What is the interpretation of salivary cortisol results showing hypocortisolism, in terms of adrenal function and potential diagnosis of cortisol imbalance, such as adrenal insufficiency or Cushing's syndrome?

Interpretation of Salivary Cortisol Results

These salivary cortisol values (0.04-0.10 µg/dL) are all below the normal reference range and suggest adrenal insufficiency, not Cushing's syndrome. The values require confirmation with serum cortisol testing and ACTH stimulation testing to establish the diagnosis and determine whether the insufficiency is primary or secondary. 1, 2

Understanding the Results

Your salivary cortisol measurements show:

• Day 1: Morning 0.10 µg/dL, Evening 0.04 µg/dL
• Day 2: Late morning 0.09 µg/dL, Evening 0.08 µg/dL

All values are markedly below the expected normal ranges:

• Normal morning salivary cortisol: approximately 0.37-0.75 µg/dL (10.2-27.3 nmol/L converted) 3
• Normal evening salivary cortisol: approximately 0.08-0.15 µg/dL (2.2-4.1 nmol/L converted) 3
• After ACTH stimulation in normal subjects: approximately 0.65-2.73 µg/dL (23.5-99.4 nmol/L converted) 3

Clinical Significance

These low values are consistent with hypocortisolism (adrenal insufficiency), not hypercortisolism (Cushing's syndrome). 3, 4

The pattern shows:

• Absent or minimal diurnal variation between morning and evening samples on Day 1, which is abnormal 5, 3
• Persistently low cortisol production across all time points 3
• Values suggesting inadequate cortisol response that would be seen in primary or secondary adrenal insufficiency 3, 4

Critical Next Steps

You must proceed with confirmatory serum testing immediately, as salivary cortisol alone cannot definitively diagnose adrenal insufficiency. 1, 2

Required Confirmatory Testing:

1. Morning serum cortisol (8 AM): A value <3 µg/dL (80 nmol/L) strongly suggests adrenal insufficiency 4, 6

2. Plasma ACTH measurement: This distinguishes primary (elevated ACTH) from secondary (low/normal ACTH) adrenal insufficiency 4

3. High-dose ACTH stimulation test (250 µg): This is the gold standard for confirming adrenal insufficiency 1, 7

   • In adrenal insufficiency, cortisol fails to rise adequately (typically <18-20 µg/dL peak) 7, 4
   • Normal response shows cortisol rising to >18-20 µg/dL at 30-60 minutes 7

Important Caveats

Do not rely solely on salivary cortisol for diagnosing adrenal insufficiency. While salivary cortisol is well-validated for screening Cushing's syndrome (where late-night values >0.13 µg/dL are abnormal), it has significant limitations for diagnosing adrenal insufficiency: 8, 1, 2

• Critical care societies specifically recommend against using salivary cortisol for diagnosing adrenal insufficiency due to limited evidence and practical challenges 1, 2
• Serum total cortisol remains the standard for evaluating adrenal insufficiency 1, 2
• Multiple confounding factors can affect salivary cortisol: age, gender, collection timing, saliva volume, and blood contamination 1, 2

Potential False Low Results:

• Medications affecting cortisol metabolism (thyroid hormones, certain psychotropic agents) 3
• Inadequate saliva volume or contamination 1, 2
• Improper collection technique 1, 2

Clinical Context Matters

If this patient has symptoms of adrenal insufficiency (fatigue, weakness, weight loss, hypotension, hyperpigmentation in primary AI), this is a medical urgency. 4

• Patients with confirmed adrenal insufficiency require immediate glucocorticoid replacement to prevent adrenal crisis 4
• Do not delay treatment if clinical suspicion is high while awaiting confirmatory testing 4
• Consider empiric hydrocortisone if the patient is acutely ill, then perform testing after stabilization 8

Risk Factors to Assess:

• Recent or chronic glucocorticoid use (including epidural steroid injections, which can cause AI in 11.8% of long-term users) 9
• Autoimmune diseases (for primary adrenal insufficiency) 4
• Pituitary or hypothalamic disorders (for secondary adrenal insufficiency) 4
• Critical illness or cirrhosis (which can cause relative adrenal insufficiency) 8

In cirrhotic patients specifically, baseline salivary cortisol <0.18 µg/dL suggests relative adrenal insufficiency, which matches your patient's values. 8