Endocrine Surgery Second Edition

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ENDOCRINE
SURGERY
Second
Edition
ENDOCRINE
SURGERY Second
Edition

Edited by

Demetrius Pertsemlidis, MD FACS

The Bradley H. Jack Professor of Surgery
Icahn School of Medicine at Mount Sinai
New York, New York, USA
William B. Inabnet III, MD FACS
Chairman, Department of Surgery
Mount Sinai Beth Israel
Eugene W. Friedman Professor of Surgery
Icahn School of Medicine at Mount Sinai
New York, New York, USA
Michel Gagner, MD FRCSC, FACS, FASMBS
Clinical Professor of Surgery
Herbert Wertheim School of Medicine
Florida International University
Miami, Florida, USA
and
Senior Consultant
Hôpital du Sacré-Cœur
Montreal, Quebec, Canada
CRC Press
Taylor & Francis Group
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Library of Congress Cataloging‑in‑Publication Data

Names: Pertsemlidis, Demetrius, 1929- editor. | Inabnet, William B., III, editor. | Gagner, Michel, editor.
Title: Endocrine surgery / [edited by] Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner.
Other titles: Endocrine surgery (Schwartz)
Description: Second edition. | Boca Raton : CRC Press, [2016] | Includes bibliographical references and index.
Identifiers: LCCN 2016021845| ISBN 9781482259599 (pack : alk. paper) | ISBN 9781482259605 (ebook PDF) | ISBN 9781498715966
(ebook Vitalsource)
Subjects: | MESH: Endocrine System Diseases--surgery | Endocrine Surgical Procedures--methods
Classification: LCC RD599 | NLM WK 148 | DDC 617.4/4--dc23
LC record available at https://lccn.loc.gov/2016021845

Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
 To Lois, my wife, sons Alexander and David, and grandchildren Sarah, Helen, and William.
In gratitude to Bradley H. Jack, philanthropist and friend, whose endowment has allowed continuation of my clinical
and academic work.

Demetrius Pertsemlidis

To my wife, Kathleen, and children, Frances and William, whose unconditional support is a true blessing. And to my
patients, who consistently put their genuine trust in me to shepherd them to improved health.

William B. Inabnet III

For France, who is always there, and sons Xavier, Guillaume, and Maxime

Michel Gagner
Contents

Foreword xi
Preface xiii
Landmarks in endocrinology and endocrine surgery xv
Contributors xix

Part 1 PITUITARY GLAND 1

1 Selective sampling of petrosal veins 3

Justin R. Mascitelli and Aman B. Patel
2 Pituitary tumors and their management 9
Christopher A. Sarkiss, Raj K. Shrivastava, and Kalmon D. Post

Part 2 THE ENDOCRINE, LUNG, AND THYMUS 31

3 Physiology and pathophysiology of pulmonary neuroendocrine cells 33

John R. Gosney
4 Bronchopulmonary and thymic carcinoids; other endocrine tumors 41
Leslie James, Andrea Wolf, and Raja Flores

Part 3 THYROID 47

5 Physiology and testing of thyroid function 49

Terry F. Davies
6 Thyroid disease: Cytopathology and surgical pathology aspects 55
Charvi A. Cassano, Arnold H. Szporn, and G. Kenneth Haines III
7 Thyroid ultrasound imaging 67
Chenchan Huang, Amish H. Doshi, Safet Lekperic, and Grace Lo
8 Thyroid radionuclide imaging and therapy in thyroid cancer 87
Josef Machac
9 Mediastinal goiters 105
Yamil Castillo Beauchamp and Ashok R. Shaha
10 Hyperthyroidism 113
Alexandria Atuahene and Terry F. Davies
11 Thyroid nodules 125
Salem I. Noureldine and Ralph P. Tufano
12 Molecular testing of thyroid nodules 133
Linwah Yip
13 Surgery for well-differentiated thyroid cancer 143
Kelly L. McCoy and Sally E. Carty
14 Medullary thyroid cancer 155
Daniel Ruan and Susan C. Pitt

vii
viii Contents

15 Anaplastic thyroid carcinoma 165

Elizabeth G. Demicco
16 Endoscopic and robotic thyroidectomy 175
Cho Rok Lee and Kee-Hyun Nam
17 Video-assisted thyroid surgery 187
Paolo Miccoli and Gabriele Materazzi
18 Principles of thyroid cancer surgery and outcomes 195
James Y. Lim and William B. Inabnet III

Part 4 PARATHYROIDS 205

19 Presentation of primary hyperparathyroidism 207

Shonni J. Silverberg and Angela L. Carrelli
20 Parathyroid ultrasound imaging 217
Richard S. Haber
21 Parathyroid radionuclide imaging 221
Josef Machac
22 4D-CT for parathyroid localization 231
Reade De Leacy and Puneet S. Pawha
23 Parathyroid surgery 245
Randall P. Owen and Wendy S. Liu
24 Reoperation for hyperparathyroidism 257
Masha J. Livhits and Michael W. Yeh

Part 5 ADRENALS 269

25 Adrenocortical function, adrenal insufficiency 271

Gillian M. Goddard and Alice C. Levine
26 Surgical pathology of the adrenal gland 277
G. Kenneth Haines III
27 Imaging of the adrenal glands 291
Eric J. Wilck
28 Adrenal vein sampling for diagnosis and localization of aldosteronoma 299
Vivek V. Patil and Robert A. Lookstein
29 Cushing’s syndrome, cortical carcinoma, and estrogen- and androgen-secreting tumors 305
Alexander Stark and O. Joe Hines
30 Primary aldosteronism 329
Mihail Zilbermint and Constantine A. Stratakis
31 Neuroblastoma 339
Marcus M. Malek
32 Pheochromocytoma 349
David S. Pertsemlidis
33 Adrenal incidentalomas 365
David C. Aron, Alexis K. Okoh, and Eren Berber
34 Laparoscopic adrenalectomy with the transabdominal lateral approach 387
Michel Gagner
35 Techniques of adrenalectomy 411
Minerva Angelica Romero Arenas, Ashley Stewart, and Nancy D. Perrier

Part 6 PANCREAS 421

36 Pathology of the endocrine pancreas 423

Hongfa Zhu
37 Imaging of the pancreas 429
William L. Simpson Jr.
 Contents ix

38 Insulinoma 439
Per Hellman and Peter Stålberg
39 Congenital hyperinsulinism 455
Christopher A. Behr and Stephen E. Dolgin
40 Gastrinoma (Zollinger–Ellison syndrome) and rare neuroendocrine tumors 465
Mark Sawicki
41 The pancreas, the neuroendocrine system, neoplasia, traditional open pancreatectomy 483
Demetrius Pertsemlidis and David S. Pertsemlidis
42 Laparoscopic management of pancreatic islet cell tumors 507
Michel Gagner

Part 7 INHERITED SYNDROMES 527

43 Multiple endocrine neoplasia 529

Stephen Farrell

Part 8 GASTRO-ENTERO-PANCREATIC SYSTEM 559

44 Radionuclide imaging of carcinoid tumors, neurendocrine tumors of the pancreas and adrenals 561
Lale Kostakoglu
45 Carcinoid tumors 589
Dani O. Gonzalez, Richard R.P. Warner, and Celia M. Divino
46 Serotonin receptors and valvular heart disease 599
Javier G. Castillo and David H. Adams
47 Neuroendocrine tumors of the gastrointestinal tract 613
Bernard Khoo, Tricia Tan, and Stephen R. Bloom
48 Multimodality management of primary neuroendocrine tumors 629
Daniel M. Tuvin and Daniel M. Labow
49 Multimodality management of metastatic neuroendocrine tumors 633
Parissa Tabrizian, Yaniv Berger, and Daniel M. Labow
50 Cytoreduction of neuroendocrine tumors 645
Michael Olausson and Bo Wängberg
51 Liver transplantation for neuroendocrine tumors 655
Nir Lubezky, Parissa Tabrizian, Myron E. Schwartz, and Sander Florman
52 Medical management of neuroendocrine gastroenteropancreatic tumors 669
Kjell Öberg

Part 9 METABOLIC SURGERY 679

53 Pancreas transplantation 681

Nir Lubezky and Richard Nakache
54 Noninsulinoma pancreatogenous hypoglycemia syndrome and postbariatric hypoglycemia 691
Spyridoula Maraka and Adrian Vella
55 Surgical management of type 2 diabetes mellitus and metabolic syndrome: Available procedures
and clinical data 699
Daniel Herron and Daniel Shouhed
56 Changes in gut peptides after bariatric surgery 707
James P. Villamere, Blandine Laferrère, and James J. McGinty

Part 10 SCIENCE AND TECHNOLOGY 717

57 Robotic endocrine surgery 719

Alexis K. Okoh and Eren Berber

Index 733
Foreword
Today’s endocrine surgery is based on the ongoing efforts
and contributions of many clinicians and scientists. The
early luminaries in surgery, Billroth, Kocher, and Halsted,
made important contributions not only to the technical
development and performance of operative procedures
on endocrine glands but also to the understanding of the
pathophysiology of the underlying diseases and of the
resulting effects of surgery. In 1902, Bayliss and Starling first
discovered that a chemical messenger from one tissue could
be transported in the bloodstream to affect the function of a
different tissue or organ. Bayliss coined the term “hormone”
to categorize this action of secretin. The subsequent identi-
fication of other hormones such as insulin by Banting and
Best and gastrin by Gregory illustrate the profound impact
that endocrinology and endocrine surgery have had on the
course of medicine and the care of patients. Endocrinology
has always been a dynamic field but now more than ever the
pace of discovery and depth of understanding of the cellular
and physiologic processes in this field has rapidly acceler-
ated. This is especially true since the publication of the first
edition of Endocrine Surgery.
Endocrine surgery is now a well recognized subspecialty
with advanced training programs that develop the required
expertise to deal with the technical and, most impor-
tantly, the intellectual aspects of the field. The complexi-
ties involved in the diagnosis, management, and treatment
options of endocrine surgical disease necessitate a multidis-
ciplinary approach to produce a comprehensive, up-to-date
clinically relevant textbook, Drs. Pertsemlides, Inabnet,
and Gagner have assembled a nationally and internation-
ally recognized group of authors from the diverse fields that
impact the care and management of the endocrine surgi-
cal patient. The depth of knowledge and experience of these
experts in endocrinology, pathology, radiology, basic sci-
ence, surgery and surgical subspecialties provides useful
approaches for the reader in all areas of endocrine surgical
disease. It emphasizes that a skilled team is needed to deal
with the multi-faceted aspects of these problems if the best
results are to be obtained. Drs. Pertsemlides, Inabnet, and
Gagner have provided a clear and integrated presentation
of the clinical signs and symptoms, diagnostic laboratory
tests, imaging findings and methods of localization, medi-
cal and surgical treatment options and the steps involved
in the operative procedures for both benign and malig-
nant disease. By emphasizing the multispecialty aspects
of endocrine surgery, the reader not only strengthens their
knowledge and understanding in their area of interest but
also becomes conversant in the scope of expertise that is the
purview of their colleagues.
This textbook brings together much new information and
knowledge that has expanded the understanding of endo-
crine and metabolic surgical disease. From the molecular
biology that underpins these diseases to the newest technol-
ogies and techniques that are being applied to the diagno-
sis, imaging and treatment of endocrine problems, the text
provides a very functional source of valuable information.
This edition will serve as the go to reference for Endocrine
Surgery. It has much to offer physicians, endocrinologists,
endocrine surgery fellows, residents and students, and non-
clinicians with research interests in the field. It elucidates
the standard approaches to current endocrine surgical
problems but also looks forward to developing techniques of
endoscopic and robotic surgery. As specialization in medi-
cine increases, it is very useful to have a comprehensive text
that deals with all aspects of a field even though one’s inter-
est may be limited to a particular area of that field. I feel that
anyone who deals with an endocrine surgical patient will
find many areas of interest in this second edition of Surgical
Endocrinology. I am sure that readers of this text will not be
disappointed and will find a vast array of useful informa-
tion in dealing with the clinical aspects of endocrine surgi-
cal disease.
Dr. Richard A. Prinz, MD, FACS
Vice Chairman of Surgery
North Shore University Health System
and
Clinical Professor of Surgery
The University of Chicago Pritzker School of Medicine
xi
Preface
This second edition of Endocrine Surgery provides the stan-
dard reference source for clinicians and scientists, house
staff, and students. The textbook is contemporary, up to
date, and complete, with its contents ranging from mor-
phology and physiology to molecular and genetic aspects of
endocrine diseases. An online version of the entire book is
also available.
All chapters have been updated, extensively revised, or
entirely rewritten. In addition, a new section on metabolic
surgery, which includes four chapters, has been added.
The authors and their educational institutions come
from across the world, making this book of universal rel-
evance. The geographical locations are in North and South
America, Europe, the Far East, the Near East, and Australia.
The goal of this book is to enhance the day-to-day prac-
tice of medical and surgical endocrinologists by including
modern applications for the care of adults and, to some
extent, adolescents and children as well.
Prominent contributing leaders in endocrinology and
endocrine surgery and the well-known publishing house of
CRC Press/Taylor & Francis Group have created this global
anthology, which merits recognition by educational institu-
tions and libraries, as well as by individual readers.
Our table of contents spans 10 parts and accommodates
57 chapters. The first two parts are devoted to pituitary,
pulmonary, and thymic endocrine neoplasms. Parts 3 and
4 are dedicated to the thyroid and parathyroids. Eleven
chapters on the adrenal glands and seven on the pancreas
constitute Parts 5 and 6. Part 7 is a single but long contribu-
tion entitled “Inherited Syndromes,” and the chapter title
is “Multiple Endocrine Neoplasias.” Nine chapters comprise
Part 8, “Gastroenteropancreatic System.” The new Part 9 is
a constellation of four important chapters, including one on
pancreas transplantation, and all welcome new additions
to this edition. Finally, and looking to the future, the last
single chapter, and Part 10, is entitled “Robotic Endocrine
Surgery.”
Demetrius Pertsemlidis
William B. Inabnet III
Michel Gagner
New York
xiii
Landmarks in endocrinology
and endocrine surgery
DEMETRIUS PERTSEMLIDIS
Endocrinology and endocrine surgery have advanced rap-
idly and rightfully gained stately recognition in the aca-
demic environment and the world of medicine. The first
biochemical assay for a hormone, secretin, was achieved at
the beginning of the last century [1]. In 1946, Ulf van Euler,
a catecholamine physiologist at the Karolinska Institute in
Sweden, discovered that norepinephrine had the properties
of a neurotransmitter. In 1970, he shared the Nobel Prize
with Sir Bernard Katz of Great Britain and Julius Axelrod
of the United States for the recognition of adrenergic neu-
rotransmitter function [2,3].
In 1954, Paul Wermer described the inherited constel-
lation of pituitary, parathyroid, and pancreatic islet cell
neoplasia and named it “familial adenomatosis of the endo-
crine glands”, later defined as MEN 1. In 1961, John Sipple
described the association of thyroid carcinoma and pheo-
chromocytoma, later termed Sipple syndrome, or MEN 2 [4].
In 1956, vanillylmandelic acid (VMA), a urinary metab-
olite of catecholamines, was discovered by M.D. Armstrong;
a second urinary metabolite, metanephrine, was discov-
ered the following year by J. Axelrod. Until the early 1950s,
about one-half of pheochromocytomas were discovered
at autopsy. These biochemical discoveries have permitted
early detection with high accuracy (up to 95%) and low sur-
gical mortality (close to zero) in the past four decades [2].
In the 1960s, Rosalyn Yalow and Solomon Berson, then
at the Bronx Veterans Administration Medical Center and
later faculty members of the Mount Sinai Hospital in New
York, developed radioimmunoassay (RIA) to identify and
characterize peptides, hormones, and amines. Solomon
Berson died prematurely, before the Nobel Prize was given
to Dr Yalow in 1977. RIA and later immunohistochemis-
try revolutionized endocrinology and endocrine surgery
through better diagnosis and surgical skills [2,3].
MOLECULAR BIOLOGY
In the 1930s, macromolecules and their crystalline proper-
ties were studied using the technique of ultracentrifugation.
In the 1950s, Linus Pauling (Nobel Prize 1954) discovered
the three-dimensional structure of proteins, and the double
helix of the DNA molecule was described by James Watson
and Francis Crick (Nobel Prize laureates in 1962) [4,5].
By the 1980s, the landscapes of endocrinology and endo-
crine surgery benefited from the rapid scientific advances of
molecular biology.
MOLECULAR ENDOCRINOLOGY
Molecular and cellular endocrinology emerged in 1974,
encompassing genetic, epigenetic, biochemical, molecular
endocrine, and cell regulation. Hormones, neurotransmit-
ters, interaction with receptors, intracellular signaling,
hormone-regulated genes, gene structure or endocrine
functions, and multiple endocrine neoplasia were integrated
into molecular endocrinology. Concepts and techniques
borrowed from molecular biology significantly expanded
the field [6].
Autoimmune diseases, type I diabetes mellitus, autoim-
mune thyroid diseases, and genetic diseases all stemmed
from deficiencies of hormones, binding proteins, or ste-
roid enzymatic biosynthesis. Hormone resistance caused
by mutations in the gene for hormone receptors; resistance
to insulin, thyroid hormone, androgen, and vitamin D; and
glucocorticoid resistance are included in molecular endo-
crinology [6].
THE HUMAN GENOME
The Human Genome Project was launched in 1990, with the
first “rough draft” of the genome completed in 2000, and final
sequence mapping completed in 2003 [7–9]. The completed
human genome and advances in molecular biology added
better understanding of molecular physiology and diseases
in all areas of medicine and endocrinology [5].
The 3.2 billion base pairs of DNA per haploid genome
contain 22 autosomes and the X and Y sex chromosomes,
coding for roughly 21,000 genes, which are transcribed into
RNA, which is then translated into more than 250,000 pro-
teins. The human genome contains 21,000 genes. Each chro-
mosome contains many genes, the source of physical and
functional units and heredity. Genes are located in specific
xv
xvi Landmarks in endocrinology and endocrine surgery
sequences of bases that encode the transition to ­proteins,
performers of the function of life. Interestingly, genes
make up only 1.5% of DNA. The remaining DNA consists
of sequences—some repetitive and most not completely
understood—that are transcribed into RNA but do not
make proteins. A large portion of this noncoding DNA has
biochemical activity, including regulating gene expression,
organizing chromosomal architecture, and controlling epi-
genetic inheritance.
From prediction to reality, studies of the genome have led
to diagnosis and treatment of diseases.
EPIGENETIC SILENCING
Classical genetics cannot explain the entire spectrum of
cancers [10]. There is no genetic explanation for how mono-
zygotic twins with identical DNA can have different pheno-
types and different susceptibilities to a disease. Epigenetic
changes such as DNA methylation and histone modification
can alter patterns of gene expression without changes in the
underlying DNA sequence.
The best-known epigenetic inactivation (silencing) is
through DNA methylation of tumor suppression genes,
and plays a critical role in controlling gene activity and
architecture of the nucleus. Epigenetic silencing has been
observed in many cancers: breast, lung, prostate, kidney,
glioma, esophagus, stomach, liver, ovaries, leukemia, and
lymphoma. Unlike mutations, DNA methylation is revers-
ible. Hypermethylated tumor suppressor genes can be reac-
tivated with drugs. Demethylating agents, however, have
not shown successful clinical antitumor activity.
MICRORNAS
MicroRNAs (miRNAs) are 19- to 23-nucleotide-long non-
coding RNAs that post-transcriptionally regulate gene
expression by interacting with messenger RNAs, triggering
degradation or translational repression [11–14]. They are
involved in nearly every physiologic process, are critical to
development, and play a significant role in cancer initiation
and progression.
MiRNAs have been shown to regulate gene expres-
sion in metabolically active tissues, including the endo-
crine pancreas, liver, and adipose tissue; their expression
has been implicated in the development of the endocrine
pancreas and may regulate the progression of diabetes
and metabolic syndrome. In the pancreas, miR-375 has
been implicated in islet cell viability and function, with
perturbations of intracellular levels of miR-375 having
significant effects on glucose metabolism [11,12]. In the
liver, miR-122 has been shown to be critical for normal
lipid metabolism [13]. Specific patterns of tumor and
serum miRNA expression have been associated with
different types of thyroid tumors, including anaplastic,
follicular, and papillary thyroid carcinomas, with varia-
tion in the sequence of a single miRNA associated with a
familiar risk for papillary thyroid carcinoma (PTC) [14].
Thus, both variation in miRNA sequence and differences
in miRNA expression add molecular tools to the diag-
nostic, prognostic, and therapeutic armamentarium of
endocrinology.
MOLECULAR ISOTOPIC IMAGING
Somatostatin is an anterior pituitary hormone and a regula-
tory peptide with receptors (somatostatin receptor (SSTR))
in numerous organs: the brain, thyroid, pancreas, gastro-
intestinal system, spleen, and kidney [15–19]. Somatostatin
has a short half-life (3–4 minutes) and is susceptible to quick
enzymatic degradation.
Somatostatin suppresses the secretion of hormones of
numerous glands and has been used to treat diseases with
hormonal hypersecretion by inhibiting adenylyl cyclase
simultaneously with hormone binding.
111Indium-DTPA (diethylenetriamine pentaacetic acid)-
octreotide and 90Yttrium octreotide have been the most
commonly used with somatostatin analog. 111In-DTPA-
octreotide has a high affinity to somatostatin receptor type
II (SSTR2).
Carcinoid tumors show higher sensitivity when octreo-
tide is labeled with 111Indium compared with 123I-MIBG
(methyl-iodo-benzylguanidine). 111In-octreotide is less sen-
sitive in detecting pheochromocytoma (originating from the
adrenal medulla or extra-adrenal) and medullary thyroid
cancer.
90Y-octreotide is very sensitive (80%–100%) in detecting
carcinoid tumors. The sensitivity for gastrinoma is 60%–
90% and for insulinoma is limited to 50%, due to low affin-
ity and small tumor size.
In the search for better nuclear medicine molecular
imaging for insulinoma, exendin-4, an analog of glucagon-
like peptide (GLP-1), was discovered. Exendin-4 offers the
highest affinity to the radiotracers 111Indium and 68Gallium,
and strong conjugation with abundant receptors in pancre-
atic β-cells.
In recent years, peptide ligands DOTA, DOTATOC, and
DOTANOC have been discovered to form complexes with
the following metal tracers: 111In, 68Ga, 64Cu, 90Y, and 177Lu.
DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-­tetraacetic
acid), DOTATOC (phenylalanine replaced by tyrosine
at molecule position 3), and DOTANOC (DOTA-1-NaI-
octreotide) have chemical purity and high affinity to neu-
roendocrine tumors. The phenylalanine replacement by
tyrosine at position 3 in the molecule increases hydrophilia
and offers stronger conjugation with SSTR2 in somatosta-
tin-avid tumors.
68Ga-DOTA-PET, a recent introduction for clini-
cal research use, markedly improved nuclear medicine
molecular imaging, especially in neuroendocrine tumors.
The sensitivity of 97% and specificity of 92% reached an
accuracy up to 96%. It has been a landmark discovery in
neuroendocrinology.
Several therapeutic radiopharmaceuticals have
been used in small nonrandomized trials, including

111In-pentareotide, 90Y-DOTA-lanreotide, 90Y-DOTATOC,
177Lu-DOTATATE, 90Y-DOTANOC, 90Y-DTPA-D-Glu1-
minigastrin, 177Lu-AMBA, 90Y-DOTAGA-substance P, and
131I-MIBG.
ENDOCRINE AND METABOLIC SURGERY
Metabolism and metabolic surgery have been ingredients
of endocrinology and endocrine surgery [4,11]. The terms
encompass changes in biosynthesis, enzymatic and biologic
degradation, biochemical interactions, and energy storage.
The surgical interventions for endocrine disorders
include modulation of hormones causing a physiologic or
pathologic metabolic effect. Common disorders encom-
pass thyrotoxicosis, hypothyroidism, goiter, pituitary
and adrenal diseases, obesity, and diabetes mellitus and
hyperlipidemia.
In recent years, the horizon of metabolic surgery has
been expanded to integrate bariatric procedures for obesity,
type II diabetes mellitus, post-gastric bypass nonpancrea-
togenous hyperinsulinemia, and nesidioblastosis in MEN 1
patients with diffuse multicentric insulinomas or hyperpla-
sia/hypertrophy of the entire pancreas.
The enormities of endocrinology and metabolism have
created complexities that at times make it difficult to distin-
guish malfunctions from diseases.
THE ENDOCRINE PATIENT
The patient expressing hormonal hypersecretion, or sus-
pected endocrinopathy, is initially directed to an endocri-
nologist by the clinician. The history, clinical findings, and
family background are recorded in detail. Biochemical test-
ing starts with a basal and, if needed, stimulated hormonal
hypersecretion or antigenic profile in both functioning and
silent neuroendocrine neoplasia.
Traditional imaging with ultrasound, computed helical
tomography, and magnetic resonance are standard nonin-
vasive, radioactive instruments.
Before exposure of a patient to nuclear medicine pro-
cedures, it is mandatory to explain in practical terms the
events, the approximate times, and the instruments to be
used. The patient preparation should include information
about diet, hydration, medication needed or restricted,
and the rationale for these requirements. The radiation
risk must be explained to the patient in writing, and that
possible consequences may occur over a long time period.
The distinction between diagnostic and therapeutic radio-
pharmaceuticals should be clarified before the consent is
signed.
The final interpretation of the results should be explained
by placing them into clinical context. Interference with per-
formance of the instruments or interpretation of the results
should be revealed to the patient.
Genetic testing and counseling is essential for the patient
if the family heredity is known, or in young patients with an
unknown family link or skipped generations.
Landmarks in endocrinology and endocrine surgery xvii
Every patient’s case is reviewed by the multidisciplinary
committee, where the discussions usually reach a maxi-
mum of indications and choice of procedures.
Current instruments, surgical techniques (endoscopy,
laparoscopy, and robotic), molecular biochemistry, isoto-
pic imaging, and genetic and genomic advancements offer
unique diagnostic and therapeutic outcomes.
CHANGES THAT IMPROVED OUTCOMES
IN ADRENALECTOMIES
Preoperative pharmacologic vasodilatation
It is common practice to start ambulatory preoperative
adrenergic blockade for 4–6 weeks, expecting expansion
of the circulating blood volume [20–22]. The described oral
dose is usually designed to control the blood pressure, heart
rate and rhythm, sweating, and metabolic activity under
conditions without stress.
Physical trauma or emotional stress will most likely
cause hypertensive or arrhythmic crisis due to insufficiency
of drug concentration in the ambulatory state.
Phenoxybenzamine, a long-acting (t½ = 2–3 hours),
nonselective oral α-adrenergic blocker is given orally three
times a day (preferably every 6 hours) to a total dose of
40–100 mg/day. After α-adrenergic blockade, a β-blocker
(metoprolol or atenolol) or calcium channel blocker (nica-
rdipine) is added.
Plasma and erythrocyte volumes in pheochromocytoma
have been proven to be within the normal range [20,21].
Preoperative attempts to create pharmacologic expansion of
the circulating volume do not prevent cardiovascular intra-
operative crises or hypotension after removal of pheochro-
mocytoma [22]. The optimal time for volume restoration
with isotonic crystalloid (rarely blood) is immediately after
tumor removal.
Unknown duality of the adrenergic system
We strictly separated paragangliomas from adrenomed-
ullary pheochromocytomas in the adrenergic system.
Common embryologic ancestry from the neural crest,
secretion of norepinephrine, and potential production of
ectopic hormones are the only similarities.
Paraganglioma patients are younger, the tumors are
derived from sympathetic ganglia, genetics differ completely,
tumor multiplicity is 30%, malignancy is more prominent,
and the association with other neoplastic syndromes is not
distinguishable. As a result, the preoperative radiologic
detection, molecular imaging, intraoperative dissection, and
postoperative surveillance are more difficult.
Choice of adrenergic blockers
We have always used only intraoperative continuous
intravenous short-acting α-1 blocker (phentolamine)
and short-acting β-1 antiarrhythmic blocker (esmolol).
xviii Landmarks in endocrinology and endocrine surgery
When phentolamine was no longer manufactured, we sub-
stituted the calcium channel blocker (nicardipine).
Long-acting adrenergic blockers are not suitable in the
operating theater. They block the catecholamine recep-
tors partially or completely, rendering them ineffective.
Substitution of effective adrenergic blockers with less effec-
tive antihypertensive medications is a mistake. We have
routinely stopped the long-acting adrenergic blockers the
day before surgery and started intravenous short-acting
blockade for 24 hours in a monitored bed.
The preoperative initiation of the continuous intrave-
nous adrenergic blockade offers a high degree of receptor
affinity and allows preparation of the appropriate concen-
tration for controlling the intraoperative crisis.
Experience in pheochromocytoma
and adrenocortical neoplasia
We, Demetrius and David Pertsemlidis, performed 245
consecutive operations (87 laparoscopic) in 225 patients
with pheochromocytomas (30 paragangliomas); there was
zero surgical mortality over a period of 4½ decades in a
single institution.
Early on, we created programmatic canons and applied
them strictly by preparing a well-organized pharmacologic
environment, working with highly skilled anesthesiolo-
gists, selecting an appropriate surgical approach conform-
ing to tumor size or anatomic location, and continuing close
monitoring during immediate postsurgical recovery, until
normo-volemia is restored.
One hundred fifty adrenocortical neoplasms were treated
by laparoscopy or open traditional methods: Cushing’s ade-
nomas, adrenocorticotropic hormone (ACTH)-dependent
hypercortisolism, adrenocortical carcinoma, aldoster-
onoma, nonfunctioning adrenocortical adenomas, and
metastases to adrenals. R0 resection margins are essential
to avoid recurrent Cushing’s hypercortisolism or tumor,
if there is a millimeter fraction of cortex left behind.
Restoration of function in the suppressed contralateral
adrenal, following unilateral adrenalectomy for Cushing’s
adenoma, may be as long as 6 months.
REFERENCES
1. Bayliss WM, Starling EH. The mechanism of pancre-
atic secretion. J Physiol 1902;28:323–53.
2. Pertsemlidis DS. Pheochromocytoma: Textbook of
Endocrine Surgery. 2nd ed. Abingdon, UK: CRC
Press, Taylor & Francis Group.
3. Yalow R, Berson S. Philadelphia: Chemical Heritage
Foundation, 2010.
4. Becker KL, Nylen ES, Snider RH Jr. Endocrinology
and the Endocrine Patient: Principles and Practice of
Endocrinology and Metabolism. 3rd ed. Philadelphia:
Lippincott Williams & Wilkins, 2002.
5. Leder P, Clayton DA, Rubenstein E, eds. Molecular
Medicine, Introduction. New York: Scientific
American, 1994.
6. Weintraub BD, ed. Molecular Endocrinology: Basic
Concepts and Clinical Correlations. New York: Raven
Press, 1994.
7. Thompson EB. The impact of genomics and pro-
teomics on endocrinology. Endocr Rev 2002;23:366–8.
8. Dattani MT, Martinez-Barbera JP. The future of
genomic endocrinology. Front Endocrinol 2011;2:1–2.
9. Collins FS, Green ED, Guttmacher AE, Guyer MS. A
vision for the future of genomics research. Nature
2003;422:836–47.
10. Esteller M. Epigenetics in cancer. N Engl J Med
2008;358:1148–59.
11. Latreille M, Herrmanns K, Renwick N et al. miR-375
gene dosage in pancreatic β-cells: Implications for
regulation of β-cell mass and biomarker develop-
ment. J Mol Med (Berl) 2015;93(10):1159–69.
12. Poy MN, Eliasson L, Krutzfeldt J et al. A pancreatic
islet-specific microRNA regulates insulin secretion.
Nature 2004;432:226–30.
13. Wen J, Friedman JR. miR-122 regulates hepatic lipid
metabolism and tumor suppression. J Clin Invest
2012;122(8):2773–6.
14. Mancikova V, Castelblanco E, Pineiro-Yanez E et al.
MicroRNA deep-sequencing reveals master regula-
tors of follicular and papillary thyroid tumors. Mod
Pathol 2015;28:748–57.
15. Al-Nahhas A, Win Z, Szyszko T et al. Gallium-68
PET: A new frontier in receptor cancer imaging.
Anticancer Res 2007;27:4088–94.
16. Advance Online Publication. Nature Reviews
Endocrinology. Macmillan Publishers Limited, 2011;
106. www.nature.com/nrendon.
17. Antunes P, Ginj M, Zhang H et al. Are radiogallium-
labelled DOTA-conjugated somatostatin analogues
superior to those labelled with other radiometals?
Eur J Nucl Med Mol Imaging 2007;34:982–93.
18. Poeppel TD, Binse I, Petersenn S et al.
68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in
functional imaging of neuroendocrine tumors. J Nucl
Med 2011;52:1864.
19. Gabriel M, Decristoforo C, Kendler D et al. PET with
68Ga-DOTA-Tyr3: Comparison of 3 imaging modali-
ties: PET, SPECT, CT. J Nucl Med 2007:48;508–18.
20. Johns VJ, Brunjes S. Pheochromocytoma. Am J
Cardiol 1962;9:120–5.
21. Sjoerdsma A, Waldman TA, Cooperman LH,
Hammond WG. Pheochromocytoma: Current con-
cepts of diagnosis and treatment; combined clinical
staff conference at the National Institutes of Health.
Am Intern Med 1996;65:1302–6.
22. Newell KA, Prinz RA, Brooks MH et al. Plasma cat-
echolamines changes during excision of pheochro-
mocytoma. Surgery 1988;104:1064–73.
Contributors

David H. Adams MD Angela L. Carrelli MD

Department of Cardiothoracic Surgery Division of Endocrinology
Icahn School of Medicine at Mount Sinai Columbia University College of Physicians
New York, New York and Surgeons
New York, New York
David C. Aron MD MS
Department of Medicine Sally E. Carty MD FACS
Case Western Reserve University School of Medicine Division of Endocrine Surgery
and Department of Surgery
Center for Quality Improvement Research University of Pittsburgh
Louis Stokes Department of Veterans Affairs Pittsburgh, Pennsylvania
Medical Center
Cleveland, Ohio Charvi A. Cassano MD
Department of Pathology
Alexandria Atuahene MD
Icahn School of Medicine at Mount Sinai
Division of Endocrinology, Diabetes and Bone Diseases
New York, New York
Icahn School of Medicine at Mount Sinai
New York, New York
Javier G. Castillo MD
Yamil Castillo Beauchamp MD Department of Cardiothoracic Surgery
Medical Pavilion Icahn School of Medicine at Mount Sinai
San Juan, Puerto Rico New York, New York

Christopher A. Behr MD Terry F. Davies MB BS MD FRCP FACE

Feinstein Institute for Medical Research Division of Endocrinology, Diabetes and
Hofstra-North Shore LIJ School of Medicine Bone Diseases
Cohen Children’s Medical Center Icahn School of Medicine at Mount Sinai
Manhasset, New York Mount Sinai Beth Israel
New York, New York
Eren Berber MD
Center for Endocrine Surgery
Reade De Leacy MBBS FRANZCR
Cleveland Clinic Lerner College of Medicine
Department of Radiology
Case Western Reserve University School of Medicine
Icahn School of Medicine at Mount Sinai
Cleveland, Ohio
New York, New York
Yaniv Berger MD
Department of Investigative Medicine Elizabeth G. Demicco MD PhD
Imperial College London Department of Pathology
London, United Kingdom Icahn School of Medicine at Mount Sinai
New York, New York
Stephen R. Bloom DSc MD FMedSci FHEA FRSB FRCP FRCPath FRS
North West London Pathology Consortium Celia M. Divino MD FACS
Division of Diabetes, Endocrinology and Metabolism Department of Surgery
Imperial College London Icahn School of Medicine at Mount Sinai
London, United Kingdom New York, New York

xix
xx Contributors

Stephen E. Dolgin MD FACS Per Hellman MD

Department of Pediatric Surgery Department of Surgical Sciences
Hofstra-North Shore Long Island Jewish School of Medicine University Hospital
Cohen Children’s Medical Center Uppsala, Sweden
New Hyde Park, New York
Daniel Herron MD FACS
Amish H. Doshi MD Department of Surgery
Department of Radiology and Neurosurgery Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai New York, New York
New York, New York
O. Joe Hines MD
Stephen Farrell MBBS FRACS Department of Surgery
St. Vincent’s and Austin David Geffen School of Medicine at UCLA
Teaching Hospitals Los Angeles, California
University of Melbourne
Royal Children’s Hospital Chenchan Huang MD
Melbourne, Australia Department of Radiology
Icahn School of Medicine at Mount Sinai
Raja Flores MD New York, New York
Department of Thoracic Surgery
Icahn School of Medicine at Mount Sinai William B. Inabnet III MD FACS
New York, New York Department of Surgery
Mount Sinai Beth Israel
Sander Florman MD FACS Icahn School of Medicine at Mount Sinai
Recanati/Miller Transplantation Institute New York, New York
Mount Sinai Hospital
New York, New York Leslie James BA
Department of Thoracic Surgery
Michel Gagner MD FRCSC FACS FASMBS The Icahn School of Medicine at Mount Sinai
Herbert Wertheim School of Medicine New York, New York
Florida International University
Miami, Florida Bernard Khoo MD
ENETS Centre for Excellence
and
Royal Free London NHS Foundation Trust
Hôpital du Sacré-Cœur London, United Kingdom
Montreal, Quebec, Canada
Lale Kostakoglu MD MPH
Gillian M. Goddard MD Department of Radiology Nuclear Medicine
Division of Endocrinology Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai New York, New York
New York, New York
Daniel M. Labow MD FACS
Dani O. Gonzalez MD Division of Surgical Oncology
Department of Surgery Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai New York, New York
New York, New York
Blandine Laferrère MD
John R. Gosney MB ChB Department of Medicine
Department of Cellular Pathology Columbia University College of Physicians and
Royal Liverpool University Hospital Surgeons
Liverpool, United Kingdom New York, New York

Richard S. Haber MD Cho Rok Lee MD

Division of Endocrinology, Metabolism and Bone Diseases Department of Surgery
Icahn School of Medicine at Mount Sinai Yonsei University College of Medicine
New York, New York Seoul, Korea

G. Kenneth Haines III MD Safet Lekperic MD

Department of Pathology Department of Radiology
Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai
New York, New York New York, New York
 Contributors xxi

Alice C. Levine MD Gabriele Materazzi MD

Division of Endocrinology, Metabolism and Department of Surgery
Bone Diseases University of Pisa
Icahn School of Medicine at Mount Sinai Pisa, Italy
New York, New York
Kelly L. McCoy MD FACS
Division of Endocrine Surgery
James Y. Lim MD
Department of Surgery
Division of Surgical Oncology
University of Pittsburgh
Oregon Health Sciences University
Pittsburgh, Pennsylvania
Portland, Oregon
James J. McGinty MD FACS
Wendy S. Liu MBBS Department of Surgery
Department of Surgery—Head and Neck Icahn School of Medicine at Mount Sinai
Surgery Mount Sinai St. Luke’s and Mount Sinai Roosevelt Hospitals
School of Medicine New York, New York
University of Western Sydney
Campbelltown, Australia Paolo Miccoli MD
Department of Surgery
Masha J. Livhits MD University of Pisa
Section of Endocrine Surgery Pisa, Italy
UCLA David Geffen School of Medicine
Los Angeles, California Richard Nakache MD
Division of General Surgery
Grace Lo MD Tel-Aviv Medical Center
Department of Radiology Affiliated with the Sackler Faculty of Medicine
Icahn School of Medicine at Mount Sinai Tel-Aviv University
New York, New York Tel-Aviv, Israel

Robert A. Lookstein MD Kee-Hyun Nam MD

Department of Radiology Department of Surgery
Icahn School of Medicine at Mount Sinai Yonsei University College of Medicine
New York, New York Seoul, Korea

Nir Lubezky MD Salem I. Noureldine MD

Department of Otolaryngology—Head and
Recanati/Miller Transplantation Institute
Neck Surgery
Mount Sinai Hospital
Johns Hopkins University School of Medicine
New York, New York
Baltimore, Maryland
Josef Machac MD
Kjell Öberg MD PhD
Department of Nuclear Medicine, Radiology
Department of Endocrine Oncology
Icahn School of Medicine at Mount Sinai
Uppsala University Hospital
New York, New York
Uppsala, Sweden
Marcus M. Malek MD FAAP
Alexis K. Okoh MD
University of Pittsburgh School of Medicine
Center for Endocrine Surgery
Children’s Hospital of Pittsburgh of UPMC
Cleveland Clinic Lerner College of Medicine
Pittsburgh, Pennsylvania
Case Western Reserve University School of Medicine
Cleveland, Ohio
Spyridoula Maraka MD
Division of Endocrinology, Diabetes, Metabolism, Michael Olausson MD
and Nutrition Department of Transplantation Surgery
Mayo Clinic Sahlgrenska University Hospital
Rochester, Minnesota Göteborg, Sweden

Justin R. Mascitelli MD Randall P. Owen MD MS FACS

Department of Neurosurgery Department of Surgery
Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai
New York, New York New York, New York
xxii Contributors

Aman B. Patel MD Myron E. Schwartz MD FACS

Department of Neurosurgery Recanati/Miller Transplantation Institute
Massachusetts General Hospital Mount Sinai Hospital
Harvard Medical School New York, New York
Boston, Massachusetts
Ashok R. Shaha MD FACS
Vivek V. Patil MD Department of Oncology—Head and
Department of Interventional Radiology Neck Surgery
Icahn School of Medicine at Mount Sinai Memorial Sloan-Kettering Cancer Center
New York, New York New York, New York
Puneet S. Pawha MD Daniel Shouhed MD
Department of Radiology Department of Surgery
Icahn School of Medicine at Mount Sinai Cedars Sinai Medical Center
New York, New York Los Angeles, California
Nancy D. Perrier MD FACS
Raj K. Shrivastava MD
Department of Surgical Endocrinology
Department of Neurosurgery in Otolaryngology
University of Texas MD Anderson Cancer Center
Icahn School of Medicine at Mount Sinai
Houston, Texas
New York, New York
David S. Pertsemlidis MD FACS
Department of Surgery Shonni J. Silverberg MD
Icahn School of Medicine at Mount Sinai Division of Endocrinology
Morristown Medical Center Columbia University College of Physicians
Morristown, New Jersey and Surgeons
New York, New York
Demetrius Pertsemlidis MD FACS
The Bradley H. Jack Professor of Surgery William L. Simpson Jr. MD
Department of Surgery Department of Radiology
Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai
New York, New York New York, New York
Susan C. Pitt MD MPHS
Peter Stålberg MD
Brigham and Women’s Hospital
Department of Surgical Sciences
Department of Surgery
University Hospital
Boston, Massachusetts
Uppsala, Sweden
Kalmon D. Post MD
Departments of Neurosurgery and Medicine Alexander Stark MD
Icahn School of Medicine at Mount Sinai Department of Surgery
New York, New York David Geffen School of Medicine at UCLA
Los Angeles, California
Minerva Angelica Romero Arenas MD MPH
Department of Endocrine Surgery Ashley Stewart MD
University of Texas University of Texas MD Anderson Cancer Center
MD Anderson Cancer Center Houston, Texas
Houston, Texas
Constantine A. Stratakis MD D(med)Sci
Daniel Ruan MD Section on Endocrinology and Genetics
Norman Parathyroid Center Program on Developmental Endocrinology
Tampa, Florida and Genetics
Christopher A. Sarkiss MD resident Eunice Kennedy Shriver National Institute of Child
Department of Neurosurgery Health and Human Development
Icahn School of Medicine at Mount Sinai National Institutes of Health
New York, New York Bethesda, Maryland

Mark Sawicki MD Arnold H. Szporn MD

Department of Surgery Department of Pathology
University of California, Los Angeles Icahn School of Medicine at Mount Sinai
Los Angeles, California New York, New York
 Contributors xxiii

Parissa Tabrizian MD Richard R.P. Warner MD

Recanati/Miller Transplantation Institute Division of Gastrointestinal Surgery
Mount Sinai Hospital Center for Carcinoid and Neuroendocrine Tumors
New York, New York Icahn School of Medicine at Mount Sinai
New York, New York
Tricia Tan MD
Department of Investigative Medicine Eric J. Wilck MD
Division of Diabetes, Endocrinology and Department of Radiology
Metabolism Icahn School of Medicine at Mount Sinai
Imperial College New York, New York
London, United Kingdom
Andrea Wolf MD
Ralph P. Tufano MD MBA FACS Department of Thoracic Surgery
Department of Otolaryngology—Head and Neck Icahn School of Medicine at Mount Sinai
Surgery New York, New York
Johns Hopkins University School of Medicine
Baltimore, Maryland Michael W. Yeh MD FACS
Section of Endocrine Surgery
Daniel M. Tuvin MD UCLA David Geffen School of Medicine
Division of Surgical Oncology Los Angeles, California
Icahn School of Medicine at Mount Sinai
New York, New York Linwah Yip MD
Department of Surgery
Adrian Vella MD University of Pittsburgh
Division of Endocrinology, Diabetes, Metabolism, Pittsburgh, Pennsylvania
and Nutrition
Mayo Clinic Hongfa Zhu MD
Rochester, Minnesota Department of Pathology
Icahn School of Medicine at Mount Sinai
James P. Villamere MD FRCSC New York, New York
Department of Surgery
Icahn School of Medicine at Mount Sinai Mihail Zilbermint MD
Mount Sinai St. Luke’s and Mount Sinai Roosevelt Department of Pediatric Endocrinology and Genetics
Hospitals National Institutes of Health
New York, New York Bethesda, Maryland
and
Bo Wängberg MD
Department of Surgery Division of Endocrinology, Diabetes, and Metabolism
Sahlgrenska University Hospital Johns Hopkins University School of Medicine
Göteborg, Sweden Baltimore, Maryland
 1
Part    

Pituitary Gland

1 Selective sampling of petrosal veins 3

Justin R. Mascitelli and Aman B. Patel
2 Pituitary tumors and their management 9
Christopher A. Sarkiss, Raj K. Shrivastava, and Kalmon D. Post

Selective sampling of petrosal veins
JUSTIN R. MASCITELLI AND AMAN B. PATEL
Introductions and rationale
Anatomy and sampling technique
Anticoagulation
Jugular vein catheterization
Inferior petrosal sinus catheterization
Venous sampling procedure
Pitfalls and complications
INTRODUCTIONS AND RATIONALE
Cushing’s syndrome (CS) describes the signs and symptoms
that are secondary to persistent hypercortisolemia, includ-
ing stigmata of hypertension, diabetes, truncal obesity,
osteopenia, bruising, abdominal striae, moon facies, gen-
eralized malaise, fatigue, and emotional lability. Cushing’s
disease (CD) is restricted to hypercortisolemia secondary to
an adrenocorticotropic hormone (ACTH)-secreting pitu-
itary adenoma. CD accounts for approximately 70% of adult
cases of CS [1]. The prompt identification and treatment of
CD is paramount since CD left untreated can carry a high
morbidity and mortality. Untreated CD has a 5-year sur-
vival rate of only 50% [2].
The differentiation of CD from CS secondary to an ecto-
pic ACTH-producing tumor generally relies on a number of
different biochemical tests, especially when MRI does not
definitively demonstrate a pituitary adenoma as the cause.
The three most commonly used tests to diagnose hyper-
cortisolism are urinary free cortisol (UFC), low-dose dexa-
methasone suppression tests (DSTs), and midnight serum
cortisol or late-night salivary cortisol, but these tests carry
variable sensitivity and specificity. Tests to further differ-
entiate CD and CS include serum ACTH, high-dose DST,
corticotropin-releasing hormone (CRH) or desmopressin
stimulation testing, and MRI of the brain [3]. The high-dose
DST has been reported to have a sensitivity of only 80% [4].
MRI has been reported to have a false-negative rate of up
to 50% [5]. This accuracy may be improved by using tech-
niques such as dynamic contrast spin echo (DC-SE) and
volume-interpolated three-dimensional spoiled gradient
echo (VI-SGE) MR sequences [6], as well as 3 T MRI [7].
1
3 Pitfalls 6
3 Complications 7
4 The Mount Sinai Hospital experience 7
4 Conclusions 7
4 Acknowledgment 7
6 References 7
6
Inferior petrosal sinus sampling (IPSS) was first reported
in 1981 to differentiate CD and CS due to an ectopic ACTH-
producing tumor [8]. IPSS with CRH stimulation is cur-
rently considered to be the gold standard in diagnosing
CD when all other methods have failed, with sensitivity
and specificity rates in the range of 96% and 100%, respec-
tively [9]. Although IPSS was traditionally advocated for all
cases with negative imaging [10], it is currently considered
in selected cases with hypercortisolemia when both labora-
tory and radiographic tests fail to make the diagnosis with a
high degree of certainty or in cases of persistent hypercorti-
solemia after hypophysectomy if not previously performed
[11,12]. In these cases, a preoperative positive MRI scan may
have represented a nonsecreting pituitary adenoma.
The rationale for IPSS is that a large proportion of the
venous drainage of the pituitary gland is via the IPSs, allow-
ing for analysis of blood samples uncontaminated from other
sources. Therefore, in CD the concentration of ACTH is
expected to be higher in the IPS draining the hemihypophy-
sis bearing the tumor than in the contralateral IPS or in the
peripheral blood [10,13]. CRH is released from the paraven-
tricular nucleus of the hypothalamus into the hypophyseal
portal system and stimulates the release of ACTH from the
anterior pituitary. CRH stimulation has long been known to
increase sensitivity and specificity of IPSS [10].
ANATOMY AND SAMPLING TECHNIQUE
Venous sampling must be obtained from a source that
represents the venous drainage of the pituitary gland. The
venous drainage of the pituitary gland is via the cavernous
sinus. The cavernous sinus then usually drains into the IPSs,
3
4 Selective sampling of petrosal veins
superior petrosal sinuses (SPSs), and basilar venous plexus.
These all have variable drainage courses into the internal
jugular vein (IJV) and paraspinal venous plexus. There are
as many as four intercavernous venous connections (the
largest of which is the basilar plexus located along the dor-
sum sellae). Despite these connections, pituitary venous
drainage is unilateral under normal circumstances [14,15].
Therefore, bilateral simultaneous sampling is required to
evaluate the side of possible pituitary microadenoma. The
IPSs are usually the best sites to obtain venous samples
from, since they usually capture a large portion of the cav-
ernous sinus drainage from their respective side.
It is important to ensure that the patient is hypercorti-
solemic at the time of IPSS; otherwise, the test may yield
a false-negative result. Midnight salivary cortisol the night
before the procedure [16] and 24-hour urinary cortisol the
day before (our protocol), and same-day analysis of the sam-
ples, offer assurance.
Anticoagulation
Venous thrombosis of the IPS, cavernous sinus, basilar
venous plexus, or IJV is an undesired event that can poten-
tially have severe consequences. Therefore, systemic antico-
agulation is maintained during the procedure [10] with a
bolus of 4000 units of intravenous heparin followed by 1000
units intravenously every hour thereafter. Alternatively, the
dosage of heparin can be titrated to maintain an activated
clotting time (ACT) of greater than 200. At the minimum,
the catheters will be in place for 30 minutes, and in cases of
difficult catheterization, it is not unusual to have a catheter
in place for a longer period of time.
Jugular vein catheterization
Bilateral venous access is established by the standard trans-
femoral approach. On one side, a 5 French (Fr.) sheath is
placed, so that concomitant peripheral venous sampling
can be obtained during the procedure. A 4 Fr. sheath is
placed into the contralateral femoral vein. The IJVs and,
subsequently, the IPSs are catheterized with 4 Fr. cath-
eters. The catheter used should have a 20°–30° angled tip,
followed by a 2 cm straight segment. Occasionally, a dif-
ferent angle or shape may be necessary depending upon
the specific anatomy. When sampling, each side should be
accessed with the respective IPS to match sampling sides
and catheters [10].
On the left, the junction of the innominate vein and the
superior vena cava (SVC) is relatively large. Once the cath-
eter is aimed in the correct direction, a hydrophilic-coated
guidewire should allow easy passage from the SVC to the left
subclavian vein. Catheterization of the left IJV can be chal-
lenging, usually because of a valve located at the thoracic
inlet. Getting the wire to enter the IJV is usually a matter
of chance with repetitive prodding during various phases of
respiration. A forceful contrast injection into the subclavian
vein will often show the location of various inflow veins as
stumps, due to the venous valve system, which can then be
used as guides.
Accessing the right IJV is usually more straightforward
than the left, as the course is relatively straight. There can
be variations that make the catheterization more difficult,
but access can usually be achieved with a small amount of
searching. The valve is usually not as much of a problem on
the left.
Inferior petrosal sinus catheterization
The venous drainage of the skull base is variable [17], mak-
ing entry of the IPSs into the jugular system more difficult
to find. In fact, advancing the catheter into the IPS is often
the most challenging aspect of the procedure. The most
common site of IPS entrance is at the apex of the jugular/
sigmoid sinus curve and is typically located anterior and
medial. Careful probing with a hydrophilic guidewire
aimed in the appropriate direction will allow one to the find
the IPS. Occasionally, a contrast injection will be needed
to identify the location of the IPS. Once the guidewire is
positioned in the IPS, the catheter can be passed into the
distal aspect of the IPS. Once the catheter is within the IPS,
anteroposterior (AP) and lateral venograms are performed
to confirm the position and to assess the venous drainage.
With good positioning, retrograde filling of both cavernous
sinuses, the contralateral IPS and basilar venous plexus, is
commonly seen (Figures 1.1 and 1.2). Occasionally, the IPS
will be too small for a 4 Fr. catheter, in which case a micro-
catheter and microwire can be used.
Normal AP
R L
Figure 1.1 Right IPS injection, AP view. Normal symmet-
ric IPSs. Note that the right-sided injection opacifies the
bilateral IPSs (arrowheads), the bilateral cavernous sinuses
(arrows), the intercavernous sinus (plus signs), and the
bilateral IJVs (stars). The catheter is well positioned in the
right IPS (arrowhead). Note that the IPS arises medially
from the IJV.
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 A PASTORAL.

The little village of my heart

Hath tangled lanes and roses,
And paths of musky hollyhocks
Wherein the wild bee noses.

’Tis summer, summer everywhere,

And drowsy pipes are playing,
Some little peace-dream all the while,
Where sweethearts go a-straying.

Just follow where the piper leads,

With Love—the gypsy rover—
You’ll find the little barefoot joys
You lost out in the clover.

Singlehurst.
 THE WHITE PINE.

’Tis not the grace of yonder beach,

Its crescent-curve and swing,
Nor bastion-crags of Manomet
Whose sarabands I sing.
Mine be those woodland symphonies
Of spirit-power divine,
Like lullabies when evening wraps
The old storm-beaten pine.
Or, be it their defiant chords,
When wintry hordes complain,
While Triton thunders down the gale,
The lightning in his train;
And I would hymn their litanies,
The incense on my breath,
Like Alp-horn notes that echo on
Oblivious of death.

Plymouth,
September 21, 1920.
THE COLONIAL PIONEER.

A soul that like a column white

Survives the wind and rain,
Immortal as the Infinite,
Thy precepts shall remain
While man shall reverence motherhood,
Or galleons sail the seas,
While Earth shall clothe thy mortal frame,
Or leaves shall clothe the trees.
E’en as a shaft of morning burns,
Thy spirit, ever new,
Shall symbol the Eternal mind,
The Brave, the Good, the True.

Knight of the Forum of the Dead,

A hero of the past,
Born of New England’s virgin soil,
Lord of the Nation’s cast
Our daily lot with common men,
Of rectitude of heart,
Give us the burdens of the world
And help us act our part.

And look! some oracle of time—

Some sorcerer of ooze and slime—
Has left a panoply most rare
For lazy-footed night to wear,
With girdle of a sombre dye,
And hung it on a rock to dry,
Where, flushed with slumber, drones a stream
To charm some lonely mermaid’s dream.
And this my heritage, more fair
Than mosque that ever called to prayer
A Moslem, bids me kneel and pray;
These simple words are all I say—
“I’ve been with God an hour or two”—
A shadow tiptoes down the blue;
And like a mother wraps the sea
In stillness of eternity.

Marshfield, August 16, 1920.

THE OLD ROCKIN’ CHAIR.

It tilts a little to the left,

An’ wiggles here and there,
It’s kind-o’ creaky in the j’ints,
An’ ’taint plumb anywhere.

But s’pose you hitch up to’rds the fire,

There, try it ’rond this way;
You’re got to git it joggin’ right,
An’ when you’re tired, w-a-l-l, say,

You’re comforted, you’re comforted,

An’ rested thru an’ thru;
Why, that old rocker’s heaven to me,
But ’taint the same to you.

I ain’t a-goin’ to tell you why,

There ain’t no fairies here,
I h’an’t hearn Annie Laurie sung
For more nor fifty year.

There’s folks what thinks they know “Ben Bolt,”

An’ “Comin’ Thru’ the Rye,”
An’ “Ride away to Boston town,
To make a rabbit pie,”

An’ “Twinkle, twinkle little star,”

But you don’t know ’bout then,
When “Jack the Giant Killer” lived,
An’ Towser ’n’ Uncle Ben.

You don’t know “When they sheared the sheep,”

 An’ “England had a King;”
You never had a trundle-bed;
There, now you’ve got the swing.

Of course it wiggles when you rock,

An’ ’taint plumb anywhere,
But ain’t you full o’ happiness,
In that old rockin’ chair?
OUT OF GETHSAMANE.
Give me the common task,
The little prayers to say,
The common, homely things of life,
To love in the old sweet way.
Give me a wounded heart,
Then bring me the flutes of May,
Teach me ye bells of the summer-grass,
Then give me your tunes to play.
 GREETINGS.
TO THE SOCIETY OF MAYFLOWER DESCENDANTS
IN AMERICA.

A cup to Elder Brewster,

A jewel for his crest,
And every Pilgrim “handed down”
By him and all the rest.
For you, betrothed and plighted,
Forever ships at sea,
Forever world’s to conquer,
And dreams to set you free.

Leagues to the East, forever,

Your spirit outward bound,
Life’s squadrons e’er returning
With treasure yet unfound.
Your soul the soul of Nation,
Your heart the heart of Youth,
Remembering our living dead!
Your sword the sword of Truth.
 LOVE O’ MY HEART.
Give me the same old road,
With its old stone walls and vines,
The same old hearth and the same old friends,
And the same old love that never ends;
Stars in the self-same-sky,
And the long lost dreams of bliss,
In the old-time way,
And my gods of clay,
And the same dear lips to kiss.
Give me the slender hands,
Ah yes, give me the tears,
The same old grief,
And the withered leaf,
The largo of the years.
 TO A FRIEND.
You dread my hand when white and cold,
When death has closed my eyes!
Will mine be then forbidding lips
Because the silence lies
So heavily upon your heart?
Ah, passing sad, ’twere so,
Stay, stay your tears and speak to me,
For I shall surely know,
And at the daybreak I shall come
And touch your face in sleep,
And breathe a thought around your soul,
So tenderly, so deep,
Like unto music it shall be,
Though you no sound shall hear,
Yet in your dreaming you will smile,
And know that I am near.
 “AUNT SALLY.”
Born at Plymouth, June 4th, 1795.

O’ I tell you she’s a picter

That no artist couldn’t draw,
As she sets there in the open kitchen door,
With the sunlight streamin’ down
On her quaint old-fashioned gown,
An’ the shadders stretchin’ in across the floor.

An’ the ivy-vines a-twinin’

Lend a sort o’ glory round,
When the listless autumn lights lie on the land,
There she takes her drowsy nap,
With her Bible in her lap,
Like as ef she’s claspin’ heaven by the hand.

There’s a sort o’ blendin’ beauty

’Twixt her cap-rim an’ her face,
An’ the hollyhocks an’ rustlin’ ripened corn,
An’ the crickets chirpin’ there,
On the soft untroubled air,
“It is harvest time, Aunt Sally, summer’s gone.”
 INTIMACY.

I am part of the greening grass,

A part of the stars and sun.
My heart is a part of the falling dew,
The rose and my soul are one.

I shall live in a silver maple

When the winds and the rain are old;
In the sunset light of a winter night
I shall sail in a ship of gold.

For I am a part of a day gone by,

A part of the years to be,
A part of the strife and the joy of life,
And they each are a part of me.
MY MOTHER’S “BIBLE-BOOK.”

Her little old red “Bible-book”

Lies here upon my stand,
So precious are its memories
I keep it close at hand.

Here on the fly-leaf is her name,

Long since ’twas written there,
Long ere she took the wander-road
In Sabbath-deeps of air.

How glad with gladness is the book,

Forever, ever new,
How dear with unforgetting love,
How sad with sadness, too.

The silver clasp is warped and worn,

And buckles with a lurch,
This Holy, Holy “Bible-book”
My mother took to church,

When I, a village six-year-old,

In dainty tier and frill,
Walked close beside, as hand in hand,
We climbed the steep, long hill.

There were no priests in white array,

How simple were the rites,
No lofty arch, no ruby glass,
Beadle nor acolytes,

But glory touched each sacred word,

 Love rippled like a brook,
As we together, side by side,
Read from this “Bible-book.”

Gone with the leaf and summer shine,

And youth, but even so,
How white and stainless is the page,
And O, how long ago

It seems since that immortal day!

But God, there is no smirch
On this—that Holy “Bible-book”
My mother took to church.
 MY FAITH.
I shall be fired with strength for that divine event—
The mightiest of life—
When these inspiring scenes, so beautiful,
Relinquish to that subtle and resistless spell
Which waiteth every man,
And every flower and leaf that grows.
I shall be given courage of a flying star,
The peerless chivalry of convoys of the air;
Half unaware I shall pursue my quest,
Same as a sea-bird mounts,
As light of wing;
The flush of morning in my face,
The flash that baffles minions of the dark,
The power that swung the constellations ’long the upper sky,
Impulse, like music, guiding me,
Song in my soul;
Still knowing I am loved, and love;
The friendly past,
The lifting present mine, as now,
I’ll not distrust,
And Life will not deceive me,
This I know.
 AN APOSTROPHE.

Old Plymouth is a rambling town,

And many leagues of beach there are,
Where echoes still the iron-sleet
And glows the crimson heart of war.

The smoke of battle pressing down

Still lurks where Liberty was bought,
And minute-men come pouring in,
Nor lust of power, or gold they sought.

Clear eyed they stand, of knotty arm,

O God of Fortune, Fate and Crown,
Make sure the bonds of brotherhood
’Twixt this old world and Plymouth-town.
 GLIMMER.
TO EUNICE.

Ever the witch in a school-girl’s eyes,

The toss and the flutter of flaxen hair,
The titter, and blush of a rosy cheek,
Are calling away from a world of care.

Leading the hours with a hop and a skip,

Down through a path where the wind-flowers grow,
White are the ribbons tied under her chin,
White are the ribbons that flutter and blow.

Ever the ring of a roguish laugh,

The swing of a rope, or a bonnet blue,
And a bright little band on a dainty hand,
Where twinkles a stone of a ruby hue,

Are daring me climb to the highest limb,

Or to jump the brook in a wild-fire race,
I’m as free and as light as the tail of a kite,
And I’ve two pouting lips for a resting place.
 A NOCTURNE.
How oft I feast with the dearest ones, now dead,
Or stroll the gardens through at night,
Indifferent to sleep.
’Tis then our footprints turn to gold,
For these are Love’s eternal hours,
That follow me in loneliness;
How often, when the leaves are listening,
I clasp white hands, I do not feel,
More delicate than touch of moonbeams in the grass;
’Tis then the thoughts arise like incense from a silver bowl.
We never hurry through the flowers,
Or miss the color of a dreaming rose,
Nor kiss too long.
But when the careless dawn comes whispering my name,
And seeking in the ashes grey, that once were fire,
We part;
And this is what has made the silences supreme.
 THE INVISIBLE.
The vast unconscious night hangs near and far,
Darkness born of day,
And sorrow born of joy;
But glowing everywhere is the tenderness of God,
Sun, moon and stars, and the living consciousness that I am I,
supreme;
A sense of nearness unto hidden mysteries that overreach the dark,
And claim my spirit as their own.
 ANTIPHONAL.
When I am gone the stones will talk of me,
The elm-trees speak together in the blast, as now,
And weep that I shall never more return;
And, be it that the dust shall grasp the throat of prayer, and strangle
it,
My hands, white-rising from the earth,
Will try again to sweep the lyre of song,
And quench the voice of death above my grave;
The day star in its flight will answer me.