The mechanism of action of Somatostatin receptor ligands, Dopamine Agonists, Steroidogenesis inhibitors, Glucocorticoid receptor antagonists, and Retinoic acid modulators will be reviewed.
Somatostatin analogs
Somatostatin analogs are drugs that mimic the action of somatostatin, a hormone that inhibits the release of other hormones, including cortisol. The most commonly used somatostatin analog is pasireotide (Signifor), which is effective in lowering cortisol levels and improving symptoms.
Retinoic acid (RA)
Retinoic acid (RA) is a medical treatment for Cushing’s syndrome. RA works by inhibiting the production of COUP-TF1, a protein that is essential for cortisol synthesis. As a result, RA can help to reduce the levels of cortisol in the body and improve the symptoms of Cushing’s syndrome. While RA is not a cure for Cushing’s syndrome, it can help to manage the condition and improve the quality of life for patients.
Steroidogenesis inhibitors
Steroidogenesis inhibitors are a class of drugs that are used to treat Cushing’s syndrome by reducing the production of cortisol. The most common agents in this class are ketoconazole, metyrapone, and mitotane. These drugs work by inhibiting the enzymes involved in cortisol synthesis in the adrenal gland. While they are effective at reducing cortisol levels, they can also cause significant side effects, such as gastrointestinal distress, adrenal insufficiency, and hepatotoxicity.
Mifepristone
Mifepristone (RU-486) is a synthetic steroid with anti-progestational and anti-glucocorticoid activity. It is a competitive inhibitor of progesterone and cortisol at the glucocorticoid receptor, and thus prevents the maturation of the corpus luteum, suppresses ovulation, and antagonizes the action of endogenous cortisol.
References
- Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40.
- Liddle GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1960 Dec;20:1539-60.
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