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      Pathology of Acromegaly

      ,

      Neuroendocrinology

      S. Karger AG

      Acromegaly, Pituitary neoplasm, Growth hormone

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          Abstract

          This review summarizes current knowledge on pituitary changes in patients with acromegaly. The histologic, immunohistochemical and electron microscopic study provided conclusive evidence that a marked diversity exists between the tumors which secrete growth hormone (GH) in excess, such as densely and sparsely granulated GH cell adenoma, the mixed GH prolactin cell adenoma and the mammosomatotrope adenoma. The latter two tumors produce GH and prolactin simultaneously. Densely granulated GH cell tumors may produce thyrotropin and α subunit as well. Somatotrope carcinomas are extremely rare. GH cell hyperplasia can also be associated with acromegaly in patients with extrapituitary GH-releasing hormone secreting tumors. The medical therapy of acromegaly is reviewed briefly, including long-acting somatostatin analogs and pegvisomant, a GH receptor blocker.

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          Most cited references 9

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          Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials

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            Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly.

            An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.
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              Circulating ghrelin levels in patients with pancreatic and gastrointestinal neuroendocrine tumors: identification of one pancreatic ghrelinoma.

              Ghrelin is a novel gastrointestinal hormone involved in several metabolic functions. Although the expression of ghrelin has been demonstrated in most gastrointestinal carcinoids and pancreatic tumors, the circulating levels of this peptide have been marginally assessed in patients with these disorders. We measured plasma ghrelin levels in 16 patients with gastrointestinal carcinoid (10 with midgut and 6 with gastric carcinoid), 24 patients with pancreatic tumor (8 with gastrinoma, 2 with insulinoma, 2 with vipoma, 1 with glucagonoma, and 11 with nonfunctioning tumor), and 35 healthy controls. Plasma ghrelin levels recorded in patients with gastroenteropancreatic tumors were similar to controls (mean +/- SE, 182.7 +/- 66.5 pM in patients vs. 329 +/- 32 pM in controls, P = not significant), and no significant difference between gastrointestinal and pancreatic, functioning and nonfunctioning, and metastatic and nonmetastatic tumors was observed. One patient with metastatic nonfunctioning pancreatic tumor had circulating ghrelin levels of 12,000 pM that were slightly reduced during chemotherapy and interferon therapy. Immunohistochemistry performed on peritoneal lesions showed an intense, focal cytoplasmic positivity for ghrelin. Despite the 50-fold increase in ghrelin concentrations, the patient had normal serum GH and IGF-I levels. In conclusion, the study showed that carcinoids and pancreatic tumors rarely cause ghrelin hypersecretion. However, in this series, 1 pancreatic ghrelinoma not associated with clinical features of acromegaly was identified.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                978-3-8055-8198-1
                978-3-318-01414-3
                0028-3835
                1423-0194
                2006
                October 2006
                16 October 2006
                : 83
                : 3-4
                : 161-165
                Affiliations
                Department of Laboratory Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Canada
                Article
                95524 Neuroendocrinology 2006;83:161–165
                10.1159/000095524
                17047379
                © 2006 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.

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                Figures: 4, References: 22, Pages: 5
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