Adrenal crisis

Synonym: Addisonian crisis

Adrenal crisis is a potentially fatal condition associated mainly with an acute deficiency of the glucocorticoid cortisol and, to a lesser extent, the mineralocorticoid aldosterone. It occurs commonly in people with long-term adrenal insufficiency - one study showed that 8% of people with Addison's disease needed annual hospital admission for adrenal crisis¹.

See the separate Adrenal Insufficiency and Addison's Disease article.

Epidemiology

Steroid-dependence among Caucasian populations has an estimated prevalence of around 600 per million and arises from two main causes²:

• Primary adrenal insufficiency, caused by autoimmune adrenal destruction or congenital adrenal hyperplasia, with other minor causes.

• Secondary pituitary insufficiency, including steroid-induced adrenal suppression.

Combined, all causes of steroid-dependence would give an estimated patient population approaching 40,000 across the UK.

Aetiology

Crisis occurs when the physiological demand for these hormones exceeds the ability of adrenal glands to produce them, most often in patients with chronic adrenal insufficiency when subject to an intercurrent illness or stress²:

• Major or minor infections. (Most commonly vomiting and/or diarrhoea due to a gastrointestinal upset.)

• Injury.

• Surgery.

• Allergy/migraine.

• Pregnancy.

• Over-exertion/dehydration.

• Bereavement/emotional distress.

• Acute hypoglycaemia in people with diabetes.

It may also occur as a result of poor patient education and treatment failure.

A common cause of adrenal crisis is abrupt withdrawal of steroids. This is because secondary adrenocortical insufficiency develops when steroids given as therapy have suppressed the hypothalamic-pituitary-adrenal axis.

Causes of sudden loss of adrenal function such as bilateral adrenal gland haemorrhage can also produce adrenal crisis. This may occur due to severe physiological stressors such as myocardial infarction, septic shock or complicated pregnancy, or with concomitant coagulopathy or thromboembolic disorders.

Risk factors

Long-term steroid therapy is the biggest risk factor for adrenal crisis. Oral steroid treatment carries the highest risk; however, inhaled and topical steroids can also on occasion cause adrenal insufficiency, and therefore predispose to adrenal crisis.

There may be potential for a single articular steroid injection to cause an adrenal crisis. Athletes in particular should be warned about this, as they have a high incidence of trauma which, in itself, is a risk.

Presentation

Symptoms include³:

• Malaise.

• Fatigue.

• Nausea or vomiting.

• Abdominal pain.

• Low-grade fever.

• Muscle pains and cramps.

These are followed by dehydration, leading to hypotension and hypovolaemic shock.

There may be confusion. Loss of consciousness and coma may occur.

Investigations⁴

• Sodium is usually moderately decreased but may be normal.

• Potassium is usually slightly increased or normal - rarely, markedly increased (risk of arrhythmias).

• Creatinine may be raised.

• Hypoglycaemia, possibly severe, is characteristic in children.

• Calcium may be slightly raised

• Blood for cortisol and ACTH should be taken, but if adrenal crisis is suspected, treatment should be initiated urgently rather than awaiting diagnostic tests. Likewise tests for precipitating causes (such as infections) should be instituted, but treatment not delayed.

Management

Adrenal crisis requires urgent admission to hospital.

Start treatment immediately, based on clinical features and not delayed for confirmation of adrenal function. Administration of glucocorticoids in supraphysiological or stress doses is the only definitive therapy. Treatment is as follows:

• Immediate administration of hydrocortisone IV or IM⁵:

  • 100 mg for an adult.

  • 50-100 mg for a child aged 6 years or more.

  • 50 mg for a child aged 1 to 5 years.

  • 25 mg for a child aged less than 1 year.

  • At these doses hydrocortisone has mineralocorticoid action so fludrocortisone is not required

• Rehydration with normal saline infusion.

• Continuous cardiac and electrolyte monitoring.

• Following rehydration, administration of 100-200 mg hydrocortisone in 5% glucose over 24 hours by IV infusion.

• Treatment of the underlying precipitating disorder - eg, infection with antibiotics.

• Once stabilised, gradual reduction of IV steroid dose and re-institution of oral therapy.

Prevention⁶

• Steroids should not be stopped suddenly if they have been used for more than two weeks.

• For those on treatment for adrenal insufficiency, early dose adjustments (eg, doubling the usual maintenance dose) are required to cover the increased glucocorticoid demand in situations such as illness, surgery, trauma, etc. Careful and repeated education of patients and their partners is the best strategy to avoid this life-threatening emergency.

• Medical emergency identification bracelet or similar and steroid cards. Letters to explain management to carry for travel. The Addison's Disease self-help group website offers a proforma for this⁷.

• People on treatment for adrenal insufficiency should have an emergency self-injection kit and be taught how to use it.

• People on treatment for adrenal insufficiency do not require cover for minor dental procedures such as fillings. For dental surgery such as root canal treatment with local anaesthetic, glucocorticoid doses should be doubled one hour before surgery and for 24 hours afterwards⁵. Extra doses may be taken if symptoms of adrenal insufficiency are experienced.

Complications

Death may be caused by circulatory collapse and arrhythmias with hypoglycaemia contributing.