Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas.

Abstract

CONTEXT:

An increased prevalence of acromegaly was found some years ago in a highly polluted area in North-Eastern Sicily, where high concentration of nonmethane hydrocarbons, volatile organic compounds, and cadmium was found. Aryl hydrocarbon receptor (AHR) pathway has a key role in detoxification of these compounds and in tumorigenesis.

OBJECTIVE:

We correlated the occurrence of AHR and/or AHR-interacting protein (AIP) gene variants with acromegaly severity according to pollution exposition.

DESIGN, SETTING, and PATIENTS:

This was an observational, perspective study conducted over 7 years in four Italian referral centers for pituitary diseases in which 210 patients with acromegaly were enrolled between 2008 and 2015.

INTERVENTION:

Genetic screening of patients for AHR and AIP variants.

MAIN OUTCOME MEASURES:

Clinical, biochemical, and radiological data of patients with and without AIP and/or AHR gene variants, living in polluted (high-risk for health, [HR]) or nonpolluted (NP) areas of five Italian regions were evaluated and compared.

RESULTS:

Among the 23 patients from HR areas, nine showed AHR or AIP variants. Mean IGF-I levels and pituitary tumor diameter were significantly higher in these nine patients (HR/VAR+) than in the other 14 (HR/VAR−) and in the 187 from NP areas (44 NP/VAR+). Somatostatin analogs significantly decreased mean GH and IGF-I levels in patients from NP areas and in HR/VAR− (GH P < .05; IGF-I times the upper limit of normal P < .01) but not in HR/VAR+ group.

CONCLUSIONS:

Genetic variants potentially inducing functional abnormalities of the aryl hydrocarbon receptor (AHR) pathway are associated with a more severe acromegaly, increased pituitary tumor size, and somatostatin analog resistance in patients living in HR areas.

• Authors: S Cannavo, M Ragonese, S Puglisi, P D Romeo, M L Torre, A Alibrandi, C Scaroni, G Occhi, F Ceccato, D Regazzo, E De Menis, P Sartorato, G Arnaldi, L Trementino, F Trimarchi, F Ferrau
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 101 Issue 4 Pg. 1872-9 (04 2016) ISSN: 1945-7197 [Electronic] United States
• PMID: 26963951 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Receptors, Aryl Hydrocarbon
• aryl hydrocarbon receptor-interacting protein
• Human Growth Hormone
• Insulin-Like Growth Factor I

Topics

• Acromegaly (blood, diagnosis, etiology, genetics)
• Adult
• Aged
• Aged, 80 and over
• Environmental Pollution (adverse effects)
• Female
• Gene-Environment Interaction
• Genetic Variation
• Genotype
• Human Growth Hormone (blood)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Intracellular Signaling Peptides and Proteins (genetics)
• Italy
• Male
• Middle Aged
• Receptors, Aryl Hydrocarbon (genetics)
• Severity of Illness Index