Exp Clin Endocrinol Diabetes 2013; 121 - P11
DOI: 10.1055/s-0033-1336693

27-years of treatment of ACTH-dependent Cushing's syndrome with mitotane

S Kacheva 1, E Fähndrich 1, W Karges 1
  • 1RWTH Aachen University, Division of Endocrinology and Diabetes, Aachen, Germany

Introduction: Mitotane is an adrenolytic agent primarily used in the treatment of adrenocortical carcinoma. Mitotane inhibits cholesterol side-chain cleavage and 11ß-hydroxylase, resulting in decreased cortisol synthesis. Mitotane alone or in combination with other adrenal blocking agents is, however, not commonly used for long-term treatment of cortisol excess in benign Cushing's syndrome (CS).

Methods: We report a 64-year-old male patient who at the age of 34yrs was diagnosed with ACTH-dependent CS in 1982 based on unequivocal clinical and laboratory findings, including elevated free urinary cortisol and elevated plasma ACTH levels. A CT scan of the head and the adrenal glands had revealed no morphological abnormality. There was no evidence of ectopic ACTH secretion. The patient was put on mitotane therapy of 500 mg daily in 1984. Subsequently, the patient was lost to follow-up. He first presented to our endocrine unit in December 2011 for evaluation.

Results: The patient was in good general health and alert. His medication included atorvastatin 20 mg daily. There were no clinical signs of hypercortisolism. Laboratory results showed persistent ACTH excess and decreased cortisol response after 250 µg ACTH stimulation. Plasma mitotane level was 2.2 mg/l. A MRI scan of the pituitary region (2012) revealed a 3 mm pituitary lesion, compatible with microadenoma. There was no clinical or laboratory evidence of mitotane-associated toxicity. The decision was made to discontinue the mitotane therapy.

Conclusion: This case demonstrates the feasibility of an uncommon treatment approach in ACTH-dependent CS, i.e. long-term low-dose mitotane. With a cumulative mitotane dose of > 4.9 kgs and low plasma drug levels (< 2.5 mg/l), mitotane was associated with adequate disease control of CS, in the absence of significant toxicity or Nelson's syndrome. As more targeted-approaches are now available, mitotane remains but a remote option for medical treatment in benign CS.