Diurnal Salivary Cortisol Profiles in Patients with Cushing's Syndrome.
Level 4 - case-series / case-control
Case-control diagnostic accuracy study comparing confirmed cases against controls
PubMed 35038761 · doi:10.1055/a-1719-5381
What was done
Salivary cortisol was measured five times daily in 428 patients evaluated for hypercortisolism to evaluate the diagnostic and subtyping utility of 24-hour profiles. The cohort included 111 patients with confirmed Cushing's syndrome (75 with Cushing's disease, 27 with adrenal Cushing's, and 9 with ectopic Cushing's), 39 with autonomous cortisol secretion, and 278 controls in whom Cushing's syndrome was excluded. Diagnostic accuracy of the 5-point profile was compared against a single late-night (11 p.m.) measurement.
What was found
Salivary cortisol was significantly elevated in Cushing's syndrome patients compared to controls at all five daily time points (p <= 0.001). Using the full diurnal profile increased overall diagnostic accuracy from 85% (single 11 p.m. sample) to 91%. Patients with ACTH-dependent Cushing's had higher cortisol levels than those with adrenal Cushing's, and morning cortisol was significantly higher in ectopic Cushing's compared to Cushing's disease (p = 0.04). However, substantial overlap between diurnal profiles resulted in low diagnostic yield for subtyping.
Why it matters
The findings support current clinical practice, demonstrating that intensive multi-point daily salivary cortisol profiling offers only minor diagnostic gains over standard single late-night testing and is not clinically useful for differentiating Cushing's syndrome etiologies.
Limits
Subgroup sample sizes were unbalanced, with only 9 patients in the ectopic Cushing's group. Specific sensitivity, specificity, cut-off values, and confidence intervals were not reported in the abstract. The case-control structure may overestimate diagnostic accuracy compared to prospective, consecutive clinical cohorts.
Cited by
- contradicts Most people with Cushing's syndrome have pathologically low cortisol early in the day and pathologically high cortisol late in the day.