What are the indications for obtaining an Adrenocorticotropic Hormone (AM) cortisol level?

Indications for Obtaining an AM Cortisol Level

AM cortisol testing is indicated for suspected adrenal insufficiency, Cushing's syndrome, adrenal incidentalomas, and monitoring of glucocorticoid therapy, with paired ACTH measurement being the most definitive diagnostic approach for adrenal disorders. 1

Primary Indications

Suspected Adrenal Insufficiency

• Symptoms suggesting adrenal insufficiency:
  • Unexplained collapse, hypotension, vomiting, or diarrhea
  • Hyperpigmentation
  • Hyponatremia, hyperkalemia, acidosis, hypoglycemia 2
  • Fatigue, weight loss, orthostatic symptoms

Suspected Cushing's Syndrome

• Evaluation of patients with clinical features of cortisol excess:
  • Central obesity, facial plethora, proximal muscle weakness
  • Hypertension, hyperglycemia, hypokalemia 2
  • Purple striae, easy bruising

Adrenal Incidentalomas

• Screening for subclinical cortisol production in incidentally discovered adrenal masses 3
• Part of hormonal evaluation to determine functionality of adrenal tumors

Monitoring Therapy

• Assessment of hypothalamic-pituitary-adrenal (HPA) axis recovery after glucocorticoid therapy
• Monitoring adequacy of replacement therapy in patients with known adrenal insufficiency

Diagnostic Approach

Optimal Timing and Collection

• Morning cortisol should be measured between 6-8 AM when levels are at their physiologic peak
• Should be collected before administration of any glucocorticoid medication
• Paired measurement with plasma ACTH is the most definitive diagnostic approach 1

Interpretation Guidelines

• Normal morning cortisol: typically >500 nmol/L (>18 μg/dL)
• Morning cortisol <110 nmol/L strongly suggests adrenal insufficiency 4
• Morning cortisol ≥300 nmol/L generally excludes adrenal insufficiency in unstressed patients 4
• Intermediate values (110-300 nmol/L) require further testing

Follow-up Testing Based on AM Cortisol Results

For Suspected Adrenal Insufficiency

• If AM cortisol is indeterminate, an ACTH stimulation test should be performed 2, 1
• A peak cortisol <500 nmol/L after ACTH stimulation confirms adrenal insufficiency 2

For Suspected Cushing's Syndrome

• Elevated AM cortisol with loss of normal diurnal variation
• Additional tests include overnight dexamethasone suppression test, 24-hour urinary free cortisol 5

Important Considerations and Pitfalls

Confounding Factors

• Stress (including acute illness) can falsely elevate cortisol levels
• Medications affecting cortisol metabolism (e.g., estrogens, certain antiepileptics)
• Altered cortisol binding proteins can affect total cortisol measurements
• Exogenous steroid use may suppress endogenous cortisol production 2

Critical Caution

• Treatment of suspected acute adrenal insufficiency should never be delayed for diagnostic testing 2
• In acute illness with suspected adrenal crisis, cortisol <400 nmol/L with elevated ACTH raises strong suspicion of primary adrenal insufficiency 2

Special Populations

• Patients on immune checkpoint inhibitors should be monitored for immune-related adrenal insufficiency 2
• Patients with adrenal incidentalomas require screening for subclinical Cushing's syndrome 3
• Patients with pituitary disorders may need evaluation for secondary adrenal insufficiency

By following these guidelines for obtaining and interpreting AM cortisol levels, clinicians can effectively diagnose adrenal disorders and initiate appropriate management to reduce morbidity and mortality associated with these conditions.