Increased prevalence of acromegaly in a highly polluted area

Cannavò, Salvatore; Ferraú, Francesco; Ragonese, M.; Curtò, Lorenzo; Torre, Maria Luisa; Magistri, Manlio; Marchese, Antônio João Tedesco; Alibrandi, Angela; Trimarchi, Francesco

doi:10.1530/eje-10-0465

Cited by 79 publications

(41 citation statements)

References 14 publications

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“…The authors postulated that the overrepresentation of women may be due to a late presentation related to economic and social factors in their country. However, the relatively young age of their patients (ranging from 17 to 50 years) compared with the whole series (median age at diagnosis 44 years) does not support this hypothesis and an impact of environmental (30) or genetic factors (31,32) cannot be ruled out. In our series, only one patient was found to have MEN1 while other patients had no family history of pituitary adenoma nor hypercalcaemia and/or MEN1-associated lesions.…”

Section: European Journal Of Endocrinologymentioning

confidence: 86%

Giant prolactinomas in women

Delgrange

Raverot²,

Bex³

et al. 2014

European Journal of Endocrinology

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Objective: To characterise distinctive clinical features of giant prolactinomas in women. Design: A multicentre, retrospective case series and literature review. Methods: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 mg/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. Results: The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female:male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P!0.05). All cases diagnosed before the age of 15 years were boys. In women (nZ34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10 000 mg/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (!2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. Conclusion: Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.

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Section: European Journal Of Endocrinologymentioning

confidence: 86%

Giant prolactinomas in women

Delgrange

Raverot²,

Bex³

et al. 2014

European Journal of Endocrinology

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“…Most are sporadic, slow-growing and diagnosed in middle-aged to older individuals [35]. Epidemiological studies are few but recent reports of increased prevalence of pituitary adenomas in high industrialized areas [19] and, possibly, after toxic spillage [20] suggested a link to environmental causes.…”

Section: Discussionmentioning

confidence: 99%

“…Further, in vivo models revealed a higher incidence of pituitary adenomas in rats treated with a mixture of endocrine disruptors [18]. In humans, epidemiological studies showed an increased prevalence of growth hormone (GH)-secreting pituitary tumors in high industrial density areas [19] and, possibly, higher incidence of pituitary neoplasia following the accidental spillage of dioxin [20]. An additional link between endocrine disruptors and pituitary tumorigenesis was provided by the discovery of mutations in the aryl hydrocarbon receptor interacting protein ( AIP ) gene in patients with pituitary tumors [21], as the aryl hydrocarbon receptor (AhR) is well-known to bind toxins and phytochemicals [22].…”

Section: Introductionmentioning

confidence: 99%

Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells

et al. 2016

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PurposeEndocrine disruptors are known to modulate a variety of endocrine functions and increase the risk for neoplasia. Epidemiological data reported increased prevalence of pituitary tumors in high industrial areas while genotyping studies showed that mutations in the aryl hydrocarbon receptor (AhR) interacting protein (AIP)—chaperone to the dioxin ligand AhR—gene are linked to predisposition to pituitary tumor development. Aim of the present study was to establish whether endocrine pollutants can induce cell proliferation in normal rat pituitary cells.MethodsPituitary primary cultures were incubated with 250, 650 and 1250 pM benzene or 2-ethyl-phthalate for up to 96 h and viability, energy content and cell proliferation assessed. Expression of pituitary tumor transforming gene (PTTG), cyclin D1 (Ccnd1), AhR and AIP was quantified by RT-qPCR.ResultsIncubation with benzene or 2-ethyl-phthalate increased viability and energy content in pituitary cells. The endocrine disruptors also increased cell proliferation as well as Ccnd1 and PTTG expression. Increased AhR and AIP expression was observed after incubation with the two pollutants.ConclusionsOur findings indicate that benzene and 2-ethyl-phthalate activate AhR/AIP expression and stimulate proliferation in normal rat pituitary cells. This study is the first demonstration that pollutants can induce normal pituitary cells to proliferate and provides a link between epidemiological and genomic findings in pituitary tumors.Electronic supplementary materialThe online version of this article (doi:10.1007/s11102-016-0777-3) contains supplementary material, which is available to authorized users.

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“…Much higher frequencies of pituitary adenomas with positive immunohistochemistry for GH has been observed in autopsies of patients without known pituitary disease [2][3][4][5]. In population studies, Daly et al [6] identified nine cases of acromegaly in a population of 71,972 inhabitants (prevalence of 125/1,000,000), and Cannavò et al [7] identified 28 cases in an area with 243,381 inhabitants (prevalence of 115/1,000,000) and 10 cases in another population of 47,554 inhabitants (prevalence of 210/1,000,000), with both populations being exposed to high industrial pollution [7]. Schneider et al [8] measured serum IGF-1 in 6,773 adult primary care patients and biochemical acromegaly was diagnosed in six patients (prevalence of 886/1,000,000), with the observation of an exuberant phenotype and pituitary adenoma confirmed by MRI in at least two (prevalence of 295/1,000,000).…”

Section: Introductionmentioning

confidence: 99%

Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population

Rosário

2010

Pituitary

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The objective of this study was to evaluate the frequency of acromegaly in adults with diabetes mellitus (DM) or glucose intolerance (GI) and to estimate its prevalence in the general population. A total of 2,270 patients with DM or GI and age from 20 to 70 years were studied. Patients with known pituitary disease and pregnant women were excluded. Serum IGF-1 was measured in all subjects and, if elevated, a new measurement was obtained together with the measurement of GH in the oral glucose tolerance test (OGTT). Patients with persistently elevated IGF-1 and inadequate suppression of GH were submitted to magnetic resonance imaging (MRI). Acromegaly was not suspected by the assistant physician in any of the patients. Six patients had persistently elevated IGF-1 and inadequate suppression of GH in the OGTT (without other conditions associated with GH or IGF-1 elevation). Pituitary adenoma was detected by MRI in three patients, and two subjects presented an acromegalic phenotype. Two patients were submitted to transsphenoidal surgery, with immunohistochemistry confirming immunoreactivity for GH. Another patient was treated with octreotide LAR which resulted in the normalization of IGF-1 and GH. Considering a prevalence of DM or GI of 20% in adults and the occurrence of these co-morbidities in 55% of patients with acromegaly, the frequency of 3/2,270 found in this study permits to estimate 480 cases/1,000,000 adults. The present results suggest that the prevalence of acromegaly is underestimated and further studies are needed to evaluate the cost-effectiveness of biochemical screening in certain groups of patients.

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Increased prevalence of acromegaly in a highly polluted area

Cited by 79 publications

References 14 publications

Giant prolactinomas in women

Giant prolactinomas in women

Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells

Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population

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