Endocrine Abstracts

Background: Mitotane is an adrenolytic drug used in the treatment of adrenocortical carcinoma (ACC). It accelerates steroid metabolism and increases corticosteroid binding globulin (CBG), necessitating higher doses of glucocorticoid replacement. At Imperial College Healthcare NHS Trust prednisolone is preferred over hydrocortisone for its once-daily dosing and stable pharmacokinetics. However, biomarkers to guide glucocorticoid dosing in mitotane-treated ACC patients remain undefined.

Methods: From 25 ACC patients, 6 met the inclusion criteria: mitotane therapy, once-daily prednisolone replacement, and available prednisolone and ACTH day curves. Clinical and treatment data were collected. Descriptive statistics explored prednisolone and ACTH trends. ACTH measurements at 2, 4, 6, and 8 hours post-dose were compared using Friedman and paired Wilcoxon tests. Spearman’s correlation assessed the relationship between prednisolone and ACTH. The ACTH reference range (10-20 ng/l) was based on optimally replaced primary adrenal insufficiency patients.

Results: Median mitotane exposure was 13 months (range 8–20). Prednisolone doses ranged from 4–20 mg once daily. CBG was elevated in 85% of patients. ACTH values were stable and highly correlated between 4–8 hours post-dose (Rs > 0.85, P < 0.0001), but differed significantly at 2 hours. No consistent correlation was found between ACTH and prednisolone levels. ACTH trends aligned more closely with clinical dose adjustments than prednisolone concentrations: median ACTH was 21.8 ng/l when doses were increased and 2.5 ng/l when decreased. No adrenal crises occurred.

Conclusion: ACTH appears to be a reliable biomarker for prednisolone dose adjustment in ACC patients on mitotane. Its stability between 4–8 hours post-dose provides a practical window for glucocorticoid titration.