From the Guidelines
To evaluate adrenal insufficiency, the most recent and highest quality study recommends starting with an early morning serum cortisol and ACTH level, followed by a standard dose ACTH stimulation test for indeterminate results, as well as evaluating for precipitating causes of crisis and considering adrenal imaging with CT or MRI 1.
Key Laboratory Tests
- Early morning (8 AM) serum cortisol and ACTH level to assess cortisol levels and ACTH stimulation
- Standard dose ACTH stimulation test for indeterminate results (AM cortisol ≥ 3 mg/dL and < 15 mg/dL) to confirm adrenal insufficiency
- Basic metabolic panel (Na, K, CO2, and glucose) to evaluate electrolyte imbalances and glucose levels
- Renin and aldosterone levels to assess primary adrenal insufficiency ### Additional Tests
- Adrenal antibodies to confirm primary adrenal insufficiency
- Adrenal imaging with CT or MRI to evaluate adrenal morphology and potential causes of primary adrenal insufficiency
- Pituitary MRI and additional pituitary hormone testing for suspected central (secondary/tertiary) adrenal insufficiency ### Diagnostic Approach The diagnostic approach should prioritize the most recent and highest quality study, which recommends a step-wise approach to evaluating adrenal insufficiency, starting with early morning cortisol and ACTH levels, followed by ACTH stimulation testing and additional tests as needed 1.
Test Interpretation
- A morning cortisol below 3 mg/dL strongly suggests adrenal insufficiency, while levels above 15 mg/dL typically rule it out
- A peak cortisol response below 18-20 μg/dL during the ACTH stimulation test indicates adrenal insufficiency
- Electrolyte imbalances, such as hyponatremia and hyperkalemia, and hypoglycemia can support the diagnosis of adrenal insufficiency
- Renin and aldosterone levels can help distinguish between primary and central adrenal insufficiency 1.
From the FDA Drug Label
Patients should be monitored regularly for blood pressure determinations and serum electrolyte determinations (see WARNINGS).
The laboratory tests indicated for patients taking fludrocortisone acetate, which may be relevant for adrenal insufficiency (Addison's disease), are:
- Blood pressure determinations
- Serum electrolyte determinations 2
From the Research
Laboratory Tests for Adrenal Insufficiency
The following laboratory tests are indicated for adrenal insufficiency (Addison's disease):
- Basal serum cortisol measurement at 8 am (<140 nmol/L or 5 mcg/dL) 3
- Adrenocorticotropic hormone (ACTH) stimulation test (cosyntropin stimulation test) to confirm the diagnosis 4, 3, 5, 6
- Measurement of plasma ACTH, renin activity, and aldosterone to diagnose primary adrenocortical insufficiency (PAI) 5
- Salivary cortisol test, which is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels, such as pregnancy 3
- 21-hydroxylase antibodies to rule out autoimmunity 3
- Testing the hypothalamic-pituitary-adrenal (HPA) axis, imaging, and ruling out systemic causes are necessary for the diagnosis of adrenal insufficiency 3
Specific Test Details
- The ACTH stimulation test is commonly performed in patients suspected of having adrenal insufficiency when the basal serum cortisol levels are inconclusive 4
- The low-dose ACTH stimulation test has been shown to be more sensitive and specific than the high-dose test, but the high-dose test is preferred since the low-dose test has not been validated 6
- Morning serum cortisol (MSC) can be used as a screening test for adrenal insufficiency, with a cutoff value of 234.2 mmol/L having a sensitivity of 83.3% and a specificity of 89.1% 7