What does a cortisol level indicate?

Understanding Cortisol Level Measurements

Cortisol level measurements primarily indicate adrenal function and can diagnose conditions such as adrenal insufficiency or Cushing's syndrome, with interpretation varying based on collection time, method, and patient factors. 1

What Cortisol Levels Show

Cortisol levels provide critical information about:

1. Adrenal Gland Function

   • Low cortisol with elevated ACTH suggests primary adrenal insufficiency
   • Low cortisol with low/normal ACTH suggests secondary adrenal insufficiency
   • Elevated cortisol levels may indicate Cushing's syndrome 1

2. Hypothalamic-Pituitary-Adrenal (HPA) Axis Integrity

   • Morning cortisol levels reflect the circadian rhythm of cortisol production
   • Response to ACTH stimulation tests indicates adrenal reserve capacity
   • Suppression after dexamethasone indicates intact negative feedback mechanisms 1

Types of Cortisol Measurements

Serum Total Cortisol

• Most commonly used initial test
• Measures both bound (90-95%) and free (5-10%) cortisol in blood
• Normal morning values depend on assay method but generally range from 5-25 μg/dL
• Limitations: affected by changes in cortisol-binding globulin (CBG) levels 2, 1

Serum Free Cortisol

• Measures only the biologically active unbound portion
• More accurate in conditions affecting binding proteins (pregnancy, oral contraceptives, liver disease)
• Correlation between free and total cortisol is only 50-60% in critically ill patients 2
• Not routinely available in most laboratories due to cumbersome techniques 2

Salivary Cortisol

• Reflects unbound (free) cortisol levels
• Particularly useful for late-night measurements to assess circadian rhythm
• Normal late-night values typically <3.6 nmol/L
• Advantages: non-invasive collection, stable at room temperature
• Limitations: affected by oral contamination, smoking, and certain medications 1, 3

Urinary Free Cortisol (UFC)

• Reflects integrated tissue exposure to free cortisol over 24 hours
• More accurate in conditions affecting binding proteins
• Normal values typically <70 μg/m² per 24 hours
• Limitations: requires complete 24-hour collection, unreliable with renal impairment (CrCl <60mL/min) 1, 4

Clinical Applications

Diagnosing Adrenal Insufficiency

• Low morning cortisol (<3 μg/dL) suggests adrenal insufficiency
• ACTH stimulation test: cortisol level >18-20 μg/dL post-ACTH indicates normal adrenal function
• Metyrapone test: measures 11-desoxycortisol and ACTH levels after blocking cortisol synthesis 1, 5

Diagnosing Cushing's Syndrome

• Elevated late-night salivary cortisol (>90% sensitivity and specificity)
• Elevated 24-hour urinary free cortisol
• Failure to suppress cortisol after overnight dexamethasone suppression test 1, 4

Monitoring Treatment

• Cortisol levels help monitor replacement therapy in adrenal insufficiency
• Used to assess remission or recurrence after treatment for Cushing's syndrome 3

Important Considerations and Pitfalls

1. Timing Matters

   • Cortisol has a strong circadian rhythm (highest in morning, lowest at midnight)
   • Interpretation must consider collection time 1

2. Assay Differences

   • Newer, more specific assays (like LC-MS/MS) give lower values than older immunoassays
   • Diagnostic thresholds need adjustment based on assay method (e.g., 350 nmol/L vs. 500 nmol/L for ACTH stimulation tests) 6

3. Interfering Factors

   • Medications affecting HPA axis (glucocorticoids, anticonvulsants, estrogens)
   • Stress, critical illness, pregnancy, and oral contraceptives alter binding proteins
   • Renal function affects urinary cortisol measurements 1, 5

4. Special Populations

   • In pregnancy or with oral contraceptives, urinary free cortisol or salivary cortisol provides more accurate assessment than total serum cortisol 1
   • In critically ill patients, free cortisol may be more informative than total cortisol 2

Cortisol level interpretation requires consideration of clinical context, collection timing, assay method, and patient factors to accurately assess adrenal function and guide appropriate management.