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Normally, cortisol levels rise during the early morning hours and are highest at about 7 a.m. They drop to very low levels in the evening and during the early phase of sleep. The factor controlling this rhythm is not completely defined and can be disrupted by a number of physical and psychological conditions. ACTH and cortisol are secreted independent of the circadian rhythm in response to physical and psychological stress. Elevated cortisol levels and a lack of diurnal variation have been identified with Cushing’s disease, phenomena of ACTH hypersecretion. Elevated circulating cortisol levels have also been identified in patients with adrenal tumors. Low cortisol levels are found in primary adrenal insufficiency, identified with Addison’s disease, and in ACTH deficiency. Due to the normal circadian variation in cortisol levels, it is difficult to distinguish normal cortisol levels from abnormally-low levels. Therefore, several daily collections are recommended. 1

Measurement of Cortisol in Human Serum by Isotope Dilution Liquid Chromatography/Mass Spectrometry and a Comparison through a Proficiency Testing