Medical treatment for Cushing’s has entered a new era due to approval by the FDA of new medicines. In her presentation on medical therapy, Dr. Ioachimescu explained that endocrinologists are still learning where these new medical treatments best fit in treatment options.

The goal in treating Cushing’s patients is to achieve long term control with few side effects. Surgery remains the first line of treatment, but not all pituitary tumors can be completely removed. Radiation is an option, but it is not effective in 100% of patients, it takes months to years to be effective and can cause deficiencies of other pituitary hormones. In years past, bilateral adrenalectomy was recommended for patients who failed surgery and radiation, but going forward, this will likely change due to the availability of new medications.

The first medications to treat Cushing’s, mifepristone (Korlym) and pasireotide (Signifor) were approved by the FDA in 2012. Before that, some drugs were used “off label”, meaning they were approved for other purposes, but were used to treat Cushing’s. Medications are sometimes used before surgery in those who are poor surgical candidates due to Cushing’s, in cases of persistent elevated cortisol after surgery and in cases that aren’t cured by surgery. Ketoconazole acts on the adrenal glands to decrease cortisol production. To date, ketoconazole has been the most used drug, but carries warnings for serious liver damage and usually can’t control cortisol long term. Mifepristone, FDA approved in 2012, blocks the action of cortisol, thus cortisol levels stay elevated, ACTH can increase and there is a potential for adrenal insufficiency symptoms, but lab results can’t verify it. Mifepristone has been shown to improve weight, appearance, depression and plasma glucose. The main side effects are low potassium and vaginal bleeding in women. Pasireotide is an FDA approved medication that acts at the pituitary level to decrease ACTH, thus cortisol levels. This medication was found to reduce urine cortisol in the majority of patients, normalized it in 25%, and improved clinical features. The biggest side effect is high blood sugar that occurs in the majority of treated patients. Pasireotide, cabergoline, (another drug that works at the pituitary level) and ketoconazole have been used in combination (off label), but further research is needed. The choice of when and what medication to use should be individualized to a particular patient.