Successful Mortality Reduction and Control of Comorbidities in Patients With Acromegaly Followed at a Highly Specialized Multidisciplinary Clinic

Mercado, Moisés; González, Baldomero; Vargas, Guadalupe; Ramírez, Claudia; Monteros, Ana Laura Espinosa de los; Sosa, Ernesto; Jervis, Paola; Roldan, Paola; Mendoza, Victoria; López-Félix, Blas; Guinto, Gerardo

doi:10.1210/jc.2014-2670

Cited by 176 publications

(128 citation statements)

References 27 publications

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“…In our cohort, the overall mortality risk was only slightly elevated and in agreement with the literature (2, 3). We recorded an increased mortality from cardiovascular disease but not from cancer, which agrees with a metaanalysis from 2008 (2), although recent surveys from single centres report increased cancer mortality (45) and low prevalence of cardiac disease (46) respectively. Moreover, in a subanalysis, we did not record a significant impact of a given treatment strategy on mortality risk, acute cardiovascular event or chronic complications.…”

Section: Discussionsupporting

confidence: 89%

Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study

Dal

Feldt‐Rasmussen

Andersen

et al. 2016

European Journal of Endocrinology

173

125

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Design: Valid data on acromegaly incidence, complications and mortality are scarce. The Danish Health Care System enables nationwide studies with complete follow-up and linkage among health-related databases to assess acromegaly incidence, prevalence, complications and mortality in a population-based cohort study. Method: All incident cases of acromegaly in Denmark (1991Denmark ( -2010 were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 10 6 person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used. Results: Mean age at diagnosis (48.7 years (CI: 95%: 47.2-50.1)) and annual incidence rate (3.8 cases/10 6 persons (95% CI: 3.6-4.1)) among the 405 cases remained stable. The prevalence in 2010 was 85 cases/10 6 persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7-5.8)), heart failure (HR: 2.5 (95% CI: 1.4-4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1-5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0-19.4)) and arthropathy (HR: 2.1 (95% CI: 1.6-2.6)). The complication risk was also increased before the diagnosis of acromegaly. Overall mortality risk was elevated (HR: 1.3 (95% CI: 1.0-1.7)) but uninfluenced by treatment modality. Conclusion: (i) The incidence rate and age at diagnosis of acromegaly have been stable over decades, and the prevalence is higher than previously reported.(ii) The risk of complications is very high even before the diagnosis.(iii) Mortality risk remains elevated but uninfluenced by mode of treatment.

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Section: Discussionsupporting

confidence: 89%

Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study

Dal

Feldt‐Rasmussen

Andersen

et al. 2016

European Journal of Endocrinology

173

125

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“…This means that age-related cancer incidence and mortality, previously not clinically apparent in acromegaly, might be unmasked from now on. In agreement with that, two recent studies have shown that mortality in acromegaly can be successfully reduced with current therapies, and in both of them, cancer was the most common cause of death, and it emerged as an independent predictor of mortality (27,33).…”

Section: Aging and Morbiditiessupporting

confidence: 76%

“…However, in two studies (18,32), patients with active disease and persistently elevated GH and IGF1 values had significantly higher mortality from cancer, particularly CRC, than those with normal IGF1 or GH levels, although overall, the cancer-related mortality was not greater than the observed mortality in the general population, and it is not affected by the duration of disease or patient's age at diagnosis (4,10,11). In a recent cohort of 442 patients with acromegaly from a single-center in Mexico City, the standardized mortality ratio (SMR) was similar to that seen in the general population, but among 22 patients who died during the follow-up, cancer was the most common cause of death, and it was a significant predictor of mortality (27). Malignancies were also an independent predictor of mortality in a recent Italian multicenter study with 1512 patients, in which reduction of SMR was linked to the disease control (33).…”

Section: Mortalitymentioning

confidence: 89%

“…A review of 17 series published between 1957 and 2015, where overall cancer incidence in acromegaly was investigated, revealed 7723 patients with 708 cases of cancer, resulting in a mean cancer incidence of 10.8%, with percentages varying from 4.8 to 21.3% (12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28). Standardized incidence ratio (SIR) was available from 11 series, and in three of them, cancer incidence was not increased (12,18,28).…”

Section: Incidence/prevalencementioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and cancer: an old debate revisited

Boguszewski

Ayuk

2016

European Journal of Endocrinology

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Based on experimental and animal models, epidemiological data from non-acromegaly populations, and longitudinal and cross-sectional cohorts of patients with acromegaly, a potential association between acromegaly and cancer has long been hypothesized, in particular colorectal cancer, and, to a lesser extent, breast, thyroid and prostate cancers. the exact mechanisms underlying this potential association have not been fully elucidated. Results from studies examining cancer incidence and mortality in acromegaly have been inconsistent, with some demonstrating increased risk, whereas others show no increase. this article reviews the existing data relating to cancer risk and mortality in acromegaly, exploring the limitations of study designs and the impact of changes in disease control and patient outcomes over time.

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“…The comparison between older and more recent occurrences of the disease is challenging because both cancer incidence in the general population and life expectancy in patients with acromegaly have dramatically changed over the past few decades, influencing the prevalence of disease-associated morbidities. In fact, recent series have found cancer as a common cause of death and an independent predictor of mortality in acromegaly [75][76][77][78]. In addition, population-based cancer registries and epidemiology may vary from site to site.…”

Section: Rycina 2 Dane Epidemiologiczne Wiążące Stężenie Igf-i W Surmentioning

confidence: 99%

Growth hormone, insulin-like growth factor system and carcinogenesis

Boguszewski

Kopchick

2015

Endokrynologia Polska

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The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. StreszczenieOś hormon wzrostu (GH)-insulinopodobny czynnik wzrostu (IGF) odgrywa istotną rolę w regulacji proliferacji i różnicowania komórek, apoptozy i angiogenezy. Oś GH-IGF wpływa na regulację cyklu komórkowego przez pobudzenie szlaku wzrostu komórki w stosunku do szlaków sygnałowych prowadzących do śmierci komórki, a ostateczny efekt oddziaływania tych dwóch sił ma podstawowe znaczenie dla prawidłowego lub nieprawidłowego wzrostu komórki. Hipotezy na temat powiązań osi GH-IGF z karcynogenezą pojawiły się wiele lat temu, głównie w oparciu o wyniki badań in vitro oraz badań z wykorzystaniem różnych zwierzęcych modeli raka występującego u ludzi. Chociaż liczne dane doświadczalne potwierdzają rolę osi GH-IGF sprzyjającą rozwojowi i progresji nowotworów, a nad kilkoma składowymi tej osi trwają obecnie badania oceniające ich przydatność jako główne cele terapii przeciwnowotworowej, to jednak siła dowodów uzyskanych u chorych z akromegalią, niedoborem GH lub osób leczonych GH jest znacznie słabsza. W niniejszej pracy przeglądowej spróbowano zebrać wszystkie te dane.

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Successful Mortality Reduction and Control of Comorbidities in Patients With Acromegaly Followed at a Highly Specialized Multidisciplinary Clinic

Abstract: Mortality in acromegaly can be successfully reduced, provided patients are treated using a multimodal approach with careful management of comorbidities.

Cited by 176 publications

References 27 publications

Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study

Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study

MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and cancer: an old debate revisited

Growth hormone, insulin-like growth factor system and carcinogenesis

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