Ectopic Cushing’s syndrome remains one of the most challenging paraneoplastic syndromes to manage, particularly when driven by aggressive neuroendocrine neoplasms (NENs), where both tumour control and rapid cortisol reduction are critical. Achieving sustained biochemical control is often difficult, and evidence – especially for newer agents and combination strategies – remains limited.

In this instructive case report, Majumder and colleagues describe a 43-year-old man with recurrent thymic NEN, presenting eight years after initial diagnosis with severe ectopic Cushing’s syndrome. Despite multiple lines of therapy, including surgery, radiotherapy and conventional steroidogenesis inhibitors, hypercortisolism remained uncontrolled. Transition to osilodrostat resulted in biochemical improvement. Following confirmation of somatostatin receptor avidity via DOTATATE imaging, subsequent peptide receptor radionuclide therapy (PRRT) led to normalisation of cortisol levels over 12 months, alongside clear clinical recovery.

This case highlights a complementary therapeutic approach: osilodrostat providing relatively rapid biochemical control, while PRRT addresses tumour burden. Although based on a single case, it illustrates a pragmatic and increasingly relevant strategy for refractory ectopic Cushing’s syndrome in complex NENs, and is therefore a valuable addition to the emerging evidence base.

Read the full article in Endocrinology, Diabetes & Metabolism Case Reports https://doi.org/10.1530/EDM-25-0138