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.2018 Apr;55(4):254-260.
doi: 10.1136/jmedgenet-2017-104957. Epub 2018 Feb 10.

Risk category system to identify pituitary adenoma patients withAIP mutations

Affiliations

Risk category system to identify pituitary adenoma patients withAIP mutations

Francisca Caimari et al. J Med Genet.2018 Apr.

Abstract

Background: Predictive tools to identify patients at risk for gene mutations related to pituitary adenomas are very helpful in clinical practice. We therefore aimed to develop and validate a reliable risk category system for aryl hydrocarbon receptor-interacting protein (AIP) mutations in patients with pituitary adenomas.

Methods: An international cohort of 2227 subjects were consecutively recruited between 2007 and 2016, including patients with pituitary adenomas (familial and sporadic) and their relatives. All probands (n=1429) were screened forAIP mutations, and those diagnosed with a pituitary adenoma prospectively, as part of their clinical screening (n=24), were excluded from the analysis. Univariate analysis was performed comparing patients with and withoutAIP mutations. Based on a multivariate logistic regression model, six potential factors were identified for the development of a risk category system, classifying the individual risk into low-risk, moderate-risk and high-risk categories. An internal cross-validation test was used to validate the system.

Results: 1405 patients had a pituitary tumour, of which 43% had a positive family history, 55.5% had somatotrophinomas and 81.5% presented with macroadenoma. Overall, 134 patients had anAIP mutation (9.5%). We identified four independent predictors for the presence of anAIP mutation: age of onset providing an odds ratio (OR) of 14.34 for age 0-18 years, family history (OR 10.85), growth hormone excess (OR 9.74) and large tumour size (OR 4.49). In our cohort, 71% of patients were identified as low risk (<5% risk ofAIP mutation), 9.2% as moderate risk and 20% as high risk (≥20% risk). Excellent discrimination (c-statistic=0.87) and internal validation were achieved.

Conclusion: We propose a user-friendly risk categorisation system that can reliably group patients into high-risk, moderate-risk and low-risk groups for the presence ofAIP mutations, thus providing guidance in identifying patients at high risk of carrying anAIP mutation. This risk score is based on a cohort with high prevalence ofAIP mutations and should be applied cautiously in other populations.

Keywords: AIP mutations; acromegaly; familial pituitary adenoma; risk category system; screening.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Area under the receiver operating characteristic curve of theAIP mutation risk category system is 0.87 (95% CI 0.84 to 0.90), indicating an excellent discriminating power.
Figure 2
Figure 2
Risk stratification forAIP mutations, classified as low risk (<5%), moderate risk (5%–19%) or high risk (≥20%). Red: risk ofAIP mutation ≥20%; orange: risk ofAIP mutation between 5% and 19%; green: risk ofAIP mutation <5%. GH, growth hormone; macro, macroadenoma; micro, microadenoma; simplex, patients with no known family history.
Figure 3
Figure 3
AIP screening algorithm based on the proposed risk category system. The overall risk category of a kindred should be based on the risk score of the family member with the highest risk. AIP, aryl hydrocarbon receptor-interacting protein. *See figure 2.
See this image and copyright information in PMC

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