Endocrine Surgery Comprehensive Board Exam Guide

Preface
Acknowledgments
Contents
Contributors
Abbreviations
I: Thyroid
	1: Thyroid Gland: Anatomy, Physiology, Pathophysiology, and Ultrasonography
		Case Presentation:
		1.1	 Thyroid Physiology
			1.1.1	 Thyroid Cellular Physiology
		1.2	 Hypothalamic-Pituitary-Thyroid Axis
		1.3	 Thyroid Function Testing
			1.3.1	 Serum TSH
			1.3.2	 Total Thyroid Hormone
			1.3.3	 Serum Free T4 and Free T3
			1.3.4	 Serum Thyroid Autoantibodies
			1.3.5	 Serum Thyroglobulin
			1.3.6	 Hypothyroidism
			1.3.7	 Hyperthyroidism
		1.4	 Thyroid Anatomy
			1.4.1	 Blood Supply and Lymphatics
		1.5	 Surgical Thyroid Anatomy
			1.5.1	 External Branch of the Superior Laryngeal Nerve
			1.5.2	 Recurrent Laryngeal Nerve
			1.5.3	 Parathyroid Glands
		1.6	 Ultrasonography of the Thyroid Gland
		References
	2: Non-toxic Thyroid Nodules and Multinodular Goitre
		Case Presentation
		2.1	 Introduction
		2.2	 Clinical Presentation
		2.3	 Natural History
		2.4	 Aetiology
		2.5	 Pathogenesis
		2.6	 Diagnosis
		2.7	 Clinical Examination
		2.8	 Thyroid Function Tests
			2.8.1	 Thyroid Ultrasound
			2.8.2	 Fine-Needle Aspiration Biopsy (FNAB)
			2.8.3	 Precision Medicine
			2.8.4	 Cross-Sectional Scans
			2.8.5	 Laryngeal Examination
		2.9	 Management
			2.9.1	 Conservative
		2.10	 Non-surgical (Means to Debulk the Thyroid)
			2.10.1	 Radio-iodine Therapy
			2.10.2	 Thermal Ablation
		2.11	 Surgical
			2.11.1	 Thyroid Surgery
			2.11.2	 Hemithyroidectomy
			2.11.3	 Subtotal Thyroidectomy or Total Thyroidectomy
			2.11.4	 Retrosternal Goitre
			2.11.5	 Video-Assisted Thoracoscopic Thyroidectomy
			2.11.6	 Transoral Thyroidectomy
		References
	3: Graves’ Disease and Toxic Nodular Goiter (Plummer’s Disease)
		Case Presentation
		3.1	 Introduction
			3.1.1	 Clinical Presentation of Hyperthyroidism
			Box 3.1 Symptoms and Manifestations of Hyperthyroidism
			Box 3.2 Signs of Hyperthyroidism
			3.1.2	 Natural History of Hyperthyroidism
			3.1.3	 Diagnosis of Hyperthyroidism
			3.1.4	 Treatment of Hyperthyroidism
				3.1.4.1	 Antithyroid Drugs
				3.1.4.2	 Radioactive Iodine (RAI)
			3.1.5	 Indications for Surgery in Hyperthyroidism
			3.1.6	 Prognosis in Hyperthyroidism
		3.2	 Graves’ Disease
			3.2.1	 Pathogenesis
			3.2.2	 Epidemiology
			3.2.3	 Clinical Presentation
			3.2.4	 Diagnosis
			3.2.5	 Treatment
				3.2.5.1	 Antithyroid Drugs
				Box 3.3 Manifestation of the Ineffectiveness of  Pharmacotherapy in GD
				3.2.5.2	 Radioactive Iodine (RAI)
			3.2.6	 Indications for Surgery and Surgical Details
			3.2.7	 Prognosis
		3.3	 Toxic Multinodular Goiter (Plummer’s Disease)
			3.3.1	 Pathogenesis
			3.3.2	 Epidemiology
			3.3.3	 Clinical Presentation
			3.3.4	 Diagnosis
			3.3.5	 Treatment
				3.3.5.1	 Radioactive Iodine (RAI)
			3.3.6	 Indications for Surgery and Surgical Details
			3.3.7	 Prognosis
		References
	4: Diagnosis and Management of Thyroiditis: Hashimoto, de Quervain, Riedel
		Case Presentation
		4.1	 Introduction
		4.2	 Clinical Presentation and Diagnosis
			4.2.1	 Hashimoto’s Thyroiditis
			4.2.2	 de Quervain’s Thyroiditis
			4.2.3	 Riedel’s Thyroiditis
		4.3	 Treatment
			4.3.1	 Hashimoto’s Thyroiditis
			4.3.2	 de Quervain’s Thyroiditis
			4.3.3	 Riedel’s Thyroiditis
		4.4	 Surgical Indications and Outcomes
			4.4.1	 Hashimoto’s Thyroiditis
			4.4.2	 de Quervain’s Thyroiditis
			4.4.3	 Riedel’s Thyroiditis
		4.5	 Association with Malignancy
		References
	5: Papillary Thyroid Carcinoma
		Case Presentation
		5.1	 Introduction
		5.2	 Clinical Presentation
		5.3	 Natural History
		5.4	 Diagnosis
		5.5	 Risk Stratification and Treatment
		5.6	 Follow-Up
		5.7	 Outcomes
		References
	6: Follicular Thyroid Cancer
		Case
		6.1	 Introduction
		6.2	 Definition
		6.3	 Epidemiology
		6.4	 Clinical Presentation
		6.5	 Molecular Pathogenesis
		6.6	 Diagnosis
		6.7	 Staging and Prognostic Features
		6.8	 Treatment
		6.9	 Recurrence
		6.10	 Summary and Conclusion
		References
	7: Hürthle Cell Carcinoma
		Case Presentation
		7.1	 Introduction
		7.2	 Clinical Presentation
		7.3	 Natural History
		7.4	 Diagnosis
		7.5	 Treatment
		7.6	 Surgical Details
		7.7	 Outcomes or Prognosis
		References
	8: Medullary Thyroid Carcinoma: Diagnosis and Treatment of Sporadic and Hereditary Tumors
		Cases
			Case 1
			Case 2
			Case 3
			Case 4
			Case 5
		8.1	 Introduction
		8.2	 Clinical Presentation
		8.3	 Ultrasonography
		8.4	 FNAB
		8.5	 FNAB and Evaluation of Ct in the Fine-Needle Aspirate
		8.6	 Carcinoembryonic Antigen
		8.7	 Procalcitonin
		8.8	 Ct
		8.9	 Interpretation of bCt Levels
		8.10	 Surgery
		8.11	 Clinically Occult MTC – “Mildly” Elevated bCt Levels
		8.12	 Biochemically and Clinically Apparent MTC – “Highly” Elevated bCt Levels
		8.13	 Surgical Strategy – Central Neck
		8.14	 Surgical Strategy – Lateral Neck
		8.15	 Locally Advanced MTC and Distant Metastasis
		8.16	 Special Situations
		8.17	 TNM Classification and Staging
		8.18	 Hereditary MTC
		8.19	 MEN 2A
		8.20	 MEN 2B
		8.21	 Prognosis and Postoperative Follow-Up
		8.22	 Unresectable, Progressive, and Symptomatic Sporadic and Hereditary MTC
		References
	9: Anaplastic Thyroid Carcinoma, Thyroid Lymphoma, and Metastases
		Case Presentation
		9.1	 Introduction
		9.2	 Clinical Presentation
		9.3	 Diagnosis
		9.4	 Treatment
		9.5	 Indications for Surgery and Surgical Details
		9.6	 Prognosis
		References
	10: Surgical Procedures. Thyroidectomy: Indications, Flexible Laryngoscopy, Operative Techniques, Recurrent Laryngeal Nerve Monitoring, and Management of Complications
		10.1	 Introduction
		10.2	 Indications for Thyroidectomy
		10.3	 Flexible Laryngoscopy
		10.4	 Operative Description and Technique
			10.4.1	 Airway and Anesthesia
			10.4.2	 Positioning (. Fig. 10.4)
			10.4.3	 Incision (. Fig. 10.5)
			10.4.4	 Creation of a Working Space to Remove the Thyroid Gland (. Fig. 10.6)
			10.4.5	 Exposure of the Thyroid Lobe
			10.4.6	 Exposure, Ligation, and Division of the Superior Pole Vessels
			10.4.7	 Identification and Preservation of the Recurrent Laryngeal Nerve (. Fig. 10.7)
			10.4.8	 Division of the Inferior Pole Vessels
			10.4.9	 Preservation of the Parathyroid Glands
			10.4.10	 Separation of the Thyroid Lobe from the Recurrent Laryngeal Nerve
			10.4.11	 Removal of the Thyroid Lobe and Isthmus
			10.4.12	 Closure
		10.5	 Intraoperative Neuromonitoring (IONM)
		10.6	 Postoperative Care
			10.6.1	 General Instructions
			10.6.2	 Duration of Observation
			10.6.3	 Pain Management
			10.6.4	 Calcium Monitoring and Supplementation
			10.6.5	 Thyroid Hormone Replacement
				10.6.5.1	 After Total Thyroidectomy
				10.6.5.2	 After Thyroid Lobectomy
		10.7	 Management of Complications
			10.7.1	 Neck Hematoma
			10.7.2	 Recurrent Laryngeal Nerve Injury
			10.7.3	 Hypocalcemia and Hypoparathyroidism
		References
	11: Neck Dissection: Indications, Extension, Operative Technique
		Case Presentation
		11.1	 Introduction
		11.2	 Applied Anatomy
			11.2.1	 Standardized Terminology in Neck Dissection
			11.2.2	 Levels of Cervical Lymph Nodes
		11.3	 Classification of Neck Dissections
		11.4	 Central Neck Dissection: Indications and Extension
			11.4.1	 Lateral Neck Dissection: Indications and Extension
		11.5	 Operative Procedure
			11.5.1	 Planning the Surgical Procedure
			11.5.2	 Intraoperative Surgical Adjuncts
			11.5.3	 Surgical Technique
				11.5.3.1	 Patient’s Preparation and Positioning
				11.5.3.2	 Skin Incision and Flap Elevation
				11.5.3.3	 Selective Lateral Neck Dissection: Levels II–Vb
				11.5.3.4	 Central Neck Dissection (Level VI–VII)
			11.5.4	 Alternate Operative Approaches (Minimally Invasive, Remote Access, and Radio-Guided Procedures)
			11.5.5	 Knowing and Avoiding Complications of ND
		References
II: Parathyroid
	12: Parathyroid Glands: Anatomy, Physiology, Pathophysiology, and Ultrasound
		12.1	 Introduction
		12.2	 Parathyroid Anatomy
			12.2.1	 Embryologic Development
			12.2.2	 Normal Parathyroid Gland Anatomy
			12.2.3	 Ectopic Parathyroid Gland Anatomy
			12.2.4	 Supernumerary Glands
		12.3	 Parathyroid Physiology
		12.4	 Parathyroid Pathophysiology
			12.4.1	 Hyperparathyroidism
				12.4.1.1	 Primary Hyperparathyroidism
				12.4.1.2	 Secondary and Tertiary Hyperparathyroidism
			12.4.2	 Hypoparathyroidism
		12.5	 Parathyroid Ultrasound
		References
	13: Diagnosis and Surgical Management of Primary Hyperparathyroidism
		Case Presentation
		13.1	 Introduction
		13.2	 Diagnosis of PHPT
		13.3	 Indications for Surgical Treatment of PHPT
		13.4	 Preoperative Radiological Studies and Surgical Treatment of PHPT
		13.5	 Preoperative Management
		13.6	 Intraoperative PTH Monitoring
		13.7	 Surgical Approach
		13.8	 PHPT During Pregnancy
		13.9	 Location of Ectopic Parathyroid Glands
		13.10	 Prediction and Treatment of Postoperative Hypocalcemia
		13.11	 Postoperative Follow-Up
		13.12	 Long-Term Effect of Parathyroidectomy in Patients with PHPT
		References
	14: Renal Hyperparathyroidism
		Case
		14.1	 Introduction
		14.2	 Clinical Presentation
			Box 14.1 Some signs and symptoms in rHPT (Adapted from Pasieka et al. [118])
		14.3	 Natural History
			14.3.1	 Chronic Kidney Disease (CKD)
			14.3.2	 FGF23, Klotho
			14.3.3	 Phosphate Retention
			14.3.4	 Vitamin D and Calcium
			14.3.5	 Parathyroid Gland Hyperplasia
			14.3.6	 Tertiary Hyperparathyroidism
		14.4	 Diagnosis
		14.5	 Non-surgical Treatment
			14.5.1	 Medical
				14.5.1.1	 Vitamin D
				14.5.1.2	 Control of Calcium and Phosphate
					Restriction of Dietary Intake
					Treatment with Phosphate Binders
					Active Vitamin D Analogs
					Calcimimetics
			14.5.2	 Renal Transplantation
		14.6	 Surgical Treatment: Parathyroidectomy
			14.6.1	 Indications
				14.6.1.1	 Is There an Absolute Threshold of PTH When PTX Is Indicated?
				14.6.1.2	 Are There Other Specific, Absolute Indications for PTX, Apart from PTH Levels?
				14.6.1.3	 Should PTX Be Performed Before or After Renal Transplantation?
				14.6.1.4	 What, Exactly, Constitutes “Medical Failure”?
			Box 14.2 Indications for operation in renal hyperparathyroidism
			14.6.2	 Surgical Technique
				14.6.2.1	 Intraoperative Measurement of Parathyroid Hormone (ioPTH)
				14.6.2.2	 Preoperative Localization
				14.6.2.3	 Intraoperative Angiography
				14.6.2.4	 Surgical Complications
				14.6.2.5	 Postoperative Management
		14.7	 Outcomes and Prognosis
		References
	15: Diagnosis and Surgical Management of Parathyroid Carcinoma
		Case Presentation
		15.1	 Introduction
		15.2	 Clinical Presentation
		15.3	 Non Functional PC
		15.4	 Natural History
		15.5	 Diagnosis
		15.6	 Treatment
			15.6.1	 Medical Treatment
			15.6.2	 Surgical Treatment
			15.6.3	 Chemotherapy
			15.6.4	 Radiotherapy
		15.7	 Prognostic Factors
		15.8	 Clinical Follow-Up
		References
	16: Surgical Procedures. Parathyroidectomy: Indications, Operative Techniques, Management of Complications, Intraoperative PTH Monitoring, Role of Parathyroid Autofluorescence and ICG
		Case Presentation
		16.1	 Introduction
		16.2	 Indications for Surgery
		16.3	 Preoperative Evaluation
		16.4	 Operative Techniques
			16.4.1	 Bilateral Exploration Parathyroidectomy
			16.4.2	 Focused Parathyroidectomy
		16.5	 Intraoperative PTH Monitoring and Gamma-Probe Localization
		16.6	 Indocyanine Green and Autofluorescence
		16.7	 Cryopreservation and Autotransplantation
		16.8	 Management of Complications
		16.9	 Outcomes and Prognosis
		References
III: Adrenals
	17: Adrenal Glands: Anatomy, Physiology, and Pathophysiology
		17.1	 Anatomy
			17.1.1	 Embryology
			17.1.2	 Macroscopic Aspect
				17.1.2.1	 Relationship to Surrounding Structures
			17.1.3	 Arterial Supply
			17.1.4	 Venous Drainage
			17.1.5	 Lymphatic Drainage
			17.1.6	 Nerve Supply
			17.1.7	 Histology
		17.2	 Physiology
			17.2.1	 The Adrenocortical Hormones
				17.2.1.1	 Glucocorticoids: Corticosterone and Cortisol
					Effects of Glucocorticoids
					Regulation of Glucocorticoid Release
				17.2.1.2	 Mineralocorticoids: Aldosterone
					Effects of Mineralocorticoids
					Regulation of Mineralocorticoid Release
				17.2.1.3	 Adrenal Androgens
					Effects of Adrenal Androgens and Estrogens
					Regulation of Adrenal Androgen Release
			17.2.2	 The Adrenomedullary Hormones
				17.2.2.1	 Effects of Epinephrine and Norepinephrine
				17.2.2.2	 Effects of Dopamine
				17.2.2.3	 Regulation of Adrenal Medullary Secretion
		17.3	 Pathophysiology
			17.3.1	 Introduction
			17.3.2	 Cushing’s Syndrome
			17.3.3	 Conn’s Syndrome
			17.3.4	 Pheochromocytoma
			17.3.5	 Adrenocortical Carcinoma
		References
	18: Adrenal Incidentaloma
		Case Presentation
		18.1	 Introduction
		18.2	 Anatomical Imaging
			18.2.1	 CT
			18.2.2	 MRI
		18.3	 Functional Imaging
			18.3.1	 FDG PET CT
		18.4	 Conclusions
		References
	19: Cushing’s Syndrome
		Case Presentation
		19.1	 Introduction
		19.2	 Clinical Presentation
		19.3	 Natural History
		19.4	 Diagnosis
		19.5	 Treatment of CS and Indications for Surgery
		19.6	 ACTH-Dependent Hypercortisolism
			19.6.1	 Pituitary-Dependent CD
			19.6.2	 Ectopic ACTH-Dependent CS
		19.7	 ACTH-Independent Hypercortisolism
			19.7.1	 Adrenal Adenoma
			19.7.2	 Adrenal Carcinoma
			19.7.3	 Primary Adrenal Hyperplasia
		References
	20: Primary Aldosteronism
		Case Presentation
		20.1	 Introduction
		20.2	 Clinical Presentation
		20.3	 Natural History
		20.4	 Diagnosis
		20.5	 Treatment
			20.5.1	 Pharmacologic Treatment
		20.6	 Indications for Surgery and Surgical Details
			20.6.1	 Adrenalectomy by the Laparoscopic Transabdominal Approach
			20.6.2	 Adrenalectomy with the Retroperitoneoscopic Approach
			20.6.3	 Complications
			20.6.4	 Postoperative Care (Correction of Potassium and Antihypertensive Medications)
		20.7	 Outcomes and Prognosis
			20.7.1	 Histopathology
			20.7.2	 Potassium and Hypertension
			20.7.3	 Long-Term Prognosis of Cardiovascular Disease and Mortality
			Box 20.1 Types of Primary Aldosteronism
			20.7.4	 Renal Function After Surgery
		References
	21: Pheochromocytoma and Paraganglioma
		Case Presentation
		Box 21.1 Laboratory Tests
		21.1	 Introduction
		21.2	 Clinical Presentation
		Box 21.2 Signs and Symptoms Associated with Catecholamine-Secreting Tumors
		21.3	 Natural History
			21.3.1	 Genetic Forms of Pheochromocytoma and Paraganglioma
		21.4	 Diagnosis
			21.4.1	 Differential Diagnosis
			Box 21.3 Medications that May Increase Measured Levels of Fractionated Catecholamines and Metanephrines
			21.4.2	 When to Do Case Detection Testing
			21.4.3	 Measurement of Fractionated Metanephrines and Catecholamines in Urine and Plasma
			21.4.4	 Genetic Testing
			21.4.5	 Localization
		21.5	 Treatment
			21.5.1	 Preoperative Management
			21.5.2	 Acute Hypertensive Crises
		21.6	 Indications for Surgery and Details
			21.6.1	 Adrenalectomy for Pheochromocytoma: Surgical Approach
			21.6.2	 Perioperative Concerns
			21.6.3	 Special Cases
			21.6.4	 Abdominal Paraganglioma
			21.6.5	 Subtotal (Partial, Cortex-Sparing) Adrenalectomy
		21.7	 Outcomes and Recurrences
		References
	22: Adrenocortical Carcinoma, Adrenal Lymphoma and Metastases to Adrenal Gland
		Case Presentation
		22.1	 Introduction
		22.2	 Adrenocortical Carcinoma
			22.2.1	 Clinical Presentation
			22.2.2	 Natural History
			22.2.3	 Diagnosis
			22.2.4	 Treatment
				22.2.4.1	 Indications for Surgery and Surgical Details
			22.2.5	 Outcomes or Prognosis
		22.3	 Metastases to the Adrenal Gland
			22.3.1	 Clinical Presentation
			22.3.2	 Natural History
			22.3.3	 Diagnosis
			22.3.4	 Treatment
				22.3.4.1	 Indications for Surgery and Surgical Details
			22.3.5	 Outcomes or Prognosis
		22.4	 Adrenal Lymphoma
			22.4.1	 Clinical Presentation
			22.4.2	 Natural History
			22.4.3	 Diagnosis
			22.4.4	 Treatment
			22.4.5	 Indications for Surgery and Surgical Details
			22.4.6	 Outcomes or Prognosis
		References
	23: Surgical Procedure: Adrenalectomy – Indications, Operative Techniques and Management of Complications
		Case Presentation
		23.1	 Introduction
		23.2	 Minimally Invasive Adrenalectomy
			23.2.1	 Laparoscopic Lateral Transabdominal Adrenalectomy
				23.2.1.1	 Right Adrenalectomy
				23.2.1.2	 Left Adrenalectomy
				23.2.1.3	 Pitfalls and Management of Complications
			23.2.2	 Posterior Retroperitoneoscopic Adrenalectomy
				23.2.2.1	 Pitfalls and Management of Complications
			23.2.3	 Robot-Assisted Adrenalectomy
			23.2.4	 Operative Technique
		23.3	 Open Approaches for Adrenalectomy
			23.3.1	 Operative Technique
				23.3.1.1	 Pitfalls and Management of Complications
		References
IV: Neuroendocrine Tumors (Thymic and Gastroenteropancreatic)
	24: Neuroendocrine Tumors (Thymic and Gastroenteropancreatic): Anatomy, Endocrine Physiology, and Pathophysiology
		Case Presentation
		24.1 Introduction
			24.1.1 Incidence and Prevalence
			24.1.2 Heredity in NET
		24.2 Clinical Presentation
			24.2.1 Gastric NET
			24.2.2 Endocrine Pancreas
			24.2.3 Duodenal NET
			24.2.4 Small Intestinal NET
			24.2.5 Appendix NET
			24.2.6 NETs of the Colon and Rectum
			24.2.7 Neuroendocrine Cancer (NEC)
			24.2.8 Thymic NET
		24.3 Natural History
		24.4 Diagnosis and Common Syndromes
			24.4.1 Classic Carcinoid Syndrome
			24.4.2 Atypical Carcinoid Syndrome
			24.4.3 Diarrhea
			24.4.4 Small Bowel Obstruction
			24.4.5 Gastrointestinal Bleeding
			24.4.6 Epigastric Pain and Dyspepsia
			24.4.7 Flushing
			24.4.8 Jaundice
			24.4.9 Effects on Blood Pressure
			24.4.10 Heart Failure
			24.4.11 Pulmonary Obstructive Disorders
			24.4.12 Abdominal Angina
			24.4.13 Pallor
			24.4.14 Hypoglycemia
			24.4.15 Hyperglycemia
			24.4.16 Tachycardia
			24.4.17 Necrolytic Migratory Exanthema
		24.5 Diagnostics
			24.5.1 Biochemical Markers
				24.5.1.1	 Chromogranin A
				24.5.1.2	 Serotonin and 5-Hydroxyindoleacetic Acid (5-HIAA)
				24.5.1.3	 Gastrin
				24.5.1.4	 Insulin, C-Peptide, and Pro-insulin
				24.5.1.5	 Glucagon, Vasoactive Intestinal Peptide (VIP), Pancreatic Polypeptide (PP), and Others
			24.5.2 Endoscopy
			24.5.3 Radiological Diagnostics
				24.5.3.1	 Nuclear Medicine Diagnostics
				24.5.3.2	 Pathology
				24.5.3.3	 TNM Staging
				24.5.3.4	 Multidisciplinary Conference
		24.6 Treatment
			24.6.1 Surgery
			24.6.2 Oncological and Medical Treatment
		24.7 Indications for Surgery and Surgical Strategy
			24.7.1 Pancreatic NET
			24.7.2 Gastric NET
			24.7.3 Duodenal NET
			24.7.4 Small Intestinal NET
			24.7.5 Appendix NET
			24.7.6 Thymic NET
			24.7.7 Other NETs
			24.7.8 Emergency Surgery in NET
		24.8 Prognosis
			24.8.1 Follow-Up
		References
	25: Neuroendocrine Tumors of the Thymus
		Case Presentation
		25.1	 Introduction
		25.2	 Clinical Presentation
		25.3	 Prognosis
		25.4	 Treatment of TNET
		25.5	 Surgical Details
		25.6	 Prophylactic Transcervical Thymectomy
		25.7	 Medical Treatment and Radiotherapy
		References
	26: Neuroendocrine Tumors: Stomach
		Case Presentation
		26.1	 Introduction
		26.2	 Classification
		26.3	 Clinical and Pathological Characteristics
		26.4	 Diagnosis and Staging
			26.4.1	 Upper Endoscopy
			26.4.2	 Imaging Studies
				26.4.2.1	 CT Scans
				26.4.2.2	 Nuclear Medicine
				26.4.2.3	 Magnetic Resonance Imaging (MRI)
			26.4.3	 Biochemical Tests
				26.4.3.1	 Gastrin
				26.4.3.2	 Chromogranin A (CgA)
		26.5	 Clinical and Pathologic Evaluation and Staging
		26.6	 Local Treatment Modalities for gNETs
		26.7	 Management of gNETs
			26.7.1	 Management of Type I gNETs
				26.7.1.1	 Medical Treatment
				26.7.1.2	 Type I gNETs’ Treatment Summary
			26.7.2	 Management of Type II gNETs
				26.7.2.1	 Type II gNETs’ Treatment Summary
			26.7.3	 Management of Type III gNETs
				26.7.3.1	 Type III gNETs’ Treatment Summary
		References
	27: Diagnosis and Management of Functional Pancreatic Neuroendocrine Tumors
		Case Presentation (Adapted from Ref. [1])
		27.1	 Introduction
		27.2	 Insulinoma
			27.2.1	 Clinical Presentation
			27.2.2	 Diagnosis
			27.2.3	 Localization
			27.2.4	 Treatment
		27.3	 Gastrinoma
			27.3.1	 Clinical Presentation
			27.3.2	 Diagnosis
			27.3.3	 Localization
			27.3.4	 Treatment
		27.4	 Other F-pNETs
			27.4.1	 Glucagonoma
			27.4.2	 VIPoma
			27.4.3	 SSomas
		References
	28: Non-functional Pancreatic Neuroendocrine Tumors
		Case Presentation
		28.1	 Introduction
		28.2	 Hereditary Tumor Syndromes
		28.3	 Clinical Presentation
		28.4	 Diagnosis
		28.5	 Treatment
			28.5.1	 Locoregional Ablative Therapy
			28.5.2	 Liver Transplantation
			28.5.3	 Medical Therapy in Advanced Disease
		28.6	 Indications for Surgery and Surgical Details
			28.6.1	 Surgery in Metastatic Patients
			28.6.2	 Palliative Surgery
			28.6.3	 Surgery in High-Grade NF-pNET
			28.6.4	 Surgery in MEN 1 Patients
		28.7	 Outcomes or Prognosis
			28.7.1	 Follow-Up
		References
	29: Small Intestine NETs
		Case Presentation and Case-Specific Questions
		29.1	 Introduction
		29.2	 Natural History
		29.3	 Incidence
		29.4	 Risk Factors
		29.5	 Prognosis
		29.6	 Clinical Presentation
			29.6.1	 Non-specific Symptoms and Intestinal Obstruction
			29.6.2	 Desmoplastic Reaction
			29.6.3	 Carcinoid Syndrome
			29.6.4	 Carcinoid Heart Disease (Hedinger Syndrome)
			29.6.5	 Carcinoid Crisis
		29.7	 Diagnostic Workup
			29.7.1	 Biochemistry
				29.7.1.1	 Chromogranin A
				29.7.1.2	 5-Hydroxy Indole Acetic Acid (5-HIAA)
				Box 29.1: Foods and Medications That Could Affect the Result of 24 h Urinary 5-HIAA
			29.7.2	 Imaging
				29.7.2.1	 Anatomical Cross-Sectional Imaging
				29.7.2.2	 Functional Imaging
			29.7.3	 Endoscopy
			29.7.4	 Biopsy and Histopathology
			29.7.5	 Cardiac Workup
		29.8	 Treatment
			29.8.1	 Surgery for siNETs
				29.8.1.1	 Indication
				29.8.1.2	 Pre- and Peri-operative Care
				29.8.1.3	 Surgery for Locoregional Disease (Stage I– III)
				29.8.1.4	 Systematic Intraoperative Exploration and Primary Tumor Resection
				29.8.1.5	 Lymphadenectomy
				29.8.1.6	 Prophylactic Cholecystectomy
				29.8.1.7	 Surgery in Metastatic Disease (Stage IV)
				29.8.1.8	 Surgery in Metastatic Liver Disease (M1a)
				29.8.1.9	 Surgery for the Primary Tumor in Inoperable Liver Disease (M1a)
				29.8.1.10	 Surgery in Cases with Peritoneal Spread
			29.8.2	 Non-surgical Treatment Options
				29.8.2.1	 Somatostatin Analogs (SSAs)
				29.8.2.2	 Interferon Alpha (IFN)
				29.8.2.3	 Everolimus
				29.8.2.4	 Peptide Receptor Radionuclide Therapy (PRRT)
				29.8.2.5	 Liver-Directed Therapy
				29.8.2.6	 Chemotherapy
				29.8.2.7	 Symptomatic Therapy for Serotonin-Induced Diarrhea
				29.8.2.8	 Treatment of Carcinoid Heart Disease (CHD, Hedinger Syndrome)
		29.9	 Follow-Up
			29.9.1	 Frequency and Duration of the Follow-Up
			29.9.2	 Investigations
		References
	30: Large Intestine NETs
		Case Presentation
		30.1	 Incidence and Presentation
		30.2	 Diagnosis
		30.3	 Treatment
			30.3.1	 Preoperative Management
			30.3.2	 Prophylactic Cholecystectomy
			30.3.3	 Endoscopic Management
			30.3.4	 Carcinoid Syndrome Management
		30.4	 Non-surgical Management of Metastatic Disease
			30.4.1	 Systemic Treatment
			30.4.2	 Liver-Directed Therapy
		30.5	 Surgical Treatment for Appendix NETs
		30.6	 Surgical Treatment for Colonic NETs
		30.7	 Surgical Treatment for Rectal NETs
		30.8	 Surgical Treatment for Liver Metastases
		30.9	 Follow-Up
		30.10 Prognosis
		References
	31: Surgical Procedure Steps and Key Points: Whipple Procedure, Enucleations, and Management of Complications
		31.1	 Introduction
		31.2	 Clinical Presentation
		31.3	 Pre-operative Evaluation: Diagnostic Imaging and Staging
		31.4	 Consideration for Method of Surgical Treatment
		31.5	 Surgical Technique
		31.6	 Post-operative Care and Complications
		31.7	 Summary
		References
V: Familial Endocrine Syndromes
	32: Familial Non-medullary Thyroid Carcinoma Syndrome (FNMTC) and Familial Syndromes Associated with Thyroid Cancer
		Case Presentation
		32.1	 Introduction
		32.2	 Definition, Screening, and Clinical Management of FNMTC
			32.2.1	 Syndromic FNMTC
				32.2.1.1	 Familial Adenomatous Polyposis
				32.2.1.2	 Cowden Syndrome
				32.2.1.3	 Carney Complex
				32.2.1.4	 Werner Syndrome
				32.2.1.5	 Pendred Syndrome
				32.2.1.6	 Ataxia-Telangiectasia
				32.2.1.7	 Bannayan-Ruvalcaba-Riley Syndrome
				32.2.1.8	 PTEN Hamartoma Tumor Syndrome
				32.2.1.9	 Peutz-Jeghers Syndrome
				32.2.1.10	 DICER1 Syndrome
				32.2.1.11	 McCune-Albright Syndrome
				32.2.1.12	 Papillary Renal Neoplasia (Non-syndromic FNMTC)
			32.2.2	 Non-syndromic FNMTC
		32.3	 Prognosis and Aggressiveness in FNMTC Compared to Sporadic Disease
		32.4	 Susceptibility Genes in Non-syndromic FNMTC
		References
	33: Familial Primary Hyperparathyroidism
		Case Presentation
		33.1	 Introduction
		33.2	 Preoperative Localization Studies
		33.3	 Role of Intraoperative PTH Measurement in Familial HPT
		33.4	 Cryopreservation
		33.5	 The Syndromes
			33.5.1	 MEN 1
				33.5.1.1	 Clinical Presentation
				33.5.1.2	 Natural History
				33.5.1.3	 Diagnosis
				33.5.1.4	 Indications for Surgery and Surgical Details
				33.5.1.5	 Outcomes/Prognosis
			33.5.2	 MEN 2A
				33.5.2.1	 Clinical Presentation
				33.5.2.2	 Natural History
				33.5.2.3	 Diagnosis
				33.5.2.4	 Indications for Surgery and Surgical Details
				33.5.2.5	 Outcomes/Prognosis
			33.5.3	 MEN 4
				33.5.3.1	 Clinical Presentation
				33.5.3.2	 Natural History
				33.5.3.3	 Diagnosis
				33.5.3.4	 Indications for Surgery and Surgical Details
			33.5.4	 Hereditary Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT)
				33.5.4.1	 Clinical Presentation
				33.5.4.2	 Natural History
				33.5.4.3	 Diagnosis
				33.5.4.4	 Surgery and Surgical Details
				33.5.4.5	 Outcomes/Prognosis
		33.6	 Non-syndromic PHPT
			33.6.1	 Familial Isolated Hyperparathyroidism (FIHPT)
				33.6.1.1	 Clinical Presentation and Natural History
				33.6.1.2	 Diagnosis
				33.6.1.3	 Surgery and Surgical Details
			33.6.2	 Familial Hypocalciuric Hypercalcemia (FHH)
				33.6.2.1	 Clinical Presentation and Natural History
				33.6.2.2	 Diagnosis
				33.6.2.3	 Treatment
				33.6.2.4	 Outcomes/Prognosis
			33.6.3	 Neonatal Severe Hyperparathyroidism (NSHPT)
				33.6.3.1	 Clinical Presentation and Natural History
				33.6.3.2	 Diagnosis
				33.6.3.3	 Medical Treatment, Surgery and Surgical Details
				33.6.3.4	 Outcomes/Prognosis
			33.6.4	 Autosomal Dominant Moderate Hyperparathyroidism (ADMH)
				33.6.4.1	 Clinical Presentation and Natural History
				33.6.4.2	 Diagnosis
				33.6.4.3	 Surgery and Surgical Details
				33.6.4.4	 Outcome
		References
	34: Familial Hypocalciuric Hypercalcemia (FHH)
		Case Presentation
		34.1	 Introduction
		34.2	 Molecular Genetics
		34.3	 Clinical Presentation
		34.4	 Natural History
		34.5	 Diagnosis
		34.6	 Treatment
		34.7	 Indications for Surgery and Surgical Details
		34.8	 Prognosis
		References
	35: Hyperparathyroidism-Jaw Tumor Syndrome
		Case Presentation
		35.1	 Introduction
		35.2	 Etiology
		35.3	 Clinical Presentation
			35.3.1	 pHPT
			35.3.2	 Jaw Tumors
			35.3.3	 Renal Involvement
			35.3.4	 Uterine Involvement
			35.3.5	 Other Features
		35.4	 Diagnosis
			Box 35.1 Indication for CDC73 genetic testing
		35.5	 Treatment
		35.6	 Surveillance
		References
	36: Multiple Endocrine Neoplasia Type 1
		Case
		36.1	 Introduction
		36.2	 Molecular Genetics of MEN1
		36.3	 Clinical Presentation and Diagnosis
			36.3.1	 Primary Hyperparathyroidism
			36.3.2	 Gastroduodenopancreatic Neuroendocrine Tumours
			36.3.3	 Pituitary Tumours
			36.3.4	 Adrenal Tumours
			36.3.5	 Bronchial and Thymic Neuroendocrine Tumours
			36.3.6	 Non-endocrine Tumours
			36.3.7	 Diagnosis
		36.4	 Surgical Management
			36.4.1	 Primary Hyperparathyroidism
			36.4.2	 Gastroduodenopancreatic Neuroendocrine Tumours
		36.5	 Genetic Counselling
			36.5.1	 Family Planning
			36.5.2	 Prenatal Testing
			36.5.3	 Preimplantation Genetic Testing
		36.6	 Surveillance
			36.6.1	 Primary Hyperparathyroidism
			36.6.2	 Gastroduodenopancreatic Neuroendocrine Tumours
			36.6.3	 Pituitary Adenoma
			36.6.4	 Adrenal Tumours
			36.6.5	 Bronchial and Thymic Carcinoids
		36.7	 Summary
		References
	37: Multiple Endocrine Neoplasia Type 2 (MEN 2)
		Case Presentation
		37.1	 Introduction
			37.1.1	 RET Proto-Oncogene
			37.1.2	 Medullary Thyroid Cancer
			37.1.3	 Medullary Thyroid Carcinoma and Biomarkers
			37.1.4	 MTC and Ectopic ACTH Secretion
		37.2	 Clinical Presentation
			37.2.1	 MEN 2A
				37.2.1.1	 Classical Type of MEN 2A
				37.2.1.2	 MEN 2A with CLA
				37.2.1.3	 MEN 2A with HD
				37.2.1.4	 FMTC
			37.2.2	 MEN 2B
		37.3	 Natural History
			37.3.1	 Classical MEN 2A Syndrome
			37.3.2	 MEN 2A with CLA
			37.3.3	 MEN 2A and HD
			37.3.4	 MEN 2B
		37.4	 Diagnosis
		37.5	 Treatment
			37.5.1	 Risk Categories for Hereditary MTC
			37.5.2	 Extent of the Initial Surgery for MTC
			37.5.3	 Systematic Treatment
		37.6	 Surgical Considerations in MEN2 Patients
			37.6.1	 Complications Related to Surgery for MTC
			37.6.2	 What About Parathyroid Transplantation During Thyroidectomy in MEN 2 Patients?
			37.6.3	 Excluding Pheochromocytoma Before Neck Surgery
			37.6.4	 Prophylactic Thyroidectomy
		37.7	 Prognosis and Follow-Up
			37.7.1	 The Importance of the Initial Operation
			37.7.2	 What About the Impact of HD in the Prognosis of MEN 2A Patients?
			37.7.3	 Follow-Up
		References
	38: Multiple Endocrine Neoplasia Type 4 (MEN 4)
		Case
			Genetic Analyses
		38.1	 Introduction
		38.2	 The MENX Syndrome
		38.3	 Molecular Genetics of MEN 4
		38.4	 Clinical Presentation of MEN 4
			38.4.1	 Primary Hyperparathyroidism
			38.4.2	 Pituitary Adenomas
			38.4.3	 Neuroendocrine Neoplasms
			38.4.4	 Other Endocrine Tumors Associated with Mutation of p27KIP1
			38.4.5	 Non-endocrine Tumors and Other Conditions Associated with Mutation of p27KIP1
		38.5	 Diagnosis
		38.6	 Genetic Counseling
		38.7	 Surgical Management
		38.8	 Surveillance and Follow-Up
		38.9	 Summary
		References
	39: Non-MEN Familial Endocrine Syndromes: Von Recklinghausen Disease, Von Hippel-Lindau Syndrome, Pheochromocytoma/Paraganglioma
		Case Presentation
		39.1	 Hereditary Pheochromocytoma and Paraganglioma
			39.1.1	 Introduction
			39.1.2	 Epidemiology and Genetics
			39.1.3	 Clinical Presentation
			39.1.4	 Diagnosis and Indications for Surgery
			39.1.5	 Preoperative Management and Radiological Studies
			39.1.6	 Surgical Techniques
			39.1.7	 Postoperative Follow-Up and Prognosis
		39.2	 Von Hippel-Lindau Syndrome
			39.2.1	 Introduction
			39.2.2	 Epidemiology and Genetics
			39.2.3	 Clinical Presentation
				39.2.3.1	 Visceral Lesions
				39.2.3.2	 CNS Lesions
				39.2.3.3	 Retina
				39.2.3.4	 Inner Ear
			39.2.4	 Diagnosis and Indications for Surgery
			39.2.5	 Preoperative Management and Radiological Studies
			39.2.6	 Surgical Techniques
			39.2.7	 Postoperative Follow-Up and Prognosis
		39.3	 Neurofibromatosis Type 1 (Von Recklinghausen Disease)
			39.3.1	 Introduction
			39.3.2	 Epidemiology and Genetics
			39.3.3	 Clinical Presentation
			39.3.4	 Diagnosis and Indications for Surgery
			39.3.5	 Preoperative Management and Radiological Studies
			39.3.6	 Surgical Techniques
			39.3.7	 Postoperative Follow-Up and Prognosis
		References
VI: Endocrine Emergencies
	40: Thyroid Storm
		Case Presentation
		40.1	 Introduction
		40.2	 Clinical Presentation
		40.3	 Natural History
			Box 40.1: Factors Precipitating the Thyroid Storm
		40.4	 Diagnosis
		40.5	 Treatment
			Box 40.2: Treatment of Thyroid Storm
		40.6	 Indications for Surgery and Surgical Details
		40.7	 Outcomes and Prognosis
		References
	41: Hypercalcemic Crisis
		Case
		41.1	 Introduction
		41.2	 Clinical Presentation
		41.3	 HC Due to PHPT in Pregnancy
		41.4	 HC in Young Patients
		41.5	 Natural History
			Box 41.1: Important Milestones in the Management of Hypercalcemia Due to Hyperparathyroidism in the Last Century
		41.6	 Histopathological Characteristics in HC
		41.7	 Assessment of the Risk of Developing HC
		41.8	 Diagnosis of HC
		41.9	 Differential Diagnosis of HC (7 Box 41.2)
			Box 41.2: Differential Diagnosis of HC
		41.10 Medical Management of HC Due to PHPT
		41.11 Surgical Management
		41.12 Outcome for Parathyroidectomy for HC
		References
	42: Endocrine Hypertensive Emergencies
		Case Presentation
		42.1	 Introduction
		42.2	 Pheochromocytoma
			42.2.1	 Diagnosis
			42.2.2	 Treatment
		42.3	 Primary Hyperaldosteronism
			42.3.1	 Diagnosis
		42.4	 Cushing’s Disease and Syndrome
			42.4.1	 Diagnosis
			42.4.2	 Treatment
		42.5	 Thyroid Disease
			42.5.1	 Diagnosis
			42.5.2	 Treatment
		References
	43: Carcinoid Crisis
		43.1	 Introduction
		43.2	 Diagnosis and Management of CS
		43.3	 Carcinoid Crisis
		43.4	 Perioperative Delivery and Management of Octreotide
		43.5	 Use of Octreotide Prophylaxis in Procedures
		43.6	 Recommendations Concerning Anesthesia
		43.7	 Conclusion
		References
VII: Miscellaneous
	44: Ethics in Endocrine Surgery
		44.1	 Introduction
		44.2	 Autonomy
			44.2.1	 Informed Consent
			44.2.2	 Operative Volume and the Role of Trainees
		44.3	 Beneficence
			44.3.1	 Surgical Decision-Making
		44.4	 Non-maleficence
			44.4.1	 Complications
			44.4.2	 Disclosure
			44.4.3	 Innovation in Surgery
		44.5	 Justice
		44.6	 Conclusions
		References
	45: How to Read and Interpret a Scientific Paper
		45.1	 Introduction
		45.2	 What Scientific Report to Read?
		45.3	 How to Structure the Reading?
		45.4	 What About Evidence and Its Grading in Medicine?
		45.5	 Checkbox Basic Questions on Study Quality and Credibility
		References
	46: Training and Board Certification in Endocrine Surgery
		46.1	 Introduction
		46.2	 Training and Volume
			46.2.1	 Thyroid Gland Surgery and Neck Dissections
			46.2.2	 Parathyroid Gland Surgery
		46.3	 Adrenal Gland Surgery
		46.4	 Surgery of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms
			46.4.1	 Summary
		46.5	 Board Certification
		46.6	 Conclusion
		References
	47: Center Accreditation for Endocrine Surgery
		47.1	 Introduction
		47.2	 Accreditation Process: Aspects to Be Certified – Hierarchy of Units
		47.3	 Requirements
			47.3.1	 Minimum Number of Interventions
				47.3.1.1	 Thyroid Surgery
				47.3.1.2	 Parathyroid Surgery
				47.3.1.3	 Adrenal or Paraganglioma Surgery
				47.3.1.4	 Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NEN)
			47.3.2	 Quality Indicators
				47.3.2.1	 Thyroid Surgery
				47.3.2.2	 Parathyroid Surgery
			47.3.3	 Requirements: Equipment, Staff, and Multidisciplinary Collaboration
				47.3.3.1	 Structure
				47.3.3.2	 Staff
				47.3.3.3	 Equipment and Diagnostic Procedures
				47.3.3.4	 Multidisciplinary Collaboration
			47.3.4	 Training and Research
				47.3.4.1	 The Trainee and Training Center
				47.3.4.2	 Research
		47.4	 Quality Control and Auditing
		47.5	 Conclusions
		References
Index