From the Guidelines
To evaluate central adrenal insufficiency, the most important laboratory tests include morning serum cortisol, ACTH levels, TSH, free T4, and electrolytes, as recommended by the most recent guideline update 1. When assessing central adrenal insufficiency, it is crucial to consider the patient's clinical presentation and laboratory findings.
- Morning serum cortisol and ACTH levels are essential for initial evaluation, with cortisol levels below 3 μg/dL suggesting adrenal insufficiency and levels above 15 μg/dL typically ruling it out.
- The ACTH stimulation test is considered the gold standard for diagnosis, where synthetic ACTH is administered, and cortisol levels are measured at baseline, 30, and 60 minutes after administration 1.
- Additional tests, such as evaluating LH and testosterone in males, FSH, and estrogen in premenopausal females, may be necessary to assess for other hormonal deficiencies.
- An MRI brain with pituitary or sellar cuts may be considered in patients with new hormonal deficiencies, severe headaches, or vision changes, as well as in those presenting with diabetes insipidus 1. The diagnosis of central adrenal insufficiency is based on the combination of clinical presentation, laboratory findings, and imaging studies, with the goal of identifying patients who require hormone replacement therapy to improve morbidity, mortality, and quality of life.
- The evaluation of central adrenal insufficiency should prioritize the assessment of morning serum cortisol, ACTH levels, and other pituitary hormones, as well as imaging studies, to guide treatment decisions and improve patient outcomes, as supported by the most recent evidence 1.
From the Research
Central Adrenal Insufficiency Diagnosis
To diagnose central adrenal insufficiency, several laboratory tests can be used, including:
- Morning serum cortisol level: A level <83 nmol/L is diagnostic for central adrenal insufficiency, while a level >414 nmol/L excludes the condition 2
- Short Synacthen Test (SST): This is the most commonly used dynamic test, with a cortisol peak >500 nmol/L indicating normal adrenal function 3
- Insulin Tolerance Test (ITT): This is considered the gold standard test for evaluating hypothalamo-pituitary-adrenal axis function, but it is cumbersome and has potential risks 4
- Glucagon Stimulation Test (GST): This test can evaluate both hypothalamo-pituitary-adrenal and growth hormone-insulin-like growth factor 1 axes, and is a good alternative to ITT 4
- Low-dose Adrenocorticotrophic Hormone (ACTH) stimulation test: This test is a sensitive and safe alternative to ITT, and can be used to evaluate hypothalamo-pituitary-adrenal axis function 4
- Corticotropin-releasing hormone (CRH) test: This test has limited sensitivity and is not recommended as a second-line test for diagnosing adrenal insufficiency 5
Interpretation of Test Results
The interpretation of test results is crucial for diagnosing central adrenal insufficiency. For example:
- A morning serum cortisol level ≤323.3 nmol/L has a sensitivity of 87.7% and a specificity of 46.1% for predicting a deficient response to ITT 2
- A peak cortisol level during SST >500 nmol/L excludes central adrenal insufficiency, while a level <500 nmol/L indicates adrenal insufficiency 3
- The cortisol response to ITT, GST, or low-dose ACTH stimulation test can be used to evaluate hypothalamo-pituitary-adrenal axis function, but cut-off levels for insufficiency should be individualized for each test 4
Clinical Considerations
When diagnosing central adrenal insufficiency, it is essential to consider the clinical background of the patient, including:
- Presence of pituitary tumors, cranial irradiation, surgery, injury, or infections, which can increase the risk of central adrenal insufficiency 3, 6
- Symptoms such as fatigue, hyponatremia, or other nonspecific signs, which can be indicative of central adrenal insufficiency 3, 6
- The need for glucocorticoid replacement therapy, which should be individualized and tailored to the patient's specific needs 3, 6