From the Guidelines
Mildly elevated morning cortisol levels should be confirmed with repeat testing, ideally with a 24-hour urine cortisol or late-night salivary cortisol test, as recommended by the most recent guideline update 1. To approach mildly elevated am cortisol, consider the following steps:
- Confirm the elevation with repeat testing to rule out laboratory error or transient stress-related elevation.
- Use a 24-hour urine cortisol or late-night salivary cortisol test for confirmation, as these tests have high sensitivity and specificity for diagnosing Cushing's syndrome 1.
- While waiting for further evaluation, focus on stress reduction techniques like meditation, regular exercise, and adequate sleep to help regulate cortisol levels.
- Limit caffeine intake to before noon, maintain a balanced diet low in processed foods, and practice good sleep hygiene to support overall hormonal balance.
- If cortisol elevation is suspected to be stress-related, adaptogenic herbs like ashwagandha (300-500mg daily) may help, though consult your doctor before starting any supplements 1.
- Persistent elevation requires medical evaluation to rule out conditions like adrenal tumors or pituitary disorders, using tests such as the low-dose dexamethasone suppression test (LDDST) or bilateral inferior petrosal sinus sampling (BIPSS) for ACTH-dependent Cushing's syndrome 1.
- Cortisol follows a natural daily rhythm, highest in the morning to help you wake up and gradually decreasing throughout the day, so understanding this rhythm is crucial for proper diagnosis and management.
- Chronic elevation can lead to weight gain, muscle weakness, high blood pressure, and impaired immune function, making proper diagnosis and management important to prevent long-term morbidity and mortality 1. Key diagnostic tests and their cut-offs include:
- 24-hour urine cortisol: >193 nmol/24 h (>70 μg/m2) 1
- Late-night salivary cortisol: based on local assay cut-off 1
- LDDST: >=50 nmol/l (>=1.8 μg/dl) 1
- BIPSS: central-to-peripheral ACTH ratio >=3 after CRH or desmopressin stimulation 1
From the FDA Drug Label
The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex.
The FDA drug label does not answer the question about mildly elevated am cortisol.
From the Research
Mildly Elevated AM Cortisol
- A mildly elevated morning cortisol level can be an indicator of various conditions, including Cushing's syndrome (CS) or adrenal insufficiency (AI) 2, 3.
- The clinical diagnosis of hyper- and hypocortisolism can be established through laboratory methods such as measurement of "free" cortisol in a 24-hour urine sample or the low-dose dexamethasone suppression test 2.
- In patients with mildly elevated morning cortisol, further testing such as plasma ACTH measurement, corticotropin-releasing hormone injection test, or high-dose dexamethasone suppression test may be necessary to determine the origin of the condition 2.
Diagnostic Tests
- The overnight 1 mg dexamethasone suppression test and 24-hour urine free cortisol (UFC) are commonly used screening tests for Cushing's syndrome, with high sensitivity and specificity 3.
- Morning serum cortisol level can be used as a screening test for adrenal insufficiency, with a cutoff value of 234.2 mmol/L having a sensitivity of 83.3% and specificity of 89.1% 4.
- However, the predictive value of basal cortisol levels for diagnosing adrenal insufficiency is low, with a positive predictive value of 18.9% and low specificity 5.
Interpretation of Results
- A morning serum cortisol level <83 nmol/L is diagnostic for central adrenal insufficiency, while a value >414 nmol/L excludes the condition 6.
- A cutoff value of ≤323.3 nmol/L for morning serum cortisol has a sensitivity of 87.7% and specificity of 46.1% for predicting a deficient response to insulin tolerance test 6.
- Revising cortisol cutoffs and incorporating symptom-based criteria may improve diagnostic accuracy for adrenal insufficiency 5.