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. 2024 Jul;101(1):32-41.
doi: 10.1111/cen.15065. Epub 2024 May 1.

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

Hui Miao  1 , Luo Wang  2 , Fengying Gong  2 , Lian Duan  2 , Linjie Wang  2 , Yong Yao  1 , Ming Feng  1 , Kan Deng  1 , Renzhi Wang  1 , Yu Xiao  3 , Qing Ling  3 , Huijuan Zhu  2 , Lin Lu  2
Affiliations

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

Hui Miao et al. Clin Endocrinol (Oxf). 2024 Jul.

Abstract

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.

Keywords: ACTH; Cushing's disease; USP8; recurrence; remission.

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