Endocrine Abstracts

The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency (21OHD). The treatment for classic (severe) 21OHD differs from treatment of most other types of adrenal insufficiency in that not only must one replace the glucocorticoid and mineralocorticoid deficiency but also attenuate the high adrenal-derived androgen production. In order to reduce the adrenocorticotropin (ACTH) driven androgen production, supraphysiologic doses of gluco...

The management of adults with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) is a challenging balance of hormone replacement, disease control, and avoidance of adverse effects. The approach should emphasize the clinical evaluation and patient goals, and laboratory tests are used secondarily as ancillary data. Upon transition from pediatric to adult care, the concerns shift from growth and pubertal development to fertility, neoplasia formation, ...

In the 60 years since primary aldosteronism (PA) was described, our understanding of its pathophysiology and approaches to diagnosis and treatment has improved remarkably. Despite this progress, <1% of patients with PA are ever screened for this condition, which accounts for 5–8% of hypertension (HTN). The resistance to screening for PA probably derives primarily from the complexities and uncertainties inherent in its evaluation and management. How many types of PA ex...

Dr Richard J Auchus is Professor of Pharmacology and Internal Medicine in the Division of Metabolism, Endocrinology, and Diabetes at the University of Michigan and Director of the Diabetes, Endocrinology, & Metabolism Fellowship Program at Michigan. He did postdoctoral work and training at the University of California, San Francisco prior to joining the faculty at UT Southwestern in Dallas. He served as Acting Chi...

Background: Hypogonadism is frequent in men with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). It has recently been demonstrated that testicular adrenal rest tumors (TART) are a source of 11-oxygenated androgens that might impair testicular function, in addition to their local compressive effects. Data on long-term course of testicular function in men with 21OHD and the role of potential influential factors such as presence of TART and 11-oxyge...

Background: Osilodrostat is an oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step in cortisol biosynthesis. In a 22-week, phase II study, osilodrostat treatment normalised mean urinary free cortisol (mUFC) in 78.9% (15/19) of patients with uncontrolled Cushing’s disease and was well tolerated. The present phase 3 study is designed to confirm the safety and efficacy of osilodrostat in patients with uncontrolled Cushing’s disease...

Introduction: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD CAH) is a rare genetic disorder resulting in impaired cortisol biosynthesis, increased steroid precursors, and excess androgen production. Inhibition of adrenocorticotropic hormone (ACTH) release via antagonism of the corticotropin-releasing factor-1 (CRF1) receptor could reduce adrenal androgen production, thereby reducing the amount of exogenous glucocorticoids required for androgen ...

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestation...

Background: 24-h mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels are complementary parameters recommended for screening and monitoring treatment response in patients with Cushing’s disease (CD). In the published core period of the Phase III LINC 3 study (NCT02180217), therapy with osilodrostat (potent oral 11β-hydroxylase inhibitor) produced rapid, sustained reductions in mUFC and LNSC alongside improvements in clinical signs of hyper...

Introduction: Corticotropin-releasing factor type 1 (CRF1) receptor antagonists, such as crinecerfont, have recently been investigated for the treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal disease characterized by cortisol deficiency, elevated adrenocorticotropic hormone (ACTH), and excess androgen production. In a study of adults with 21OHD, treatment with crinecerfont for 14 days led to median ...