A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.
Clin Endocrinol (Oxf)
; 101(1): 32-41, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38691659
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endopeptidases
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Neuroendocrine Tumors
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Ubiquitin Thiolesterase
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ACTH-Secreting Pituitary Adenoma
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Endosomal Sorting Complexes Required for Transport
Limits:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Clin Endocrinol (Oxf)
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido