From the Guidelines
The workup for adrenal insufficiency should begin with morning cortisol and ACTH levels, followed by an ACTH stimulation test if initial results are inconclusive, as recommended by the most recent and highest quality study 1. The diagnostic process for adrenal insufficiency involves several key steps.
- Evaluate ACTH and cortisol levels in the morning to determine the relationship between these hormones and to distinguish between primary and secondary adrenal insufficiency.
- If the results are inconclusive, consider an ACTH stimulation test to assess the adrenal gland's response to ACTH stimulation.
- Additional testing should include electrolytes, blood glucose, and renin levels to evaluate for any electrolyte imbalances or other hormonal abnormalities.
- For primary adrenal insufficiency, consider testing for adrenal antibodies and imaging the adrenal glands with CT or MRI to determine the underlying cause.
- For suspected secondary adrenal insufficiency, pituitary MRI is recommended to evaluate the pituitary gland. During the diagnostic process, if the patient shows signs of adrenal crisis, immediate treatment with hydrocortisone 100 mg IV should be initiated, followed by fluid resuscitation with normal saline, without waiting for test results, as recommended by 1 and 1. The workup is essential because untreated adrenal insufficiency can lead to life-threatening adrenal crisis, while proper diagnosis allows for appropriate hormone replacement therapy. Some key points to consider in the workup and management of adrenal insufficiency include:
- Patients on corticosteroids for management of other conditions will have low morning cortisol as a result of iatrogenic, secondary adrenal insufficiency, and ACTH will also be low in these patients, as noted in 1.
- All patients need education on stress dosing and a medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by EMS, as recommended by 1.
- Endocrine consultation prior to surgery or any procedure for stress-dose planning is also crucial, as noted in 1.
From the Research
Adrenal Insufficiency Workup
- Adrenal insufficiency is a rare disease characterized by cortisol deficiency, and its evaluation 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 performed in patients suspected of having adrenal insufficiency when basal serum cortisol levels are inconclusive 2.
- Technical aspects such as time of day, type of assay, and sample source used for cortisol measurement can impact the clinical value of the ACTH stimulation test 2.
Diagnostic Tests
- Morning serum cortisol examinations and short ACTH tests are popular screening tests for unstressed patients suspected of having adrenal insufficiency 3.
- A mean basal morning serum cortisol of ≥ 300 nmol/L excludes the possibility of adrenal insufficiency, while a level of < 110 nmol/L suggests adrenal insufficiency 3.
- A basal cortisol value of > 236 nmol/L can predict adrenal sufficiency with sensitivity of 84% and specificity of 71% 4.
- High- and low-dose ACTH stimulation tests have similar diagnostic accuracy in adults and children using different peak serum cortisol cutoffs 5.
Cutoff Values
- A threshold of 14.6 μg/dL for cortisol at 60 minutes after ACTH stimulation is recommended for the Abbott Architect immunoassay 6.
- The use of assay-specific cutoffs is essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 6.
- Different assays may have different cutoff values, such as the Roche Elecsys II assay, which uses a monoclonal antibody and has lower thresholds compared to polyclonal antibody-based immunoassays 6.