Matthew P. Lungren
Michael R.B. Evans
Editors
Practical
ClinicalMedicine
Clinical
Endocrinology
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Subtitle
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Peter Igaz
Clinical
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Practical Clinical Endocrinology
Peter Igaz
Editor
Practical Clinical
Endocrinology
Editor
Peter Igaz
2nd Department of Internal Medicine,
Faculty of Medicine
Semmelweis University
Budapest, Hungary
ENETS Center of Excellence
Semmelweis University
Budapest, Hungary
Department of Endocrinology,
Department of Internal Medicine and Oncology,
Faculty of Medicine
Semmelweis University
Budapest, Hungary
MTA-SE Molecular Medicine Research Group,
Hungarian Academy of Sciences and Semmelweis University
Budapest, Hungary
ISBN 978-3-030-62010-3 ISBN 978-3-030-62011-0 (eBook)
/>© Springer Nature Switzerland AG 2021
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V
Preface
Endocrinology is a fascinating field of medicine. It is very versatile and
stimulating. Practicing endocrinology promotes our abilities in differential diagnosis and complex thinking.
This book of endocrinology aims to give the reader an overall and
deep presentation of contemporary endocrine practice. In order to
highlight its practical approach, diseases are presented via endocrine
cases where the questions and pitfalls in diagnosis and treatment are
discussed similar to real life experiences. Moreover, an unconventional
question-answer format is used where the most important features of
the diseases are underlined as questions.
As the book focuses on the practice, that is, symptoms, diagnosis, differential diagnosis, and treatment issues related to a wide variety of
endocrine diseases, only minimal theory of endocrinology is included
wherever it aids comprehension. This book is therefore designed for
those who have some basic knowledge in endocrinology.
Practical Clinical Endocrinology is dedicated primarily to adult endocrinology; however, some important endocrine diseases from childhood
that are certainly continued to be treated in adults, for example, congenital adrenal hyperplasia, are also discussed.
The book is comprised of seven parts along the most important
endocrine organs – Part 1: Diseases of the Pituitary and the Hypothalamus; Part 2: Diseases of the Thyroid; Part 3: Diseases of the Parathyroid and Metabolic Bone Diseases; Part 4: Diseases of the Adrenal; Part
5: Diseases of the Gonads; Part 6: Neuroendocrine Tumors and Paraneoplastic Endocrine Syndromes; and Part 7: Multiple Endocrine Neoplasia Syndromes. There are 52 chapters in the book that aim to cover
the most common diseases in endocrinology. Apart from the most
important and most common endocrine diseases, many rare but interesting diseases (e.g., hormone resistance syndromes) are also discussed.
In addition to chronic diseases that constitute the major part of endocrinology, important emergency conditions and complications such as
thyroid storm, adrenal crisis, and the management of hormone-related
electrolyte disturbances are also discussed.
The book contains 117 figures and 107 tables to facilitate understanding.
Who can find this book useful? The book is meant for a broad audience, but first of all to medical residents in training and preparing for a
board exam in internal medicine and/or endocrinology. Moreover, this
book can also be useful for established specialists in endocrinology or
internal medicine to deepen or refresh their knowledge. The book can
also be interesting to university students, most notably the chapters on
common diseases from which exam questions are frequently prepared.
Some questions from the book can even be asked and therefore be interesting both for students and examiners.
VI
Preface
I do really hope that this book represents a novel way of learning and
refreshing our knowledge in endocrinology and the reader will find it
interesting.
Last but not least, I would like to thank all the authors for their devotion to make this book, which I hope was worth the efforts.
Peter Igaz
Budapest, Hungary
2020
VII
Contents
I
Diseases of the Pituitary and Hypothalamus
1
Prolactinoma ����������������������������������������������������������������������������������������������������������������� 3
Beatrix Sármán
2
Acromegaly������������������������������������������������������������������������������������������������������������������� 15
Judit Dénes and Erika Hubina
3
Cushing’s Disease ����������������������������������������������������������������������������������������������������� 25
Sabina Zacharieva and Ivayla Uzunova
4
Non-functioning Pituitary Adenoma��������������������������������������������������������� 35
Sabina Zacharieva and Atanaska Elenkova
5
Craniopharyngioma ����������������������������������������������������������������������������������������������� 49
Réka Kollár and Nikolette Szücs
6
Hypopituitarism��������������������������������������������������������������������������������������������������������� 55
Nikolette Szücs
7
allmann Syndrome (Hypogonadotropic
K
Hypogonadism) ��������������������������������������������������������������������������������������������������������� 65
Nikolette Szücs
8
Hypophysitis����������������������������������������������������������������������������������������������������������������� 71
Sandra Pekic, Dragana Miljic, Marko Stojanovic,
Frédérique Albarel, Jean-Francois Bonneville, and Vera Popovic
9
Diabetes Insipidus ��������������������������������������������������������������������������������������������������� 89
Eleonora Seelig and Jonas Rutishauser
10
yndrome of Inappropriate Antidiuretic
S
Hormone Secretion (SIADH, SIAD) and the
Clinical Management of Hyponatremia��������������������������������������������������� 99
Ivica Lazúrová
VIII
Contents
II
Diseases of the Thyroid
11
Hypothyroidism and Hashimoto’s Thyroiditis�������������������������������������115
Peter Reismann
12
Graves’ Disease and Hyperthyroidism �����������������������������������������������������127
Peter Reismann
13
Thyroid Storm �������������������������������������������������������������������������������������������������������������139
Gabor Laszlo Kovacs
14
Endocrine Orbitopathy�����������������������������������������������������������������������������������������149
Endre V. Nagy
15
Thyroid Nodule and Multinodular Goiter�����������������������������������������������157
Tamas Solymosi
16
Subacute (de Quervain’s) Thyroiditis���������������������������������������������������������171
Peter Reismann
17
Amiodarone-Induced Thyroiditis �����������������������������������������������������������������179
Endre V. Nagy and Miklós Bodor
18
Differentiated Thyroid Cancer�������������������������������������������������������������������������183
Emese Mezősi
19
Medullary Thyroid Cancer ���������������������������������������������������������������������������������195
Géza Nagy
20
Thyroid Hormone Resistance���������������������������������������������������������������������������205
Luca Persani and Irene Campi
21
yper- and Hypothyroidism in Pregnancy,
H
Postpartum Thyroiditis�����������������������������������������������������������������������������������������217
Miklós Bodor
III
Diseases of the Parathyroid and
Metabolic Bone Diseases
22
Primary Hyperparathyroidism �����������������������������������������������������������������������229
Judit Tőke
Contents
23
IX
Hypoparathyroidism ���������������������������������������������������������������������������������������������239
Szilvia Mészáros
24
Osteoporosis�����������������������������������������������������������������������������������������������������������������249
Csaba Horvath
25
Osteomalacia ���������������������������������������������������������������������������������������������������������������261
Csaba Horvath
IV
Diseases of the Adrenal
26
Adrenal Incidentaloma�����������������������������������������������������������������������������������������275
Prerna Dogra and Irina Bancos
27
Adrenal Cushing’s Syndrome���������������������������������������������������������������������������289
Peter Igaz
28
Primary Aldosteronism�����������������������������������������������������������������������������������������297
Teresa Maria Seccia
29
Secondary Aldosteronism ���������������������������������������������������������������������������������309
Károly Pócsai, Csaba Sumánszki, and Judit Tőke
30
Adrenocortical Cancer�������������������������������������������������������������������������������������������319
Massimo Terzolo and Soraya Puglisi
31
ddison’s Disease and Autoimmune Polyendocrine
A
Syndrome Type 2�������������������������������������������������������������������������������������������������������327
Abel Decmann and Peter Igaz
32
Salt Wasting 21-Hydroxylase Deficiency�������������������������������������������������337
Dóra Tưrưk and Judit Tőke
33
Simple Virilizing 21-Hydroxylase Deficiency���������������������������������������345
Dóra Tưrưk and Judit Tőke
34
Late-Onset 21-Hydroxylase Deficiency ���������������������������������������������������353
Peter Igaz
35
17α-Hydroxylase/17, 20-Lyase Deficiency���������������������������������������������359
Peter Igaz
X
Contents
36
Glucocorticoid Resistance ���������������������������������������������������������������������������������367
Nicolas C. Nicolaides and Evangelia Charmandari
37
Pheochromocytoma �����������������������������������������������������������������������������������������������373
Letizia Canu, Giuseppina De Filpo, and Massimo Mannelli
38
Malignant Paraganglioma ���������������������������������������������������������������������������������383
Andrea Uhlyarik and Peter Igaz
V
39
Diseases of the Gonads
Polycystic Ovary Syndrome�������������������������������������������������������������������������������391
Carmen E. Georgescu
40
Turner Syndrome�������������������������������������������������������������������������������������������������������405
Judit Major and Peter Igaz
41
Primary Ovarian Insufficiency�������������������������������������������������������������������������413
Attila Molvarec
42
Klinefelter Syndrome���������������������������������������������������������������������������������������������419
Nikolette Szücs
43
Complete Androgen Insensitivity Syndrome���������������������������������������425
Monika Grymowicz, Ewa Rudnicka, Katarzyna Smolarczyk,
Roman Smolarczyk, Anna Szeliga, Agnieszka Podfigurna,
and Błażej Męczekalski
VI
Neuroendocrine Tumors and
Paraneoplastic Endocrine Syndromes
44
arcinoid Syndrome Caused by a Small Intestinal
C
Neuroendocrine Tumor����������������������������������������������������������������������������������������435
Peter Igaz
45
ctopic ACTH Syndrome Caused by a Bronchial
E
Neuroendocrine Tumor����������������������������������������������������������������������������������������447
Géza Nagy
46
Insulinoma���������������������������������������������������������������������������������������������������������������������459
Gerlies Treiber and Peter Igaz
Contents
47
XI
Factitious Hypoglycemia�������������������������������������������������������������������������������������467
Peter Igaz
48
Gastrinoma �������������������������������������������������������������������������������������������������������������������471
Kira Oleinikov, Arie Ariche, Simona Ben-Haim,
Karine Atlan, and Simona Grozinsky-Glasberg
49
Humoral Hypercalcemia of Malignancy���������������������������������������������������481
Júlia Lohinszky and Andrea Uhlyarik
VII Multiple Endocrine Neoplasia Syndromes
50
Multiple Endocrine Neoplasia Type 1��������������������������������������������������������491
Aleksandra Gilis-Januszewska, Malgorzata Trofimiuk-Müldner,
Anna Skalniak, and Alicja Hubalewska-Dydejczyk
51
Multiple Endocrine Neoplasia Type 2��������������������������������������������������������505
Peter Igaz
52
Von Hippel–Lindau Syndrome �����������������������������������������������������������������������515
Peter Igaz
Supplementary Information
Appendix ��������������������������������������������������������������������������������������������������������������������522
Index������������������������������������������������������������������������������������������������������������������������������525
Contributors
Frédérique Albarel, MD Aix-Marseille Université, Institut National de la
Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical
Genetics (MMG), Marseille, France
Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de
l’hypophyse HYPO, 13005, Marseille, France
Arie Ariche, MD Department of Surgery, Hadassah-Hebrew University Medical
Center, Jerusalem, Israel
Karine Atlan, MD Department of Pathology, Hadassah-Hebrew University
Medical Center, Jerusalem, Israel
Irina Bancos, MD Division of Endocrinology, Diabetes, Metabolism, and
Nutrition, Mayo Clinic, Rochester, MN, USA
Simona Ben-Haim, MD Department of Nuclear Medicine, Hadassah-Hebrew
University Medical Center, Jerusalem, Israel
Institute of Nuclear Medicine, University College Hospitals, NHS Trust,
London, UK
Miklós Bodor, MD, PhD Department of Clinical Pharmacology, University of
Debrecen, Debrecen, Hungary
Division of Endocrinology, Department of Medicine, Faculty of Medicine,
University of Debrecen, Debrecen, Hungary
Jean-Francois Bonneville, MD, PhD Professeur Invité, CHU de Liège14, Chemin des Rochets, Fontain, France
Irene Campi, MD, PhD Department of Endocrine and Metabolic Diseases &
Lab of Endocrine and Metabolic Research, San Luca Hospital, IRCCS Istituto
Auxologico Italiano, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan,
Milan, Italy
Letizia Canu, MD, PhD Department of Experimental and Clinical Biomedical
Sciences, University of Florence, Florence, Italy
Evangelia Charmandari, MD, MSc, PhD, MRCP(UK), CCT(UK) Division of
Endocrinology, Metabolism and Diabetes, First Department of Pediatrics,
National and Kapodistrian University of Athens Medical School ‘Aghia Sophia’
Children’s Hospital, Athens, Greece
Division of Endocrinology and Metabolism, Center of Clinical, Experimental
Surgery and Translational Research, Biomedical Research Foundation of the
Academy of Athens, Athens, Greece
Contributors
XIII
Abel Decmann, MD, PhD 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis
University, Budapest, Hungary
Judit Dénes, MD, PhD 2nd Department of Internal Medicine, Military Hospital
Medical Centre, Budapest, Hungary
Prerna Dogra, MBBS Division of Endocrinology, Diabetes, Metabolism, and
Nutrition, Mayo Clinic, Rochester, MN, USA
Atanaska Elenkova, MD Department of Endocrinology, Faculty of Medicine,
Medical University, Sofia Bulgaria, Sofia, Bulgaria
Expert Center of Rare Endocrine Diseases - Sofia, Sofia, Bulgaria
Giuseppina De Filpo, MD Department of Experimental and Clinical Biomedical
Sciences, University of Florence, Florence, Italy
Carmen E. Georgescu, MD, PhD, Dr habil Department of Endocrinology, Iuliu
Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Endocrinology Clinical Unit, Cluj County Emergency Hospital, Cluj-Napoca,
Romania
Aleksandra Gilis-Januszewska, MD, PhD Department of Endocrinology,
Jagiellonian University, Medical College, Krakow, Poland
Simona Grozinsky-Glasberg, MD Neuroendocrine Tumor Unit, Endocrinology and Metabolism Department, Hadassah-Hebrew University Medical
Center, Jerusalem, Israel
ENETS Center of Excellence, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel
Monika Grymowicz, MD, PhD Department of Gynecological Endocrinology,
Medical University of Warsaw, Faculty of Medicine, Warsaw, Poland
Csaba Horvath, MD, PhD, DSc Department of Internal Medicine and Oncology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
Alicja Hubalewska-Dydejczyk, MD, PhD Department of Endocrinology,
Jagiellonian University, Medical College, Krakow, Poland
Erika Hubina, MD, PhD 2nd Department of Internal Medicine, Military Hospital
Medical Centre, Budapest, Hungary
Peter Igaz, MD, MSc, PhD, DSc 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
ENETS Center of Excellence, Semmelweis University, Budapest, Hungary
XIV
Contributors
Department of Endocrinology, Department of Internal Medicine and Oncology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences
and Semmelweis University, Budapest, Hungary
Réka Kollár, MD 2nd Department of Internal Medicine, Faculty of Medicine,
Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis
University, Budapest, Hungary
Gabor Laszlo Kovacs, MD, PhD 1st Department of Internal Medicine, Flor
Ferenc Hospital, Kistarcsa, Hungary
Ivica Lazúrová, MD, PhD, DSc, FRCP 1st Department of Internal Medicine,
Medical Faculty, P.J. Šafárik University Košice, Košice, Slovakia
Júlia Lohinszky, MD 2nd Department of Internal Medicine, ENETS Center of
Excellence, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Hematology, Faculty of Medicine,
Semmelweis University, Budapest, Hungary
Judit Major, MD 2nd Department of Internal Medicine, Csolnoky Ferenc
County Hospital, Veszprém, Hungary
Massimo Mannelli, MD Department of Experimental and Clinical Biomedical
Sciences, University of Florence, Florence, Italy
Błażej Męczekalski, MD, PhD Department of Gynecological Endocrinology,
Poznan University of Medical Sciences, Faculty of Medicine, Poznan, Poland
Szilvia Mészáros, MD, PhD Department of Internal Medicine and Oncology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
Emese Mezősi, MD PhD Division of Endocrinology and Metabolic Disorders,
1st Department of Internal Medicine, University of Pécs, Pécs, Hungary
Szentagothai Research Centre, University of Pécs, Pécs, Hungary
Dragana Miljic, MD, PhD Medical Faculty, University of Belgrade, Belgrade,
Serbia
Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical
Center of Serbia, Belgrade, Serbia
Contributors
XV
Attila Molvarec, MD, PhD, DSc Department of Obstetrics and Gynecology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
Endre V. Nagy, MD, PhD, DSc Division of Endocrinology, Department of
Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Géza Nagy, MD, PhD 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Hematology, Faculty of Medicine,
Semmelweis University, Budapest, Hungary
Nicolas C. Nicolaides, MD, PhD Division of Endocrinology, Metabolism and
Diabetes, First Department of Pediatrics, National and Kapodistrian University
of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece
Division of Endocrinology and Metabolism, Center of Clinical, Experimental
Surgery and Translational Research, Biomedical Research Foundation of the
Academy of Athens, Athens, Greece
Kira Oleinikov, MD Neuroendocrine Tumor Unit, Endocrinology and
Metabolism Department, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel
ENETS Center of Excellence, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel
Sandra Pekic, MD, PhD Medical Faculty, University of Belgrade, Belgrade, Serbia
Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical
Center of Serbia, Belgrade, Serbia
Luca Persani, MD, PhD Department of Medical Biotechnology & Translational Medicine, University of Milan, Milan, Italy
Department of Endocrine & Metabolic Diseases, IRCCS Istituto Auxologico
Italiano, Milan, Italy
Károly Pócsai, MD, PhD 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis
University, Budapest, Hungary
Agnieszka Podfigurna, MD, PhD Department of Gynecological Endocrinology,
Poznan University of Medical Sciences, Faculty of Medicine, Poznan, Poland
Vera Popovic, MD, PhD, FRCP Medical Faculty, University of Belgrade,
Belgrade, Serbia
XVI
Contributors
Soraya Puglisi, MD Division of Internal Medicine, Department of Clinical
and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano,,
Turin, Italy
Peter Reismann, MD, PhD 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
Department of Endocrinology, Department of Internal Medicine and Oncology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
Ewa Rudnicka, MD, PhD Department of Gynecological Endocrinology, Medical
University of Warsaw, Faculty of Medicine, Warsaw, Poland
Jonas Rutishauser, MD Division of Endocrinology, Diabetes and Metabolism,
University Hospital, Basel, Switzerland
Beatrix Sármán, MD, PhD 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Hematology, Faculty of Medicine,
Semmelweis University, Budapest, Hungary
Teresa Maria Seccia, MD, PhD Department of Internal Medicine – DIMED,
University of Padua, Padova, Italy
Eleonora Seelig, MD Division of Endocrinology, Diabetes and Metabolism,
University Hospital, Basel, Switzerland
Anna Skalniak, PhD, MSc Department of Endocrinology, Jagiellonian University,
Medical College, Krakow, Poland
Katarzyna Smolarczyk, MD, PhD Department of Dermatology and Venerology,
Medical University of Warsaw, Faculty of Medicine, Warsaw, Poland
Roman Smolarczyk, MD, PhD Department of Gynecological Endocrinology,
Medical University of Warsaw, Faculty of Medicine, Warsaw, Poland
Tamas Solymosi, MD, PhD Thyroid Department, Bugát Hospital, Gyöngyös,
Hungary
Marko Stojanovic, MD, PhD Medical Faculty, University of Belgrade,
Belgrade, Serbia
Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical
Center of Serbia, Belgrade, Serbia
Csaba Sumánszki, MD 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
Contributors
XVII
Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis
University, Budapest, Hungary
Anna Szeliga, MD Department of Gynecological Endocrinology, Poznan
University of Medical Sciences, Faculty of Medicine, Poznan, Poland
Nikolette Szücs, MD, PhD 2nd Department of Internal Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
Department of Endocrinology, Department of Internal Medicine and Oncology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
Massimo Terzolo, MD Division of Internal Medicine, Department of Clinical
and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano,
Turin, Italy
Judit Tőke, MD, PhD 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Department of Endocrinology, Department of Internal Medicine and Oncology,
Faculty of Medicine, Semmelweis University, Budapest, Hungary
Dóra Török, MD, PhD 2nd Department of Pediatrics, Faculty of Medicine,
Semmelweis University, Budapest, Hungary
Gerlies Treiber, MD Department of Internal Medicine, Division for Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
Malgorzata Trofimiuk-Müldner, MD, PhD Department of Endocrinology,
Jagiellonian University, Medical College, Krakow, Poland
Andrea Uhlyarik, MD 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
ENETS Center of Excellence, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Ivayla Uzunova, MD Department of Endocrinology, Faculty of Medicine,
Medical University, Sofia, Bulgaria
Expert Centre of Rare Endocrine Diseases, Sofia, Bulgaria
Sabina Zacharieva, MD, PhD, DMedSci Department of Endocrinology, Faculty
of Medicine, Medical University, Sofia, Bulgaria
Expert Center of Rare Endocrine Diseases, Sofia, Bulgaria
About the Editor
Peter Igaz
is full professor of medicine and endocrinology at the
Semmelweis University in Budapest, Hungary. He
began working at the 2nd Department of Internal Medicine in 1997 after finishing his medical studies, where
he cleared board exams in internal medicine, endocrinology, and clinical genetics. Besides his medical degree,
Dr. Igaz has degrees also in molecular biology and law.
From July 2016 till May 2020, he was the director of the
2nd Department of Medicine, since 2017 as full professor. Since May 2020, due to the restructuring of Semmelweis University, he is heading the Department of
Endocrinology at the Department of Internal Medicine
and Oncology.
He was awarded a PhD in 1999 and the Doctor of
Sciences title by the Hungarian Academy of Sciences in
2013. His clinical activity in endocrinology is broad, but
his primary clinical interests are focused on adrenal diseases, neuroendocrine tumors, and multiple endocrine
neoplasia syndromes. Under his leadership, the 2nd
Department of Internal Medicine was awarded the title
of Center of Excellence by ENETS (European Neuroendocrine Tumor Society) in 2019, and Dr. Igaz serves as a
co-head of the center. In research, Dr. Igaz is dealing
mainly with genomics, non-coding RNAs, and microRNAs in endocrine (mostly adrenal) tumors. His research
group was among the first to describe the microRNA
profiles of adrenocortical and adrenomedullary tumors
and they identified novel potential markers for diagnosis. Novel pathogenic pathways were also revealed by the
genomics studies performed by his group. Dr. Igaz has
over 150 scientific papers. Since 2017, he is also heading
the Molecular Medicine Research Group of the Hungarian Academy of Sciences and Semmelweis University.
Dr. Igaz has supervised seven PhD students to date, and
six of them have already been awarded the PhD degree.
Prior to editing this book, he edited two books for
Springer in the Experientia Supplementum Book Series:
Circulating microRNAs in Disease Diagnostics and Their
Biological Relevance (2015) and, together with Prof.
Attila Patócs as co-editor, Genetics of Endocrine Diseases and Syndromes (2019).
XIX
Abbreviations
5-HIAA
5-hydroxyindolacetic acid
17-OH-progesterone
or 17-OHP17-hydroxyprogesterone
21-OHD
21-hydroxylase deficiency
25-OH-D or 25(ΟΗ)D 25 hydroxyvitamin D
AAdrenaline
A/CAldosterone to cortisol ratio in adrenal venous
sampling
AC
Atypical carcinoid
ACC
Adrenocortical cancer
ACEIAngiotensin converting enzyme inhibitor
ACTHAdrenocorticotropic hormone/adrenocorticotropin
ADAndrostenedione
ADH
Antidiuretic hormone
ADHDAttention deficit hyperactivity disorder
AE
Androgen excess
AFC
Antral follicle count
AGEAdvanced glycosylation end products
AI
Adrenal incidentaloma
AIPAryl hydrocarbon receptor interacting protein
AIS
Androgen insensitivity
AMHAnti-Müllerian hormone
APAAldosterone producing adenoma
APSAutoimmune polyendocrine syndrome
AR
Androgen receptor
ARBAngiotensin receptor blocker
ARRAldosterone-to-renin ratio
ASTAndrogen-secreting tumor
ATAAmerican Thyroid Association
AVSAdrenal venous sampling
aTGAnti-thyroglobulin antibody
aTPO or anti-TPOAnti thyroid peroxidase antibody
AVP
Arginine vasopressin
AVSAdrenal venous sampling
AVPR2Arginine vasopressin type 2 receptor
BA
Bilateral adrenalectomy
BAHBilateral adrenal hyperplasia
βHCGHuman chorionic gonadotropin β
BHOB
β-hydroxy-butyrate
BIPSSBilateral inferior petrosal sinus sampling
BMAHBilateral macronodular adrenal hyperplasia
BMD
Bone mineral density
BMI
Body mass index
BWPSBurch-Wartofsky point scale
XX
Abbreviations
CACatecholamine
CaCrCRCreatinine clearance ratio
CAHCongenital adrenal hyperplasia
CAISComplete androgen insensitivity syndrome
CAPTEMCapecitabine-temozolomide
CASClinical activity score (for endocrine orbitopathy)
CaSRCalcium-sensing receptor
CD
Cushing’s disease
CECTContrast-enhanced computed tomography
COCCombined oral contraceptive
CgA
Chromogranin A
CNS
Central nervous system
CPA
Cyproterone acetate
CPMCentral pontine myelinolysis
CRHCorticotropin releasing hormone
CS
Cushing’s syndrome
CSF
Cerebrospinal fluid
CSWSCerebral salt wasting syndrome
CT
Computed tomography
CYP11B1Cortisol synthase gene (11β-hydroxylase type 1)
CYP11B2Aldosterone synthase gene (11β-hydroxylase type 2)
CYP1717α-hydroxylase/17,20 lyase gene
CYP21A221-hydroxylase gene
DADopamine
DDAVPDesmopressin, desamino-8D-arginine vasopressin
DHEADehydroepiandrosterone
DHEAS
Dehydroepiandrosterone sulfate
DI
Diabetes insipidus
DIDMOAD syndromeDiabetes insipidus, diabetes mellitus, optic atrophy,
deafness
DRC
Direct renin concentration
DSD
Disorder of sex development
DST
Dexamethasone suppression test
DT
Doubling time
DTC
Differentiated thyroid cancer
DXA
Dual-energy X-ray absorptiometry
DXMDexamethasone
DxWBS
Diagnostic whole-body scan
E2Estradiol
EBRT
External beam radiation therapy
ECFV
Extracellular fluid volume
ECLEnterochromaffin-like
eGFR
Estimated glomerular filtration rate
ENSATEuropean Network for the Study of Adrenal Tumors
EO
Endocrine orbitopathy
EPM
Extrapontine myelinolysis
ER
Endoplasmic reticulum
ESE
European Society for Endocrinology
Abbreviations
ESR
ETA
ETE
EUS
XXI
Erythrocyte sedimentation rate
European Thyroid Association
extrathyroidal extension
Endoscopic ultrasound
18FDG-PET-CT
18Fluoro-deoxyglucose
FGF-23
FHA
FHH
FIPA
FNA
FNAB
FNAC
FRAX
FSG
FSH
FT
fT4
fT3
FTC
positron emission
computed tomography
Fibroblast growth factor-23
Functional hypothalamic amenorrhea
Familial hypocalciuric hypercalcemia
Familial isolated pituitary adenoma
Fine needle aspiration
Fine needle aspiration biopsy
Fine needle aspiration cytology
Fracture risk assessment tool
Fasting serum gastrin
Follicle stimulating hormone
Free testosterone
Free T4
Free T3
Follicular thyroid cancer
GD
Graves’ disease
GDM
Gestational diabetes mellitus
GERD
Gastroesophageal reflux disease
GFR
Glomerular filtration rate
GH
Growth hormone
GHRH
Growth-hormone-releasing hormone
GIGastrointestinal
GLP-1
Glucagon-like peptide 1
GnRH
Gonadotropin-releasing hormone
GRS
Glucocorticoid resistance syndrome
HCGHuman chorionic gonadotropin (=human chorionic
gonadotropin β)
hGR
Human glucocorticoid receptor
HDDST
High-dose dexamethasone suppression test
HEENT
Head, eyes, ears, nose, and throat examination
HHM
Humoral hypercalcemia of malignancy
HNPGL
Head and neck paragangliomas
HOMA-indexHomeostasis model assessment of insulin resistance
HPA
Hypothalamus–pituitary–adrenal axis
HPT-JT
Hyperparathyroidism-jaw tumor syndrome
HRT
Hormone replacement therapy
HSD11B211β-hydroxysteroid dehydrogenase type 2
HU
Hounsfield unit
ICSI
Intracytoplasmatic sperm injection
ICTPCarboxy-terminal telopeptide of type I collagen
IFNInterferon
IGF-1
Insulin-like growth factor 1
XXII
Abbreviations
IL-6Interleukin-6
IMRT
Intensity-modulated radiotherapy
ITT
Insulin tolerance test
IU
International unit
LBW
LH
LOH
Low-birth weight
Luteinizing hormone
Local osteolytic hypercalcemia
MACS
Mild autonomous cortisol secretion
MAH
Malignancy-associated hypercalcemia
MAIS
Mild androgen insensitivity
MEN
Multiple endocrine neoplasia
MIBIMethoxyisobutylisonitrile
MNMetanephrine
MRHEMineralocorticoid responsible hyponatremia
in the elderly
MRI
Magnetic resonance imaging
MRKH syndrome Mayer-Rokitansky-Küster-Hauser syndrome
mTOR
Mechanistic target of rapamycin
MTC
Medullary thyroid cancer
NANoradrenaline
NAFLD
Non-alcoholic fatty liver disease
NCAHNon-classical CAH (congenital adrenal hyperplasia)
NEN
Neuroendocrine neoplasm
NET
Neuroendocrine tumor
NFPA
Non-functional pituitary adenoma
NMNNormetanephrine
NSAID
Non-steroidal anti-inflammatory drug
NSE
Neuron specific enolase
OC
ODS
OGTT
Oral contraceptive
Osmotic demyelination syndrome
Oral glucose tolerance test
PA
Primary aldosteronism
PAC
Plasma aldosterone concentration
PAI
Primary adrenal insufficiency
PAIS
Partial androgen insensitivity
PC
Pulmonary carcinoid
PCOM
Polycystic ovary morphology
PCOS
Polycystic ovary syndrome
PEI
Percutaneous ethanol sclerotherapy
PET-CTPositron emission tomography – computed tomography
PFS
Progression-free survival
PGGRPrimary generalized glucocorticoid resistance
PHPTPrimary hyperparathyroidism
POI
Primary ovarian insufficiency
POsm
Plasma osmolality
Abbreviations
PPGLPheochromocytoma/paraganglioma
PPI
Proton pump inhibitor
PPNADPrimary pigmented nodular adrenal hyperplasia
PPT
Postpartum thyroiditis
PRA
Plasma renin activity
PRRT
Peptide receptor radionuclide therapy
PRLProlactin
PTC
Papillary thyroid cancer
PTH
Parathyroid hormone
PTHrP
Parathyroid hormone-related protein
PTUPropylthiouracil
RAAS
Renin-angiotensin-aldosterone system
RAIRadioiodine
RAIT
Radioiodine therapy
RANKLReceptor activator of nuclear factor kappa-beta ligand
RECIST
Response evaluation criteria in solid tumors
REE
Resting energy expenditure
RFA
Radiofrequency ablation
rhTSH
Recombinant human TSH
RTRadiotherapy
rT3
Reverse triiodothyronine
RTH
Thyroid hormone resistance
SACT
Selective arterial calcium stimulation
SAI
Secondary adrenal insufficiency
SCLC
Small cell lung cancer
SERM
Selective estrogen receptor modulators
SGLT2
Sodium-glucose cotransporter 2
SHBG
Sex hormone binding globulin
SIAD
Syndrome of inappropriate antidiuresis
SIADH
Syndrome of inappropriate ADH secretion
SIRT
Selective internal radiation therapy
SNA+
Serum Na+ concentration
SPECT-CT
Single photon emission computed tomography
SRI
Somatostatin receptor imaging
SRS
Stereotactic radiosurgery
SRY
Sex determining region of chromosome Y
SSA
Somatostatin analogue
SSIR
Severe insulin resistant syndromes
SSTR
Somatostatin receptor
SV-CAH
Simple virilizing form of congenital adrenal hyperplasia
SW-CAH
Salt-wasting form of congenital adrenal hyperplasia
SWS
Salt-wasting syndrome
TTestosterone
T2D
Type 2 diabetes mellitus
T3Triiodothyronine
T4Thyroxine
XXIII
XXIV
Abbreviations
TACE
Transarterial chemoembolization
TART
Testicular adrenal rest tissue
TESE
Testicular extraction of sperm
TBG
Thyroid binding globulin
TC
Typical carcinoid
TFT
Thyroid hormone function test
TgThyroglobulin
TgAb
Anti-thyroglobulin antibody
TGT
Transient gestational thyrotoxicosis
TH
Thyroid hormone
TIRADS
Thyroid imaging reporting and data systems
TIH
Thiazide-induced hyponatremia
TKI
Tyrosine kinase inhibitor
TN
Thyroid nodule
TNM
Tumors nodes metastases
TRAb
TSH (thyrotropin) receptor antibody
TRα
Thyroid hormone receptor alpha
TRβ
Thyroid hormone receptor beta
TRH
Thyrotropin releasing hormone
TRIAC
Triiodothyroacetic acid
TSA
Transsphenoidal adenomectomy
TSH
Thyroid stimulating hormone (thyrotropin)
TSH-oma TSH-secreting pituitary adenomas
TSS
Transsphenoidal surgery
TT
Total testosterone
UFC
Urinary free cortisol
ULN
Upper limit of normal
UNa+
Urine sodium concentration
UOsm
Urine usmolality
USUltrasound
VHL
VIP
VTE
VUS
Von Hippel-Lindau syndrome
Vasoactive intestinal peptide
Venous thromboembolism
Variant of unknown/uncertain significance
WBS
Whole body scan
XGH
Xanthogranulomatous hypophysitis
ZES
Zollinger-Ellison syndrome
1
Diseases of the
Pituitary and
Hypothalamus
The pituitary gland is the master regulator of the endocrine system.
The anterior lobe of the pituitary secretes prolactin, growth
hormone, and several other very important hormones that regulate
major endocrine organs such as the thyroid, adrenal glands, and the
gonads. The thyroid, adrenal cortex, and gonads are not capable of
hormone secretion on their own, as the stimulating hormones from
the pituitary are essential for their functioning. The pituitary,
however, is not autonomous either since various factors from the
hypothalamus regulate hormone secretion from the anterior
pituitary. The regulatory axes for the thyroid, adrenal cortex, and
gonads thus include three components, for example, hypothalamic-
pituitary-
thyroid or hypothalamic-pituitary-adrenal axes. These
axes involve negative feedback regulation, that is, the product of
the peripheral hormone-producing organ (e.g., cortisol from the
adrenal cortex) inhibits the secretion of the respective stimulating
hormones from the hypothalamus (corticotropin releasing
hormone) and pituitary (adrenocorticotropic hormone).
In contrast to the anterior lobe, the posterior lobe of the pituitary does
not produce hormones on its own, but stores the hormones produced
by hypothalamic nuclei (antidiuretic hormone and oxytocin).
Based on the three-level regulation of the hypothalamic-pituitary-
thyroid/adrenal/gonad axes, hormone deficiency due to the
disease of the peripheral hormone-producing organs (thyroid,
adrenal cortex, or gonads) is termed primary insufficiency, whereas
pituitary and hypothalamic insufficiency are termed secondary
and tertiary, respectively.
In this part of the book, the major diseases of the pituitary and
hypothalamus are discussed. The first chapters (7 Chaps. 1, 2, 3, 4,
and 5) present diseases associated with pituitary tumors (and
I