A long‐term prognosis study of human USP8‐mutated ACTH‐secreting pituitary neuroendocrine tumours.

Objective: Somatic variants in the ubiquitin‐specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. Design, patients and measurements: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow‐up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. Results: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p =.022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47‐ vs. 24‐year‐olds, p =.033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p =.037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long‐term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence‐free survival presented a tendency to be shorter in USP8‐mutated individuals (76.7 vs. 109.2 months, p =.068). Conclusions: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long‐term follow‐up revealed a tendency toward shorter recurrence‐free survival in USP8‐mutant patients. [ABSTRACT FROM AUTHOR]