Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis

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Abstract

Objective

To compare the acromegaly mortality rates with those expected for the general population from studies published before and after 2008.

Methods

We performed a systematic review and included observational studies in which the number of deaths observed in acromegaly was compared with the expected mortality for the general population mortality observed/expected (O/E). The following electronic databases were used as our data sources: EMBASE, MEDLINE and LILACS. From the observed and expected deaths, we recalculated all standardized mortality ratios (SMR) and their respective confidence intervals (95% CI), which were plotted in a meta-analysis using the software RevMan 5.3.

Results

We identified 2303 references, and 26 studies fulfilled our eligibility criteria. From the 17 studies published before 2008, the mortality in acromegaly was increased, while from the nine studies published after 2008, the mortality was not different from the general population (SMR: 1.35, CI: 0.99–1.85). In six studies where somatostatin analogs (SAs) were used as adjuvant treatment, acromegaly mortality was not increased (SMR: 0.98, CI: 0.83–1.15), whereas in series including only patients treated with surgery and/or radiotherapy, mortality was significantly higher (SMR: 2.11; CI: 1.54–2.91). In studies published before and after 2008, the mortality was not increased in patients who achieved biochemical control, while it was higher in those with active disease. Cancer has become a leader cause of deaths in acromegaly patients in the last decade, period in which life expectancy improved.

Conclusion

Mortality in acromegaly is normalized with biochemical control and decreased in the last decade with the more frequent use of SAs as adjuvant therapy. Increased life expectancy has been associated with more deaths due to cancer.

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Most cited references 31

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Systemic complications of acromegaly: epidemiology, pathogenesis, and management.

Annamaria Colao, Diego Ferone, Paolo Marzullo … (2004)

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.

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Factors influencing mortality in acromegaly.

Ian M Holdaway, Raja C Rajasoorya, Greg D Gamble (2004)

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.

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Guidelines for acromegaly management: an update.

S Melmed, A Colao, A Barkan … (2009)

The Acromegaly Consensus Group reconvened in November 2007 to update guidelines for acromegaly management. The meeting participants comprised 68 pituitary specialists, including neurosurgeons and endocrinologists with extensive experience treating patients with acromegaly. EVIDENCE/CONSENSUS PROCESS: Goals of treatment and the appropriate imaging and biochemical and clinical monitoring of patients with acromegaly were enunciated, based on the available published evidence. The group developed a consensus on the approach to managing acromegaly including appropriate roles for neurosurgery, medical therapy, and radiation therapy in the management of these patients.

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Author and article information

Journal

Title: European Journal of Endocrinology

Publisher: Bioscientifica

ISSN (Print): 0804-4643

ISSN (Electronic): 1479-683X

Publication date Created: July 2018

Publication date (Print): July 2018

Volume: 179

Issue: 1

Pages: 59-71

Affiliations

[1 ]1Department of Internal Medicine, Botucatu Medical School, State University/UNESP, Sao Paulo, Brazil

[2 ]2Endocrine Division (SEMPR), Department of Internal Medicine, Federal University of Parana, Curitiba, Brazil

Article

DOI: 10.1530/EJE-18-0255

PubMed ID: 29764907

SO-VID: 4ea2d518-e53b-4ea8-a014-567ca54cd03a

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