Use of glucocorticoid receptor antagonists in combination with glucocorticoids to treat adrenal insufficiency
This invention provides for a method of treating secondary adrenal insufficiency by co-administrating therapeutically effective amounts of a glucocorticoid and a glucocorticoid receptor antagonist to the patient in need thereof. In some embodiments, the method includes the proviso that the patient not be otherwise in need of treatment with a glucocorticoid and a glucocorticoid receptor antagonist. The treatment method can increase the patient's morning or basal cortisol level to at least about 12 μg/dL or a standard control level, and in turn, expedite significantly the recovery of the HPA axis. The method provided herein can improve health outcomes and life-threatening complications associated with secondary adrenal insufficiency.
1. A method of treating adrenal insufficiency due to exogenous Cushing's syndrome, the method comprising co-administering a therapeutically effective amount of a glucocorticoid (GC) and mifepristone to a patient in need thereof, wherein said administering mifepristone comprises initially administering doses of 150 milligrams per day (mg/day) or less of mifepristone for one week, and then administering doses of greater than 150 mg/day of mifepristone, effective to increase said patient's morning plasma levels of cortisol to at least 12 μg/dL, whereby said adrenal insufficiency due to exogenous Cushing's syndrome is treated.
2. The method of claim 1 , wherein the glucocorticoid is hydrocortisone.
3. The method of claim 1 , wherein the patient is initially administered doses of 150 milligrams per day (mg/day) or less of mifepristone for a period of time of more than one week, and then is administered doses of greater than 150 mg/day of mifepristone.
4. The method of claim 1 , wherein the glucocorticoid is selected from the group consisting of hydrocortisone, prednisone, dexamethasone, a glucocorticoid analogue, a synthetic glucocorticoid analogue, and derivatives thereof.
5. A method of treating adrenal insufficiency due to exogenous Cushing's syndrome, the method comprising co-administering a therapeutically effective amount of a glucocorticoid (GC) and mifepristone to a patient in need thereof, wherein said patient is initially administered doses of 150 milligrams (mg) or less of mifepristone every other day, then is administered doses of 600 mg of mifepristone every day, effective to increase the patient's morning plasma levels of cortisol to at least 12 μg/dL, whereby said adrenal insufficiency due to exogenous Cushing's syndrome is treated.
6. The method of claim 5 , wherein the glucocorticoid is selected from the group consisting of hydrocortisone, prednisone, dexamethasone, a glucocorticoid analogue, a synthetic glucocorticoid analogue, and derivatives thereof.
7. The method of claim 5 , wherein the glucocorticoid is hydrocortisone.
8. The method of claim 5 , wherein the patient is initially administered doses of 150 mg of mifepristone every other day for a period of time, then is administered doses of 300 mg of mifepristone every other day for two months, then is administered doses of 300 mg of mifepristone every day for one month, then is administered doses of 600 mg of mifepristone every day for one month, and then is administered doses of mifepristone of 300 600 mg every other day for two months.
9. The method of claim 5 , wherein the patient is initially administered doses of 150 mg of mifepristone every other day for two months, then is administered doses of 300 mg of mifepristone every other day for one month, then is administered 300 mg of mifepristone every day for one month, then is administered 600 mg of mifepristone every day for three months, and then is administered 300 mg mifepristone every other day for two months.