What is the most appropriate test to diagnose a 40-year-old woman with a one-month history of fatigue, weakness, and bone pain, worsening over the past 3 days, presenting with hypotension (blood pressure 80/60), tachycardia (heart rate 110), increased pigmentation on her fingers, and diffuse tenderness on palpation?

Most Appropriate Diagnostic Test for Primary Adrenal Insufficiency

The most appropriate test to diagnose this patient's condition is paired morning serum cortisol and plasma ACTH measurement, followed by a cosyntropin stimulation test if initial results are equivocal. 1

Clinical Presentation Strongly Suggests Primary Adrenal Insufficiency (Addison's Disease)

This 40-year-old woman presents with the classic triad that should immediately raise suspicion for primary adrenal insufficiency:

• Hypotension (80/60 mmHg) with tachycardia (110 bpm) indicating hemodynamic instability 2
• Hyperpigmentation of fingers and extremities (pathognomonic for primary adrenal insufficiency due to elevated ACTH stimulating melanocytes) 2
• Chronic fatigue, weakness, and bone pain progressing over one month with acute worsening 2
• Diffuse abdominal tenderness (consistent with gastrointestinal manifestations of adrenal crisis) 2

Immediate Diagnostic Algorithm

Step 1: Obtain Morning Cortisol and ACTH Before Treatment

Draw blood immediately for serum cortisol and plasma ACTH before administering any corticosteroids. 1 The Endocrine Society emphasizes that morning serum cortisol (<140 nmol/L or <5 µg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency. 1

Critical pitfall to avoid: Never delay treatment of suspected acute adrenal crisis to obtain diagnostic tests—if the patient is clinically unstable (which this patient is with BP 80/60), immediately administer 100 mg IV hydrocortisone and 0.9% saline infusion at 1 L/hour after securing blood samples. 1

Step 2: Complete Metabolic Panel

Obtain a basic metabolic panel simultaneously, as it will reveal: 1

• Hyponatremia (present in 90% of newly diagnosed cases) 1
• Hyperkalemia (present in approximately 50% of primary adrenal insufficiency cases) 1

The consensus statement on primary adrenal insufficiency confirms that hyponatremia and hyperkalaemia, while not always present, increase clinical suspicion when combined with hypotension and hyperpigmentation. 2

Step 3: Confirmatory Testing if Initial Results Are Equivocal

If morning cortisol is between 140-500 nmol/L (5-18 µg/dL), perform the cosyntropin stimulation test as the gold standard confirmatory test: 1

• Administer 0.25 mg cosyntropin intramuscularly or intravenously 1
• Measure serum cortisol at 30 and 60 minutes post-administration 1
• A peak cortisol <500-550 nmol/L (<18-20 µg/dL) is diagnostic of adrenal insufficiency 1

The 2014 consensus statement confirms that paired measurement of serum cortisol and plasma ACTH is the diagnostic test for primary adrenal insufficiency, with a synacthen (tetracosactide) stimulated peak serum cortisol <500 nmol/L being diagnostic. 2

Why Other Tests Are Less Appropriate

Complete blood count: While useful for detecting anemia, eosinophilia, and lymphocytosis that may accompany adrenal insufficiency 2, it is not diagnostic and should be obtained as part of the baseline evaluation but not as the primary diagnostic test. 3, 4

Imaging studies (CT/MRI): These are indicated for etiologic workup AFTER biochemical diagnosis is confirmed, not as initial diagnostic tests. 1 CT imaging of the adrenals should be obtained if 21-hydroxylase autoantibodies are negative to evaluate for hemorrhage, metastatic disease, tuberculosis, or other structural abnormalities. 1

21-hydroxylase autoantibodies: This is part of the etiologic workup to determine the cause of primary adrenal insufficiency (autoimmunity accounts for 85% of cases in Western populations), but should be obtained after biochemical diagnosis is established. 1

Supporting Laboratory Findings to Expect

Additional laboratory abnormalities that support the diagnosis include: 2

• Low serum aldosterone with elevated plasma renin activity 2
• Low dehydroepiandrosterone sulphate (DHEAS) 2
• Mildly elevated TSH (4-10 IU/L range) due to lack of cortisol's inhibitory effect 2
• Possible mild hypercalcemia (10-20% of patients) 2

The diagnosis should never be delayed by waiting for these additional tests—treatment must begin immediately in hemodynamically unstable patients while diagnostic samples are being processed. 1