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

Context: An increased prevalence of acromegaly was found some years ago in a highly polluted area in North-Eastern Sicily, where high concentration of non-methanic 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) genes vari- ants with acromegaly severity, according to pollution exposition. Design: Observational, perspective study conducted over 7 years. Setting: Four Italian referral centers for pituitary diseases. Patients: 210 patients with acromegaly have been enrolled from 2008 and 2015. Interventions: 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 genes variants, living in polluted (HR) or non polluted (NP) areas of five Italian regions were evaluated and compared. Results:Amongthe23 patients fromHRareas, 9showedAHRor AIPvariants.MeanIGF-1 levels and pituitary tumor diameter were significantly higher in these 9 patients (HR/VAR⫹ve) than in the other 14 (HR/VAR-ve) and in the 187 from NP areas (44 NP/VAR⫹ve). Somatostatin analogs (SSa) significantly decreased mean GH and IGF-1 levels in patients from NP areas and in HR/VAR-ve (GH p⬍0.05; IGF-1xULN p⬍0.01) but not in HR/VAR⫹ve group. Conclusions: Genetic variants potentially inducing functional abnormalities of the AHR pathway are associated with a more severe acromegaly, increased pituitary tumor size and SSa resistance in patients living in highly polluted areas.