Cortisol Test: Purpose, Test Details & Results

Purpose of Cortisol Test

Cortisol, often called the "stress hormone," plays a vital role in regulating the body's response to stress, metabolism, immune function, and more. Measuring cortisol through various tests helps healthcare providers diagnose and monitor disorders involving the adrenal glands, such as Addison’s disease (adrenal insufficiency) and Cushing’s syndrome (excess cortisol production). Understanding the purpose of a cortisol test is the first step in demystifying why this test is so important for health and well-being.

Diagnosing Adrenal Disorders

Cortisol testing is central to diagnosing diseases where there is either too little or too much cortisol:

• Addison’s disease: Characterized by deficient cortisol production, leading to fatigue, weight loss, and low blood pressure. Testing confirms low cortisol and helps differentiate from other causes of similar symptoms 1 2.
• Cushing’s syndrome: Marked by excess cortisol, which can cause obesity, high blood pressure, and skin changes. Testing helps confirm the diagnosis and guides further investigation 1.

Monitoring Treatment and Disease Progression

For patients already diagnosed with adrenal disorders, cortisol testing is essential to monitor:

• Treatment effectiveness: Ensures medications or surgeries are working as intended.
• Adrenal recovery: Especially after suppression due to long-term steroid use, as in patients recovering hypothalamo-pituitary-adrenal (HPA) axis function 10.

Screening and Risk Assessment

In certain cases, cortisol tests are used to screen individuals at risk for adrenal insufficiency, especially when clinical symptoms suggest the possibility. Morning serum cortisol is often used as a first-line screening tool, potentially reducing the need for more complex stimulation tests 2.

Cortisol Test Details

Cortisol can be measured in blood, saliva, urine, and even sweat. The choice of test, sample type, and timing all impact the results and their interpretation. Recent advances in assay technology and innovative sensor designs have improved accuracy, convenience, and accessibility.

Laboratory-Based Cortisol Tests

Immunoassays and Enzyme Immunoassays (EIA):

• Widely used in clinical labs due to automation and sensitivity.
• Potential for cross-reactivity unless extraction and purification steps are performed 1.

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS):

• Considered the gold standard for cortisol measurement.
• Offers high specificity and is less prone to interference.
• Used as a reference for calibrating newer immunoassays 1 3 5.

Sample Types and Timing

• Serum (Blood): Most common; typically measured in the morning when cortisol peaks 2 5.
• Saliva: Non-invasive and useful for detecting diurnal variation or nighttime elevations (e.g., late-night salivary cortisol for Cushing’s screening) 1 5.
• Urine: 24-hour urinary free cortisol is useful for assessing total daily secretion, especially for Cushing’s syndrome 1 11.
• Sweat: Emerging technology allows for rapid, non-invasive measurement, particularly useful for stress and circadian studies 9.

Rapid and Point-of-Care Testing

Innovations have led to the development of novel devices for faster, more convenient cortisol measurement:

• Electrochemical Sensors: Ultra-sensitive, rapid, and antibody-free, suitable for point-of-care or wearable applications 6 9.
• Paper-Based Immunosensors: Quick and cost-effective screening, particularly in resource-limited settings 8.
• Surface Plasmon Resonance (SPR) Biosensors: High sensitivity and selectivity using optical fiber technology 7.

Test Procedures

• Standard Dose Cosyntropin (ACTH) Stimulation Test: Measures adrenal response to synthetic ACTH; samples typically taken at baseline, 30, and 60 minutes post-injection 3 4 10.
• Dexamethasone Suppression Test: Used to evaluate for Cushing’s syndrome by assessing cortisol suppression after dexamethasone administration 11.

Cortisol Test Results & Follow-Up

Interpreting cortisol test results requires careful consideration of the test method, timing, and patient context. Cut-off values differ based on assay type and sample, and results must be integrated with clinical findings to guide next steps.

Understanding Your Results

Serum Cortisol:

• Morning levels are highest; a value within the reference range suggests normal adrenal function.
• Low levels, especially when tested in the morning, may indicate adrenal insufficiency 2 5.

ACTH (Cosyntropin) Stimulation Test:

• Normal response is a cortisol rise above assay-specific cut-offs (e.g., >411 nmol/L at 30 minutes using LC-MS/MS) 3 4.
• A blunted response suggests adrenal insufficiency.
• Recent studies indicate that lower cut-offs may be appropriate with newer assays, highlighting the importance of method-specific reference values 3 4.

Salivary and Urinary Cortisol:

• Elevated late-night salivary cortisol or increased 24-hour urinary free cortisol may indicate Cushing’s syndrome 1 11.
• Salivary and sweat-based tests are increasingly used for dynamic or non-invasive monitoring 5 9.

Follow-Up Steps

If Results Are Abnormal:

• Additional testing may be needed to confirm the diagnosis (e.g., repeat ACTH stimulation, dexamethasone suppression, imaging studies) 2 10.
• Consideration of medications, stress, and time of day is crucial, as these factors can influence cortisol levels 1 3 5.
• Treatment plans, such as steroid replacement for Addison’s disease or surgery for Cushing’s syndrome, are guided by test results and clinical evaluation.

For Monitoring:

• Repeat testing may be necessary to track recovery of adrenal function, especially after discontinuation of steroids or treatment of underlying disease 10.
• Wearable or rapid sensors may offer new ways to monitor cortisol trends in real time 6 7 9.

Conclusion

Cortisol testing is a cornerstone of diagnosing and managing adrenal disorders. It has evolved from traditional laboratory assays to include rapid, non-invasive, and wearable technologies. Understanding the test’s purpose, method, and interpretation is key to accurate diagnosis and effective treatment.

Main Points Covered:

• Cortisol tests are essential for diagnosing Addison’s disease, Cushing’s syndrome, and monitoring adrenal health 1 2 5.
• Multiple sample types and methods exist, each with unique advantages and limitations 1 3 5 6 7 8 9.
• Reference ranges and interpretation depend on method, timing, and clinical context 3 4 5 10 11.
• Rapid and point-of-care technologies are expanding access and convenience for cortisol measurement 6 7 8 9.
• Accurate interpretation and follow-up of results are crucial for effective management and recovery tracking 2 3 4 10.

Whether for diagnosis, monitoring, or screening, cortisol testing continues to grow in importance and accessibility—empowering both patients and clinicians in the pursuit of adrenal and overall health.