Disclosed herein are methods of treating a disease or disorder characterized by an increased secretion of adrenocorticotropic hormone (e.g., Cushing's disease). Also disclosed herein are methods of identifying compounds for use in treating said diseases or disorders.

Applicant discloses herein methods for differentially diagnosing adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in a patient where the differential diagnosis is between ectopic ACTH syndrome and Cushing Disease. The methods include administration of an amount of a glucocorticoid receptor antagonist (GRA) effective to increase ACTH in patients with ectopic ACTH syndrome but not in those with Cushing's Disease. Method steps may include administering a GRA dose sufficient to increase ACTH from the pituitary gland by at least two fold in persons with normal HPA function (e.g., 300 to 1500 milligrams); waiting for at least two hours; and obtaining from the patient an ACTH concentration ratio derived from the ACTH concentrations in blood samples obtained from an inferior petrosal venous sinus and from a peripheral vein. The patient is diagnosed with Cushing Disease if the ACTH concentration ratio is greater than 3.

Methods for treating and differential diagnosis between ACTH-Dependent and ACTH-Independent Cushing's syndrome are disclosed, in which a glucocorticoid receptor antagonist (GRA) is administered to a Cushing's syndrome patient with a basal ACTH level less than about 25 pg/mL. If i) the patients blood ACTH and ii) the patients blood cortisol, or adrenal hormone, or adrenal pre-hormone levels rise, or if the ACTH:cortisol ratio increases, then ACTH-Dependent Cushing's syndrome is diagnosed. If those levels do not rise, or if the ACTH:cortisol ratio decreases, then ACTH-Independent Cushing's syndrome is diagnosed. In some instances, the patient is recovering from surgery to remove an ACTH secreting tumor, and the method described herein is used to determine if the tumor resection was successful or complete. The GRA may be mifepristone, or a non-steroidal GRA having a heteroaryl-ketone fused azadecalin backbone, an octahydro fused azadecalin backbone, a cyclohexyl pyrimidine backbone, or a fused azadecalin backbone.

This invention provides for an improved method for differentially diagnosing ACTH-dependent Cushing's syndrome. Current practice for differentially diagnosing ectopic ACTH syndrome and Cushing's Disease measures relative ACTH concentrations from the inferior petrosal venous sinus compared to fluid obtained from a periphery venous sample. This is performed before and after administration of exogenous corticotropin releasing factor, or after administration of metyrapone. This invention uses glucocorticoid receptor antagonists to induce release of endogenous CRH which stimulates ACTH to increase in patients with ectopic ACTH syndrome but not in those with Cushing's Disease.

This invention provides for an improved method for differentially diagnosing ACTH-dependent Cushing's syndrome. Current practice for differentially diagnosing ectopic ACTH syndrome and Cushing's Disease measures relative ACTH concentrations from the inferior petrosal venous sinus compared to fluid obtained from a periphery venous sample. This is performed before and after administration of exogenous corticotropin releasing factor, or after administration of metyrapone. This invention uses glucocorticoid receptor antagonists to induce release of endogenous CRH which stimulates ACTH to increase in patients with ectopic ACTH syndrome but not in those with Cushing's Disease.

This invention provides for an improved method for differentially diagnosing ACTH-dependent Cushing's syndrome. Current practice for differentially diagnosing ectopic ACTH syndrome and Cushing's Disease measures relative ACTH concentrations from the inferior petrosal venous sinus compared to fluid obtained from a periphery venous sample. This is performed before and after administration of exogenous corticotropin releasing factor, or after administration of metyrapone. This invention uses glucocorticoid receptor antagonists to induce release of endogenous CRH which stimulates ACTH to increase in patients with ectopic ACTH syndrome but not in those with Cushing's Disease.

This invention provides for an improved method for differentially diagnosing ACTH-dependent Cushing's syndrome. Current practice for differentially diagnosing ectopic ACTH syndrome and Cushing's Disease measures relative ACTH concentrations from the inferior petrosal venous sinus compared to fluid obtained from a periphery venous sample. This is performed before and after administration of exogenous corticotropin releasing factor, or after administration of metyrapone. This invention uses glucocorticoid receptor antagonists to induce release of endogenous CRH which stimulates ACTH to increase in patients with ectopic ACTH syndrome but not in those with Cushing's Disease.

This invention provides for an improved method for differentially diagnosing ACTH-dependent Cushing's syndrome. Current practice for differentially diagnosing ectopic ACTH syndrome and Cushing's Disease measures relative ACTH concentrations from the inferior petrosal venous sinus compared to fluid obtained from a periphery venous sample. This is performed before and after administration of exogenous corticotropin releasing factor, or after administration of metyrapone. This invention uses glucocorticoid receptor antagonists to induce release of endogenous CRH which stimulates ACTH to increase in patients with ectopic ACTH syndrome but not in those with Cushing's Disease.

This invention provides for an improved method for differentially diagnosing ACTH-dependent Cushing's syndrome. Current practice for differentially diagnosing ectopic ACTH syndrome and Cushing's Disease measures relative ACTH concentrations from the inferior petrosal venous sinus compared to fluid obtained from a periphery venous sample. This is performed before and after administration of exogenous corticotropin releasing factor, or after administration of metyrapone. This invention uses glucocorticoid receptor antagonists to induce release of endogenous CRH which stimulates ACTH to increase in patients with ectopic ACTH syndrome but not in those with Cushing's Disease.

A method for detecting adrenocorticotropic hormone comprising: bringing a liquid sample containing adrenocorticotropic hormone into contact with gelled casein to adsorb adrenocorticotropic hormone to the gelled casein; and detecting the adrenocorticotropic hormone adsorbed to the gelled casein is disclosed. An adsorbent of adrenocorticotropic hormone comprising gelled casein is also disclosed.