Canadian Laboratory Units for Diagnosing Addison's Disease
In Canada, the key diagnostic laboratory values for Addison's disease use the following units: serum cortisol in nmol/L, ACTH in pmol/L (or pg/mL), sodium and potassium in mmol/L, with a cosyntropin stimulation test requiring peak cortisol >550 nmol/L to exclude adrenal insufficiency. 1
Initial Diagnostic Laboratory Panel
- Morning serum cortisol should be measured in nmol/L, with values <250 nmol/L (<9 μg/dL) plus elevated ACTH being diagnostic of primary adrenal insufficiency in the setting of acute illness 1, 2
- Plasma ACTH is measured in pmol/L or pg/mL, with markedly elevated levels (>300 pg/mL when cortisol <140 nmol/L) indicating primary adrenal insufficiency 1, 3
- Serum sodium is reported in mmol/L, with hyponatremia present in approximately 90% of newly diagnosed cases 1
- Serum potassium is reported in mmol/L, with hyperkalemia occurring in about 50% of patients at diagnosis 1
Cosyntropin Stimulation Test Parameters
- The standard test involves administering 0.25 mg (250 mcg) cosyntropin intramuscularly or intravenously 1, 2
- Serum cortisol is measured at baseline, 30 minutes, and/or 60 minutes post-administration 1
- A peak cortisol >550 nmol/L (>18-20 μg/dL) at either 30 or 60 minutes is considered normal and excludes adrenal insufficiency 1, 2
- A peak cortisol <500-550 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 1, 2
Additional Laboratory Findings
- Aldosterone is measured in ng/dL or pmol/L, with low levels indicating mineralocorticoid deficiency 4
- Plasma renin activity is measured in mg/dL/hour or ng/mL/hour, with elevated levels (>6.0 mg/dL/hour) supporting primary adrenal insufficiency 4
- Mild to moderate hypercalcemia, anemia, mild eosinophilia, and lymphocytosis are common findings 1
- Elevated liver transaminases may be present 1
Critical Diagnostic Caveats
- Normal cortisol does not exclude early Addison's disease - approximately 10% of patients with confirmed primary adrenal insufficiency present with normal basal cortisol concentrations (>350 nmol/L) but have markedly elevated ACTH 4, 3
- The combination of normal-to-high cortisol with clearly elevated ACTH (>300 pg/mL) is indicative of evolving primary adrenal insufficiency when clinical history is suggestive 3
- Basal cortisol between 250-400 nmol/L with elevated ACTH in acute illness generates strong suspicion and requires cosyntropin stimulation testing 2
Etiologic Testing
- 21-hydroxylase autoantibodies should be the first test to establish autoimmune etiology, accounting for approximately 85% of cases 1, 5
- If autoantibodies are negative, CT imaging of the adrenals and measurement of very long-chain fatty acids should be performed 1