Corticotroph Tumour Progression 37 Years After Bilateral Adrenalectomy with Temozolomide-Naive Response to Pembrolizumab.

Corticotroph tumour progression (CTP) following bilateral adrenalectomy for Cushing's disease usually emerges within the first decade; substantially delayed presentations are uncommon and longer term surveillance recommendations remain imprecise. We report a patient presenting with CTP 37 years after adrenalectomy, representing one of the latest onset cases in the literature. Tumour profiling demonstrated an aggressive molecular phenotype including ATRX loss, MEN1 inactivation and CDK4 amplification, with a Ki-67 index of 10% and absent PD-L1 expression. Pembrolizumab, administered for a concurrent metastatic melanoma, was associated with a rapid and sustained biochemical and radiological response, making this the fifth reported case of CTP post-adrenalectomy responding to immune checkpoint inhibitor (ICI) therapy and notably the first without prior temozolomide exposure. This case illustrates three clinically relevant points: 1. lifelong post-adrenalectomy surveillance requires a structured long-term framework; 2. comprehensive molecular profiling of aggressive corticotroph tumours may inform prognosis and facilitate access to targeted therapies; and 3. ICI response in corticotrophinomas may occur despite PD-L1 negativity and without temozolomide-induced hypermutation, supporting the rationale for evaluating earlier immunotherapy in this biologically distinct subtype.