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      Acromegaly is associated with increased cancer risk: a survey in Italy

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          Abstract

          It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18–1.68, P < 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07–2.58, P = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55–5.34, P < 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32–6.87, P < 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk.

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          Most cited references43

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          Acromegaly: an endocrine society clinical practice guideline.

          The aim was to formulate clinical practice guidelines for acromegaly.
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            Acromegaly pathogenesis and treatment.

            Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder.
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              Factors influencing mortality in acromegaly.

              Studies of acromegaly have shown a doubling of mortality compared with the general population. With the development of new modalities of treatment, it has become important to identify prognostic factors relating to mortality. Between 1964 and 2000, 208 acromegalic patients were followed for a mean of 13 yr at Auckland Hospital. Treatment was by surgery or radionuclide pituitary implantation, and all except 27 patients received pituitary radiation. Over the duration of the study, 72 patients died at a mean age of 61 +/- 12.8 yr. Those dying were significantly older at diagnosis, had a higher prevalence of hypertension and diabetes, and were more likely to have hypopituitarism. The observed to expected mortality ratio (O/E ratio) fell from 2.6 (95% confidence interval, 1.9-3.6) in those with last follow-up GH greater than 5 microg/liter to 2.5 (1.6-3.8), 1.6 (0.9-3), and 1.1 (0.5-2.1) for those with GH less than 5, less than 2, and less than 1 microg/liter, respectively (P < 0.001). Serum IGF-I, expressed as an SD score, was significantly associated with mortality, with O/E mortality ratios of 3.5 (95% confidence interval, 2.8-4.2) for those with an SD score greater than 2, 1.6 (0.6-2.6) for those with an SD score less than 2 (normal or low levels), and 1.0 (0.1-3) for those with an SD score less than zero. When assessed by multivariate analysis, last serum GH (P < 0.001), age, duration of symptoms before diagnosis (P < 0.03), and hypertension (P < 0.04) were independent predictors of survival. If IGF-I was substituted for GH, then survival was independently related to last IGF-I SD score (P < 0.02), indicating that GH and IGF-I act equivalently as predictors of mortality. These findings indicate that reduction of GH to less than 1 microg/liter or normalization of serum IGF-I reduces mortality to expected levels.

                Author and article information

                Journal
                Endocrine-Related Cancer
                Bioscientifica
                1351-0088
                1479-6821
                September 2017
                September 2017
                September 2017
                September 2017
                : 24
                : 9
                : 495-504
                Article
                10.1530/ERC-16-0553
                28710115
                31894f38-9431-4277-a89f-ee3d8b92f48c
                © 2017

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