Question: Can women on female hormone replacement therapy or birth control pills obtain meaningful results from an overnight dexamethasone suppression test?

Answer: It is well accepted that high levels of female hormones cause changes in the blood that can create a falsely high cortisol measurement. In cases of true hormone replacement therapy, the levels of hormones are usually low enough that false positive results are not a problem. In the case of birth control pills, the levels are sometimes high enough for false positive results to be obtained.

Cortisol is normally present in the blood both as free cortisol and bound to a protein called transcortin or cortisol-binding globulin (CBG). It is the increased free cortisol that causes the symptoms of Cushing’s. High levels of female hormones cause the liver to increase production of CBG, which increases the total plasma cortisol level, the level measured in the usual laboratory tests. Because the normal output of cortisol is higher early in the morning, more cortisol is bound to circulating CBG at that time. This can create an artifactually high morning cortisol measurement. Since cortisol does not bind to CBG very tightly, plasma cortisol levels fall quite rapidly once cortisol secretion falls. Therefore, plasma cortisol levels at 8 a.m. after an overnight dexamethasone suppression test (dexamethasone taken at 11 p.m.) are usually within the expected range.

If the results are equivocal, measurement of bedtime plasma cortisol and the standard 2-day dexamethasone suppression test are the first alternatives I would consider. This allows cortisol sufficient time to dissociate from CBG and be cleared from the circulation. Since it is only the free cortisol that is excreted by the kidney, and since the free cortisol is essentially normal in patients on birth control pills, urine free cortisol is also usually a reliable index of dexamethasone suppression in the 2-day test. If the results are still equivocal, it many be necessary to discontinue the birth control pills for six to eight weeks and repeat the tests.

By Dr. David Orth MD (November, 1996)