Fasting Requirements for Cortisol and ACTH Testing
No, fasting is not required for morning cortisol and ACTH measurements. The diagnostic guidelines for adrenal insufficiency specify only that these tests should be performed in the morning (preferably around 8 AM) to capture peak physiological cortisol levels, with no mention of fasting requirements 1.
Timing Requirements for Testing
Morning collection (around 8 AM) is essential because cortisol follows a diurnal rhythm with peak levels in the early morning, making this the optimal time to detect adrenal insufficiency 1.
The paired measurement of serum cortisol and plasma ACTH should be obtained simultaneously as the first-line diagnostic test for suspected primary adrenal insufficiency 1.
What Actually Matters for Accurate Testing
Critical Medication Considerations
Exogenous steroids must be held before testing, as they suppress the hypothalamic-pituitary-adrenal axis and confound results 2.
Hydrocortisone should be held for 24 hours before testing, while other steroids including prednisone require longer washout periods 2.
Prednisolone, dexamethasone, and inhaled steroids like fluticasone can all suppress the HPA axis and lead to false-negative findings 1, 2.
Drugs That Affect Cortisol Metabolism
Anti-epileptics, antituberculosis medications, antifungal drugs, etomidate, and topiramate increase hydrocortisone requirements and may affect test interpretation 1.
Grapefruit juice and liquorice decrease hydrocortisone requirements and should be avoided 1.
Diagnostic Interpretation
Basal cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in the presence of acute illness is diagnostic of primary adrenal insufficiency 1, 2.
Basal cortisol <400 nmol/L with elevated ACTH in acute illness raises strong suspicion of primary adrenal insufficiency 1.
A morning cortisol ≥300 nmol/L effectively excludes adrenal insufficiency in unstressed patients 3, 4.
When morning cortisol is equivocal (between 110-300 nmol/L), proceed with cosyntropin stimulation testing to definitively rule in or rule out adrenal insufficiency 1, 2.
Special Considerations for Your Patient
Autoimmune Thyroiditis Context
Patients with autoimmune hypothyroidism have increased risk of coexisting autoimmune adrenal insufficiency (Addison's disease), making screening appropriate if symptoms are present 1, 5.
Approximately 85% of primary adrenal insufficiency cases in Western populations are autoimmune in origin 2.
If adrenal insufficiency is confirmed, corticosteroids must be started several days before initiating or adjusting thyroid hormone replacement to prevent precipitating adrenal crisis, as thyroid hormone increases cortisol metabolism 2, 6.
Clinical Red Flags Warranting Testing
Unexplained hypotension, postural hypotension, or collapse 1, 2.
Hyponatremia, hyperkalemia, or hypoglycemia 1.
Critical Pitfall to Avoid
Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures 1, 2. If your patient is clinically unstable with suspected adrenal crisis, immediately administer IV hydrocortisone 100 mg and 0.9% saline infusion at 1 L/hour, drawing blood for cortisol and ACTH before treatment if possible but not delaying therapy 2, 7.