TY - JOUR
T1 - Aryl hydrocarbon receptor-interacting protein and pituitary adenomas
T2 - A population-based study on subjects exposed to dioxin after the Seveso, Italy, accident
AU - Pesatori, Angela Cecillia
AU - Baccarelli, Andrea
AU - Consonni, Dario
AU - Lania, Andrea
AU - Beck-Peccoz, Paolo
AU - Bertazzi, Pier Alberto
AU - Spada, Anna
PY - 2008/12
Y1 - 2008/12
N2 - 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 chaperone protein with multifunction properties, including modulation of the transcriptional activity of the aryl hydrocarbon receptor, which mediates toxicological and carcinogenic dioxin effects. 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 and 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, I 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 the 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 (three cases in zones A and B) of pituitary tumors in subjects exposed to high-intermediate dioxin concentrations in comparison with nonexposed population suggests the need for extended follow-up.
AB - 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 chaperone protein with multifunction properties, including modulation of the transcriptional activity of the aryl hydrocarbon receptor, which mediates toxicological and carcinogenic dioxin effects. 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 and 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, I 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 the 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 (three cases in zones A and B) of pituitary tumors in subjects exposed to high-intermediate dioxin concentrations in comparison with nonexposed population suggests the need for extended follow-up.
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U2 - 10.1530/EJE-08-0593
DO - 10.1530/EJE-08-0593
M3 - Article
C2 - 18787049
AN - SCOPUS:58149359291
VL - 159
SP - 699
EP - 703
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 6
ER -