When is checking cortisol levels warranted?

Reasons That Warrant Checking Cortisol Levels

Cortisol levels should be checked in patients with clinical features suggestive of cortisol excess (Cushing's syndrome) or deficiency (adrenal insufficiency), as well as in all patients with adrenal incidentalomas regardless of symptoms. 1

Clinical Presentations Warranting Cortisol Testing

1. Suspected Hypercortisolism (Cushing's Syndrome)

Clinical Features:

• Physical findings:

  • Central obesity with supraclavicular fat accumulation
  • Dorsocervical fat pad ("buffalo hump")
  • Facial plethora (ruddy complexion)
  • Purple and wide (>1 cm) striae
  • Easy bruising and ecchymoses
  • Thinned skin
  • Proximal muscle weakness or wasting
  • Hirsutism (in females)

• Medical conditions:

  • Severe or difficult-to-control hypertension
  • Diabetes mellitus with poor glycemic control
  • Osteoporosis (especially early onset)
  • Unexplained weight gain
  • Menstrual irregularities
  • Sleep disturbances
  • Depression or mood disorders

Testing Approach:

• First-line screening tests: 1

  • Late-night salivary cortisol (LNSC) - at least 2-3 samples
  • 1 mg overnight dexamethasone suppression test (DST)
  • 24-hour urinary free cortisol (UFC)

• Interpretation:

  • Normal cortisol suppression to <1.8 μg/dL (50 nmol/L) after DST excludes Cushing's syndrome
  • Values between 1.8-5.0 μg/dL (50-138 nmol/L) suggest possible autonomous cortisol secretion
  • Values >5.0 μg/dL (138 nmol/L) strongly suggest cortisol hypersecretion

2. Adrenal Incidentalomas

• All patients with adrenal incidentalomas should be screened for autonomous cortisol secretion regardless of symptoms. 1
• The 1 mg DST is the preferred screening test for identifying autonomous cortisol secretion in these patients
• Patients with adrenal incidentalomas and hypertension/hypokalemia should also be tested for primary aldosteronism using aldosterone/renin ratio

3. Suspected Adrenal Insufficiency

Clinical Features:

• Fatigue, weakness, weight loss
• Hypotension or orthostatic symptoms
• Hyperpigmentation (in primary adrenal insufficiency)
• Hyponatremia, hyperkalemia
• Hypoglycemia

Testing Approach:

• Morning cortisol levels as initial screening
• ACTH stimulation test for confirmation (normal response: peak cortisol >18-20 μg/dL) 2

4. Special Clinical Scenarios

• Ectopic ACTH production:

  • Patients with small cell lung cancer or bronchial carcinoid tumors should be evaluated for ectopic Cushing's syndrome 1
  • Clinical features include rapid onset of Cushing's syndrome symptoms with more prominent hyperpigmentation
  • Diagnosis is critical as hypercortisolism increases risk for therapy-induced complications and mortality

• Refractory shock:

  • Patients with septic shock refractory to vasopressors should be evaluated for adrenal insufficiency 2

• Cirrhosis:

  • Approximately 49% of patients with cirrhosis present with relative adrenal insufficiency 2

Common Pitfalls in Cortisol Testing

1. False positive results in DST may occur with:

   • Rapid absorption/malabsorption of dexamethasone
   • Concomitant treatment with CYP3A4 inducers (phenobarbital, carbamazepine, St. John's wort)
   • Increased corticosteroid binding globulin levels (oral estrogens, pregnancy) 1

2. False negative results in DST may occur with:

   • Medications that inhibit dexamethasone metabolism (fluoxetine, cimetidine, diltiazem)
   • Decreased binding protein levels (nephrotic syndrome) 1

3. LNSC limitations:

   • Should not be performed in night-shift workers or those with disrupted day/night cycles
   • Multiple samples recommended due to potential for cyclic cortisol excess 1

4. UFC limitations:

   • High variability (up to 50%)
   • Influenced by renal function, urinary volume, and patient collection technique
   • Not recommended for patients with renal impairment or significant polyuria 1

By following these guidelines for appropriate cortisol testing, clinicians can identify patients with cortisol disorders early, leading to improved morbidity, mortality, and quality of life outcomes.