Endocrine Abstracts

Purpose: To investigate the kinetics of adrenocorticotropin (ACTH) following oral metyrapone administration and describe differences between ACTH-deficient and non ACTH-deficient subjects.

Methods: Patients from a tertiary endocrine center at a University Hospital in Munich, Germany, were tested. Metyrapone (Metopirone, HRA Pharma, France) was administered with a dosage of 40 mg/kg bodyweight at 0800 h. Consecutive levels of ACTH were determined at 0, 60, 120, 180, and 240 min. Patients were categorized according to their need of glucocorticoid substitution. The study was approved by the local Ethics Committee with a limitation to 25 patients.

Results: Of 25 patients, 15 (60%) were female. Mean age was 52.3 years (range 21–79). ACTH (mean (± S.D.)) was 12.3 (±8.7) pg/ml before stimulation and 104.7 (±114.9), 84.9 (±65.4), 82.2 (±65.1), and 102.7 (±83.5) pg/ml at 60, 120, 180, and 240 min, respectively. Cortisol (mean (±S.D.)) was 10.6 (±5.1) μg/dl before stimulation and 2.6 (±2.1), 1.7 (±0.9), 1.6 (±0.9), and 1.6 (±0.9) μg/dl at 60, 120, 180, and 240 min, respectively. There was an 8.51-fold and a 7.65-fold rise in ACTH compared to the basal level (t=0) at 60 and 120 min, respectively.

Analyzing groups as categorized by the course of clinical follow up (±13.6 months; range 0–39 months), there were significant differences in ACTH concentrations at 60 min (166.2 vs 21.3 pg/ml; P<0.001) and at 120 min (121.8 vs 27.7 pg/ml; P<0.001). Using ROC analysis of those patients who remained free of glucocorticoid substitution with ACTH at 60 min, and ACTH at 120 min, AUCs of 0.83 (P=0.007) and 0.92 (P=0.001) were achieved, respectively.

Conclusion: In contrast to previous reports, we found a significant rise in ACTH concentration as soon as one hour after oral metyrapone administration. Early ACTH values seem to estimate the pituitary corticotrophic function.