Fluconazole and acetazolamide in the treatment of ectopic Cushing's syndrome with severe metabolic alkalosis

Abstract

SummaryCushing's syndrome (CS) due to ectopic ACTH production accounts for about 10% of all types of CS and is frequently associated with metabolic alkalosis. Treatment of CS involves surgical resection and/or medical therapy to control hypercortisolism. We present the case of an 80-year-old woman affected by CS due to an unknown cause. The patient had severe metabolic alkalosis with refractory hypokalemia. To treat the underlying CS, fluconazole was initiated due to unavailability of ketoconazole. In spite of markedly decreasing cortisol levels, metabolic alkalosis persisted. Treatment of metabolic alkalosis with acetazolamide was thus initiated and pH levels successfully lowered. This case report shows that hypercortisolism can be effectively treated with fluconazole in cases where ketoconazole is unavailable or not tolerated and that persistent severe metabolic alkalosis caused by glucocorticoid excess can be safely and successfully treated with acetazolamide.Learning points Hypercortisolism can be effectively treated with fluconazole where ketoconazole is unavailable or not tolerated.Glucocorticoid excess can cause severe metabolic alkalosis.Persistent severe metabolic alkalosis can be safely and successfully treated with acetazolamide.

Fluconazole treatment in severe ectopic Cushing syndrome

“…The patient had severe metabolic alkalosis with refractory hypokalemia that responded to the administration of acetazolamide. She then developed pancytopenia caused by myelodysplasia and died 1 month after diagnosis (3). There are two other case reports of the use of fluconazole in the treatment of CS, one in Cushing’s disease and the other in adrenocortical carcinoma, albeit neither were SCS (4, 5).…”

“…Then the dose had to be decreased to 400 mg/day because the liver transaminases increased 3 times over the normal upper limit. The dose of fluconazole reported in the literature is 200–1200 mg/day (1, 2, 3, 4, 5).

Figure 1Cortisol response to treatment with fluconazole (Flu).

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“…It can be administered either orally or intravenously. There is only a case report about the use of fluconazole in Cushing syndrome in an elderly female patient with EAS (3). Its efficacy and safety in SCS have not been tested.…”

Clinical-Pathological Conference Series from the Medical University of Graz

“…Beyond these diagnostic procedures for primary aldosteronism, it should be emphasized that one important differential diagnosis for patients with profound hypokalemia and hypertension is ectopic, i.e. adrenocorticotropic hormone dependent Cushing syndrome that is usually accompanied by significant metabolic alkalosis and very rapid disease progression requiring early diagnosis and treatment [ 46 ]. Some drugs such as beta-adrenergic blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may also impact on the ARR and it is desirable to withdraw these drugs for at least 4 weeks before testing.…”

Manage severe Cushing’s syndrome with urgent control of metabolic disturbances and serum cortisol levels

“…• Fluconazole Clinical experience with oral and intravenous formulations limited to case reports, although it may be less toxic than ketoconazole [17]. • Pasireotide Subcutaneously administered somatostatin analogue that targets ACTH-secreting tissues [2].…”