Endocrine Abstracts

Background: HSD-1 converts cortisone to cortisol in tissues in which cortisol excess is associated with morbidity including liver, adipose, bone, and brain. SPI-62 is a potent HSD-1 inhibitor in clinical development for treatment of Cushing’s syndrome and autonomous cortisol secretion, and as adjunctive therapy to prednisolone in polymyalgia rheumatica. In Phase 1 clinical trials SPI-62 was generally well tolerated and associated with maximal liver and brain HSD-1 inhibit...

Endocrinologists focus on circulating and excreted cortisol for diagnosis of, and to assess severity and treatment response in, Cushing’s syndrome (Cs). However, in Cs, morbidity is mediated by excess cortisol binding to intracellular glucocorticoid (GC), mineralocorticoid (MC), and non-genomic receptors. We and others have demonstrated that 11b-hydroxysteroid dehydrogenase type 1 (HSD-1) is the source of about half of intrahepatocellular cortisol in healthy adults, patie...

11β-hydroxysteroid dehydrogenase type 1 (HSD-1) controls the intracellular cortisol pool that has access to cytosolic glucocorticoid and mineralocorticoid receptors. HSD-1 activity is elevated in patients with Cushing’s syndrome (CS).1 Patients with CS and constitutionally low HSD-1 activity showed no hypercortisolism-related symptoms despite very high 24-hour urine free cortisol.2, 3 A recent pilot trial of a HSD-1 inhibitor in patients with classical or mild CS sho...

Background: HSD-1, an intracellular enzyme, converts cortisone to cortisol in tissues where cortisol excess is associated with morbidity including liver, adipose, bone, brain, muscle, skin, and eye. SPI-62 is a potent and specific HSD-1 inhibitor in development for treatment of Cushing’s syndrome and autonomous cortisol secretion, and as adjunctive therapy to prednisolone in polymyalgia rheumatica. In Phase 1 clinical trials SPI-62 was generally well tolerated and associa...

Background: HSD-1, an intracellular enzyme, converts cortisone to cortisol in tissues where cortisol excess is associated with morbidity including liver, adipose, bone, brain, muscle, skin, and eye. SPI-62 is a potent and specific HSD-1 inhibitor in development for treatment of autonomous cortisol secretion (ACS) and Cushing’s syndrome, and as adjunctive therapy to prednisolone in polymyalgia rheumatica. In Phase 1 clinical trials SPI-62 was generally well tolerated and a...