Paired Serum Cortisol and Plasma ACTH Measurement
In a patient with hyponatremia and an adrenal mass on CT scan, you should immediately measure paired serum cortisol and plasma ACTH levels to evaluate for primary adrenal insufficiency (PAI), which is the most critical diagnosis to exclude given the potentially life-threatening implications. 1
Diagnostic Approach
The presence of an adrenal mass combined with hyponatremia raises immediate concern for adrenal insufficiency, which can present with hyponatremia as a cardinal feature. The guideline is explicit: paired measurement of serum cortisol and plasma ACTH is the diagnostic test for primary PAI 1.
Key Diagnostic Thresholds
When interpreting these results in the context of acute illness or suspected acute adrenal insufficiency:
- Serum cortisol <250 nmol/L with elevated ACTH is diagnostic of primary PAI 1
- Serum cortisol <400 nmol/L with elevated ACTH raises strong suspicion of PAI 1
- If results are equivocal, proceed with a synacthen (tetracosactide) stimulation test (0.25 mg IM or IV); a peak serum cortisol <500 nmol/L confirms PAI 1
Additional Laboratory Findings Supporting PAI
Look for these concurrent abnormalities that increase clinical suspicion 1:
- Hyperkalaemia (from aldosterone deficiency)
- Acidosis
- Hypoglycaemia (especially in children)
- Elevated plasma renin activity (PRA) with low aldosterone
- Low DHEAS levels
- Mild hypercalcaemia (10-20% of cases)
Critical Pitfall to Avoid
Do not delay treatment if acute adrenal insufficiency is suspected 1. The guideline explicitly states that treatment should never be delayed by diagnostic procedures. Draw the blood samples for cortisol and ACTH, then immediately initiate hydrocortisone if clinical suspicion is high (unexplained collapse, hypotension, vomiting, diarrhea with hyponatremia).
Why This Takes Priority Over Standard Hyponatremia Workup
While the standard hyponatremia evaluation includes serum osmolality, volume status assessment, urine sodium, and urine osmolality 2, 3, the presence of an adrenal mass fundamentally changes your diagnostic priority. Adrenal insufficiency is a reversible cause of hyponatremia with significant mortality risk if missed 4, 5. The basal cortisol and ACTH values may appear deceptively normal in some cases, particularly when cortisol levels are "inappropriately low for the disease state" 1, making it essential to interpret results in clinical context.
Subsequent Etiologic Investigation
Once PAI is confirmed, determine the cause by measuring serum 21-hydroxylase (anti-adrenal) autoantibodies. If negative, the CT scan you already have will help evaluate for structural causes, though in males you should also check very long-chain fatty acids to exclude adrenoleukodystrophy 1.