english.prescrire.org > Spotlight > Archives : 2016 > Ketoconazole and endogenous Cushing's syndrome: effective but tricky to use

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Ketoconazole and endogenous Cushing's syndrome: effective but tricky to use

FEATURED REVIEW Endogenous Cushing's syndrome is a rare but serious disease. Ketoconazole was effective in over 50% of cases in non-comparative series in a total of 800 patients. However, ketoconazole is hepatotoxic and interacts with many other drugs.
Full review (2 pages) available for download by subscribers.

Summary

  • Endogenous Cushing's syndrome is caused by chronic excessive secretion of cortisol, a glucocorticoid, which is due to hypersecretion of ACTH (adrenocorticotrophic hormone) by a pituitary adenoma in about three-quarters of cases ("Cushing's disease") or by an ectopic (often pulmonary) tumour in 10% of cases. In the other 15% of cases, the cortisol hypersecretion is due to an adrenal tumour.
     
  • Ketoconazole is an azole antifungal that inhibits the synthesis of adrenal steroids (cortisol and aldosterone) and gonadal steroids by inhibiting several cytochrome P450 isoenzymes.
     
  • In patients with endogenous Cushing's syndrome, ketoconazole reduces cortisol secretion and manifestations of excess cortisol, in preparation for surgery or radiation therapy, or as an adjunct to inadequately effective treatment.
     
  • Its use is delicate, however: liver enzyme tests must be regularly performed, patients must be monitored for adrenal insufficiency, and numerous drug interactions must be taken into account.
     
  • With these provisos, long-term data, mainly in Cushing's disease, show that ketoconazole has a favourable harm-benefit balance.

©Prescrire 1 March 2016

"Ketoconazole and endogenous Cushing's syndrome" Prescrire Int 2016; 25 (169): 65-66. (Pdf, subscribers only)
Download the full review.
Pdf, subscribers only