What are the signs and symptoms of adrenal crisis in patients with a history of adrenal gland disorders or those taking long-term corticosteroid therapy?

Signs and Symptoms of Adrenal Crisis

Adrenal crisis presents as a life-threatening emergency with hypotension (often severe or shock), dehydration, nausea, vomiting, abdominal pain, and profound malaise, typically accompanied by hyponatremia in 90% of cases, hyperkalemia in 50%, and hypoglycemia especially in children. 1

Cardinal Clinical Features

Cardiovascular Manifestations

• Hypotension is the hallmark finding, progressing to shock if untreated 1, 2, 3
• Orthostatic (postural) hypotension occurs early, before supine hypotension develops, representing a critical early warning sign 1
• Severe volume depletion and circulatory collapse in advanced cases 4, 5

Gastrointestinal Symptoms

• Nausea and vomiting are present in 20-62% of patients and are often severe 6, 1
• Abdominal pain is common, which can mimic an acute surgical abdomen and lead to misdiagnosis 1, 7
• Anorexia occurs in 43-73% of patients 6

Constitutional Symptoms

• Profound malaise and fatigue affecting 50-95% of patients 6, 1
• Severe dehydration is a key pathophysiologic feature 1, 3
• Muscle pain and cramps 1, 2
• Weight loss may precede acute crisis 4

Neurological Manifestations

• Impaired cognitive function and confusion are common 1, 3
• Loss of consciousness and coma in severe untreated cases 1, 3
• Altered mental status requiring urgent intervention 6

Dermatologic Signs (Primary Adrenal Insufficiency)

• Hyperpigmentation of skin due to elevated ACTH levels, particularly in skin creases, pressure points, and mucous membranes 1, 3
• This sign is absent in secondary adrenal insufficiency 1

Laboratory Abnormalities

Electrolyte Disturbances

• Hyponatremia is present in approximately 90% of newly presenting cases, making it the most common laboratory finding 1
• Hyperkalemia occurs in approximately 50% of patients 1
• The absence of hyperkalemia does not exclude adrenal crisis 1

Metabolic Derangements

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

Renal Function

• Increased creatinine and BUN due to prerenal renal failure from volume depletion 1
• Prerenal azotemia reflecting severe dehydration 4

Hormonal Findings

• Serum cortisol below normal range (<5 µg/dL or <250 nmol/L) 1, 6
• Markedly elevated plasma ACTH level diagnostic of primary adrenal insufficiency 1
• Low or low-normal ACTH in secondary adrenal insufficiency 6

Common Precipitating Factors

Infectious Causes

• Gastrointestinal illness with vomiting/diarrhea is the most common trigger, accounting for the majority of cases 1, 2, 7
• Any type of infection can precipitate crisis 1, 5
• The inability to absorb oral glucocorticoids during GI illness creates a dangerous situation where patients cannot take medication when they need it most 1

Physical Stressors

• Surgical procedures without adequate steroid coverage 1, 2
• Physical injuries or trauma 1, 2
• Pronounced physical activity or strenuous exercise 8

Medical Events

• Myocardial infarction 1
• Severe allergic reactions 1
• Severe hypoglycemia in diabetic patients 1

Medication-Related

• Failure to increase glucocorticoid doses during intercurrent illness despite patient education 1, 5
• Forgetting or discontinuing glucocorticoid therapy 8
• Medications that accelerate cortisol clearance without dose adjustment 1
• Starting thyroid hormone replacement before adequate glucocorticoid replacement can trigger crisis in patients with multiple hormone deficiencies 4, 1

Chronic Predisposing Factors

• Chronic under-replacement with fludrocortisone combined with low salt consumption 4, 1
• Poor compliance with mineralocorticoid therapy 4
• Underlying psychiatric disorders affecting medication adherence 4, 1

Critical Clinical Pearls

Diagnostic Approach

• Treatment must never be delayed for diagnostic procedures when adrenal crisis is suspected 1, 2, 3
• Draw blood for cortisol, ACTH, and electrolytes before treatment begins, but do not wait for results 1, 2
• Consider adrenal crisis in any patient with unexplained collapse, hypotension, vomiting, or diarrhea, especially with electrolyte abnormalities 1

Common Pitfalls to Avoid

• Even mild gastrointestinal upset may precipitate crisis because patients cannot absorb oral medication when they need it most 1
• The absence of hyperkalemia should not prevent treatment if clinical suspicion is high, as it is present in only half of cases 1
• Fever may be due to adrenal insufficiency itself, not just infection 1
• Orthostatic hypotension occurs before supine hypotension—do not wait for supine blood pressure changes 1

Special Populations

• Patients on immune checkpoint inhibitors who develop hypophysitis are at particular risk, especially during rapid corticosteroid tapers 4, 1
• Pediatric patients are more vulnerable to hypoglycemia and require frequent glucose monitoring 1
• Patients with recurrent crises should be evaluated for chronic under-replacement, poor compliance, and psychiatric disorders 4, 1