Endocrine Abstracts

A 51-year-old gentleman presented in June 2022 with pneumobilia, staph liver abscesses and rapidly conducted atrial fibrillation requiring ITU admission. He had a 2-year history of typical Cushingoid features and hypogonadism, 4 agent hypertension since 2012, fragility fractures, previous renal calculi, pulmonary emboli and diabetes. He had not been able to walk unaided for a year (was mobilising with crutches on admission). In retrospect, he had previously had a cortisol of 726nmol/l at 1pm in 2017. His past medical history included type A thoracic aortic aneurysm dissection, open repair (and cardiac arrest) in 2016. His admission was complicated by pneumonia, Covid and Influenza and he became bed-bound. He was noted to be hypokalaemic with a cortisol >1750nmol/l, ACTH of 78ng/L. His cortisol levels post-8mg dexamethasone suppression test was 1590nmol/l. MR pituitary showed a 9mm hyper-enhancing lesion in the anterior pituitary which on retrospect had been visible on previous CT imaging in 2011. CT adrenals showed diffusely enlarged adrenal glands. He was unable to tolerate sufficient metyrapone and ketoconazole to achieve biochemical control of his Cushing’s syndrome and so he was commenced on intravenous etomidate and transferred to St Bartholomew’s Hospital (Nov 22). In order to facilitate outpatient medical preparation for pituitary surgery, compassionate use of Osilodrostat was obtained, titrating from a starting dose of 2mg bd to 30mg twice a day over several weeks whilst continuing with maximally tolerated ketoconazole. Osilodrostat was well tolerated. He walked out of hospital for respite over Christmas, with good control of his cortisol, returning in January 23 for pre-transsphenoidal surgery. His post-operative Day 1 cortisol was 12nmol/l. Osilodrostat, a novel steroidogenic inhibitor targeting the 11β-hydroxylase, is now approved for the treatment of Cushing’s disease (CD) in the United States and Cushing syndrome in Europe. Although the mainstay of treatment for CD is surgery, medical therapy is often required, to control hypercortisolism to minimise pre, peri and post-operative complications. Osilodrostat works similarly to metyrapone and a study comparing metyrapone and Osilodrostat showed that Osilodrostat works faster in achieving target cortisol levels and controlling blood pressure. The long-term outcomes of Osilodrostat in CD showed good tolerability with a small proportion of adverse effects. Hence, Osilodrostat proves to be a good alternative to metyrapone in optimising Cushing’s when cortisol levels need to be reduced rapidly and for patients intolerant to metyrapone although more head-to-head clinical trials are needed to analyse this in a larger cohort.