Endocrine Abstracts

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...

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...

Background: Hyponatremia (Na+≤134 mmol/L), the most common electrolyte derangement, is caused by inappropriate vasopressin-mediated water resorption in the kidney. Treating symptomatic hyponatremia is difficult and risky; as difficult as maintaining normal sodium levels. We tested if tolvaptan, an oral vasopressin V2 receptor antagonist, improves hyponatremia and self-reported health outcomes.Methods: Two multicenter, randomized, double-blind, plac...