Risk of recurrence after successful surgery for Cushing's disease and association with USP8 genotype and tumour size: an international, retrospective, longitudinal cohort study
Authors' conclusion
Combined USP8 genotype-tumour size identified patients at increased risk of recurrence, particularly in largely heterogeneous groups of patients with non-invasive tumours or low postoperative serum cortisol not considered high risk in standard care. Implementing this combined genetic-clinical stratification could provide more accurate risk assessment, indicate those at higher risk of recurrence, and ultimately personalise long-term follow-up in patients with Cushing's disease.
Study context
- Population
- Patients with clinically diagnosed and pathologically confirmed CD after first pituitary surgery (Jan 1, 1989–April 1, 2024), follow-up ≥3 months, known postsurgical outcome and tissue or known USP8 status; 8 tertiary centres in east Asia, Europe and North America371 in immediate remission
- Participants
- 435 patients
- Exposure
- USP8-variant tumours vs wildtype microadenomas vs wildtype macroadenomas
- Outcome
- Recurrence and time to recurrence after first surgery
Methodological detailsinternational, longitudinal, eight tertiary centres, 558 patients' records retrieved; 123 excluded
- International
- Longitudinal
- Eight tertiary centres
- 558 patients' records retrieved; 123 excluded
Main finding
As reported in the abstract
Recurrence rate · 10 years
Each group vs wildtype microadenomasHazard ratio (95% CI)P value
USP8-variant tumours
2.41(1.19–4.87)
P = 0.014Wildtype macroadenomas
4.48(2.11–9.52)
P < 0.0001- Recurrence in patients in immediate remission
- 66 (18%) of 371
Observational data: associations, not effects.
Further findings
- USP8 variants detected
- 195 (45%)
Original publication
Risk of recurrence after successful surgery for Cushing's disease and association with USP8 genotype and tumour size: an international, retrospective, longitudinal cohort study. Lancet Diabetes Endocrinol. Published 2 March 2026. doi:10.
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