Cushing Syndrome (cont.)
George P Chrousos, MD, FAAP, MACP, MACE
Shehnaz Shaikh, MD
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS
Mary L Windle, PharmD
George T Griffing, MD
IN THIS ARTICLE
Metyrapone (Metopirone) blocks the final step in corticosteroid synthesis. Side effects are high blood pressure, acne, and hirsutism (overabundance of hair). This is the only drug that can be used during pregnancy.
Ketoconazole (Nizoral) is probably the most popular and effective drug for long-term use and is usually the drug of choice. It blocks several key enzymes in the body that are essential for the production of corticosteroids. Side effects of ketoconazole include headache, sedation, nausea, irregular menses, decreased libido, impotence, gynecomastia (excessive development of the male mammary gland), and impaired liver function tests. The drug is contraindicated during pregnancy. Additionally, ketoconazole interacts with numerous drugs, typically increasing other drugs' blood levels and causing toxicity. H2 blockers, such as cimetidine (Tagamet), ranitidine (Zantac), or famotidine (Pepcid) decrease ketoconazole's effectiveness. Proton pump inhibitors, such as omeprazole (Prilosec), lansoprazole (Prevacid), or pantoprazole (Protonix) also decrease effectiveness of ketoconazole.
Aminoglutethimide (Cytadren) blocks one of the steps in corticosteroid production. It is a relatively weak enzyme inhibitor at doses that can be tolerated. Side effects of aminoglutethimide include increased sleepiness, headache, a generalized itchy rash, hypothyroidism, and increased size of the thyroid gland. In rare cases, it may cause bone marrow suppression.
Trilostane (Modrastane) inhibits an enzyme required for the synthesis of corticosteroid. It is no longer available in the United States and is not as well studied. It is not a first-choice agent because it is a weak inhibitor of corticosteroid synthesis.
Etomidate (Amidate) has to be administered intravenously (into the vein); therefore, its use is limited.
Mitotane (Lysodren) causes death of adrenal cells. For this reason, it is used in the treatment of adrenal cancer. Unfortunately, mitotane is expensive, and its utility is limited by adverse gastrointestinal and neurological effects, including nausea, diarrhea, dizziness, and ataxia (an inability to coordinate muscle activity during voluntary movement). Other side effects include rash, arthralgias (pain in joints and leukopenia [decrease in white blood cells]). It is a potential teratogen (a drug that causes abnormal development of the fetus) and can cause abortion; therefore, it is relatively contraindicated in women interested in remaining fertile.
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