What is an Addisonian crisis and what are its signs and symptoms?

What is an Addison's Crisis?

An Addison's crisis (also called adrenal crisis or Addisonian crisis) is a life-threatening emergency caused by acute adrenocortical insufficiency—when the body's cortisol production is insufficient to meet acute physiologic demands. 1 This occurs either in patients with known adrenal insufficiency who experience a precipitating stressor, or as the first presentation of undiagnosed Addison's disease. 2

The crisis represents primarily a state of both glucocorticoid and mineralocorticoid deficiency in primary adrenal insufficiency, leading to cardiovascular collapse, severe volume depletion, and metabolic derangements. 3 Even mild stressors like an upset stomach can precipitate crisis because patients cannot absorb their oral medications when they need them most. 4

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Signs and Symptoms of Addison's Crisis

Cardiovascular Manifestations

• Severe hypotension (often <90/60 mmHg) is the hallmark finding and may progress rapidly to shock 1, 2
• Orthostatic (postural) hypotension develops before supine hypotension—this is an early warning sign that should prompt immediate evaluation 1
• Tachycardia accompanies the hypotensive state 2
• Progressive loss of vasomotor tone occurs due to impaired alpha-adrenergic receptor responsiveness 1

Gastrointestinal Symptoms

• Severe nausea and vomiting are extremely common presenting features 1, 5
• Abdominal pain can mimic an acute surgical abdomen 1, 5
• Diarrhea may be present 2
• These GI symptoms prevent oral medication absorption, worsening the crisis 4

Neurological Manifestations

• Non-specific malaise and fatigue are early warning signs 1, 5
• Altered mental status progressing from confusion to obtundation 1
• Loss of consciousness and coma in severe untreated cases 1, 5
• Somnolence and impaired cognitive function 1

Volume Status and Metabolic Signs

• Severe dehydration with marked volume depletion 1, 2
• Muscle pain and cramps 1, 5
• Fever may be present and can be due to the adrenal insufficiency itself, not just infection 1
• Hyperpigmentation of skin (in chronic primary adrenal insufficiency due to elevated ACTH) 1

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Laboratory Findings in Addison's Crisis

Electrolyte Abnormalities

• Hyponatremia is present in approximately 90% of newly presenting cases 1
• Hyperkalemia occurs in about 50% of patients 1
• The absence of hyperkalemia does not exclude the diagnosis 1

Renal Function

• Increased creatinine and BUN due to prerenal renal failure from severe volume depletion 1, 2

Metabolic Derangements

• Hypoglycemia is common in children but less frequent in adults 1
• Mild hypercalcemia occurs in 10-20% of patients 1
• Metabolic acidosis due to impaired renal function and aldosterone deficiency 1

Hormonal Findings

• Serum cortisol <250 nmol/L (<10 mcg/dL) with increased ACTH is diagnostic of primary adrenal insufficiency 1, 2
• Markedly elevated plasma ACTH level confirms primary adrenal insufficiency 1, 2

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Common Precipitating Factors

Gastrointestinal illness with vomiting/diarrhea is the single most common trigger for adrenal crisis. 1, 5 Other major precipitants include:

• Any type of infection (respiratory, urinary, systemic) 1, 5
• Surgical procedures performed without adequate steroid coverage 1, 5
• Physical trauma or injuries 1, 5
• Myocardial infarction 1
• Severe allergic reactions 1
• Medication non-compliance or abrupt cessation of chronic glucocorticoid therapy 6, 7
• Failure to increase glucocorticoid doses during intercurrent illness despite patient education 1
• Starting thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies 1
• Chronic under-replacement with fludrocortisone combined with low salt consumption 1

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Critical Clinical Pearls

Treatment must never be delayed for diagnostic confirmation—mortality increases with delayed intervention. 1, 2, 5 If you suspect adrenal crisis based on the constellation of hypotension, dehydration, vomiting, and electrolyte abnormalities, give hydrocortisone 100 mg IV immediately and start aggressive fluid resuscitation. 1

Consider adrenal crisis in any patient with unexplained collapse, hypotension, vomiting, or diarrhea, especially with electrolyte abnormalities. 2 The symptoms are non-specific and can mimic sepsis or other acute processes. 8

Even patients on glucocorticoid therapy can develop adrenal crisis if they are taking prednisolone or prednisone, which have minimal mineralocorticoid activity and do not protect against acute mineralocorticoid deficiency. 3

Persistent fever should not be attributed solely to infection—it may be due to adrenal insufficiency itself, and steroid supplementation should not be reduced while the patient is febrile. 1