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      Long-term effects of pegvisomant on comorbidities in patients with acromegaly: a retrospective single-center study

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          Abstract

          Context

          The effect of pegvisomant on IGF1 levels in patients with acromegaly is well documented, but little is known of its long-term impact on comorbidity.

          Aim

          The aim of this retrospective study was to evaluate the effects of long-term pegvisomant therapy on cardiorespiratory and metabolic comorbidity in patients with acromegaly.

          Patients and methods

          We analyzed the long-term (up to 10 years) effect of pegvisomant therapy given alone ( n=19, 45%) or in addition to somatostatin analogues and/or cabergoline ( n=23, 55%) on echocardiographic, polysomnographic and metabolic parameters in respectively 42, 12 and 26 patients with acromegaly followed in Bicêtre hospital.

          Results

          At the first cardiac evaluation, 20±16 months after pegvisomant introduction, IGF1 levels normalized in 29 (69%) of the 42 patients. The left ventricular ejection fraction (LVEF) improved significantly in patients whose basal LVEF was ≤60% and decreased in those whose LVEF was >70%. The left ventricular mass index (LVMi) decreased from 123±25 to 101±21 g/m 2 ( P<0.05) in the 17 patients with a basal LVMi higher than the median (91 g/m 2), while it remained stable in the other patients. Pegvisomant reduced the apnoea–hypopnea index and cured obstructive sleep apnea (OSA) in four of the eight patients concerned. Long-term follow-up of 22 patients showed continuing improvements in cardiac parameters. The BMI and LDL cholesterol level increased minimally during pegvisomant therapy, and other lipid parameters were not modified.

          Conclusions

          Long-term pegvisomant therapy not only normalizes IGF1 in a large proportion of patients but also improves cardiac and respiratory comorbidity.

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          Most cited references53

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          Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

          To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)
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            Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.

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              Medical progress: Acromegaly.

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                Author and article information

                Journal
                Eur J Endocrinol
                Eur. J. Endocrinol
                EJE
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0804-4643
                1479-683X
                November 2015
                17 August 2015
                : 173
                : 5
                : 693-702
                Affiliations
                [1]Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction , F-94275, Le Kremlin Bicêtre, France
                [2]Service de Cardiologie , F-94275, Le Kremlin Bicêtre, France
                [3]Service de Génétique moléculaire, Pharmacogénétique et Hormonologie , F-94275, Le Kremlin Bicêtre, France
                [4]Univ Paris-Sud, Université Paris-Saclay, Faculté de Médecine Paris-Sud, Unité Mixte de Recherche-S1185 , F-94276, Le Kremlin Bicêtre, France
                [5]Institut National de la Santé et de la Recherche Médicale (INSERM) U1185 , F-94276, Le Kremlin Bicêtre, France
                Author notes
                Correspondence should be addressed to P Chanson philippe.chanson@ 123456bct.aphp.fr
                Article
                EJE150500
                10.1530/EJE-15-0500
                4592912
                26429918
                17d1dd4e-eb21-470f-b301-f101a4377252
                © 2015 The authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 16 May 2015
                : 17 August 2015
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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