Transsphenoidal surgery achieves 73.88% remission rate in Cushing's DiseaseFactors linked to higher remission rates in Cushing's Disease surgery

This meta-analysis evaluated the efficacy of transsphenoidal surgery (TSS) for Cushing's Disease (CD) by pooling data from multiple studies. The analysis included 11,666 patients treated with TSS, with a mean follow-up of 53.29 months. The primary outcome was remission rate after TSS, defined by normalization of cortisol levels. Secondary outcomes included post-operative serum cortisol, ACTH, and urinary-free cortisol (UFC) levels.

The overall remission rate was 73.88% across all patients. Several clinical factors were associated with significantly higher remission rates. Patients with positive MRI results had a remission rate of 78.47% versus 66.11% in those with negative MRI (P < 0.01). Microadenomas (79.16% vs 64.70% for macroadenomas, P < 0.01) and absence of cavernous sinus invasion (78.50% vs 47.54%, P < 0.01) also predicted better outcomes. First-time TSS achieved 81.98% remission compared to 63.80% for repeat surgery (P < 0.01). Selective adenectomy (81.24% vs 64.54% for other surgical types, P < 0.01) and positive adenoma pathology (80.37% vs 54.65%, P < 0.01) were additional favorable predictors. Post-operative serum cortisol, ACTH, and UFC levels were significantly lower in patients who achieved long-term remission.

Safety and tolerability data were not reported in this meta-analysis, so no conclusions can be drawn about adverse events. The risk of bias across included studies was reported as low, but specific limitations of the meta-analysis were not provided. The study identifies predictors for improved treatment planning rather than establishing a direct causal mechanism.

Compared to prior studies, these results confirm TSS as a highly effective first-line treatment for CD, with remission rates consistent with previous reports. The large sample size strengthens the evidence for clinical predictors of success. However, the lack of safety data and the observational nature of the included studies limit the ability to make definitive causal claims.

For clinicians, these findings emphasize the importance of preoperative MRI, tumor size assessment, and surgical experience in predicting remission. Patients with microadenomas, positive MRI, and no cavernous sinus invasion are most likely to benefit. Repeat surgery and macroadenomas carry lower success rates, which may inform shared decision-making. Post-operative cortisol monitoring remains essential for confirming remission.

Unanswered questions include the long-term durability of remission beyond the mean follow-up of 53 months, the impact of surgical technique variations, and the role of adjuvant therapies for non-remission. Future research should standardize remission definitions and report safety outcomes to better guide clinical practice.