How are cortisol levels normally regulated?
Adrenal production of cortisol is stimulated by the pituitary hormone adrenocorticotropin (ACTH).
ACTH production is stimulated by the hypothalamic hormones corticotropin-releasing hormone (CRH) and vasopressin (ADH). Cortisol feeds back to the pituitary and hypothalamus to suppress levels of ACTH and CRH.
Under nonstress conditions, cortisol is secreted with a pronounced circadian rhythm, with higher levels early in the morning and lower levels late in the evening.
Under stressful conditions, secretion of CRH, ACTH, and cortisol increases, and the circadian variation is blunted.
Because of the wide variation in cortisol levels over 24 hours and appropriate elevations during stressful conditions, it may be difficult to distinguish normal secretion from abnormal secretion.
For this reason, the evaluation of a patient with suspected Cushing’s disease is often complex and confusing.