From the Guidelines
If your cortisol level is 4 μg/dL, you should next check ACTH (adrenocorticotropic hormone) levels to determine if the low cortisol is due to primary adrenal insufficiency or secondary/tertiary adrenal insufficiency. A morning cortisol of 4 μg/dL is concerning for adrenal insufficiency, as normal morning levels typically range from 10-20 μg/dL. In addition to ACTH, consider an ACTH stimulation test (Synacthen test), which evaluates how well your adrenal glands respond to stimulation, as recommended by the ASCO guideline update 1.
Key Considerations
- Complete thyroid function tests, electrolytes (particularly sodium and potassium), and glucose levels are also important to check, as adrenal insufficiency can affect these parameters.
- If ACTH is elevated with low cortisol, this suggests primary adrenal insufficiency (Addison's disease), while low or normal ACTH with low cortisol points to secondary (pituitary) or tertiary (hypothalamic) causes.
- These follow-up tests are crucial because untreated adrenal insufficiency can lead to serious complications including adrenal crisis, which requires immediate medical attention.
- The management of adrenal insufficiency should be guided by the most recent and highest quality evidence, such as the ASCO guideline update 1, which provides recommendations for the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy.
Additional Tests
- Basic metabolic panel (Na, K, CO2, and glucose) should be evaluated, as well as renin and aldosterone levels, to assess for any electrolyte imbalances or abnormalities in the renin-angiotensin-aldosterone system.
- Consider evaluating for precipitating causes of crisis, such as infection, and perform an adrenal CT for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency, as recommended by the ASCO guideline update 1.
Importance of Early Detection and Treatment
- Early detection and treatment of adrenal insufficiency are critical to prevent serious complications, including adrenal crisis, which can be life-threatening.
- The ASCO guideline update 1 emphasizes the importance of early endocrinology consultation and education on stress dosing, emergency injectables, and medical alert bracelets for patients with adrenal insufficiency.
From the Research
Next Steps for AM Cortisol 4
- If the morning serum cortisol level is 4, which is below the threshold of 13 mcg/dL, further evaluation is needed to rule out adrenal insufficiency 2.
- The next step would be to perform a cosyntropin stimulation test (CST) to assess the adrenal gland's response to adrenocorticotropic hormone (ACTH) 2, 3.
- The CST can be performed using a 250 mcg or 1 mcg dose of cosyntropin, with the 1 mcg test having better diagnostic discrimination 2, 4.
- The test involves measuring cortisol levels at baseline and after stimulation with cosyntropin, with a normal response indicating adequate adrenal function 3, 5.
- The interpretation of the CST results depends on the assay used to measure cortisol levels, with newer assays requiring lower cutoff values to diagnose adrenal insufficiency 5, 6.
- A cortisol level below the assay-specific cutoff after stimulation may indicate impaired adrenocortical reserve, and further evaluation or treatment may be necessary 4, 6.