Relative sensitivity and responsivity of serum cortisol and two adrenal androgens to alpha-adrenocorticotropin-(1-24) in normal and obese, nonhirsute, eumenorrheic women.

The alpha ACTH-(1-24) threshold dose and the response slope were determined for cortisol (F), delta 4-androstenedione (A), and dehydroepiandrosterone (DHEA) in 10 normal and 16 obese eumenorrheic nonhirsute women matched for age. Each woman received 1 mg dexamethasone at 2300 h and again at 0700 h the next morning. At 0700 h, a continuous alpha ACTH-(1-24) infusion was begun at an initial dose of 30 ng/1.5 m2 body surface area X hr. The ACTH infusion rate was doubled every hour for 5 consecutive h to a maximum dose of 480 ng/1.5 m2 X h. Blood samples were collected for steroid assays before the infusion and at the end of each hour. The ACTH threshold dose was defined as the dose that produced a steroid response significantly above the basal level. The ACTH threshold dose for serum F and DHEA stimulation was not different between the groups, but the threshold dose for A was significantly lower in the obese women. Basal and stimulated serum DHEA to F ratios were significantly higher in the obese women. In both groups, the mean F response slope was significantly higher than that for DHEA, which in turn, was significantly higher than that for A. The mean DHEA response slope was significantly greater in the obese women. The F and A response slopes were not different between the groups. We conclude that the relative responsivity of the steroids to ACTH was the same in both groups: F greater than DHEA greater than A; in the obese women, the ACTH threshold dose for F stimulation was lower (greater sensitivity) than for DHEA or A stimulation; and in the obese women, the ACTH threshold dose for A was significantly lower (increased sensitivity) and the slope of the DHEA response to ACTH was steeper (greater responsivity) than in normal women.