What is the significance of an elevated bedtime salivary cortisol level of 0.046, indicating hypercortisolism?

From the Guidelines

Bedtime salivary cortisol level of 0.046 μg/dL is within normal range, suggesting normal adrenal function. Typically, normal evening salivary cortisol levels fall below 0.1 μg/dL, with values varying slightly between laboratories 1. This result indicates your hypothalamic-pituitary-adrenal (HPA) axis is functioning properly with appropriate diurnal cortisol rhythm (higher in morning, lower at night). No specific intervention is needed for this normal result. Cortisol follows a natural daily pattern, peaking in early morning and declining throughout the day to reach its lowest point at night. Elevated bedtime cortisol can indicate conditions like Cushing's syndrome, chronic stress, or sleep disorders, while abnormally low levels might suggest adrenal insufficiency.

Key Points to Consider

• The diagnosis of Cushing's syndrome involves various tests, including UFC excretion, serum cortisol circadian rhythm study, late-night salivary cortisol, LDDST, and overnight dexamethasone test 1.
• The late-night salivary cortisol test has a high sensitivity and specificity for diagnosing Cushing's syndrome, with a cut-off value based on local assay cut-off 1.
• If you were tested due to specific symptoms despite this normal result, consider discussing with your healthcare provider as other hormonal or non-hormonal causes may need investigation.

Additional Considerations

• Other tests, such as plasma ACTH, CRH test, and pituitary MRI scan, may be necessary to confirm the diagnosis of Cushing's disease 1.
• Bilateral inferior petrosal sinus sampling for ACTH may be offered to confirm a central source of ACTH excess in patients with confirmed ACTH-dependent Cushing's syndrome and no identified adenoma on pituitary MRI 1.

From the Research

Bedtime Salivary Cortisol

• The measurement of late-night salivary cortisol is a mainstay in the diagnosis of Cushing syndrome, as stated in the study by 2.
• Salivary cortisol and cortisone can be reliably measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in small volumes of saliva, according to 2.
• The upper limit of normal of salivary cortisol by enzyme immunoassay (EIA) for bedtime samples was found to be lower than the previously published upper limit of normal with sampling required at 2300 to 2400 hours, as reported in 2.

Relationship between Salivary Cortisol and Urinary-Free Cortisol

• The utility of repeated salivary cortisol sampling as a substitute for 24-hour urinary-free cortisol (UFC) assessment was examined in a study by 3.
• The results demonstrated that mean, maximum, and amplitude (maximum minus minimum) for salivary cortisol all correlated positively with urinary cortisol, but the associations of these variables with urinary-free cortisol excretion were relatively small, as stated in 3.
• A single salivary sample taken at wake-up was found to be as good an indicator of overall cortisol production as the measures derived from multiple salivary samples, according to 3.

Diagnosis and Treatment of Adrenal Insufficiency

• The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the test and cutoff levels used, and the severity of illness, as reported in 4.
• The low-dose adrenocorticotropic hormone (ACTH) stimulation test has been shown to be more sensitive and specific than the high-dose test, but the high-dose test is preferred since the low-dose test has not been validated, according to 4.
• Administration of low-dose corticosteroids for a longer duration decreases both the amount of time that vasopressors are required and mortality at 28 days, as stated in 4.

Diagnostic Cutoffs for Adrenal Insufficiency

• The accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol, as reported in 5.
• New diagnostic thresholds for the Abbott Architect immunoassay were established by comparing the measurements of the level of cortisol using three immunoassays, according to 5.
• The optimized threshold for cortisol using the Abbott assay was found to be 14.6 μg/dL at 60 minutes after stimulation, as stated in 5.

Intramuscular ACTH Stimulation Test

• The intramuscular ACTH stimulation test using Acton Prolongatum was found to be effective in evaluating adrenal function in all suspected cases of primary or secondary adrenal insufficiency, according to 6.
• Basal cortisol level has poor sensitivity to diagnose adrenal insufficiency, with a sensitivity of 60% and specificity of 100% compared to ACTH-stimulated cortisol levels, as reported in 6.