The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Navigating Medication Availability: Combination Fluconazole and Metyrapone to Treat Ectopic Cushing’s Syndrome (#273)

Jennifer Snaith 1 2 , David Chipps 1 2 , Christian Girgis 1 2 3
  1. Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia
  2. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
  3. The Westmead Institute for Medical Research, Westmead, NSW , Australia

Introduction. Small cell lung cancer (SCLC) is a neuroendocrine tumour with the capacity to secrete a number of polypeptide hormones including ACTH resulting in a Cushing’s syndrome (CS). ACTH-secreting SCLC is associated with a poorer prognosis than SCLC alone. Although critically important, the management of hypercortisolaemia in this context is challenged by the lack of availability of first line option ketoconazole, and the expense and toxicity profile of other anti-adrenal agents. There is little experience using alternative options.

Case. A 63-year-old female with metastatic SCLC (involving pleura, bone and liver) was diagnosed with ectopic ACTH secretion after presenting with severe hypokalaemia, hypertension and hyperglycaemia. She was unsuitable for resection of primary lung tumour and at diagnosis, her condition was deemed incurable. She was not fit to undergo bilateral adrenalectomy. Ketoconazole was unavailable. Hypertension was controlled with spironolactone 100mg bd. Metyrapone 500mg tds improved morning serum cortisol levels from 1274nmol/L to 222nmol/L. Serum cortisol rose to 1887nmol/L after metyrapone was inadvertently withheld. Metyrapone 500mg tds was restarted with fluconazole 200mg bd and serum cortisol levels improved again to 502nmol/L then remained stable. This combination of ketoconazole, metyrapone and spirolactone allowed a reduction in potassium supplementation from 160mmol intravenous and 124mmol oral potassium chloride, to 72mmol potassium chloride orally daily. Disease course was complicated by pulmonary embolism, and the patient passed 4 months after SCLC diagnosis.

Conclusion. This is the first report of combined use of metyrapone and fluconazole in the management of ectopic Cushing’s syndrome related hypercortisolaemia. This combination is a suitable well-tolerated option especially when traditional options are unavailable.