Treatment of, and differential diagnosis between, ACTH-dependent Cushing's syndrome and ACTH-independent Cushing's syndrome

A method of treating Cushing's syndrome in a patient and differentially diagnosing between adrenocorticotropin hormone (ACTH)-Dependent Cushing's syndrome and ACTH-Independent Cushing's syndrome during the treatment, the method comprising:

• (a) selecting a patient having Cushing's syndrome, having a basal level of plasma or serum cortisol, and having a basal level of plasma or a basal level of serum ACTH having a numerical value that is between about 5 picograms per milliliter (pg/mL) and about 25 μg/mL;
• (b) determining a basal ACTH:cortisol ratio by dividing the numerical value of the plasma or serum basal ACTH level by a numerical value of the corresponding plasma or serum basal cortisol level to provide said basal ACTH:cortisol ratio;
• (c) administering to the patient for at least 6 weeks a daily dose of a glucocorticoid receptor antagonist (GRA) selected from:
• a dose of mifepristone of between about 300 milligrams (mg) and about 1200 mg, and a dose of between about 25 mg and about 550 mg of a GRA compound selected from the group of GRA compounds having a non-steroidal backbone consisting of a GRA compound having a cyclohexyl pyrimidine backbone, a GRA compound having a fused azadecalin backbone, a GRA compound having a heteroaryl-ketone fused azadecalin backbone, and a GRA compound having an octahydro fused azadecalin backbone,
• wherein said GRA administration comprises a treatment of said Cushing's syndrome;
• (d) measuring a level of ACTH to determine a numerical value of the ACTH level and a level of cortisol to determine a numerical value of the cortisol level in an after-GRA plasma sample or a serum sample obtained from the patient after said 6 weeks of daily GRA administration, wherein said after-GRA sample is a plasma or serum sample corresponding to the type of sample from which the basal level was determined;
• (e) determining an after-GRA ACTH:cortisol ratio by dividing the numerical value of the plasma or serum ACTH level measured after GRA administration by the numerical value of the corresponding plasma or serum cortisol level measured after said at least six weeks of daily GRA administration to provide said after-GRA ACTH:cortisol ratio;
• and
• differentially diagnosing between adrenocorticotropin hormone (ACTH)-Dependent Cushing's syndrome and ACTH-Independent Cushing's syndrome by comparing said basal ACTH:cortisol ratio to said after-GRA ACTH:cortisol ratio, wherein
• if the basal ACTH:cortisol ratio is greater than the after-GRA ACTH:cortisol ratio by at least about 10% of the basal ACTH:cortisol ratio, then the patient is diagnosed with ACTH-independent Cushing's syndrome;
• and
• if the basal ACTH:cortisol ratio is smaller than the after-GRA ACTH:cortisol ratio by at least about 10% of the basal ACTH:cortisol ratio, then the patient is diagnosed with ACTH-dependent Cushing's syndrome,
• whereby Cushing's syndrome is further treated with said GRA administration or with surgical treatment to remove a tumor depending on the differential diagnosis between a) ACTH-Dependent Cushing's syndrome and between b) ACTH-Independent Cushing's syndrome in the patient.