What is the appropriate management for elevated morning (AM) cortisol levels?

From the Guidelines

Elevated morning cortisol levels should be managed by confirming the elevation with repeat testing, ideally with a 24-hour urinary free cortisol test or late-night salivary cortisol, and then referring to an endocrinologist for further evaluation and treatment, which may include medications such as ketoconazole, metyrapone, or mifepristone, depending on the underlying cause, as recommended by the most recent guidelines 1. The appropriate management of elevated morning cortisol levels depends on identifying and treating the underlying cause.

• First, confirm the elevation with repeat testing, ideally with a 24-hour urinary free cortisol test or late-night salivary cortisol to establish a complete cortisol rhythm pattern.
• If Cushing's syndrome is suspected, referral to an endocrinologist is necessary for further evaluation including dexamethasone suppression testing.
• For exogenous causes, gradually tapering corticosteroid medications under medical supervision is recommended.
• Lifestyle modifications can help manage mild elevations, including stress reduction techniques (meditation, yoga), regular exercise, adequate sleep hygiene, and reducing caffeine intake.
• Dietary changes such as limiting sugar, alcohol, and processed foods while increasing anti-inflammatory foods may be beneficial.
• For stress-related elevations, addressing the underlying stressors through cognitive behavioral therapy or other psychological interventions can be effective.
• Medications are typically reserved for specific diagnoses like Cushing's syndrome, which may require surgery, radiation, or medications such as ketoconazole, metyrapone, or mifepristone depending on the cause, as supported by recent studies 1. These interventions help normalize the hypothalamic-pituitary-adrenal axis function, which regulates cortisol production and maintains appropriate diurnal variation. In cases where cortisol levels are persistently elevated, consideration should be given to changing treatment or using combination therapy, as suggested by recent guidelines 1. It is also important to note that the management of elevated cortisol levels may involve a multidisciplinary approach, including endocrinology consultation, as highlighted in recent studies 1.

From the FDA Drug Label

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT. The FDA drug label does not answer the question.

From the Research

Elevated Morning Cortisol Management

Elevated morning (AM) cortisol levels can be an indicator of Cushing's syndrome or other hypercortisolism conditions. The management of elevated AM cortisol levels involves a series of tests to confirm the diagnosis and rule out other potential causes.

Diagnostic Tests

• The overnight 1-mg dexamethasone suppression test is a commonly used screening test for Cushing's syndrome, but it has limitations in patients with mild and/or episodic hypercortisolism 2.
• The low-dose dexamethasone suppression test has been recommended for biochemical screening when Cushing's syndrome is suspected, but the criterion for normal suppression of cortisol after dexamethasone is controversial 3.
• Quantification of serum dexamethasone in dexamethasone suppression test samples may improve test performance and reduce false positive results 4.
• The 24-hour urine free cortisol test is also used to screen for Cushing's syndrome, but it has its own pitfalls and limitations 5.

Interpretation of Test Results

• A morning cortisol level above 5 microg/dL after overnight dexamethasone suppression is often used as a cut-off for Cushing's syndrome, but this cut-off may not be suitable for all patients 2.
• Method-specific cortisol and dexamethasone thresholds can increase the clinical specificity of the dexamethasone suppression test for Cushing's syndrome 4.
• The interpretation of cortisol results should take into account the circadian rhythm of cortisol secretion, as elevated cortisol levels can occur at any time during the 24-hour period 6.

Clinical Considerations

• The diagnosis of Cushing's syndrome is often delayed due to variable clinical features and its rarity, highlighting the need for simple and accurate screening tests 5.
• Elevated cortisol levels can be found in many diseases, and anti-cortisol therapy may be beneficial in some cases 6.
• A standardized cortisol circadian rhythm chart can help to unveil the role of cortisol in diseases and enable a more accurate comparison with cortisol values obtained under pathological conditions 6.