Management of Recurrent Cushings Disease: Biochemical Normalization and Complications of Treatment

Introduction: Cushing’s disease (CD) caused by an adrenocorticotropic hormone (ACTH) secreting pituitary adenoma is a rare disease with severe complications and increased mortality. Surgery is the first-line treatment with successful management of recurrent CD remaining a challenge with frequent need for a multimodal treatment regimen. In this study we sought to determine remission rates and complications after second transsphenoidal surgery (TSS) in patients with recurrent CD.

Methods: Retrospective review (2006-2022) of an IRB-approved registry. Electronic medical record data for patients with recurrent CD after initial remission following first TSS was collected. Age, gender, treatment modality, endocrine deficiencies, recurrence rate, remission rate, urinary free cortisol (UFC), late night salivary cortisol (LNSC), and biochemical and clinical normalization at 3 months were recorded. Data analyzed using student t-test on Excel Version 2209 (Build 15629.20208).

Results: 57 patients were identified with recurrent CD at mean 5.7±6.7 years from first TSS; of which 7 were lost to follow up, 28 had second TSS (56.0%), 18 medical therapy (36.0%), and 4 radiation plus bridge medical therapy (8.0%). Visible tumor on MRI was present in 51.9% of those who had 2nd TSS vs 31.8% who underwent alternative treatment. The overall number of endocrine deficiencies at the time of recurrence was 0.68±0.86 in surgical and 0.86±0.89 in non-surgical group (p=0.121). Following 2nd TSS, 13 (46.4%) achieved remission; 7(57.1%) of those with visible tumor achieved remission vs 4(30.8%) in non-visible tumor cohort (p=0.17). There was no difference in number of new endocrine deficiencies between patients who did and did not achieve remission (0.30±0.67 vs 0.37±0.60, p=0.781).

Conclusion : In this large, long-term institutional series, remission rate following second surgery for recurrent CD is similar with reported rates in the literature. Repeat surgery in carefully selected patients with visible tumor on imaging could improve biochemical normalization and clinical features in patients with CD.