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Aryl hydrocarbon receptor interacting protein and pituitary adenomas: a population-based study on subjects exposed to dioxin after the Seveso, Italy, accident

A Pesatori, EPOCA Research Center, Dept of Occupational and Environmental Health, University of Milan, Milan, Italy
A Baccarelli, Center of Molecular and Genetic Epidemiology, Dept Of Occupational and Environmental Health, University of Milan, Milan, Italy
D Consonni, Epidemiology Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
A Lania, Endocrine Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena,, Milan, Italy
P Beck-Peccoz, Endocrine Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy
P Bertazzi, EPOCA Research Center, Dept of Occupational and Environmental Health, University of Milan, Milan, Italy
A Spada, Endocrine Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy

Correspondence: Angela Pesatori, Email: angela.pesatori{at}unimi.it

Abstract

Objective. The pathogenesis of sporadic pituitary tumors is unknown. Loss-of-function mutations of aryl-hydrocarbon receptor interacting protein (AIP) have been identified in patients with familial pituitary tumors. AIP is a chaperon protein with multifunction properties, including modulation of the transcriptional activity of the aryl-hydrocarbon receptor (AhR), which mediates toxicologic and carcinogenic dioxin effetcs.

Design. We investigated the incidence of pituitary tumors in the Seveso population exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin following an industrial accident in 1976.

Methods. Through the hospital discharge registration system of Lombardy Region we identified incident cases of pituitary adenomas between 1976-1996 in the Seveso population, subdivided in zone A (n=804), B (n=5.941) and R (n=38.624) according to high, intermediate and low exposure to dioxin, respectively, and in the surrounding non-contaminated area, as reference (n=232745)

Results. We identified 42 pituitary adenomas in the reference area, 1 prolactinoma in Zone A (rate ratio (RR) 6.2; 95% CI 0.9-45.5, p= 0.07), 2 nonfuctioning pituitary tumors (NFPAs) in zone B (RR 1.9; 95% CI 0.5-7.7, p=0.39) and 3 prolactinomas and 2 NFPAs in zone R (RR 0.7 ; 95% CI 0.3-1.8, p=0.48).

Conclusions. The study is unique with regard to availability of epidemiological and clinical data in an area of relatively pure dioxin exposure. The study indicates no statistically significant increase of incident pituitary tumors in this area, although the tendency toward a higher risk (3 cases in zones A and B) of pituitary tumors in subjects exposed to high-intermediate dioxin concentrations in comparison to non-exposed population suggests the need for extended follow-up.