Adrenal Insufficiency

Adrenal insufficiency is where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone. Steroids are essential for life and therefore the condition is life-threatening unless the hormones are replaced.

Addison’s Disease refers to the specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. This is also called Primary Adrenal Insufficiency. The most common cause is autoimmune.

Secondary Adrenal Insufficiency is a result of inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary gland. This can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy. There is also a condition called Sheehan’s syndrome where massive blood loss during childbirth leads to pituitary gland necrosis.

Tertiary Adrenal Insufficiency is the result of inadequate CRH release by the hypothalamus. This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus. When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.



  • Fatigue
  • Nausea
  • Cramps
  • Abdominal pain
  • Reduced libido



  • Bronze hyperpigmentation to skin (ACTH stimulates melanocytes to produce melanin)
  • Hypotension (particularly postural hypotension)


Hyponatraemia (low sodium) is a key biochemical clue. Sometimes the only presenting feature of adrenal insufficiency is hyponatraemia.

Hyperkalaemia (high potassium) is also possible.

Early morning cortisol (8-9am) has a role but is often falsely normal.

A short synacthen test is the test of choice to diagnose adrenal insufficiency.

ACTH. In primary adrenal failure the ACTH level is high as the pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol. In secondary adrenal failure the ACTH level is low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH.

Adrenal autoantibodies are present in 80% of autoimmune adrenal insufficiency: adrenal cortex antibodies and 21-hydroxylase antibodies

CT / MRI adrenals if suspecting an adrenal tumour, haemorrhage or other structural pathology (not recommended by NICE for autoimmune adrenal insufficiency).

MRI pituitary gives further information about pituitary pathology.


Short Synacthen Test (ACTH stimulation test)

The short synacthen test is the test of choice for adrenal insufficiency. It is ideally performed in the morning when the adrenal glands are most “fresh”. The test involves giving synacthen, which is synthetic ACTH. The blood cortisol is measured at baseline, 30 and 60 minutes after administration. The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol and the cortisol level should at least double. A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).


Long Synacthen Test

The long synacthen test is rarely used anymore because we can now measure ACTH levels. It was used to distinguish between primary adrenal insufficiency and adrenal atrophy secondary to prolonged under stimulation in secondary adrenal insufficiency. It involves giving an infusion of ACTH over a long period.

  • In primary adrenal failure there is no cortisol response as the adrenals no longer function.
  • In adrenal atrophy (secondary adrenal insufficiency), the prolonged ACTH eventually gets the adrenals going again and cortisol rises.

Now we can simply measure ACTH and this indicates the underlying cause.



Treatment of adrenal insufficiency is with replacement steroids titrated to signs, symptoms and electrolytes. Hydrocortisone is a glucocorticoid hormone and is used to replace cortisol. Fludrocortisone is a mineralocorticoid hormone and is used to replace aldosterone if aldosterone is also insufficient.

Patients are given a steroid card and an emergency ID tag to alert emergency services that they are dependent on steroids for life. Doses should not be missed as they are essential to life. Doses are doubled during an acute illness until they have recovered to match the normal steroid response to illness.


Addisonian Crisis (AKA Adrenal Crisis)

Addisonian crisis is the term used to describe an acute presentation of severe Addisons, where the absence of steroid hormones leads to a life threatening presentation. They present with:

  • Reduced consciousness
  • Hypotension
  • Hypoglycaemia, hyponatraemia, hyperkaemia
  • Patients can be very unwell

It can be the first presentation of Addisons Disease or triggered by infection, trauma or other acute illness in someone with established Addisons. It can present in someone on long term steroids suddenly withdrawing those steroids.

Do not wait to perform investigations and establish a definitive diagnosis before treating someone with suspected Addisonian Crisis as this is life threatening and they need immediate treatment.


Management of Addisonian Crisis

  • Intensive monitoring if unwell
  • Parenteral steroids (i.e. IV hydrocortisone 100mg stat then 100mg every 6 hours)
  • IV fluid resuscitation
  • Correct hypoglycaemia
  • Careful monitoring of electrolytes and fluid balance


Last updated November 2018