the body, the hypothalamus, the pituitary glands, and the adrenal glands work together to produce hormones that control many body systems. If any part of their signalling and feedback system is not working it can cause major disruptions and illness within the body.

Cortisol is a glucocorticoid hormone, produced by the adrenal cortex. Among its many roles, cortisol affects the metabolism of carbohydrates, proteins, and fats, affects glucose levels in the blood, acts as an anti-inflammatory agent, and helps the body react to stress. Aldosterone, a mineralocorticoid hormone that is also produced by the adrenal cortex, manages the salt and potassium balance in the blood. Without enough of these two hormones, the body becomes weak and dehydrated, unable to maintain an adequate blood pressure or to respond properly to stress.

Adrenal insufficiency affects about 1-4 people per 100,000. It is found in patients of all ages and affects both males and females equally.


Addison’s disease is a term used as a synonym for primary adrenal insufficiency, caused by damage to the adrenal cortex; it does not present itself until 80 - 90% has been destroyed. The term “Addison’s disease” is often used incorrectly to refer to both primary and secondary adrenal insufficiency.

About 70% of primary adrenal insufficiency is due to an autoimmune process. About 30% of the time the adrenal damage is due to other causes, such as: tuberculosis (a common cause in areas of the world where tuberculosis is more prevalent); bacterial, viral and fungal infections; adrenal haemorrhage; and the spread of cancer into the adrenal glands. Rarely, it may be due to a genetic abnormality of the adrenal glands.

Secondary adrenal insufficiency is due to a decrease in the production of the pituitary hormone ACTH (adrenocorticotropic hormone). ACTH is a pituitary messenger - it tells the adrenal cortex to produce cortisol. If there is insufficient ACTH - due to pituitary damage, a pituitary tumour, or some other cause -- then cortisol production is not stimulated. Secondary adrenal insufficiency can also arise when corticosteroid therapy (such as prednisone, which may be given to relieve inflammation in conditions such as rheumatoid arthritis) is abruptly halted. These treatments suppress natural cortisol production and it can take several weeks or months for normal production to resume. With secondary adrenal insufficiency, aldosterone production is usually not affected.

Signs and symptoms

The symptoms associated with adrenal insufficiency are often vague and nonspecific. They may emerge slowly, first appearing during times of stress, then increasing in intensity over a period of several months. Symptoms may include:

  • Fatigue and weakness
  • Abdominal pain
  • Dehydration (only in Addison’s disease)
  • Diarrhoea or constipation
  • Dizziness and fainting
  • Fatigue
  • Hyperpigmentation (only in Addison’s disease - dark patches of skin, especially in the folds of the skin. Sometime black freckles on the forehead and face and/or discolouration around areas such as the nipples, lips, and rectum)
  • Joint and muscle aches
  • Low blood pressure
  • Hypoglycaemia
  • Salt craving (only in Addison’s disease)
  • Vomiting
  • Weight loss
  • Decreased body hair

Sometimes, however, the signs and symptoms of adrenal insufficiency may appear suddenly. About 25% of the time, adrenal insufficiency is diagnosed during a crisis (also called an Addisonian crisis). This crisis may be caused by a period of increased stress, trauma, surgery, or a severe infection. If left untreated it can be fatal. In acute adrenal failure (Addisonian crisis), the signs and symptoms may include:

  • Low blood pressure
  • Severe pain in the lower back, abdomen or legs
  • Severe vomiting and diarrhoea, leading to dehydration
  • Shock
  • Kidney failure
  • Loss of consciousness

Tests and treatment

Symptoms such as hyperpigmentation, weakness, low blood pressure, and salt cravings may cause a doctor to suspect adrenal insufficiency, especially if these symptoms appear to worsen during periods of stress. Laboratory tests are used to determine whether adrenal insufficiency is present, to distinguish between primary and secondary insufficiencies, and to try to determine the underlying cause of the condition. Tests are also ordered to evaluate a patient’s electrolyte balance, glucose level, and kidney function. During an Addisonian crisis, they are ordered to determine the severity of the imbalances (the glucose and sodium will often be low, the potassium high) and to monitor the effectiveness of treatment.

Laboratory tests

  • Cortisol. ACTH levels normally vary in the blood, peaking in the early morning. If the adrenal gland is either not functioning normally or not being stimulated by ACTH, then cortisol levels will be consistently low. Cortisol levels are used, along with ACTH and ACTH stimulation tests, to help diagnose adrenal insufficiency.
  • ACTH is a pituitary hormone that signals the adrenal glands to produce cortisol. This test is primarily ordered as a baseline test to evaluate whether or not the pituitary is producing appropriate amounts of ACTH. In a patient with adrenal insufficiency, low ACTH levels indicate secondary adrenal insufficiency, while high levels indicate primary adrenal insufficiency (Addison’s disease). The ACTH test is often ordered along with the ACTH stimulation test.
  • ACTH stimulation test. This test involves measuring the level of cortisol in a patient’s blood before and after an injection of synthetic ACTH. If the adrenal glands are functional, cortisol levels will rise in response to the ACTH stimulation. If they are damaged, then their response to ACTH will be minimal.
  • Aldosterone. Blood or urine aldosterone levels are measured to help diagnose Addison’s disease - to determine whether the adrenal gland is producing aldosterone. If the levels are low, it is another indication that the patient may have a primary adrenal insufficiency.
  • Electrolytes (sodium, potassium, chloride and bicarbonate) are measured to help detect and evaluate the severity of an existing electrolyte imbalance, and to monitor the effectiveness of treatment. Electrolytes may be affected by many conditions; with Addison’s disease, the sodium, chloride, and bicarbonate levels are often low, while the potassium level may be very high.
  • Urea and creatinine are tests done to monitor kidney function.
  • Glucose levels may be very low during an Addisonian crisis. Glucose may be ordered help monitor a patient during a crisis.

Occasionally used tests

  • Insulin-induced hypoglycaemia test. Occasionally a doctor will order this test to assist in the detection of secondary adrenal insufficiency due to pituitary failure. Glucose and cortisol levels are measured at predetermined intervals after an injection of insulin is used to stress the pituitary glands. In healthy people, blood glucose levels fall and cortisol concentrations increase. In those with adrenal insufficiency, cortisol levels will remain low and glucose levels will fall then recover slowly.
  • Renin. Renin activity is elevated in primary adrenal insufficiency because a lack of aldosterone causes increased renal sodium losses. This lowers blood sodium levels and decreases the amount of fluid in the blood (which lowers blood volume and pressure), which in turn stimulates renin production.
  • Adrenal autoantibodies are sometimes ordered as part of the diagnostic process when autoimmune Addison’s disease is suspected. They are considered a good marker of autoimmune Addison's disease, but are not widely used at this time.

Non-laboratory tests

  • X-rays may be used to look for calcification on the adrenal cortex that may be due to a tuberculosis infection.
  • CT (computerised tomography) or MRI (magnetic resonance imaging) scans, are sometimes used to look at the size and shape of the adrenal glands and the pituitary. The adrenal glands can be enlarged with infections and cancers. With autoimmune diseases and secondary adrenal insufficiency, the adrenal glands are often normal or small in size.


Treatment for adrenal insufficiency involves hormone replacement or substitution. The specific replacement depends on whether cortisol or aldosterone are both deficient. If the condition is due to an adrenal infection, the affected person may regain some adrenal function when the infection resolves. Even when people have extensive and permanent damage to their adrenal cortex, they should be able to live healthy, relatively normal lives by replacing the missing hormones and observing a few precautions.

In the case of secondary adrenal insufficiency, it is very rare for a patient to respond to treatment if the cause is pituitary damage or disease. However, if the underlying condition can be resolved, such as if the insufficiency is due to corticosteroid therapy, cortisol production may eventually resume.

An adrenal crisis can be life-threatening and is treated with intravenous (IV) injections of glucocorticoids and large volumes of intravenous saline solution with the sugar dextrose. This treatment usually brings rapid improvement. Initiation of treatment as early as possible improves outcomes.

Last Updated: Thursday, 1st June 2023

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