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 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:Wecorrelated the occurrence ofAHRand/or AHR-interacting protein (AIP)genevariants 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. 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 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.