Inhibition of synthesis of adrenal and other steroid hormones

These agents have use in diagnosis of adrenal disease and in controlling excessive production of corticosteroids, e.g. by corticotropin producing tumours of the pituitary (Cushing's syndrome) or by adrenocortical adenoma or carcinoma where the cause cannot be removed. They must be used with special care since they can precipitate acute adrenal insufficiency. Some members inhibit other steroid synthesis.

Metyrapone inhibits the enzyme, steroid 11(3-hydroxylase, that converts 11-deoxy precursors into hydrocortisone, corticosterone and aldosterone. It affects synthesis of aldosterone less than that of glucocorticoids.

Trilostane blocks the synthetic path earlier (3(3-hydroxysteroid dehydrogenase) and thus also inhibits aldosterone synthesis.

Formestane is a specific inhibitor of the aromatase which converts androgens to oestrogens. A depot injection of 250 mg i.m. is given twice a month in the treatment of some patients with carcinoma of the breast who relapse on tamoxifen.

Aminoglutethimide blocks even earlier, preventing the conversion of cholesterol to pregnenolone. It therefore blocks synthesis of all steroids, hydrocortisone, aldosterone and sex hormones (including the conversion of androgens to oestrogens); it has a use in breast cancer.

Ketoconazole is an effective antifungal agent by virtue of its capacity to block sterol /steroid synthesis (ergosterol in the case of fungi). In man it inhibits steroid synthesis in gonads and adrenal cortex and it has been used in Cushing's syndrome and prostatic cancer.

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