What is the initial workup for a patient with suspected adrenal insufficiency?

Initial Workup for Suspected Adrenal Insufficiency

The initial diagnostic workup for suspected adrenal insufficiency should include paired measurement of morning serum cortisol and plasma ACTH, along with basic metabolic panel to assess electrolytes. 1

Clinical Presentation and When to Suspect

• Consider adrenal insufficiency in patients presenting with unexplained collapse, hypotension, vomiting, diarrhea, hyperpigmentation, hyponatremia, hyperkalemia, acidosis, or hypoglycemia 1
• Common symptoms include fatigue (50%-95%), nausea and vomiting (20%-62%), anorexia, and weight loss (43%-73%) 2
• Treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 1

Diagnostic Algorithm

Step 1: Initial Laboratory Tests

• Morning (8 AM) serum cortisol and plasma ACTH 1
• Basic metabolic panel (sodium, potassium, CO2, glucose) 1
• In acute illness, cortisol <250 nmol/L (9 μg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency 1
• Cortisol <400 nmol/L (14.5 μg/dL) with elevated ACTH in acute illness raises strong suspicion of primary adrenal insufficiency 1

Step 2: For Equivocal Results

• ACTH stimulation test (synacthen/cosyntropin test): administer 0.25 mg ACTH intramuscularly or intravenously 1, 3
• Measure serum cortisol at baseline, 30 and/or 60 minutes after ACTH administration 1
• Peak cortisol <500 nmol/L (18 μg/dL) is diagnostic of adrenal insufficiency 1

Determining Etiology

Once adrenal insufficiency is confirmed, determine the cause:

Primary Adrenal Insufficiency

• Characterized by low cortisol with high ACTH levels 2
• Measure 21-hydroxylase (anti-adrenal) autoantibodies 1
• If antibodies are negative, obtain adrenal CT imaging to evaluate for hemorrhage, tumor, or infection 1
• In male patients, measure very long-chain fatty acids to check for adrenoleukodystrophy 1

Secondary Adrenal Insufficiency

• Characterized by low cortisol with low or inappropriately normal ACTH levels 2
• Consider MRI of the brain with pituitary/sellar cuts in patients with multiple endocrine abnormalities or new severe headaches 1
• Evaluate for other pituitary hormone deficiencies: TSH, FT4, LH, FSH, testosterone/estradiol 1

Management of Acute Adrenal Crisis

• Administer IV or IM hydrocortisone 100 mg immediately, followed by 100 mg every 6-8 hours until recovered 1
• Provide isotonic (0.9%) sodium chloride solution at an initial rate of 1 L/hour until hemodynamic improvement 1
• Identify and treat the underlying precipitant of adrenal crisis (e.g., infection) 1

Common Pitfalls to Avoid

• Delaying treatment in suspected acute adrenal insufficiency while waiting for test results 1
• Misinterpreting cortisol levels in patients taking exogenous steroids (oral, inhaled, or topical) 2, 4
• Relying solely on the ACTH stimulation test for secondary adrenal insufficiency, as it may give false normal results 5
• Failing to consider adrenal insufficiency in patients who have recently tapered or discontinued glucocorticoids 2, 4
• Not accounting for the timing of cortisol measurement or assay variability when interpreting results 3

By following this systematic approach to the diagnosis of adrenal insufficiency, clinicians can ensure timely identification and appropriate management to prevent potentially life-threatening adrenal crisis.