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      Pegvisomant in acromegaly: an update

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          Abstract

          Background

          In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety.

          Aim

          We here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the most recent literature.

          Results

          The clinical use of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite satisfactorily with many clinical issues including major safety issues, such as the concerns about possible tumour (re)growth under PEG. The positive or neutral impact of PEG on glucose metabolism has been highlighted, and the clinical experience, although limited, with sleep apnoea and pregnancy has been reviewed. Finally, the current concept of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered.

          Conclusions

          PEG increasingly appears to be an effective and safe medical option for many patients not controlled by SRL but its use still needs to be optimized.

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          Most cited references128

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

            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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              A consensus on criteria for cure of acromegaly.

              The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. EVIDENCE/CONSENSUS PROCESS: Relevant assays, biochemical measures, clinical outcomes, and definition of disease control were discussed, based on the available published evidence, and the strength of consensus statements was rated. Criteria to define active acromegaly and disease control were agreed, and several significant changes were made to the 2000 guidelines. Appropriate methods of measuring and achieving disease control were summarized.
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                Author and article information

                Contributors
                a.giustina@libero.it
                Journal
                J Endocrinol Invest
                J. Endocrinol. Invest
                Journal of Endocrinological Investigation
                Springer International Publishing (Cham )
                0391-4097
                1720-8386
                7 February 2017
                7 February 2017
                2017
                : 40
                : 6
                : 577-589
                Affiliations
                [1 ]GRID grid.15496.3f, Chair of Endocrinology, , Vita-Salute San Raffaele University, ; Milano, Italy
                [2 ]GRID grid.415845.9, Clinic of Endocrinology and Metabolism Disease, , Ospedali Riuniti di Ancona, ; Ancona, Italy
                [3 ]ISNI 0000 0004 1757 3729, GRID grid.5395.a, Department of Clinical and Experimental Medicine, , University of Pisa, ; Pisa, Italy
                [4 ]ISNI 0000 0001 2178 8421, GRID grid.10438.3e, Department of Clinical and Experimental Medicine, , University of Messina, ; Messina, Italy
                [5 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Department of Clinical Medicine and Surgery, , University of Naples Federico II, ; Naples, Italy
                [6 ]ISNI 0000 0001 0941 3192, GRID grid.8142.f, Pituitary Unit, , Catholic University School of Medicine, ; Rome, Italy
                [7 ]Department of Internal Medicine, General Hospital, Montebelluna (TV), Italy
                [8 ]ISNI 0000 0004 1757 2064, GRID grid.8484.0, Section of Endocrinology and Internal Medicine, Department of Medical Sciences, , University of Ferrara, ; Ferrara, Italy
                [9 ]ISNI 0000 0001 0120 3326, GRID grid.7644.1, Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, , University of Bari Aldo Moro, ; Bari, Italy
                [10 ]Endocrinology, Diabetology and Metabolism, AOU Città della Salute e della Scienza of Turin, Turin, Italy
                [11 ]ISNI 0000 0004 1756 8807, GRID grid.417728.f, Endocrinology Unit, Department of Biomedical Sciences, , Humanitas University and Humanitas Research Hospital, ; Rozzano, Italy
                [12 ]ISNI 0000 0004 1760 2630, GRID grid.411474.3, Department of Medicine (DIMED), 3rd Medical Clinic, , Azienda Ospedaliera Padova, ; Padova, Italy
                [13 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Department of Clinical and Surgery Medicine, Endocrinology and Metabolism, , University of Naples, ; Naples, Italy
                [14 ]ISNI 0000 0001 2336 6580, GRID grid.7605.4, Department of Medical Sciences, School of Medicine, , University of Turin, ; Turin, Italy
                Article
                614
                10.1007/s40618-017-0614-1
                5443862
                28176221
                24c1c9ac-d053-4ade-92fb-dfcb9089a08b
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 18 August 2016
                : 10 January 2017
                Funding
                Funded by: Ipsen, Novartis and Pfizer
                Funded by: Pfizer, Novartis and Ipsen
                Funded by: Pfizer, Novartis and Ipsen
                Funded by: Pfizer and Novartis
                Categories
                Review
                Custom metadata
                © Italian Society of Endocrinology (SIE) 2017

                acromegaly,pegvisomant,review,srl resistance,metabolic effects,igf-i

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