When a Patient Requests Cortisol Testing
Order cortisol testing only when the patient has specific clinical features that suggest Cushing syndrome or adrenal insufficiency—do not test cortisol simply because a patient requests it without appropriate clinical indications. 1, 2
Clinical Features That Justify Cortisol Testing
For Suspected Cushing Syndrome (Hypercortisolism)
Screen patients who present with the following combination of features:
- Central obesity with growth deceleration (in children/adolescents—highly sensitive and specific) 3
- Hypertension plus diabetes with unexplained weight gain 1, 4
- Proximal muscle weakness combined with easy bruising 1, 2
- Wide purple striae (>1 cm), facial plethora, and supraclavicular fat accumulation 1, 4
- All patients with adrenal incidentalomas must be screened for autonomous cortisol secretion 1
For Suspected Adrenal Insufficiency
Test patients presenting with:
- Unexplained fatigue, weakness, weight loss with hypotension 5
- Hyperpigmentation (in primary adrenal insufficiency) 6
- History of exogenous steroid use being tapered or discontinued 3
First-Line Testing Algorithm
If Cushing Syndrome is Suspected:
Step 1: Choose initial screening test based on clinical context 1, 2
For adrenal incidentalomas: Start with 1 mg overnight dexamethasone suppression test (DST)—give 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM the next morning 1, 2
For clinical suspicion of Cushing syndrome: Use one of three first-line tests 2, 4
Step 2: If initial test is positive, confirm with a second different test 2
Step 3: Measure plasma ACTH to determine if hypercortisolism is ACTH-dependent (pituitary/ectopic) or ACTH-independent (adrenal) 2
- Normal or elevated ACTH (>1.1 pmol/L or >5 ng/L) indicates ACTH-dependent 3, 2
- Low/undetectable ACTH indicates ACTH-independent 2
If Adrenal Insufficiency is Suspected:
Step 1: Measure morning (8 AM-12 PM) serum cortisol 5
- <275 nmol/L warrants dynamic testing (96.2% sensitivity for adrenal insufficiency) 5
- For afternoon samples (12 PM-6 PM), use <250 nmol/L cutoff (96.1% sensitivity) 5
Step 2: If morning cortisol is indeterminate, perform ACTH stimulation test 6, 5
- High-dose (250 μg) cosyntropin stimulation test remains standard 3
- Peak cortisol <430-500 nmol/L at 30 or 60 minutes indicates adrenal insufficiency (assay-dependent) 3, 6
Critical Pitfalls to Avoid
Before any testing, confirm the patient is not taking exogenous glucocorticoids—this is the most common cause of abnormal cortisol results and will render testing meaningless 2
Do not use ACTH stimulation testing in critically ill patients with septic shock to decide on hydrocortisone treatment—the Surviving Sepsis Campaign guidelines recommend against this approach 3
Be aware of assay limitations: 7
- Automated immunoassays lack specificity and show significant inter-assay differences 7
- Results can be misleading in patients with altered serum protein concentrations 7
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers better specificity but cutoffs are not yet fully validated 7
Remember cyclic Cushing syndrome—if clinical suspicion remains high despite negative initial testing, repeat testing over time 2
The 1 mg DST may be unreliable in women taking oral estrogens and is preferred for shift workers with disrupted circadian rhythms 1
For patients on corticosteroids for other conditions (e.g., immune-related adverse events from checkpoint inhibitors), hold hydrocortisone for 24 hours before assessing endogenous function; other steroids require longer washout periods 3
When NOT to Test
Do not order cortisol testing for: