Sections

Endogenous Cushing Syndrome

Medication

Medication Summary

The goal of pharmacotherapy is to reduce morbidity and prevent complications.

Class Summary

Osilodrostat is the first drug approved by the FDA to reduce overproduction of cortisol.

Osilodrostat (Isturisa)

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An orally administered steroidogenesis inhibitor, osilodrostat (Isturisa) acts on 11-beta-hydroxylase, an enzyme that catalyzes the last step of cortisol synthesis in the adrenal cortex. It is indicated for adults with Cushing disease who cannot undergo pituitary surgery or in whom the operation has not been curative.

Class Summary

Somatostatin analogs bind and activate human somatostatin receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.

Pasireotide (Signifor)

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Pasireotide is a cyclohexapeptide somatostatin analog that binds to human somatostatin receptors (HSSTs) 1, 2, 3, 4 and 5. This action results in the inhibition of ACTH secretion, which in turn leads to decreased cortisol secretion. It is indicated for treatment of adults with Cushing disease in whom pituitary surgery is not an option or has not been curative.

Class Summary

These agents inhibit key steps in the synthesis of adrenal glucocorticoids.

Metyrapone (Metopirone)

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Inhibitor of endogenous adrenal corticosteroid synthesis. Inhibits 11-B-hydroxylation reaction in the adrenal cortex.

Ketoconazole

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Ketoconazole is an imidazole broad-spectrum antifungal agent that inhibits cytochrome P450 enzyme system and 17,20-lyase. These enzymes are involved in the synthesis and catabolism of steroids. Ketoconazole may also inhibit the pituitary corticotroph function, which in turn inhibits ACTH secretion.

Etomidate (Amidate)

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Etomidate, an imidazole-derivative anesthetic agent, decreases corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 17-20 yase and 11-beta-hydroxylase at non-hypnotic doses. It is used intravenously at 0.3 mg/kg/h. Its use is limited by the requirement for administration by intravenous route. However, it rapidly decreases cortisol concentration and may be used as an adjunct to impending surgical procedure.

Class Summary

Agents in this class that decrease cortisol production and alter the peripheral metabolism of steroids may reduce morbidity.

Mitotane (Lysodren)

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Mitotane is an adrenolytic agent that acts by inhibiting 11-beta hydroxylase and several cholesterol side-chain cleavage enzymes. This drug also leads to mitochondrial destruction and necrosis of adrenocortical cells in the zona fasciculata and reticularis.

Class Summary

Cortisol receptor blockers inhibit the effect of cortisol at the glucocorticoid receptor.

Mifepristone (Korlym, Mifeprex, Ru486)

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Mifepristone is an antiprogestational agent, which, at low doses competitively binds to the intracellular progesterone receptor while, at high doses, competitively binds to the glucocorticoid receptor. It helps to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery, or are not candidates for surgery.

Questions

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Media Gallery

Physical findings in Cushing syndrome.
Diagnosis of Cushing syndrome.
Etiology of Cushing syndrome.
High power H and E of a pituitary adenoma showing a monotonous proliferation of bland cells. Not all pituitary adenomas result in Cushing syndrome, only those that produce ACTH.
Intermediate power H and E of an adrenal adenoma showing a monotonous proliferation of bland cells. Not all adrenal adenomas or carcinomas result in Cushing's syndrome; only those that produce ACTH.

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Author

Ha Cam Thuy Nguyen, MD Fellow, Department of Endocrinology, University of Pittsburgh Medical Center

Ha Cam Thuy Nguyen, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Medical Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Catherine Anastasopoulou, MD, PhD, FACE Associate Professor of Medicine, The Steven, Daniel and Douglas Altman Chair of Endocrinology, Sidney Kimmel Medical College of Thomas Jefferson University; Einstein Endocrine Associates, Einstein Medical Center

Catherine Anastasopoulou, MD, PhD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Society for Bone and Mineral Research, Endocrine Society, Philadelphia Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Gail K Adler, MD, PhD, Associate Professor of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School.

Disclosure: Nothing to disclose.

Susanna L Dipp, MD Fellow, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School

Disclosure: Nothing to disclose

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Disclosure: Nothing to disclose

Endogenous Cushing Syndrome Medication

Medication Summary

Steroidogenesis Inhibitors