What are the signs and symptoms of adrenal crisis in a patient with adrenal insufficiency?

Signs and Symptoms of Adrenal Crisis

Adrenal crisis presents with a constellation of cardiovascular, gastrointestinal, neurological, and metabolic manifestations that progress rapidly and can be fatal if not immediately recognized and treated. 1, 2

Cardiovascular Manifestations

Volume-resistant hypotension is the cardinal sign, but orthostatic hypotension appears first and represents a critical early warning sign before supine hypotension develops. 1, 3

• Monitor both sitting/standing and supine blood pressure to detect orthostatic changes early—do not wait for supine hypotension to develop 1
• Progressive loss of vasomotor tone occurs due to impaired alpha-adrenergic receptor responses 1
• Hypovolemic shock and cardiovascular collapse develop in advanced cases if untreated 3, 4
• Severe hypotension (often <90/60 mmHg) with orthostatic changes is a key presenting feature 2

Gastrointestinal Symptoms

Nausea, vomiting, and abdominal pain are extremely common presenting symptoms, occurring in 20-62% of patients, and often mimic acute surgical abdomen. 4, 5

• Severe, persistent vomiting that prevents oral medication absorption 6
• Abdominal pain that can be mistaken for other acute abdominal conditions 3, 7
• Anorexia and weight loss (43-73% of patients) 4
• Diarrhea may accompany vomiting, particularly when gastrointestinal illness is the precipitating factor 7

Neurological Manifestations

Altered mental status progresses from non-specific malaise to obtunded consciousness, confusion, and potentially coma if treatment is delayed. 1, 3

• Non-specific malaise and somnolence are early warning signs 1
• Cognitive dysfunction and confusion develop as crisis progresses 3
• Loss of consciousness and coma occur in severe, untreated cases 3, 7
• Seizures may occur, particularly in pediatric patients with hypoglycemia 5

Constitutional Symptoms

Profound fatigue, weakness, and muscle/joint pain develop rapidly, often within hours, even in previously well patients. 4, 6

• Extreme asthenia (weakness) that is disproportionate to the clinical situation 7
• Muscle pain and cramps are common musculoskeletal manifestations 3, 6
• Symptoms may develop out of robust health within few hours 6

Laboratory Abnormalities

Hyponatremia is present in approximately 90% of cases, but its absence does not exclude adrenal crisis. 2, 3

• Hyperkalemia occurs in approximately 50% of patients, primarily in primary adrenal insufficiency 2, 3
• Hypoglycemia is common in children but less frequent in adults 3, 4
• Increased creatinine and BUN due to prerenal renal failure from volume depletion 3
• Metabolic acidosis due to impaired renal function and aldosterone deficiency 3
• Mild hypercalcemia occurs in 10-20% of patients 3

Additional Clinical Features

Persistent pyrexia may be due to adrenal insufficiency itself, not just infection, and should not prompt steroid withdrawal. 1

• Fever can be a manifestation of the crisis itself, not necessarily indicating sepsis 1, 5
• Hyperpigmentation of skin (in primary adrenal insufficiency) due to elevated ACTH levels 3
• Dehydration is a key feature contributing to circulatory collapse 3, 7

Critical Clinical Pitfalls

The most dangerous pitfall is attributing these non-specific symptoms to other common conditions and delaying treatment—adrenal crisis should be suspected in any patient with unexplained collapse, hypotension, vomiting, or diarrhea, especially with electrolyte abnormalities. 3, 7

• Even mild gastrointestinal upset can precipitate crisis as patients cannot absorb oral medications when they need them most 3
• The absence of hyperkalemia does not exclude crisis, as it is present in only half of cases 2
• Normal or even elevated plasma cortisol levels do not exclude relative adrenal insufficiency in physiologically stressed patients 1
• Treatment must never be delayed for diagnostic confirmation when clinical suspicion exists 2, 3

Chronic Prodromal Signs (May Precede Acute Crisis)

Patients may exhibit warning signs for weeks to months before acute decompensation, including polydipsia, pronounced salt craving, and skin darkening. 7

• Excessive salt consumption and craving for salty foods 7
• Polydipsia (excessive thirst) 7
• Progressive skin darkening, particularly noticeable after sun exposure 7
• Unexplained weight loss over weeks to months 4