Adrenal Insufficiency

• Types of steroid hormones

  • Cortisol
  • Aldosterone
• Adrenal insufficiency is where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone
• Steroids are essential for life. Therefore, the condition is life-threatening unless the hormones are replaced
• Addison’s disease refers specifically to when the adrenal glands have been damaged, resulting in reduced cortisol and aldosterone secretion. This is called primary adrenal insufficiency
• Causes of primary adrenal insufficiency

  • Autoimmune
• Secondary adrenal insufficiency results from inadequate adrenocorticotropic hormone (ACTH) and a lack of stimulation of the adrenal glands, leading to low cortisol. This is the result of loss or damage to the pituitary gland
• Causes of secondary adrenal insufficiency

  • Tumours (e.g., pituitary adenomas)
  • Surgery to the pituitary
  • Radiotherapy
  • Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
  • Trauma
• Tertiary adrenal insufficiency results from inadequate corticotropin-releasing hormone (CRH) release by the hypothalamus. This is usually the result of patients taking long-term oral steroids (for more than 3 weeks), causing suppression of the hypothalamus (via negative feedback)
• Adrenal insufficiency


  Result of patients taking long-term oral steroids (for more than 3 weeks), causing suppression of the hypothalamus (via negative feedback). When exogenous steroids (originating outside the body) are suddenly withdrawn, the hypothalamus does not “wake up” fast enough, and endogenous steroids (originating inside the body) are not adequately produced. Therefore, long-term steroids must be tapered slowly to allow the adrenal axis to regain normal function
• Symptoms of adrenal insufficiency

  • Fatigue
  • Muscle weakness
  • Muscle cramps
  • Dizziness and fainting
  • Thirst and craving salt
  • Weight loss
  • Abdominal pain
  • Depression
  • Reduced libido
• Signs of adrenal insufficiency

  • Bronze hyperpigmentation of the skin, particularly in creases
  • Hypotension (particularly postural hypotension – with a drop of more than 20 mmHg on standing)
• Bronze hyperpigmentation


  Caused by excessive ACTH stimulating melanocytes to produce melanin, mainly affecting skin creases (e.g., on the palms), scars, lips, and buccal mucosa
• In an OSCE exam, check for a medical alert bracelet worn by a patient with adrenal insufficiency to alert medical services that they are steroid-dependent if they become unconscious
• Investigations for adrenal insufficiency


  • Hyponatraemia (low sodium)
  • Hyperkalaemia (high potassium)
  • Hypoglycaemia (low glucose)
  • Raised creatinine and urea due to dehydration
  • Hypercalcaemia (high calcium)
  • Early morning cortisol (8 – 9 am)
  • Short Synacthen test
• Autoantibodies may be present in autoimmune adrenal insufficiency: Adrenal cortex antibodies, 21-hydroxylase antibodies
• Tests for diagnosing adrenal insufficiency

  • Short Synacthen test (ACTH stimulation test)
  • Adrenocorticotropic hormone (ACTH) measurement
  • CT or MRI of the adrenal glands
  • MRI of the pituitary
• Short Synacthen test


  Also known as the ACTH stimulation test. It is the test of choice for diagnosing adrenal insufficiency. It involves giving a dose of Synacthen, which is synthetic ACTH. The blood cortisol is checked before and 30 and 60 minutes after the dose. The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol. The cortisol level should at least double. A failure of cortisol to double indicates either primary adrenal insufficiency (Addison’s disease) or very significant adrenal atrophy after a prolonged absence of ACTH in secondary adrenal insufficiency
• The long Synacthen test was used to distinguish between primary adrenal insufficiency and adrenal atrophy due to secondary adrenal insufficiency
• Signs of very significant adrenal atrophy in Addison’s disease

  • Very significant adrenal atrophy after a prolonged absence of ACTH
• Test to distinguish between primary adrenal insufficiency and adrenal atrophy due to secondary adrenal insufficiency

  Long Synacthen test
• The Long Synacthen test is rarely used because checking the ACTH level will give the same answer
• ACTH level in primary adrenal insufficiency

  High
• ACTH level in secondary adrenal insufficiency

  Low
• Treatment of adrenal insufficiency

  Replacement steroids titrated to signs, symptoms, and electrolytes
• Hydrocortisone


  • Used to replace cortisol
• Fludrocortisone


  • Used to replace aldosterone if aldosterone is also insufficient
• Items given to patients with adrenal insufficiency

  • Steroid card
  • ID tag
  • Emergency letter
• Doses of steroids should not be missed as they are essential to life
• Doses are doubled during an acute illness to match the normal steroid response to illness
• Management of adrenal crisis

  1. ABCDE approach to initial assessment and arrange transfer to hospital

  2. Intramuscular or intravenous hydrocortisone (initial dose is 100mg, followed by an infusion or 6 hourly doses)

  3. Intravenous fluids

  4. Correct hypoglycaemia (e.g., IV dextrose)

  5. Careful monitoring of electrolytes and fluid balance
• Do not wait to perform investigations and establish a definitive diagnosis before starting treatment in suspected adrenal crisis
• Adrenal crisis, also known as Addisonian crisis, describes an acute presentation of severe adrenal insufficiency, where the absence of steroid hormones leads to a life-threatening emergency