What is the workup for adrenal insufficiency?

From the Guidelines

The workup for adrenal insufficiency should begin with evaluating morning ACTH and cortisol levels, followed by a basic metabolic panel, renin, and aldosterone, and considering an ACTH stimulation test for indeterminate results, as recommended by the most recent guidelines 1. The initial step in the workup involves assessing morning serum cortisol and ACTH levels, with cortisol levels below 3 mg/dL suggesting adrenal insufficiency and levels above 15 mg/dL typically excluding it. Key components of the workup include:

• Evaluating AM levels of ACTH and cortisol
• Basic metabolic panel (Na, K, CO2, and glucose)
• Renin and aldosterone levels
• Considering a standard dose ACTH stimulation test for indeterminate results (AM cortisol between 3 mg/dL and 15 mg/dL)
• Evaluating for precipitating causes of crisis, such as infection
• Adrenal CT for metastasis or hemorrhage in cases of primary adrenal insufficiency It is crucial to note that during acute presentations, treatment with hydrocortisone should not be delayed while awaiting test results, and initiating treatment with hydrocortisone 100 mg IV immediately after collecting blood samples for diagnostic testing is recommended 1. Additional considerations include:
• Differentiating between primary and secondary adrenal insufficiency using plasma ACTH levels
• Assessing for electrolyte abnormalities, such as hyponatremia and hyperkalemia
• Evaluating glucose levels for hypoglycemia
• Considering adrenal antibodies and adrenal imaging with CT or MRI in primary adrenal insufficiency
• Recommending pituitary MRI for suspected secondary adrenal insufficiency The most recent and highest-quality study 1 provides the basis for these recommendations, emphasizing the importance of a stepwise approach to diagnosing and managing adrenal insufficiency.

From the FDA Drug Label

INDICATIONS & USAGE Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. ACTIONS Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states.

The workup for adrenal insufficiency is not directly addressed in the provided drug labels.

• The labels discuss replacement therapy for adrenocortical insufficiency, but do not outline the diagnostic workup.
• Key points to consider in a workup for adrenal insufficiency are not mentioned in the labels, such as clinical presentation, laboratory tests, and imaging studies. 2 and 3

From the Research

Workup for Adrenal Insufficiency

The workup for adrenal insufficiency involves a combination of clinical assessment, biochemical tests, and stimulation tests. The diagnosis is based on the measurement of basal hormone levels and the response to stimulation tests 4, 5, 6, 7.

Biochemical Tests

• Basal serum cortisol measurement at 8 am (<140 nmol/L or 5 mcg/dL) coupled with adrenocorticotrophin (ACTH) levels remain the initial tests of choice 7
• Measurement of electrolyte levels, including sodium and potassium, to assess for mineralocorticoid deficiency
• Measurement of adrenal androgen levels, such as dehydroepiandrosterone sulfate (DHEA-S), to assess for adrenal androgen deficiency

Stimulation Tests

• Cosyntropin stimulation (short synacthen) test to confirm the diagnosis of adrenal insufficiency 5, 7
• Insulin tolerance test, which is the gold standard for secondary adrenal insufficiency 5
• Salivary cortisol test, which is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels, such as pregnancy 7

Imaging and Other Tests

• Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), to evaluate the adrenal glands and pituitary gland
• Testing the hypothalamic-pituitary-adrenal (HPA) axis to assess for secondary or tertiary adrenal insufficiency
• Evaluation for underlying causes of adrenal insufficiency, such as autoimmune disorders, cancer, or infection 6, 7

Special Considerations

• Children and infants require lower doses of cosyntropin for testing 7
• Patients with adrenal insufficiency require close follow-up and permanent dose adjustment during different somatic situations to prevent adrenal crisis 8
• Certain medications, such as bulking agents, may interfere with glucocorticoid absorption and trigger acute adrenal crisis in patients with adrenal insufficiency 8