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.