The following is a summary of “Discontinuation of Drug Treatment in Cushing’s Disease Not Cured by Pituitary Surgery,” published in the April 2024 issue of Endocrinology by Ghalawinji, et al.

In cases where transsphenoidal surgery (TSS) fails to cure Cushing’s disease (CD), patients have several treatment options, including drug treatment (DT), second TSS (2nd TSS), bilateral adrenalectomy (BA), and pituitary radiotherapy (PR). While DT is appealing, its long-term effectiveness remains to be determined, prompting this evaluation.

The retrospective study, conducted in a center prioritizing 2nd TSS, involved 36 patients, 19 with TSS failure and 17 with recurrence, out of 119 patients with CD treated with initial TSS. The average follow-up was 6.1 years (95% CI 5.27-6.91). Control was defined as the normalization of urinary free cortisol (UFC), and the final treatment (FT) was the therapy achieving control at the last follow-up. Discontinuation rates of DT in published CD prospective clinical trials were also analyzed.

Control was achieved in 33 out of 36 patients (92%). DT was initiated in 29 patients (81%), resulting in at least one normal UFC in 23 patients (79%), but it was discontinued before the last follow-up in 18 patients (62%). DT was deemed FT in 11 patients (38%), all treated with cortisol synthesis inhibitors. The second TSS was FT in 8 out of 16 patients (50%), BA in all 14 patients (100%), and PR in none out of 5. In published trials, DT discontinuation rates ranged from 11% to 51% at 1 year and 32% to 74% before 5 years.

While DT led to at least one normal UFC in 23 out of 29 patients (79%), achieving long-term control in only 11 out of 29 (38%), the discontinuation rate was high, consistent with published data. Successful 2nd TSS discontinued effective and well-tolerated DT in 5 patients. Future studies will determine whether alternative strategies using cortisol synthesis inhibitors may reduce discontinuation rates in patients ineligible for 2nd TSS, potentially avoiding BA in these individuals.

Reference: academic.oup.com/jcem/article-abstract/109/4/1000/7420189