Endocrine Neoplasia (eBook)

Sturgeon_Frontmatter.pdf 1
Anchor 1 4
Anchor 2 7
Sturgeon_Part1.pdf 10
Sturgeon_Ch01.pdf 11
Chapter 1 11
The Biology of Thyroid Oncogenesis 11
Introduction 11
Common Genetic Alterations 12
BRAF 13
RET/PTC 15
RAS 16
TRK 17
PAX8/PPARg 17
P53 17
Epigenetic Mechanisms 17
DNA Methylation 18
Other Epigenetic Mechanisms 19
Role of Stem Cells in Thyroid Cancer 20
Clinical Applications 21
Improvements in FNA Cytology-Based Diagnoses 21
Novel Targeted Therapies 22
Kinase Inhibitors 22
PPARg Agonists 23
Epigenetic Modulators 23
Conclusion 24
References 24
Sturgeon_Ch02.pdf 30
Chapter 2 30
Evaluation of the Thyroid Nodule 30
Epidemiology 30
Diagnostic Evaluation 31
Risk Factor Assessment 31
Physical Examination 32
Laryngoscopy 32
Diagnostic Tests 33
Imaging 33
Laboratory Studies 34
Fine Needle Aspiration Biopsy 35
Management of Asymptomatic Thyroid Nodules 35
Management of Symptomatic Thyroid Nodules 38
Summary 39
References 39
Sturgeon_Ch03.pdf 42
Chapter 3 42
Differentiated Thyroid Cancers of Follicular Cell Origin 42
Genetics of Differentiated Thyroid Cancer 42
Biology of Differentiated Thyroid Cancer 45
Treatment of Differentiated Thyroid Cancer 47
TSH Suppression 53
Surveillance 53
Long-Term Outcomes 55
Recurrent/Persistent Disease 55
Distant Metastasis 56
References 57
Sturgeon_Ch04.pdf 64
Chapter 4 64
Sporadic Medullary Thyroid Cancer 64
Introduction 64
Diagnosis 65
Biochemical Markers in Medullary Thyroid Cancer 65
Screening for Familial Disease 66
Staging 67
Treatment 67
Surgical Treatment of Primary Tumors 67
Persistent or Recurrent Medullary Thyroid Cancer 73
Adjuvant Treatment for Medullary Thyroid Cancer 74
Prognosis 76
Conclusion 76
References 77
Sturgeon_Ch05.pdf 82
Chapter 5 82
Anaplastic Thyroid Cancer 82
Recent Patient Presentation 82
Patient 1 82
Patient 2 84
Definition/Introduction 85
Pathology/Etiology 85
Molecular Biology 85
Clinical Presentation 86
Diagnosis 86
Treatment 87
Surgery 87
Radiotherapy 87
Chemotherapy 88
Combination Therapy 88
Clinical Trials and Novel Therapies 88
Clinical Trials 88
Novel Therapies 88
Treatment Recommendations 89
Summary 89
References 90
Sturgeon_Part2.pdf 92
Sturgeon_Ch06.pdf 93
Chapter 6 93
Primary Hyperparathyroidism 93
Introduction 93
Epidemiology 93
Differential Diagnosis and Clinical Presentation 94
Differential Diagnosis 94
Clinical Presentation 95
Parathyroid Localization Studies 96
Nuclear Imaging 96
Ultrasound 96
Intraoperative Adjuncts 97
Radioguided Surgery 97
Intraoperative PTH Monitoring 98
Bilateral Internal Jugular Venous Sampling 99
Principles of Management 99
Medical Management 100
Surgical Management 101
Risks and Benefits of Parathyroidectomy 103
Benefits 103
Risks 104
Management of Persistent/Recurrent PHPT 105
Summary 105
References 106
Sturgeon_Ch07.pdf 110
Chapter 7 110
Parathyromatosis and Parathyroid Cancer 110
Introduction 110
Demographics 110
Clinical Presentation 111
Preoperative Localization Studies 112
Pathology 113
Management: Operative 115
Management: Calcium-Lowering Medications/Chemotherapy/Radiation 116
Prognosis/Outcomes 118
Parathyromatosis 119
References 120
Sturgeon_Part3.pdf 122
Sturgeon_Ch08.pdf 123
Chapter 8 123
Incidentaloma 123
Introduction 123
Embryology of the Adrenal Glands 123
Prevalence 125
Biochemical Evaluation 125
Pheochromocytoma 125
Cushing’s 127
Biochemical Evaluation 127
Serum Cortisol Levels 127
Dexamethasone Suppression Test 128
Urinary Free Cortisol Levels 128
Late Night Salivary Cortisol Level 128
Aldosteronoma 129
Radiographic Evaluation 130
CT Scan 131
MRI 132
PET Scan 132
Operative Approach 133
Natural History and Long-Term Follow Up 133
Patients with a History of Cancer 134
References 135
Sturgeon_Ch09.pdf 139
Chapter 9 139
Pheochromocytoma and Paraganglioma 139
Introduction 139
Nomenclature 139
Epidemiology 140
Embryology 141
Anatomy 141
Pathology 142
Catecholamine Synthesis and Metabolism 142
Clinical Presentation 144
Classic 144
Pheochromocytoma (Adrenergic) Crisis 145
Pediatric 145
Familial 146
Malignant Disease 146
Definition 146
Clinical Features 147
Pathology 147
Prognosis 147
Approach to Diagnosis 148
Biochemical Evaluation 148
Tumor Localization 149
Treatment of Pheochromocytoma 150
Medical Preparation for Surgery 150
Operative Approach 151
Postoperative Management 152
Treatment Options for Malignant Disease 152
Pheochromocytoma/Paraganglioma Syndromes 153
Von Hippel–Lindau Syndrome 153
Multiple Endocrine Neoplasia Type 2 156
Neurofibromatosis Type 1 156
Familial Pheochromocytoma/Paraganglioma Syndromes 157
Carney Triad 157
Genetic Testing 158
Pathogenesis 158
Genetic Mechanisms of Tumorigenesis 158
Succinate Dehydrogenase 159
HIF and EglN3/PHD Pathways 159
Conclusion 160
References 161
Sturgeon_Ch10.pdf 167
Chapter 10 167
Functional Cortical Neoplasms 167
Introduction 167
Primary Hyperaldosteronism and Aldosteronoma 168
Symptoms and Signs 169
Laboratory Studies 169
Pathology 172
Radiologic Studies 172
Treatment 175
Cushing’s Syndrome and Cortisol Producing Adrenal Tumors 177
Symptoms and Signs 179
Laboratory Studies 179
Radiologic Studies 182
Treatment 183
Virilizing and Feminizing Adrenal Tumors 184
Diagnostic Tests 185
Treatment 186
References 186
Sturgeon_Ch11.pdf 191
Chapter 11 191
Adrenocortical Carcinoma 191
Introduction 191
Clinical Aspects of ACC 191
Epidemiology 191
Presentation 192
Diagnosis 192
Staging 192
Treatment 193
Surgical Resection 193
Mitotane 193
Chemotherapy 194
Radiotherapy 194
Prognosis 194
Molecular Aspects of Adrenocortical Carcinomas 195
Hereditary Tumor Syndromes 195
Genes Associated with Sporadic Adrenocortical Tumors 195
TP53 Gene 195
IGF2 Genes 196
Menin Gene 197
CYP21B Gene 197
PRKAR1A Gene 198
Guanine Nucleotide-Binding Protein, Alpha-Stimulating Activity Polypeptide (GNAS) Gene 198
Signaling Pathways in Adrenocortical Tumors 198
ACTH/cAMP/PKA Pathway 199
Wnt Pathway 200
Crosstalk Between cAMP and Wnt/b.-Catenin Pathways 201
Clonal Analysis of Adrenocortical Tumors 202
Comparative Genomic Hybridization Analysis 202
Loss of Heterozygosity Analysis 202
Microarray Gene Expression Profiling Studies 203
Molecular Markers in the Diagnosis of Adrenocortical Tumors 204
Molecular Markers in the Prognosis of Adrenocortical Carcinomas 207
Conclusion 207
References 208
Sturgeon_Part4.pdf 215
Sturgeon_Ch12.pdf 216
Chapter 12 216
Gastrinoma 216
Introduction 216
Historical Aspects 216
Pathophysiology 217
Genetic Basis 217
Clinical Features and Diagnosis 218
Site and Localization of Primary Tumors 220
Metastatic Disease 223
Management and Operative Strategy 223
Management of Advanced and Metastatic Disease 226
Management of Gastrinoma in Patients with MEN1 229
Summary 231
References 232
Sturgeon_Ch13.pdf 237
Chapter 13 237
Insulinoma 237
History 238
Physiology 238
Epidemiology 239
Clinical Presentation 239
Diagnostic Evaluation 241
Biochemical Testing 241
Noninsulinoma Pancreatogenous Hyperinsulinemia Syndrome 242
Localization 242
Computed Tomography (CT scan) 243
Transabdominal Ultrasound 244
Endoscopic Ultrasound (EUS) 244
Arteriography with Selective Arterial Calcium Stimulation (SACS) 246
Intraoperative Ultrasound (IOUS) 246
Nuclear Imaging 246
Magnetic Resonance Imaging (MRI) 247
Management 248
Perioperative care 248
Surgical Treatment 249
Open Approach 249
Laparoscopic Approach 250
Special Consideration: MEN 1 250
Postoperative care 251
Complications 251
Follow-up 252
Malignant Disease 252
References 253
Sturgeon_Ch14.pdf 255
Chapter 14 255
Rare Neuroendocrine Tumors of the Pancreas 255
Presentation 256
VIPoma 258
Glucagonoma 259
Somatostatinoma 261
PPoma and Non-functioning Neuroendocrine Tumor 262
Diagnosis 263
Operative Management 264
Liver-Directed Therapies 265
Nonoperative Management 266
Prognosis 267
Summary 267
References 268
Sturgeon_Part5.pdf 273
Sturgeon_Ch15.pdf 274
Chapter 15 274
The Menin Gene 274
Introduction 274
The MEN-1 Gene 274
History and Cloning 274
MEN-1 Mutations: Germline Vs. Somatic 275
Transcriptional Regulation of the MEN-1 gene 276
Gene Expression 277
The Menin Protein 277
Interactions with Transcriptional Regulators 277
Interactions with Proteins to Regulate Genome Stability, Cell Cycle and Division 279
Menin Target Genes 279
Animal Models of MEN-1 Tumorigenesis 280
Men-1 Knockout Mice 280
Conditional Inactivation of Men-1 282
Prospects and Future Directions 283
References 283
Sturgeon_Ch16.pdf 288
Chapter 16 288
Multiple Endocrine Neoplasia Type 1: Clinical Manifestations and Management 288
Introduction 288
Parathyroid Disease 289
Enteropancreatic Disease 292
Gastrinoma/ZES 293
Insulinoma 295
Pituitary Disease 297
Other manifestations of MEN-1 298
Conclusion 299
References 299
Sturgeon_Ch17.pdf 304
Chapter 17 304
The RET Protooncogene 304
The RET Protooncogene 304
Normal Structure and Function of RET 304
Abnormal RET Activation in MEN-2 Syndromes 307
Genotype-Phenotype Correlations in MEN-2 Syndromes 308
MEN-2B and Alterations in the Kinase Domain 310
MEN-2A, FMTC, and Mutations in the Cysteine-Rich Region 311
Other Mutations 312
RET Mutations in Sporadic Thyroid Carcinomas 312
Targeting RET in Chemotherapeutics 314
Conclusions 314
References 314
Sturgeon_Ch18.pdf 321
Chapter 18 321
Multiple Endocrine Neoplasia Type 2: Clinical Manifestations and Management 321
Clinical Features of MEN-2 Syndromes 321
MEN-2A 321
FMTC 324
MEN-2B 324
Screening for MEN-2 and the Impact of RET Mutation Testing 325
Hereditary Medullary Thyroid Carcinoma 326
Preventive Surgery 327
Surgical Management of MTC in Adults with MEN-2 Syndromes 329
Postoperative Surveillance and Long-Term Management 330
Pheochromocytoma 331
Primary Hyperparathyroidism 332
Conclusions 333
References 333
Sturgeon_Backmatter.pdf 338