Endocrine Abstracts

We present three cases of ACTH-dependent Cushing’s syndrome, successfully managed with osilodrostat.

Case 1: A 42-year-old woman diagnosed with ACTH-dependent Cushing’s disease was initially treated with osilodrostat dose-titration approach, as MRI of the pituitary did not identify a clear surgical target. By week five, serum cortisol levels fully normalised. Salivary and 24 hr urinary free cortisol (UFC) normalised on a maintenance dose of 10 mg/24 h (Table1). After 11 weeks of treatment, 11C-Methionine PET CT revealed a methionine-avid lesion in the pituitary gland. She underwent a successful trans-sphenoidal surgery (TSS).

Case 2: A 65-year-old woman diagnosed with a grade 2 neuroendocrine tumour presented with florid Cushing’s syndrome, characterised by elevated ACTH 169 ng/l and cortisol >1000 nmol/l. Gallium-DOTATATE PET/CT imaging confirmed liver metastases and a presumed metastatic deposit in the pituitary gland. She was started on osilodrostat dose-titration regimen and eventually required a block and replaced regimen with osilodrostat and prednisolone. Osilodrostat fully suppressed her endogenous cortisol production allowing her to undergo chemotherapy for her neuroendocrine tumour.

Case 3: A 38-year-old woman was diagnosed with ACTH-dependent Cushing’s disease secondary to pituitary macroadenoma. However, pre-operative evaluation revealed an internal carotid artery aneurysm which required a period of flow diversion and dual antiplatelet therapy, thus delaying TSS for one year. During this period, her serum and UFC levels fully normalised using an osilodrostat dose-titration regimen (Table 2).

Conclusion: These cases highlight the extraordinary efficacy and safety of osilodrostat, a potent inhibitor of 11-beta-hydroxylase, in the management of ACTH-dependent Cushing’s syndrome.