Cushing’s syndrome (CS) is an endocrine disorder marked by excessive adrenocortical steroid production. Steroidogenesis enzyme inhibitors, such as the antifungal medication ketoconazole, as well as metyrapone, mitotane, and aminoglutethimide, are among the most often used pharmacological therapies for CS. Osilodrostat, a new addition to this medicine family, was recently authorized by the US Food and Drug Administration (FDA) for the treatment of Cushing’s Disease. Steroidogenesis enzyme inhibitors block several enzymes along the cortisol biosynthetic pathway and can be used either preoperatively to lower cortisol levels and minimize surgical risk associated with tumor removal or postoperatively when surgery and/or radiation therapy are not curative. Because their selectivities for steroidogenic enzymes differ, they can be used together to enable relatively quick management of severe hypercortisolemia.
Unfortunately, all known inhibitors had substantial undesirable side effects that limit dose and frequently led to therapy failures. Although it was best recognized as a general anesthetic induction agent, etomidate is a steroidogenesis enzyme inhibitor medication. It is the only inhibitor that may be administered parenterally and decreases cortisol production largely by blocking 11-hydroxylase. However, etomidate’s sedative-hypnotic properties restrict its utility as an acute CS therapy option. As a result, others advocated for its usage solely in acute care units.
For a study, researchers looked at how etomidate was initially created as an anesthetic, then as a CS therapy, and how recent developments in dosage and drug development had separated sedative-hypnotic and adrenostatic pharmacological effects to make CS treatment easier in non-critical care settings.