Why test cortisol levels in a patient with elevated Aspartate Aminotransferase (AST) who works night shifts from 7pm-7am?

Cortisol Testing in Patients with Elevated AST and Night Shift Work

For patients with elevated AST, cortisol testing should be performed using the overnight dexamethasone suppression test rather than late-night salivary cortisol, as the latter is unreliable in night shift workers due to disrupted circadian rhythms. 1

Connection Between Elevated AST and Cushing's Syndrome

Elevated AST (Aspartate Aminotransferase) may warrant cortisol testing for several important reasons:

1. Liver involvement in hypercortisolism: Cushing's syndrome can cause hepatic steatosis and elevated liver enzymes including AST
2. Metabolic effects: Excess cortisol can lead to insulin resistance, diabetes, and obesity, all of which can cause non-alcoholic fatty liver disease with elevated AST
3. Screening for adrenocortical carcinoma: Some adrenal tumors that cause Cushing's syndrome may present with elevated liver enzymes due to metastatic disease 1

Appropriate Cortisol Testing for Night Shift Workers

For someone working night shifts (7pm-7am), the standard cortisol testing protocols must be modified:

Recommended Testing Approach:

1. Overnight 1-mg Dexamethasone Suppression Test (DST):

   • Preferred test for shift workers with disrupted circadian rhythms 1
   • Give 1 mg dexamethasone orally at 11:00 pm (or equivalent time before sleep) 2
   • Draw blood for plasma cortisol at 8:00 am the following morning (or 8 hours after sleep)
   • Normal response: cortisol < 1.8 μg/dL (50 nmol/L)

2. 24-hour Urinary Free Cortisol (UFC):

   • Collect 2-3 separate 24-hour urine samples
   • Independent of circadian rhythm disruption
   • Advantage: not affected by sleep/wake cycle alterations 1

Tests to Avoid in Night Shift Workers:

• Late-night salivary cortisol (LNSC): This test should NOT be performed in patients with disruption of the normal day/night cycle, such as night-shift workers 1
  • Night work is associated with elevated cortisol secretion regardless of disease status 3
  • The cortisol nadir is tightly entrained to sleep onset, not time of day 1

Special Considerations for Night Shift Workers

• Cortisol profiles appear to be blunted during night work and days off in permanent night workers 4
• Recovery from night shift takes longer time for cortisol rhythm normalization 5
• Consider collecting samples during days off when the patient has had at least one week to readapt to a normal sleep schedule 5
• If using DST, measure dexamethasone levels concurrently with cortisol to reduce risk of false-positive results 1

Follow-up Testing if Initial Screening is Positive

If initial testing suggests hypercortisolism:

1. Confirm ACTH status: Measure morning plasma ACTH to determine if Cushing's is ACTH-dependent or independent 1
2. Additional confirmatory testing: Low-dose dexamethasone suppression test (LDDST) over 48 hours 1
3. Imaging: MRI of pituitary or adrenal glands depending on ACTH results 1

Common Pitfalls to Avoid

• False positives: Night shift work itself can elevate cortisol levels 3
• Timing issues: Ensure dexamethasone is taken at the appropriate time relative to the patient's sleep schedule, not the clock time
• Medication interactions: Check for medications that affect dexamethasone metabolism (fluoxetine, cimetidine, diltiazem) 1
• Repeat testing: Single abnormal results should be confirmed with additional testing due to the possibility of cyclic cortisol excess 1

By following these guidelines, you can appropriately evaluate for hypercortisolism in a patient with elevated AST who works night shifts, avoiding the pitfalls associated with circadian rhythm disruption.