What is the initial workup for a patient presenting with new adrenal insufficiency of unknown cause?

From the Guidelines

The initial workup for a patient presenting with new adrenal insufficiency of unknown cause should begin with evaluating morning ACTH levels and cortisol levels, as well as basic metabolic panel, renin, and aldosterone, and consider an adrenal CT for metastasis or hemorrhage, as recommended by the most recent guidelines 1. The workup should include:

• Evaluating AM levels of ACTH (if > 23 ULN) and cortisol level (if < 3 mg/dL) to confirm the diagnosis and determine its etiology
• Basic metabolic panel (Na, K, CO2, and glucose) to assess for any electrolyte imbalances or metabolic disturbances
• Renin and aldosterone levels to evaluate for any abnormalities in the renin-angiotensin-aldosterone system
• Consider a standard dose ACTH stimulation test for indeterminate results (AM cortisol > 3 mg/dL and < 15 mg/dL) to confirm the diagnosis of adrenal insufficiency
• Evaluate for precipitating cause of crisis such as infection, and perform appropriate cultures or serologic testing if suspected
• Adrenal CT for metastasis or hemorrhage, which are the most common causes of primary adrenal insufficiency, as recommended by the guidelines 1 This approach is supported by the most recent guidelines, which prioritize the evaluation of ACTH and cortisol levels, as well as adrenal imaging, in the workup of patients with new-onset adrenal insufficiency 1. Additionally, the guidelines recommend considering the patient's clinical presentation and medical history when determining the need for further testing, such as pituitary MRI or testing for other pituitary hormones 1. It is also important to note that the diagnosis and treatment of adrenal insufficiency should be guided by the most recent and highest-quality evidence, and that the guidelines may be updated as new evidence becomes available 1.

From the Research

Initial Workup for New Adrenal Insufficiency of Unknown Cause

The initial workup for a patient presenting with new adrenal insufficiency of unknown cause involves a stepwise diagnostic approach to confirm the underlying diagnosis and rule out other differential diagnostic possibilities 2.

• Clinical Presentation: The patient's clinical presentation, including symptoms such as fatigue, weight loss, and hypotension, should be evaluated to determine the likelihood of adrenal insufficiency before testing 3.
• Laboratory Tests: Basal serum cortisol levels and adrenocorticotropic hormone (ACTH) stimulation test can be performed to evaluate the cortisol status and diagnose adrenal insufficiency 3.
• Imaging Studies: Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), may be necessary to evaluate the adrenal glands and pituitary gland for potential causes of adrenal insufficiency, such as tumors or autoimmune adrenalitis 2, 4.
• Autoantibody Tests: Tests for autoantibodies against adrenal steroid 21-hydroxylase may be performed to diagnose autoimmune adrenalitis, a common cause of primary adrenal insufficiency 5.

Diagnostic Considerations

When interpreting the results of the ACTH stimulation test, clinicians should consider the clinical presentation, time of day the test is performed, type of assay and sample source used for cortisol measurement, and other technical factors that can affect cortisol values and diagnostic accuracy 3.

• Primary Adrenal Insufficiency: Primary adrenal insufficiency is most frequently caused by autoimmune adrenalitis, and the diagnosis can be confirmed by the presence of autoantibodies against adrenal steroid 21-hydroxylase and characteristic laboratory findings, such as elevated plasma renin and serum aldosterone levels 2, 5.
• Secondary Adrenal Insufficiency: Secondary adrenal insufficiency is most often caused by pituitary tumors and their treatment, and the diagnosis can be confirmed by imaging studies and laboratory findings, such as low ACTH levels and normal or low serum cortisol levels 2, 4.

Treatment and Management

The treatment and management of adrenal insufficiency involve chronic replacement therapy with glucocorticoids and, in primary adrenal insufficiency, mineralocorticoids, as well as careful monitoring and education on how to adjust hydrocortisone doses in stressful situations 2, 4, 5.

• Glucocorticoid Replacement: Hydrocortisone is commonly used for glucocorticoid replacement, and the dose should be adjusted based on clinical judgment and laboratory findings 4.
• Mineralocorticoid Replacement: Fludrocortisone is commonly used for mineralocorticoid replacement, and the dose should be adjusted to achieve normotension, normokalaemia, and a plasma renin activity in the upper normal range 4.