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Neuroendocrine TumorsA Comprehensive Guide to Diagnosis and ManagementInterScience InstituteInterScience InstituteGregg MamikunianAaron I. VinikThomas M. O’DorisioEugene A. WolteringVay Liang W. Go

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NeuroendocrinETumorSA Comprehensive Guide toDiagnosis and ManagementFourth EditionGregg MamikunianAaron I. VinikThomas M. O’DorisioEugene A. WolteringVay Liang W. Go

Inter Science InstituteGI CouncilChairmanEugene A. Woltering, MD, FACSThe James D. Rives Professor of Surgery and NeurosciencesChief of the Sections of Surgical Endocrinology and OncologyDirector of Surgery ResearchThe Louisiana State University Health Sciences CenterNew Orleans, LouisianaExecutive MembersAaron I. Vinik, MD, PhD, FCP, MACPProfessor of Medicine, Pathology and NeurobiologyDirector of Strelitz Diabetes Research InstituteEastern Virginia Medical SchoolNorfolk, VirginiaVay Liang W. (Bill) Go, MDProfessor of MedicineDavid Geffen School of Medicine at UCLAUniversity of California at Los AngelesLos Angeles, CaliforniaThomas M. O’Dorisio, MDProfessor of MedicineDirector of Neuroendocrine Tumor ProgramClinical Attending, Holden Comprehensive Cancer CenterUniversity of Iowa College of MedicineIowa City, IowaGregg Mamikunian, MSChief Executive OfficerInter Science Instituteii

PrefaceAccretion“ . . . the wisdom that accrues with age . . .”It is a fitting tribute that the 4th edition of the Neuroendocrine Tumors handbook falls onthe 40th anniversary of Inter Science Institute (ISI).The publication arising since the third edition is testimony to the progress of the scienceof Neuroendocrinology in the treatment of carcinoid tumors specifically andneuroendocrine sciences in general. The accretion of knowledge and its particularapplications of these accreted test procedures have placed ISI at the forefront ofproviding the highly specialized tests and assays for usage by the medical establishment.This has been the simple mantra of ISI since its inception, “stay small but perform withdistinction”. The accretion of leadership, performance, experience, commitment, andthe delivery of accurate dependable analytical data, that correlates with the clinicalmanifestation, is the ultimate hallmark of ISI’s capabilities.Thus, we have arrived at this fortieth juxtaposition with a certain degree of pride and agreater degree of satisfaction. Clinical laboratory discipline is a dynamic science, and itmust be nurtured by accruing talented scientists in the specific disciplines it serves.Consequently my high esteem is owed to the GI Council members who have providedISI the catalyst to distinction in recommending test procedures that are novel andclinically significant.Thus a debt of gratitude is owed to the Council members, who are embarking on theirsecond five-year terms, and have served tirelessly resulting in the authorship of the 3rdand 4th editions of the Neuroendocrine Tumors handbooks.Finally I can assure the Carcinoid community—patients, their physicians, clinicians andsupport groups—that ISI’s commitment, dedication, and support will not take recess aslong as I am at the helm.Gregg MamikunianInter Science Institute 2009iii

Acknowledgments to theFourth EditionThe authors of the 4th edition of the Neuroendocrine Tumors handbook sincerelyappreciate the contribution of M. Sue O’Dorisio, MD, PhD for the second chapter of thehandbook. It is a great honor and privilege to have professor Sue O’Dorisio’s hithertounpublished chapter appear in the ISI Neuroendocrine book.The GI Council welcomes professor Joy Ardill, MD, of Royal Victoria Hospital of NorthernIreland, (UK), for her scientific collaborative association with Inter Science Institute.The Council acknowledges Donald W. Richardson, MD of Eastern Virginia MedicalSchool (EVMS) for his contribution on sections of pituitary tumors, Cushings anddiabetes insipidus.Our thanks to Debbie Godsey for updating the ICD-9 codes throughout the chapters ofthe 3rd and 4th editions. Also, our thanks to Etta Vinik for her work on certain sections ofthe handbook.A special thanks to Mia Tepper for the months of diligent attention to details inreviewing the manuscript.The executive members of the council gratefully acknowledges the dedication,foresight and leadership of its chairman Eugene A. Woltering, MD.The enormous contributions of Arthur A. Vinik, MD, Thomas M. O’Dorisio, MD, and VayLiang W. (Bill) Go, MD, encompassing the scientific matrix and its accretion into aclinically useful and diagnostically relevant format must be applauded.Gregg MamikunianInter Science Institute 2009iv

Acknowledgments to theThird EditionThe GI Council of Inter Science Institute presents this comprehensive guide todiagnosis and management of neuroendocrine tumors to provide information andinspiration to all levels of clinicians, from novices to those professionally engaged inthe field of neuroendocrine research, treatment, and analyses. This guidebook addsthe new dimension of patient monitoring, not only through powerfully discriminatingassays but through the recognition of clinical presentations and syndromes. Thisexpertise is made possible by more than 150 years of cumulative experience of theadvisory council.Since the publication of the first GI Handbook in 1977 up to the current edition ofNeuroendocrine Tumors, Inter Science Institute has been at the forefront of bridgingthe gap between academic medicine and the availability of the most current tests forpatient diagnosis. In the intervening three and a half decades, unparalleled progresshas been made both in the diagnosis and treatment of gastrointestinal, pancreatic,and neuroendocrine tumors.This book is meant to be a beacon not only for listing tests but for all aspects ofneuroendocrine tumors. Its publication represents a move from static text to themodern era of communication which allows for dynamic, continuously updating linksto the ISI website, interscienceinstitute.com, as well as endotext.com as referencesources. Additionally, the book combines several references from the previous editionwith an updated bibliography, in recognition of past contributions to the present.Special thanks to our dedicated reviewers of this publication, Etta J. Vinik andMia S. Tepper.Finally, my appreciation and thanks to professors Vinik, Woltering, O’Dorisio, and Gofor imparting their knowledge to the synergistic confluence that has given birth to thisunique edition. Thank you, Arthur, Gene, O’Do, and Bill.Gregg MamikunianInter Science Institute 2006Reprinted from Inter Science Institute’s Neuroendocrine Tumors: A Comprehensive Guideto Diagnosis and Management handbook 2006.v

Acknowledgments to theSecond EditionThe current 1997 edition of the GI, Pancreatic Hormones, Related Peptides andCompounds handbook presents comprehensive information for many rare proceduresand tests that have been requested in the course of the past twenty-eight years.The handbook reflects the tremendous advances that have been made since 1977.The number of tests offered has increased six-fold in addition to increasing specificity,sensitivity of antibodies, and purity of the standards. The protocols dealing withchallenges and provocative testing has been expanded with the latest information.The section on the physiology of the GI and Pancreatic Hormones has been updatedas an adjunct to the various procedures in the handbook.Furthermore, the handbook covers a vast area of gastrointestinal, pancreatic, andother related procedures. Many of these procedures are clearly out of the realm ofroutine testing and request. On the other hand, quite a number of the proceduresare indicators in the clinical confirmation of certain syndromes and disease states.Inter Science has witnessed the phenomenon over the years of the transformationof research-oriented procedures becoming useful, routine, and critical determiningfactors in the diagnosis and management of certain GI-related endocrinopathies.A special acknowledgment to Alan C. Kacena for his dedication and service oftwenty-five years at Inter Science Institute and in bringing the current edition of theGI Hormones handbook into reality.Gregg MamikunianInter Science Institute 1997Reprinted from Inter Science Institute’s GI, Pancreatic Hormones, Related Peptidesand Compounds handbook, 1997.vi

Acknowledgments to theFirst EditionThe great majority of the gastrointestinal and pancreatic peptide hormones andpolypeptide assays listed in this handbook would not have been even remotelypossible had it not been for the tremendous generosity and cooperation of allthe individuals listed below. Without their assistance, the establishment of the GIHormones Laboratory at Inter Science Institute would not have been a reality.Inter Science Institute gratefully acknowledges and thanks Professor V. Mutt ofGI Hormones Laboratory of Karolinska Institute (Sweden) for his immense assistanceand encouragement; Professor N. Yanaihara (Japan); Dr I.M. Samloff (USA); ProfessorJ.C. Brown (Canada); Dr R. Geiger (Germany); Dr R.E. Chance (USA); ProfessorA.G.E. Pearse (England); Dr J.E. Hall (England); Dr R.I. Harvey (England) and ProfessorM. Bodanszky (USA).Our sincerest appreciation to Professor John H. Walsh of the University of Californiaat Los Angeles for his collaboration over the many years and his review and manysuggestions regarding this presentation.Finally, a special acknowledgment to Dr Herbert Gottfried of Inter Science Institute forhis long and dedicated years in bringing the GI Hormones Laboratory into fruition.Gregg MamikunianInter Science Institute 1997Reprinted from Inter Science Institute’s GI & Pancreatic Hormones and Polypeptides handbook, 1977.vii