What are the signs of adrenal insufficiency?

Signs of Adrenal Insufficiency

Adrenal insufficiency should be suspected in any patient presenting with unexplained collapse, hypotension, vomiting or diarrhea, with hyperpigmentation, hyponatremia, hyperkalemia, acidosis and hypoglycemia increasing clinical suspicion. 1

Cardinal Clinical Features

Symptoms (Nonspecific but Common)

• Fatigue is the most prevalent symptom, occurring in 50-95% of patients 2
• Nausea and vomiting occur in 20-62% of cases, often accompanied by poor appetite 3, 2
• Anorexia and weight loss are present in 43-73% of patients 2, 4
• Unexplained collapse or syncope should immediately raise suspicion for adrenal crisis 1, 5
• Severe abdominal pain is a prominent crisis symptom 6
• Diarrhea is a recognized gastrointestinal manifestation 1, 6

Physical Examination Findings

• Hypotension and postural hypotension result from volume depletion due to aldosterone loss in primary adrenal insufficiency 1, 6, 4
• Hyperpigmentation is a distinguishing feature of primary adrenal insufficiency caused by elevated ACTH levels—this does NOT occur in secondary adrenal insufficiency 1, 4
• Salt craving is characteristic of primary adrenal insufficiency 4

Laboratory Abnormalities

Electrolyte Disturbances

• Hyponatremia is present in 90% of newly presenting cases, though often only marginally reduced 3, 1
• Hyperkalemia occurs in approximately 50% of patients at diagnosis due to aldosterone deficiency—the absence of hyperkalemia cannot rule out adrenal insufficiency 3, 1
• In the presence of severe vomiting, hypokalemia and alkalosis may paradoxically be present instead of the expected hyperkalemia 1

Other Laboratory Findings

• Hypoglycemia is more common in children but can occur in adults, with hypoglycemic seizures possible 1, 5, 7
• Mild to moderate hypercalcemia occurs in 10-20% of patients at presentation 1, 6
• Acidosis is a recognized metabolic abnormality 1, 6
• Anemia, mild eosinophilia, and lymphocytosis may be present 1, 6
• Elevated liver transaminases can occur 1, 6

Severity Grading

Grade 1 (Mild)

• Asymptomatic or mild symptoms where patients can perform daily activities 1, 6

Grade 2 (Moderate)

• Symptoms affect daily activities but patients remain able to perform activities of daily living 1, 6

Grade 3-4 (Severe/Adrenal Crisis)

• Medically significant or life-threatening consequences with inability to perform activities of daily living 1, 6
• Adrenal crisis is a life-threatening emergency that requires immediate treatment and should never be delayed by diagnostic procedures 1, 8

High-Risk Clinical Scenarios

• Any patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise 3
• Hypotension requiring high-dose vasopressors or multiple vasopressor agents that remains refractory to treatment is a critical indication to consider adrenal insufficiency 3
• Vasopressor-resistant hypotension attributed to adrenal insufficiency may respond to stress-dose hydrocortisone alone 3

Critical Pitfalls to Avoid

• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—between 10-20% of patients have mild or moderate hypercalcemia at presentation, and some may have normal electrolytes 3
• The classic combination of hyponatremia and hyperkalemia is not always present, making diagnosis challenging 1
• Diagnosis is usually delayed because the initial presentation is often non-specific—physician awareness must be improved to avoid adrenal crisis 4
• Treatment of suspected acute adrenal insufficiency should NEVER be delayed by diagnostic procedures—if unstable, give 100 mg IV hydrocortisone immediately 3, 1