From the Guidelines
Diagnosing adrenal insufficiency requires a combination of clinical assessment and laboratory testing, starting with a morning cortisol level and ACTH stimulation test, as recommended by the American Society of Clinical Oncology clinical practice guideline 1. The initial evaluation should include a morning cortisol level and ACTH stimulation test. For the ACTH stimulation test, synthetic ACTH (cosyntropin 250 mcg) is administered intravenously, with cortisol levels measured at baseline, 30 minutes, and 60 minutes after administration.
- A peak cortisol level below 18 μg/dL (500 nmol/L) indicates adrenal insufficiency, as suggested by the Endocrine Society guideline 1.
- To distinguish between primary and secondary adrenal insufficiency, measure ACTH levels - elevated ACTH suggests primary adrenal insufficiency (Addison's disease), while low or normal ACTH indicates secondary adrenal insufficiency. Additional testing may include:
- Aldosterone levels, renin activity, and adrenal antibodies for primary insufficiency
- Pituitary imaging for secondary causes Symptoms that should prompt testing include:
- Fatigue
- Weakness
- Weight loss
- Hyperpigmentation
- Salt craving
- Hypotension
- Electrolyte abnormalities (hyponatremia, hyperkalemia) Early diagnosis is crucial as untreated adrenal insufficiency can lead to life-threatening adrenal crisis, characterized by severe hypotension, shock, and electrolyte imbalances requiring immediate treatment with hydrocortisone 100 mg IV, fluids, and glucose, as recommended by the Society for Immunotherapy of Cancer toxicity management working group 1. In cases of suspected adrenal insufficiency, emergent therapy with dexamethasone is recommended, as it allows for a stimulation test to still be performed, and if the diagnosis is already confirmed, hydrocortisone 100 mg can be used 1.
From the Research
Adrenal Insufficiency Diagnosis
- Adrenal insufficiency is a rare disease characterized by cortisol deficiency, and its diagnosis can be challenging due to the rarity of the disease and limitations in biochemical assessment of cortisol status 2.
- The adrenocorticotropic hormone (ACTH) stimulation test is commonly used to diagnose adrenal insufficiency, and its interpretation should take into account the clinical presentation and technical factors that can affect cortisol values 2, 3.
- 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 3.
- Basal cortisol levels have poor sensitivity to diagnose adrenal insufficiency, and the ACTH stimulation test is more effective in evaluating adrenal function 4.
- 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% 5.
- New diagnostic cutoffs for adrenal insufficiency after cosyntropin stimulation have been established for the Abbott Architect cortisol immunoassay, with a threshold of 14.6 μg/dL at 60 minutes after stimulation having a sensitivity of 92% and a specificity of 96% 6.
Diagnostic Tests
- ACTH stimulation test: commonly used to diagnose adrenal insufficiency, with low-dose and high-dose tests available 2, 3.
- Morning serum cortisol (MSC): can be used as a screening test for adrenal insufficiency, with a cutoff value of 234.2 mmol/L 5.
- Cosyntropin stimulation test: used to diagnose adrenal insufficiency, with new diagnostic cutoffs established for the Abbott Architect cortisol immunoassay 6.
- Intramuscular ACTH stimulation test: can be used to evaluate adrenal function, with a cutoff value of 18.0 microg/dl for post-ACTH serum cortisol 4.
Diagnostic Cutoffs
- Historical cutoff for polyclonal antibody-based immunoassays: 18 μg/dL 6.
- New diagnostic cutoff for Abbott Architect cortisol immunoassay: 14.6 μg/dL at 60 minutes after stimulation 6.
- Cutoff value for post-ACTH serum cortisol: 18.0 microg/dl 4.
- Cutoff value for morning serum cortisol (MSC): 234.2 mmol/L 5.