Question: What are the normal values for a serum cortisol, a 24-hour urine, and ACTH? Also, what is the generally accepted cortisol cut off point for an overnight low dose dexamethasone suppression test? Does the absolute number for these tests vary between labs?

Answer: Normally, cortisol is secreted in short bursts and blood levels are usually highest early in the morning, decreasing gradually throughout the day and reaching a low point in the late evening. Consequently, normal levels of plasma cortisol constitute a broad range; the levels found in Cushing’s syndrome may at any given time fall within the “normal” range. Also, even when laboratories use the same assay techniques, results vary somewhat from lab to lab. When assessed with a typical radioimmunoassay (the most commonly used method), cortisol levels range from about 10 to 20 micrograms per deciliter (ug/dl) in the early morning (within one hour of the usual time of awakening), from 3 to 10 ug/dl at 4 PM, and are usually less than 5 ug/dl after the usual bedtime, but there is a great deal of variation. There is an increase in cortisol secretion in response to eating and exercise as well as to physical and psychological stress. It is also important to recognize that these assays measure ‘total’ cortisol, most of which is bound to proteins in the bloodstream. Only the unbound cortisol is biologically active. Things that raise the levels of the binding proteins, e.g. estrogen, will result in higher cortisol levels without causing Cushing’s syndrome.

Although urinary cortisol constitutes a small fraction of daily cortisol secretion, it does integrate the day’s serum free cortisol concentration and has become one of the standard methods for diagnosis of Cushing’s syndrome. Measurement techniques for urinary cortisol excretion have improved. Some older assays have higher normal ranges (20 to 90?100 ug/day) than newer ones, which typically have normal ranges of about 10 to 55 ug/day.

Like cortisol, ACTH is secreted in bursts with a daily rhythm. Interpretation of plasma ACTH levels must be done in the context of simultaneous plasma cortisol levels. ACTH assays are also relatively touchy, although they have improved as well. Normal ranges for ACTH are fairly broad and like cortisol levels are time-dependent. They also vary from assay to assay. A typical normal range for an 8AM sample using the new assays is 10 to 50 picograms per milliliter (pg/ml); levels are usually less than 20 pg/ml at 4 PM and less than 5-10 pg/ml at midnight. Older assays have somewhat wider ranges.

The standard cut-off value for the overnight 1 mg dexamethasone suppression test is <5ug/dl. However, it is becoming increasingly clear that some patients with mild Cushing’s syndrome demonstrate unusual sensitivity to dexamethasone suppression; therefore, cut?offs at this 5ug/dl level may fail to detect some patients with Cushing’s syndrome. Two recent studies suggested using lower cutoffs – < 1.8 ug/dl and <2.5 ug/dl. Although these cutoffs would miss fewer patients with Cushing’s, the downside is that they would falsely identify many people who actually did not have Cushing’s syndrome.

By Dr. David Aron MD (Winter, 2001)