title: Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas.
abstract: 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.
  
  
  
  We correlated the occurrence of AHR and/or AHR-interacting protein (AIP) gene variants with acromegaly severity according to pollution exposition.
  
  
  
  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.
  
  
  
  Genetic screening of patients for AHR and AIP variants.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cannavo
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ragonese
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Puglisi
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: P D
authors.initials: PD
authors.lastname: Romeo
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Torre
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Alibrandi
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Scaroni
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Occhi
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ceccato
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Regazzo
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: E
authors.initials: E
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authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Sartorato
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: G
authors.initials: G
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authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Trementino
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Trimarchi
authors.affiliation: Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
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mesh_terms: D000172:Acromegaly / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004787:Environmental Pollution / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D005838:Genotype; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018336:Receptors, Aryl Hydrocarbon; C103265:aryl hydrocarbon receptor-interacting protein; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I