Recurrent Cushing Disease: An Extensive Review on Pros and Cons of Different Therapeutic Approaches

Recurrent Cushing disease (CD) is characterized by the reappearance of clinical and hormonal aspects of hypercortisolism that occur more than 6 months after an initial post-treatment remission.

We performed a systematic review and meta-analysis to synthesize the evidence about remission and complication rates after transsphenoidal surgery (TSS) radiotherapy (RT) and medical therapy (MT) in recurrent CD patients. A quantitative systematic review was performed. Article selection was performed by searching MEDLINE (using PubMed), and Cochrane electronic bibliographic databases through 2020.

We noted 61 articles described therapeutic management of recurrent CD patients with representative outcome. A total of 723 patients received different therapeutic modality for their recurrent CD. The remission rates were 0.65 (95% confidence interval [CI] 0.60-0.70), 0.57 (95% CI 0.51-0.63), and 0.75 (95% CI 0.60-0.86) in the TSS, RT, and MT subgroups, respectively. The total remission rate after therapeutic approaches on recurrent CD patients was 0.64 (95% CI 0.60-0.68). A test for subgroup differences revealed there was a statistically significant difference between different subgroups (P = 0.01). The post hoc test showed that in comparison with RT, TSS (P = 0.0344) and MT (P = 0.0149) had a higher rate of remission. However, there was no statistically significant difference between separate therapeutic modalities in terms of complications including diabetes insipidus (P = 1.0) and hypopituitarism (P = 0.28).

Compared MT and TSS, RT has a statistically lower rate of remission. Although there is robust superiority of surgery over RT, interpretation of MT data must considered with caution due to the small number of included cases and wide CI range.