What labs should be followed in patients with adrenal insufficiency?

Laboratory Monitoring for Adrenal Insufficiency

Patients with established adrenal insufficiency require regular monitoring of morning cortisol and ACTH levels, basic metabolic panel (sodium, potassium, CO2, glucose), and blood pressure measurements to assess adequacy of replacement therapy and detect complications. 1, 2, 3

Initial Diagnostic Laboratory Panel

When first diagnosing adrenal insufficiency, obtain:

• Morning (8 AM) serum cortisol and plasma ACTH - These paired measurements distinguish primary from secondary adrenal insufficiency and establish baseline values 1, 2, 3, 4
• Basic metabolic panel - Assess for hyponatremia (present in 90% of newly diagnosed cases), hyperkalemia (present in ~50% of primary AI), and hypoglycemia 1, 2, 4
• Dehydroepiandrosterone sulfate (DHEAS) - Low levels support the diagnosis, particularly in primary adrenal insufficiency 4

Confirmatory Testing When Initial Results Are Indeterminate

• ACTH stimulation test (cosyntropin/Synacthen test) - Administer 0.25 mg cosyntropin intramuscularly or intravenously, then measure serum cortisol at 30 and/or 60 minutes post-administration 2, 4, 5
• Peak cortisol <500 nmol/L (18 μg/dL) is diagnostic of adrenal insufficiency 2, 4
• The test should be performed in the morning, though not strictly necessary 2

Etiologic Workup for Primary Adrenal Insufficiency

Once primary adrenal insufficiency is confirmed biochemically (high ACTH, low cortisol):

• 21-hydroxylase (anti-adrenal) autoantibodies - Identifies autoimmune etiology, the most common cause 2, 3
• Adrenal CT imaging - If autoantibodies are negative, evaluate for metastasis, hemorrhage, tumor, or infection 1, 2, 3
• Very long-chain fatty acids - In male patients, to screen for adrenoleukodystrophy 3

Ongoing Monitoring for Patients on Replacement Therapy

Routine Laboratory Monitoring

• Serum electrolytes (sodium, potassium) - Monitor regularly to assess mineralocorticoid replacement adequacy in primary AI and detect over-replacement 1, 6
• Blood pressure measurements - Check at regular intervals to detect hypertension from over-replacement or hypotension from under-replacement 6
• Morning cortisol levels - Periodic measurement helps assess if replacement dosing is appropriate, though interpretation is complex in patients on exogenous steroids 1, 4

Important Monitoring Considerations

Hydrocortisone must be held for 24 hours and other steroids for longer before endogenous cortisol function can be accurately assessed - Therapeutic steroids interfere with cortisol assays 1

In patients with a history of corticosteroid treatment for other conditions, test the HPA axis for recovery after 3 months of maintenance therapy with hydrocortisone - Exogenous steroid use can cause isolated central adrenal insufficiency 1

For patients on fludrocortisone (mineralocorticoid replacement), check serum potassium levels at frequent intervals - Potassium-depleting diuretics and amphotericin B enhance hypokalemia risk 6

Critical Pitfalls to Avoid

• Never delay treatment of suspected acute adrenal crisis to obtain diagnostic tests - Adrenal crisis is life-threatening and requires immediate IV hydrocortisone and fluid resuscitation 2, 3, 4
• Do not rely solely on electrolyte abnormalities for diagnosis - Hyperkalemia is present in only 50% of primary AI cases, and hyponatremia may be only marginally reduced 2
• Laboratory confirmation of AI should not be attempted in patients on high-dose corticosteroids for other conditions until treatment is ready to be discontinued - Results will be uninterpretable 1
• ACTH stimulation testing can give false-negative results early in hypophysitis - Adrenal reserve declines slowly after pituitary stimulation is lost; if clinical uncertainty exists, opt for replacement and retest at 3 months 1

Special Monitoring Situations

For patients on immune checkpoint inhibitors - Monitor glucose at baseline and with each treatment cycle while on therapy and at follow-up visits for at least 6 months to detect checkpoint inhibitor-associated diabetes mellitus 1

Before surgery or procedures - Ensure endocrine consultation for stress-dose planning and verify adequate cortisol coverage 2