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

From the Guidelines

The initial workup for a patient suspected of having adrenal insufficiency should begin with a morning serum cortisol level and an ACTH stimulation test, as recommended by the most recent and highest quality study 1. The morning serum cortisol level should be obtained between 6-8 AM when cortisol is naturally at its peak. A morning cortisol level below 5 μg/dL strongly suggests adrenal insufficiency, while levels above 15 μg/dL generally rule it out. The ACTH stimulation test is the gold standard diagnostic test and involves measuring cortisol levels before and after administering 0.25 mg of synthetic ACTH (cosyntropin) intravenously or intramuscularly, as stated in 1. Blood samples are collected at baseline, 30 minutes, and 60 minutes post-administration. A normal response is a peak cortisol level above 550 nmol L1, as indicated in 1; failure to reach this threshold confirms adrenal insufficiency. Additional laboratory tests should include:

• Serum ACTH level (elevated in primary adrenal insufficiency, low or normal in secondary)
• Electrolytes (looking for hyponatremia, hyperkalemia)
• Blood glucose (hypoglycemia)
• Complete blood count Measuring renin and aldosterone levels can help assess mineralocorticoid deficiency in primary adrenal insufficiency. If secondary adrenal insufficiency is suspected, additional pituitary hormone testing and pituitary imaging may be necessary, as suggested in 1. It is crucial to note that treatment should never be delayed because of the need to carry out diagnostic procedures, especially if there is a clinical suspicion of impending acute adrenal crisis, as emphasized in 1 and 1. In such cases, the patient should be given intravenous hydrocortisone immediately and a physiologic saline infusion, as recommended in 1 and 1. These tests are crucial for diagnosis as adrenal insufficiency can be life-threatening if untreated, with symptoms often being nonspecific and developing gradually over time. The diagnostic workup should be guided by the clinical presentation and suspicion of adrenal insufficiency, as outlined in 1. In cases where the diagnosis is uncertain, a cosyntropin stimulation test may be necessary to confirm the diagnosis, as stated in 1. The test involves administering 0.25 mg of cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol after 30 and/or 60 minutes, as described in 1. One of these values should exceed 550 nmol L1 to be deemed normal, as indicated in 1. Overall, the initial workup for adrenal insufficiency should be guided by the most recent and highest quality evidence, with a focus on prompt diagnosis and treatment to prevent morbidity and mortality, as emphasized in 1 and 1.

From the FDA Drug Label

2.1 Important Information Before Conducting Cosyntropin for Injection Testing • In general, stop glucocorticoids and spironolactone on the day of cosyntropin for injection testing. • Stop estrogen-containing drugs four to six weeks before cosyntropin for injection testing 2.5 Administration Information • Obtain blood sample for baseline serum cortisol. • Obtain blood samples again for assessment of cortisol levels exactly 30 minutes and 60 minutes after administration of cosyntropin for injection. 2.6 Interpretation of Plasma Cortisol Levels after Cosyntropin for Injection • Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency.

The initial workup for a patient suspected of having adrenal insufficiency involves:

• Stopping glucocorticoids and spironolactone on the day of testing
• Stopping estrogen-containing drugs four to six weeks before testing
• Obtaining a baseline serum cortisol blood sample
• Administering cosyntropin for injection and obtaining blood samples for assessment of cortisol levels at 30 and 60 minutes after administration
• Interpreting plasma cortisol levels to determine the presence of adrenocortical insufficiency, with levels less than 18 mcg/dL at 30 or 60 minutes post-injection being suggestive of the condition 2

From the Research

Initial Workup for Adrenal Insufficiency

The initial workup for a patient suspected of having adrenal insufficiency involves several steps, including:

• Morning serum cortisol examinations and short corticotropin (ACTH) tests are popular screening tests for unstressed patients suspected of having adrenal insufficiency 3
• A mean basal morning serum cortisol of > or = 300 nmol/L excludes the possibility of adrenal insufficiency, and a level of < 110 nmol/L suggests adrenal insufficiency 3
• The short ACTH test or insulin tolerance test should be performed in patients with a morning cortisol level < 300 nmol/L or with clinical symptoms highly suggestive of adrenal insufficiency 3

Diagnostic Tests

Diagnostic tests for adrenal insufficiency include:

• Short synacthen test, which is regarded as the gold standard 4
• Insulin tolerance test (ITT) 5
• Unstimulated early morning cortisol in saliva and serum, which can be used as a first-line parameter to assess adrenal function in patients with suspected secondary adrenal insufficiency 5
• Basal salivary cortisol (BSaC) and basal serum cortisol (BSeC) levels, which can be used to diagnose adrenal insufficiency, with upper and lower cutoffs of 470 and 103 nmol/l for BSeC, and 21.1 and 5.0 nmol/l for BSaC, respectively 5

Interpretation of Test Results

The interpretation of test results for adrenal insufficiency includes:

• A basal cortisol value of > 236 nmol/l can predict adrenal sufficiency with sensitivity 84% and specificity 71% 6
• A basal cortisol value of > 375 nmol/l can predict adrenal sufficiency with sensitivity and specificity of 95% 6
• A morning cortisol level > 214 nmol/l may obviate the need for SST in patients with known pituitary disease, although 330 nmol/l gives a specificity of 95% 6