Clinical Information

Cortisol levels are regulated by adrenocorticotropic hormone (ACTH), which is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH). Cushing syndrome results from overproduction of glucocorticoids as a result of either primary adrenal disease (adenoma, carcinoma, or nodular hyperplasia) or an excess of ACTH (from a pituitary tumor or an ectopic source). ACTH-dependent Cushing syndrome due to a pituitary corticotroph adenoma is the most frequently diagnosed subtype; most commonly seen in women in the third through fifth decades of life.

CRH is released in a cyclic fashion by the hypothalamus, resulting in diurnal peaks (elevated in the morning) and nadirs (low in the evening) for plasma ACTH and cortisol levels. The diurnal variation is lost in patients with Cushing and these patients have elevated levels of evening plasma cortisol. The measurement of late-night salivary cortisol is an effective and convenient screening test for Cushing syndrome.(1) In a recent study from the National Institute of Health, nighttime salivary cortisol measurement was superior to plasma and urine free cortisol assessments in detecting patients with mild Cushing syndrome.(2) The sensitivity of nighttime salivary cortisol measurements remained superior to all other measures. The distinction between Cushing syndrome and pseudo-Cushing states is most difficult in the setting of mild to moderate hypercortisolism. Subtle increases in salivary cortisol at the midnight cortisol (cortisol of nadir) appear to be 1 of the earliest abnormalities in Cushing syndrome.