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      Positive Metabolic Impact of Treatment with Pegvisomant in an Acromegalic Patient

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          Abstract

          Background: Glucose intolerance and diabetes mellitus are important complications of acromegaly. Somatostatin analogues (SSAs) exert a dual effect on carbohydrate metabolism. Normalisation of the growth hormone/insulin-like growth factor I (GH/IGF-I) axis could improve metabolic balance, but inhibition of insulin secretion could worsen glucose tolerance. Case Description: We report a case of an acromegalic patient with diabetes mellitus that was resistant to SSA therapy. Results: Treatment with SSAs typically induces mild reductions in GH and IGF-I levels, but rarely results in normalisation of these parameters. In addition, glucose levels as well as glycosylated haemoglobin levels (HbA<sub>1c</sub>) show marked deterioration. In contrast, pegvisomant (PEG) treatment normalises IGF-I levels, and glucose, insulin and HbA<sub>1c</sub> levels gradually decrease. During SSA therapy, this patient required an increase in the dose and type of hypoglycaemic agents. During PEG treatment, however, hypoglycaemic drugs are often reduced. Conclusion: Patients with acromegaly whose disease is inadequately controlled by SSA therapy can achieve normalisation of IGF-I levels and full control of the disease, including strong improvement of glucose homeostasis despite marked reduction of antidiabetic therapy, when treated with the GH antagonist, PEG.

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          Most cited references 12

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          Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria

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            Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist

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              Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant.

              In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. This was a multicenter, open-label, 32-wk trial study. The study was performed at outpatient clinics. Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study. Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28. The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, and safety during the first 12 wk after conversion. At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P < or = 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 [n = 15; fasting glucose, -1.7 mmol/liter (P < or = 0.0001); HbA1c -0.2% (P = 0.03)]. Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas. Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-8255-1
                978-3-318-01446-4
                1663-2818
                1663-2826
                2007
                February 2007
                15 February 2007
                : 67
                : Suppl 1
                : 174-176
                Affiliations
                Division of Endocrinology and Metabolism, University of Turin, Turin, Italy
                Article
                97576 Horm Res 2007;67:174–176
                10.1159/000097576
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Tables: 2, References: 17, Pages: 3
                Categories
                Adult Clinical Case Sessions

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