Under the influence of high estrogen levels, the suppression of total serum cortisol in the dexamethasone test has often been found to be incomplete. Its measurement for the purpose of excluding Cushing's disease or adrenal tumors in women taking oral contraceptives is, therefore, considered unreliable. This study was designed to compare the reliability of measurements of total cortisol, unbound cortisol and ACTH suppression during chronic hyperestrogenaemia. An overnight suppression test with 2 mg of dexamethasone was performed in 19 women receiving long-term contraceptive treatment (group A) and in 12 controls (group C). Baseline and post-dexamethasone morning levels of ACTH, total serum cortisol and unbound salivary cortisol were determined by RIA. In addition, unbound serum cortisol was measured by equilibrium dialysis. Mean baseline levels of all four parameters were significantly higher in group A. This result points towards the possibility of a direct stimulatory effect of estrogens upon the corticotroph axis which is independent from CBG-mediated increase of total cortisol. Post-dexamethasone values of total and unbound cortisol showed no statistically significant differences, while ACTH suppression in group A was even slightly better than in group C. From these data it is concluded that there is no need for post-dexa routine measurement of ACTH or unbound cortisol under contraceptive treatment since neither one of these parameters provides any additional information in comparison to total cortisol.
PIP: Endocrinologists from University Hospital in Frankfurt, West Germany, compared data on 19 women 20-36 years old who had taken oral contraceptives (OCs) for at least 4 months before the study (cases) with those of 12 age matched women who took no OCs for at least 6 months before the study (controls). The goal of the study was determine the reliability of total cortisol, unbound salivary and serum cortisol, and adrenocorticotropic hormone (ACTH) parameters in the dexamethasone (2mg) suppression test under conditions of chronically high estrogen levels due to OC use. Radioimmunoassay techniques were used to measure baseline and post-dexamethasone levels of all parameters. Equilibrium dialysis was used to measure unbound serum cortisol. The mean baseline levels for all parameters were considerably greater in the cases than in the controls: total serum cortisol (32.7 mcg/dl vs. 15.6mcg/dl; p .001), free salivary cortisol (9.6ng/ml vs. 5.6ng/ml; p .01), ACTH (50.8pg/ml s. 34.2pg/ml; p .05), and free serum cortisol (6.3 mg/ml vs. 4.2 ng/ml; p .01). This suggested that estrogens exert a direct stimulatory effect on the corticotroph axis separate from a corticosteroid-binding globulin mediated increase of total cortisol. TOtal and free salivary cortisol levels after the dexamethasone suppression test for the 1 groups were not statistically significant (2.3 mcg/dl vs. 1.7 mcg/ml vs. 1.1ng/ml, respectively). On the other hand, ACTH suppression was significantly better for cases than it was for controls (2.2pg/ml vs. 5.3 pg/ml; p .001). These data indicate that post-dexamethasone measurements of ACTH or free cortisol in women taking OCs are not needed since total cortisol measurements provide the information needed. Therefore physicians should not use the dexamethasone suppression test to diagnose Cushing's disease in women using OCs.