Adrenal Crisis (Addisonian Crisis)

Adrenal crisis is a life threatening emergency in patients with primary (classic addisonian crisis), or secondary adrenal failure. It is often precipitated by stress, surgery or intercurrent illness such as infection or MI due to an inadequate glucocorticoid response.

Although patients with secondary adrenal insufficiency may suffer from adrenal crisis, they usually do not have the same degree of volume depletion, because their renin–angiotensin– aldosterone axis is intact.

Diagnosis – This is often difficult as the patient may have vague symptoms and just appear “unwell”, or symptoms are presumed to be part of the presenting illness. It is important to consider this diagnosis and have a low index of suspicion. Patients with adrenal insufficiency often have an alert bracelet or an alert on their patient notes.

Pathophysiology

Glucocorticoids are produced in the adrenal cortex under the regulation of the hypothalamic–pituitary–adrenal (HPA) axis.

Cortisol has many important metabolic and endocrine functions that are essential for human survival, particularly during stress. Surgery, anaesthesia, trauma, and severe illnesses result in elevated plasma ACTH and cortisol levels. Cortisol is required for the metabolism of carbohydrates, lipids and proteins, and for the maintenance of vascular tone and endothelial integrity. It also potentiates the vasoconstrictor actions of catecholamines and has anti-inflammatory effects on the immune system.

Aldosterone is synthesised in the adrenal cortex under the control of the renin–angiotensin system. It regulates sodium and potassium balance and intravascular volume.

Primary adrenal insufficiency / Addison’s

-is due to intrinsic adrenal gland dysfunction and results in decreased cortisol and aldosterone production. Approximately 90% of the gland must be destroyed for clinical adrenal insufficiency to develop. The commonest cause in developed countries is autoimmune adrenalitis. Other causes include infection (e.g. tuberculosis, HIV), drugs, adrenal haemorrhage, sarcoidosis, metastases, and congenital adrenal hyperplasia.

Secondary adrenal insufficiency

-is due to hypothalamic-pituitary dysfunction causing inadequate ACTH production. This results in cortisol deficiency only. This may be caused by withdrawal of prolonged steroid therapy, pituitary disease or pituitary injury such as trauma, tumour, irradiation or surgery.

Signs and Symptoms

  • Severe vomiting and diarrhoea
  • Dehydration, hypotension or shock – may be out of proportion to severity of current illness
  • Confusion
  • Loss of consciousness
  • Abdominal pain
  • Unexplained hypoglycaemia
  • Fever
  • Hyponatremia, hyperkalemia, uraemia, hypercalcemia, or eosinophilia

Adrenal Crisis - Investigations

If suspicion of adrenal crisis:

  • Immediate blood glucose using a bedside glucometer.
  • Serum glucose, urea, sodium and potassium.
  • Venous blood gas to check acid-base status.

If the patient is not known to have adrenal insufficiency the following investigations will help with diagnosis:

  • 2mL of clotted blood (serum tube) for cortisol and 17 hydroxyprogesterone levels.
  • 2mL of blood in EDTA tube for plasma renin activity and ACTH levels - this should be sent on ice.
  • A sample of urine (aim for 5-10mL if possible) for a urinary steroid profile and urinary sodium level.

Where possible, these investigations should be performed prior to administration of steroid, as this helps greatly with interpretation. However, if this is not possible proceed with urgent steroid administration.

Patients will also need appropriate investigation of their current symptoms and possible precipitating cause for the adrenal crisis.

Adrenal Crisis - Treatment

1. IV fluids

Initial treatment with normal saline 10-20mL/kg depending on level of dehydration. Rehydrate as needed.

2. Steroid replacement

Hydrocortisone100mg IV, then 100mg every 6 hours until stable. Hydrocortisone has glucocorticoid and mineralocorticoid effects. This can be provided as a 24 hour infusion of 300-400mg and dose requirements in some patients may vary, consult Endocrinologist.

3. Correct hypoglycaemia

Treat hypoglycaemia (BGL <4 mmol/L)

4. Hyperkalaemia

Hyperkalaemia usually responds to volume replacement and hydrocortisone — IV insulin and glucose should be avoided.

If K >6.0 place patient on cardiac monitor if not already monitored.

See the ECI Hyperkalaemia tool.

5. Treat underlying disease

Consider precipitants, e.g. sepsis, myocardial infarction, pancreatitis, and treat as appropriate.

Adrenal Crisis - Further References and Resources

MJA Management of adrenal insufficiency during the stress of medical illness and surgery

Clinical Excellence Commission: Patient Safety Watch 1/15 - Adrenal Insufficiency: Diagnostic and Management Dilemmas

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