From the Guidelines
Diagnosing adrenal insufficiency requires a combination of clinical assessment and laboratory testing, starting with the measurement of morning serum cortisol and ACTH levels, as recommended by the American Society of Clinical Oncology 1. The initial evaluation should include measurement of morning serum cortisol and ACTH levels.
- Morning serum cortisol level
- ACTH level Followed by an ACTH stimulation test, which is the gold standard diagnostic test, as suggested by the Journal of Internal Medicine 1. For the ACTH stimulation test, synthetic ACTH (cosyntropin/Synacthen) is administered at a dose of 250 μg intravenously, with cortisol levels measured at baseline, 30 minutes, and 60 minutes after administration.
- A normal response is a peak cortisol level above 18-20 μg/dL (500-550 nmol/L); failure to reach this threshold suggests adrenal insufficiency. Primary adrenal insufficiency is characterized by low cortisol with elevated ACTH levels, while secondary insufficiency shows low cortisol with low or inappropriately normal ACTH levels. Additional testing may include electrolytes (looking for hyponatremia and hyperkalemia), blood glucose (hypoglycemia), and adrenal antibodies to determine etiology. In suspected secondary adrenal insufficiency, pituitary imaging with MRI is recommended. Patients with symptoms of adrenal crisis (severe hypotension, shock, altered mental status) should receive immediate treatment with hydrocortisone 100 mg IV before completing diagnostic testing, as delaying treatment can be life-threatening, as emphasized by the Journal of Internal Medicine 1. The insulin tolerance test and metyrapone test are alternative diagnostic options but are less commonly used due to safety concerns and availability issues. It is essential to note that treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures, as stated in the Journal of Internal Medicine 1. The diagnostic test for primary PAI should be paired measurement of serum cortisol and plasma ACTH, and in equivocal cases, a synacthen (tetracosactide) stimulated peak serum cortisol <500 nmol L1 is diagnostic of PAI, as recommended by the Journal of Internal Medicine 1.
From the Research
Diagnostic Criteria for Adrenal Insufficiency
The diagnostic criteria for adrenal insufficiency, also known as Addison's disease, involve a combination of clinical suspicion, laboratory tests, and imaging studies. The diagnosis is often challenging due to the non-specific symptoms and variable clinical course [ 2, 3, 4, 5, 6 ].
Clinical Presentation
The clinical presentation of adrenal insufficiency can range from mild, non-specific symptoms such as fatigue, to life-threatening adrenal crisis with hemodynamic instability [ 2 ]. The symptoms can be insidious, making it essential to have a high index of suspicion [ 5 ].
Laboratory Tests
The diagnosis of adrenal insufficiency is made by demonstrating low basal and/or stimulated serum cortisol [ 4, 6 ]. The cosyntropin stimulation test is a specific test used to confirm the diagnosis [ 2, 6 ]. The insulin tolerance test is the gold standard for secondary adrenal insufficiency [ 6 ].
Diagnostic Clues
Important diagnostic clues include:
- Hyponatremia
- Hyperkalemia
- Hypotension refractory to fluids and vasopressors [ 5 ]
- Low baseline cortisol (<100 nmol/L) alongside raised adrenocorticotropic hormone (ACTH) [ 6 ]
Investigation and Management
A strategic approach to investigation can help identify the underlying cause of adrenal insufficiency [ 6 ]. Patient education and empowerment are crucial in managing the condition [ 4, 6 ]. Regular monitoring for features of under- and over-replacement is essential during follow-up [ 4 ].