24-hour serum concentration profile of cortisol in patients with Cushing's disease

To evaluate whether or not patients with Cushing's disease can be differentiated from those with obesity by the determination of 24-hour integrated serum concentrations of cortisol we studied healthy, nonobese males (n = 5), as well as patients with marked obesity (n = 5) and with Cushing's disease (n = 7) in whom diagnosis was established biochemically and subsequently confirmed by surgery. Serum cortisol concentrations in samples collected continuously by a portable blood withdrawal pump during 24 hours (08:00-08:00h) were 6.6 +/- 1.7 micrograms/dl and 8.4 +/- 1.5 micrograms/dl in nonobese and obese individuals, respectively. Patients with Cushing's disease presented a mean cortisol concentration of 21.4 +/- 6.4 micrograms/dl (p vs normal: less than 0.005; vs obesity: less than 0.005). Collecting consecutive samples in 4-h periods the decline of serum cortisol from peak to nadir values was 73 +/- 10% and 57 +/- 23% in normal males and obese subjects, respectively, while a decline of only 22 +/- 8% was seen in patients with Cushing's disease. Three of the patients with Cushing's disease exhibited a circadian rhythm of cortisol albeit on an elevated level. These results may reflect variable stages of autonomy in pituitary ACTH-production and hence a possible criteria for differentation of hypothalamic and pituitary forms of Cushing's disease. In regard to differential diagnosis between Cushing's disease and obesity the 24-hour cortisol profile obtained by multiple sampling did not provide additional information to that obtained by a single sample pooled for 24 hours, which was diagnostic in each case.