Acromegaly: Re-thinking the cancer risk

Loeper, Siobhan; Ezzat, Shereen

doi:10.1007/s11154-007-9063-z

Cited by 114 publications

(102 citation statements)

References 186 publications

(187 reference statements)

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“…Acromegaly is accompanied by organomegaly, metabolic deterioration, comorbidities, and increased mortality (4). Neoplasms are often found, but their incidence is controversial (6).…”

Section: Discussionmentioning

confidence: 99%

“…IGF-I acts by means of two mechanisms: increasing proliferation and reducing apoptosis. It was demonstrated that IGF-I increases proliferation of porcine thyroid cells and FRTL-5 rat thyroid cells, and potentiates TSH-mediated thyroid cell proliferation (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In physiological conditions, thyroid follicular cells express IGF-I receptors.…”

Section: Discussionmentioning

confidence: 99%

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Thyroid nodules in acromegaly

Rogozinski

Furioso

Glikman

et al. 2012

Arq Bras Endocrinol Metab

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Objective: We made a prospective study evaluating the prevalence of thyroid nodular disease in acromegalic patients. Subjects and methods: Thyroid ultrasound and ultrasound-guided fine needle aspiration biopsy were performed when nodules were detected. Nodules were characterized by cytology and histopathology. Results: We found high prevalence of nodular thyroid disorder, 23/34 (67%) in acromegalic patients. High risk and malignant cytology were significantly higher in acromegalic patients than in our non-acromegalic population (25% vs. 9%). Differentiated thyroid carcinoma was present in 11% of the acromegalic patients. Conclusions: We strongly recommend periodic thyroid evaluation by ultrasound in patients with acromegaly. Fine needle aspiration biopsy should be performed in nodules larger than 10 mm, and in all suspicious nodules, regardless of the size. Arq Bras Endocrinol Metab. 2012;56(5):300-4 Keywords Acromegaly; thyroid nodules; thyroid ultrasonography; fine needle aspiration biopsy; thyroid carcinoma RESUMO Objetivo: Realizamos um estudo prospectivo avaliando a prevalência de patologia nodular tireói dea em 34 pacientes acromegálicos. Sujeitos e métodos: Avaliamos os pacientes com ecografia tireóidea e punção biópsia com agulha fina quando se detectavam nódulos. Resultados: Encontramos uma alta prevalência de patologia nodular tireóidea 23/34 (67%) em acromegálicos. A citologia tireóidea de alto risco e maligna foi significativamente mais elevada em pacientes acromegálicos que em uma população não acromegálica (25% vs. 9%). O grupo acromegálico apresentou carcinoma diferenciado de tireoides em 11%. Conclusões: Recomendamos fortemente a ecografia periódica tireóidea em pacientes acromegálicos. Uma punção biópsia aspirativa com agulha fina deve ser realizada em presença de nódulos tireóideos maiores que 10 mm e daqueles com critérios ecográficos suspeitos de malignidade, independentemente do tamanho deles. Arq Bras Endocrinol Metab. 2012;56(5):300-4

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“…Acromegaly is accompanied by organomegaly, metabolic deterioration, comorbidities, and increased mortality (4). Neoplasms are often found, but their incidence is controversial (6).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thyroid nodules in acromegaly

Rogozinski

Furioso

Glikman

et al. 2012

Arq Bras Endocrinol Metab

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“…Most authorities now accept that patients with acromegaly have an increased risk of colorectal neoplasia, even if the exact degree of risk remains uncertain (18,(21)(22)(23)(24)(25)(26)(27). In the non-acromegalic population, the majority of colonic cancers develop from pre-malignant colonic adenomas, and several studies have demonstrated that colonoscopic screening and removal of adenomas reduce the incidence of colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Repeated colonoscopic screening of patients with acromegaly: 15-year experience identifies those at risk of new colonic neoplasia and allows for effective screening guidelines

Dworakowska

Gueorguiev²,

Kelly³

et al. 2010

European Journal of Endocrinology

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Objective: It is suggested that patients with acromegaly have an increased risk of colorectal cancer and pre-malignant adenomatous polyps. However, the optimum frequency with which colonoscopic screening should be offered remains unclear. Design: To determine the optimum frequency for repeated colonoscopic surveillance of acromegalic patients. Methods: We retrospectively reviewed the case records of all patients with acromegaly seen in our centre since 1992: 254 patients had at least one surveillance colonoscopy, 156 patients had a second surveillance colonoscopy, 60 patients had a third surveillance colonoscopy and 15 patients had a fourth surveillance colonoscopy. Results: The presence of hyperplastic or adenomatous polyps was assessed in all patients, while one cancer was detected at the second surveillance. At the third surveillance, mean (GS.D.) serum IGF1 levels (ng/ml) in patients with hyperplastic polyps were significantly higher than those with normal colons (P!0.05). The presence of an adenoma rather than a normal colon at the first colonoscopy was associated with a significantly increased risk of adenoma at the second (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.9-10.4) and at the third (OR 8.8, 95% CI 2.9-26.5) screens. Conversely, a normal colon at the first surveillance gave a high chance of normal findings at the second (78%) or third surveillance (78%), and a normal colon at the second colonoscopy was associated with normality at the third colonoscopy (81%). Conclusions: Repeated colonoscopic screening of patients with acromegaly demonstrated a high prevalence of new adenomatous and hyperplastic colonic polyps, dependent on both the occurrence of previous polyps and elevated IGF1 levels.

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“…A meta-analysis showed an association between high circulating IGF-I and IGF-II concentrations and increased risk of colorectal cancer (6,7). Acromegalic patients whose hypersecretion of growth hormone is accompanied by elevated IGF-I levels have an elevated incidence of colorectal adenomas and cancer (8,9). These epidemiologic data are supported by an in vivo study in the mouse showing genetically deleted IGF-I expression in the liver, which reduced the circulating IGF-I concentration by 75% and delayed the growth of an orthotopic xenograft.…”

Section: Introductionmentioning

confidence: 99%

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Matsunaka

Miyamoto

Shitara

et al. 2010

Molecular Cancer Therapeutics

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Insulin-like growth factors (IGF-I and IGF-II) play important roles in intestinal tumorigenesis. To investigate the effectiveness of IGF-targeting strategies, we conducted an in vivo study using anti-mouse neutralizing antibodies IGF-I (KM3168) and IGF-II (KM1468). Six-and 10-week-old Apc +/− mice were given KM3168 and/or KM1468 i.p. at two doses (0.01 or 0.1 μg/g weight) once or twice weekly for 4 weeks. To clarify the source of IGFs in vivo, we evaluated the expression levels of IGFs in the liver, normal small intestine, and polyps of the small intestine of Apc +/− mice. The phosphorylation status of IGF signalrelated molecules was examined using immunostaining to understand the mechanism underlying the effects of IGF-neutralizing antibody. The plasma half-life was 168 for KM3168 and 85 hours for KM1468. In two lineages of Apc +/− mice (Apc 1309 and Apc Min/+ ), a low dose (0.01 μg/g weight) of KM3168 and KM1468 significantly reduced the number of polyps when given once and twice weekly, respectively. Combined administration of the effective dose of each antibody had an additive effect. The liver was the main source of IGF-I, whereas the polyps of the small intestine and normal small intestine were the main source of IGF-II. IGF-neutralizing antibodies decreased the phosphorylation of IGF type 1 receptor and inhibited the signal transduction of the Akt pathway. These results suggest that IGF-I and IGF-II play important roles in polyp formation in Apc +/− mice and that specific antibodies to IGF-I and IGF-II may be promising antitumor agents. Mol Cancer Ther; 9(2); 419-28. ©2010 AACR.

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Acromegaly: Re-thinking the cancer risk

Cited by 114 publications

References 186 publications

Thyroid nodules in acromegaly

Thyroid nodules in acromegaly

Repeated colonoscopic screening of patients with acromegaly: 15-year experience identifies those at risk of new colonic neoplasia and allows for effective screening guidelines

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

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