Etomidate as an emergency treatment for uncontrolled hypercortisolism in metastatic adrenocortical carcinoma

Abstract

Adrenocortical carcinoma is a rare malignancy of poor prognosis with frequent excessive secretion of cortisol or androgens or both. The treatment could be challenging, especially in advanced or metastatic cases. We present the case of a 26-year-old woman with a multiple metastatic adrenocortical carcinoma. A few months prior to diagnosis, she developed clinical signs of virilization and a Cushing's syndrome. Mitotane and ketoconazole combination therapy was initiated after histopathological confirmation. A surgical resection of the left adrenal gland was performed. The tumor was classified pT2Nx (score Weiss 9, Ki67 10%). Cisplatin-Etoposide chemotherapy was started 20 days postoperatively. In the presence of persistent severe and life-threatening hypercortisolism (Urinary free cortisol [UFC] > 20-fold the upper limit of the normal range [ULN]), adding metyrapone was indicated but this drug is not available in Belgium. An alternative urgent treatment with etomidate (0.3 mg/kg/hour) by continuous intravenous infusion was administrated for 24 hours. The inhibition of the adrenal cortisol production was rapid prompting a need for a substitution by hydrocortisone (8 hours after treatment initiation). UFC decreased to less than 5-fold the ULN. One month later, the medical evaluation shows normalized UFC and regression of metastasis after 2 cycles of chemotherapy. Etomidate, mostly known as anesthetic, is a strong enzymatic inhibitor of the 11β-hydroxylase implicated in the last step of the adrenal cortisol steroidogenesis. There are only limited data on its use in severe hypercortisolism. This case illustrates its utility and efficacy in acute phase of hypercortisolism while waiting for action of other adrenal-directed therapies.