]> 2026-07-31T07:51:34+00:00 WBR0886 0 en 11-deoxycortisol 11-deoxycortisol the substrate of 11β-hydroxylase inhibited by metyrapone accumulates after initiation of therapy. Corticosterone Corticosterone is one of the products of 11β-hydroxylase and would decrease rather than increase with metyrapone therapy. Aldosterone Aldosterone is one of the products of 11β-hydroxylase and would decrease rather than increase with metyrapone therapy. 17-hydroxypregnenolone 17-hydroxypregnenolone is unaffected by inhibition of 11β-hydroxylase. Pregnenolone Pregnenolone is unaffected by inhibition of 11β-hydroxylase. Metyrapone is an agent used mainly for diagnosing adrenal insufficiency via blocking steroid synthesis and monitoring the hypothalamic-pituitary-adrenal axis for increase in steroidogenesis. Failure of detecting an increase in ACTH or 11-deoxycortisol levels support the diagnosis of adrenal insufficiency. Metyrapone acts by inhibiting the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase. It is also used in the treatment of Cushing's disease (not very common practice) to decrease the corticoid load. Typically, if 11β-hydroxylase is inhibited, it's substrate would accumulate. After initiation of therapy, serum levels of 11-deoxycortisol would be expected to increase. Urine levels of 17-hydroxysteroids, the breakdown products of 11β-hydroxylase are also expected to increase.<br/> '''Educational Objective:''' Metyrapone inhibits the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase.<br/> '''References:''' Avgerinos PC, Yanovski JA, Oldfield EH, Nieman LK, Cutler GB. The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. Ann Intern Med. 1994;121(5):318-27.<br> First Aid 2014 page 317 Pharmacology Physiology A 53-year-old man presents to the endocrinology clinic after his primary care physician documented new-onset diabetes mellitus poorly responding to oral antidiabetics with an HbA1C of 9.3%. The patient reports adhering to a strict diet but despite this feels like he has gained much weight in the past 3 months. He also reports significant lower extremity weakness and fatigue recently. His physical exam is notable for a blood pressure of 174/89 mmHg, significant abdominal obesity, proximal muscle weakness, and fat collection at the base of neck. After a series of tests, the physician diagnoses Cushing's disease and decides to start the patient on metyrapone therapy. What would you expect to increase after the initiation of therapy? A Endocrine 2020-10-28T01:59:38Z 2459150.5830787 WBR0886