What is the initial step in the workup of a patient suspected of having adrenal insufficiency?

From the Guidelines

The initial step in the workup of a patient suspected of having adrenal insufficiency is to evaluate ACTH, cortisol level, and basic metabolic panel, as recommended by the most recent guidelines 1. This approach allows for the assessment of adrenal function and helps distinguish between primary and secondary adrenal insufficiency.

Key Components of the Initial Workup

• Evaluate ACTH (AM) and cortisol level (AM) to assess adrenal function
• Basic metabolic panel (Na, K, CO, glucose) to evaluate electrolyte balance and glucose levels
• Consider ACTH stimulation test for indeterminate results, as suggested by 1

Importance of Early Diagnosis and Treatment

Early diagnosis and treatment of adrenal insufficiency are crucial to prevent adrenal crisis and improve patient outcomes.

• If primary adrenal insufficiency is suspected, evaluate for precipitating causes of crisis, such as infection, and perform an adrenal CT for metastasis/hemorrhage, as recommended by 1
• The simultaneous measurement of ACTH and cortisol helps distinguish between primary adrenal insufficiency (elevated ACTH) and secondary/tertiary forms (low or inappropriately normal ACTH), as noted in 1

Considerations for Special Populations

• In patients with a recent history of treatment with corticosteroids, the HPA axis should be tested for recovery after 3 months of maintenance therapy with hydrocortisone, as suggested by 1
• Laboratory confirmation of adrenal insufficiency should not be attempted in patients given high-dose corticosteroids for other irAEs until treatment is ready to be discontinued, as recommended by 1

From the Research

Adrenal Insufficiency Workup

The initial step in the workup of a patient suspected of having adrenal insufficiency involves assessing cortisol levels.

• A morning serum cortisol level can be used to rule out adrenal insufficiency, with levels above a certain threshold indicating that the condition is unlikely 2, 3, 4.
• The specific threshold values may vary, but a morning serum cortisol level >13 mcg/dL has been suggested as a reliable indicator to rule out adrenal insufficiency 2.
• Other studies propose different thresholds, such as a morning serum cortisol of <275 nmol/L to identify subnormal-stimulated cortisol with high sensitivity 4.
• If the morning serum cortisol level is inconclusive, further evaluation with the cosyntropin stimulation test (CST) may be necessary 5, 2.
• The CST can help confirm the diagnosis of adrenal insufficiency, but its interpretation should consider clinical presentation and technical factors that can affect cortisol values 5.

Diagnostic Criteria

Diagnostic criteria for adrenal insufficiency based on serum cortisol levels include:

• A morning serum cortisol level <275 nmol/L to identify subnormal-stimulated cortisol with 96.2% sensitivity 4.
• An afternoon serum cortisol level <250 nmol/L to achieve 96.1% sensitivity 4.
• A mean basal morning serum cortisol of >300 nmol/L to exclude the possibility of adrenal insufficiency, and a level <110 nmol/L to suggest adrenal insufficiency 3.

Testing Considerations

When interpreting test results, clinicians should consider:

• The clinical presentation and likelihood of adrenal insufficiency before testing 5.
• Technical factors that can affect cortisol values, such as the time of day the test is performed and the type of assay used 5, 4.
• The use of basal salivary cortisol (BSaC) instead of basal serum cortisol (BSeC) as a first-line parameter to assess adrenal function, which offers advantages such as painless sampling 6.