Pharmacology and toxicity of adrenal enzyme inhibitors and adrenolytic agents
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
These compounds have been used to study the enzymes involved in steroid synthesis, to evaluate the hypothalamic-pituitary axis (metyrapone), and to treat some patients with endogenous excess of cortisol, androgen, or mineralocorticoid secretion.
Indications for the use of these compounds include rapid control of severe hypercortisolism for any etiology of endogenous Cushing's syndrome, persistent hypercortisolism following pituitary surgery for Cushing's disease, while awaiting the control from radiotherapy for Cushing's disease and control of excess steroid production in adrenocortical carcinoma or ectopic corticotropin (ACTH) syndrome.
This topic provides an overview of the compounds that inhibit glucocorticoid biosynthesis or action. Their use in the treatment of Cushing's syndrome and adrenocortical carcinoma is reviewed in greater detail separately. (See "Medical therapy of hypercortisolism (Cushing's syndrome)" and "Treatment of adrenocortical carcinoma", section on 'Adjuvant mitotane'.)
ADRENAL ENZYME INHIBITORS
Ketoconazole, metyrapone, etomidate, and mitotane block one or more of the enzymes in the cortisol and other steroid synthetic pathway. The subsequent decrease in cortisol secretion results in a compensatory rise in corticotropin (ACTH) release for most of these compounds. This tends to override the drug-induced cortisol blockade but can also result in accumulation of precursor steroids. These drugs usually do not cause adrenal insufficiency in patients with normal hypothalamic-pituitary-adrenal function  but can do so in those with limited pituitary or adrenal reserve. (See "Medical therapy of hypercortisolism (Cushing's syndrome)", section on 'Oral drugs'.)
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