Steroid biosynthesis inhibitors in the therapy of hypercortisolism: Theory and practice

P. Igaz, Z. Tömböl, P. M. Szabó, I. Likó, K. Rácz

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Cushing's syndrome is a rare disease with significant morbidity and mortality. Surgical intervention represents the most effective treatment option in both adrenocorticotropin-dependent and -independent forms of hypercortisolism. It is not uncommon, however, that surgery fails to cure or control the disease. Pharmacotherapy with drugs inhibiting steroid biosynthesis can be effectively used in these cases in order to alleviate symptoms or even to induce chemical adrenalectomy. A few drugs inhibiting single or multiple steps in adrenal steroid biosynthesis can be used in clinical practice. Drugs predominantly inhibiting single enzymatic steps include the 11β-hydroxylase inhibitor metyrapone and the 3β-hydroxysteroid dehydrogenase inhibitor trilostane, whereas mitotane, aminoglutethimide, ketoconazole and etomidate block multiple enzymatic reactions. Etomidate is the only agent available for parenteral administration that renders it as a treatment of choice in critically ill patients requiring a rapid control of hypercortisolemia. Ketoconazole, metyrapone and aminoglutethimide can be used alone or in combination for the treatment of hypercortisolism caused by benign adrenocorticotropin- or cortisol-secreting tumors. The clinical utility of trilostane is variable. Besides blocking multiple steps in adrenal steroid biosynthesis, the DDT (insecticide) analogue mitotane also has adrenolytic properties by inducing mitochondrial degeneration that renders it superior to other drugs in the treatment of adrenocortical cancer. Severe side effects may develop during therapy with each aforementioned drug that include hepatic, endocrine and neurological toxicity. After summarizing the chemical and biological properties of steroid biosynthetic inhibitors, the authors describe their possible clinical applications and limitations.

Original languageEnglish
Pages (from-to)2734-2747
Number of pages14
JournalCurrent medicinal chemistry
Volume15
Issue number26
DOIs
Publication statusPublished - Nov 1 2008

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Keywords

  • Adrenolytic
  • Cushing's syndrome
  • Cytochrome
  • Inhibition
  • Steroid biosynthesis
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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