Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis.
Pituitary
; 22(4): 435-442, 2019 Aug.
Article
in En
| MEDLINE
| ID: mdl-31273566
ABSTRACT
PURPOSE:
Cushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (~ 50%). Few studies have reported the distribution between MICs-MACs related to USP8-mutations and their genotype-phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs-MACs from a unique center and to perform a systematic review and meta-analysis.METHODS:
DNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n = 630).RESULTS:
We identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p ≤ 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p < 0.1 × 10-4). Among the 5 series, the remission rates were higher in patients with USP8-mutated-alleles than in those with the USP8-WT-alleles (p < 0.1 × 10-4).CONCLUSION:
Our data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endopeptidases
/
Ubiquitin Thiolesterase
/
Pituitary ACTH Hypersecretion
/
Endosomal Sorting Complexes Required for Transport
/
Mutation
Type of study:
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Humans
Language:
En
Journal:
Pituitary
Journal subject:
ENDOCRINOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Brazil