Endocrine Abstracts

Introduction: Etomidate is an imidazole derivative which inhibits several enzymatic steps (11β-hydroxylasey, 17β-hydroxylase, 17,20-lyase, cholesterol side-chain cleavage). Intravenous etomidate at sub-anaesthetic doses remains an important option when i.v. administration is required for rapid treatment of severely ill patients with hypercortisolaemia (Cushing’s syndrome, CS) and is almost always very effective.

Case series: A 49-year-old woman with left adrenocortical carcinoma (T4N1M1, stage IV during ENSAT2008, Ki-67: 15%) and CS, relapsed 6 months after surgical removal of the primary tumour while she had received chemotherapy and adrenolytic therapy. Recurrence involved new liver metastases and an increase in cortisol values with recurrence of CS. She received 2.4 mg/h of etomidate intravenously for 7 days; serum cortisol (F) and 24-h urine cortisol concentrations (UFC) decreased (pre-treatment F: 1456.5 μg/dl, post-treatment F: 613.8 μg/dl, pre-treatment UFC: 773.5 mg/24 h, post-treatment UFC: 615 mg/24 h). The patient died because of sepsis one month later. A 72-year-old man with atypical lung neuroendocrine neoplasm (NEN) (T1aNxMx,Ki-67: 4–7%) and ectopic secretion of ACTH (ACTH: 78.7 pg/ml) had surgical removal of the primary tumour followed by chemotherapy and somatostatin analogues. He had disease recurrence 6 years later. He was treated with metyrapone and ketoconazole without adequate control of CS (pre-treatment-UFC: 709 mg/24 h, post-treatment-UFC:416 mg/24 h). Etomidate was administered at a dose of 3–3.3 mg/h intravenously and hypercortisolaemia was controlled (pre-treatment-F: 44 μg/dl, post-treatment-F: 23 μg/dl). A bilateral adrenalectomy was performed to control hypercortisolaemia. A 51-year-old woman with medullary thyroid carcinoma (T3NxM1, stage IV), liver metastases and ectopic secretion of ACTH (ACTH: 153 pg/ml, F: 74 μg/dl) underwent thyroidectomy without resolution of CS. She received etomidate intravenously at a dose of 2.6 mg/h with a decrease in cortisol levels (pre-treatment-F: 273.8 μg/dl, post-treatment-F:79.2 μg/dl). The patient died because of a septic shock 2 days later.

Conclusion: Etomidate may be used as first-line treatment in severely ill patients with CS. However, it needs to be very carefully monitored, because of sedation that may be apparent in higher doses, and adjustments should be made with regards to renal failure and stressed situations such as sepsis.