{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:44:20Z","timestamp":1790671460779,"version":"4.1.0"},"reference-count":14,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"Summary<\/jats:title>\n \n Ketoconazole was a first-line agent for suppressing steroidogenesis in Cushing's disease. It now has limited availability. Fluconazole, another azole antifungal, is an alternative, although its\n in vivo<\/jats:italic>\n efficacy is unclear. A 61-year-old female presented with weight gain, abdominal striae and worsening depression. HbA1c increased to 76\u200ammol\/mol despite increasing insulin. Investigations confirmed cortisol excess; afternoon serum cortisol was 552\u200anmol\/l with an inappropriate ACTH of 9.3\u200apmol\/l. In total, 24-h urinary free cortisol (UFC):creatinine ratio was 150\u200anmol\/mmol with failure to suppress after 48\u200ah of low-dose dexamethasone. Pituitary MRI revealed a 4-mm microadenoma. Inferior petrosal sinus sampling confirmed Cushing's disease. Transsphenoidal resection was performed and symptoms improved. However, disease recurred 6 months later with elevated 24-h UFC >2200\u200anmol\/day. Metyrapone was commenced at 750\u200amg tds. Ketoconazole was later added at 400\u200amg daily, with dose reduction in metyrapone. When ketoconazole became unavailable, fluconazole 200\u200amg daily was substituted. Urine cortisol:creatinine ratio rose, and the dose was increased to 400\u200amg daily with normalisation of urine hormone levels. Serum cortisol and urine cortisol:creatinine ratios remain normal on this regimen at 6 months. In conclusion, to our knowledge, this is the first case demonstrating prolonged\n in vivo<\/jats:italic>\n efficacy of fluconazole in combination with low-dose metyrapone for the treatment of Cushing's disease. Fluconazole has a more favourable toxicity profile, and we suggest that it is a potential alternative for medical management of Cushing's disease.\n <\/jats:p>\n \n Learning points<\/jats:title>\n \n \n \n Surgery remains first line for the management of Cushing's disease with pharmacotherapy used where surgery is unsuccessful or there is persistence of cortisol excess.<\/jats:p>\n <\/jats:list-item>\n \n Ketoconazole has previously been used to treat cortisol excess through inhibition of CYP450 enzymes 11-\u03b2-hydroxylase and 17-\u03b1-hydroxylase, though its availability is limited in many countries.<\/jats:p>\n <\/jats:list-item>\n \n Fluconazole shares similar properties to ketoconazole, although it has less associated toxicity.<\/jats:p>\n <\/jats:list-item>\n \n Fluconazole represents a suitable alternative for the medical management of Cushing's disease and proved an effective addition to metyrapone in the management of this case.<\/jats:p>\n <\/jats:list-item>\n 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2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny E","family":"Gunton","sequence":"additional","affiliation":[{"name":"1 Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, 2145, Australia"},{"name":"2 Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, 2145, Australia"},{"name":"4 St Vincent's Clinical School, University of New South Wales, Sydney, 2010, Australia"},{"name":"5 Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, 2010, Australia"},{"name":"6 Department of Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, 2045, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"key20160208163644184_bib1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1517\/14728210903413522","article-title":"Drugs in the medical treatment of Cushing's 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