Endocrine Surgery meets the needs of surgeons in higher training and practising consultants for a contemporary and evidence-based account of this sub-specialty that is relevant to their general surgical practice. It is a practical reference source incorporating the most current information on recent developments, management issues and operative procedures. The text is thoroughly referenced and supported by evidence-based recommendations wherever possible, distinguishing between strong evidence to support a conclusion, and evidence suggesting that a recommendation can be reached on the balance of probabilities.
This is a title in the Companion to Specialist Surgical Practice series whose eight volumes are an established and highly regarded source of information for the specialist general surgeon.
- The Companion to Specialist Surgical Practice series provides a current and concise summary of the key topics within each major surgical sub-specialty.
- Each volume highlights evidence-based practice both in the text and within the extensive list of references at the end of every chapter.
- An expanded authorship team across the series includes additional European and World experts with an increased emphasis on global practice.
- The contents of the series have been extensively revised in line with recently published evidence.
- All the chapters reflect the multidisciplinary approach to the subject with up-to-date information on cytopathology, assays of hormones, localisation techniques, anaesthetic requirements, genetic implications and, of course, histopathology and adjuvant treatments.
- Minimally invasive approaches continue to be promoted and developed throughout the book.
- The text has a closer emphasis on practical and pragmatic approaches to clinical scenarios.
Endocrine Surgery meets the needs of surgeons in higher training and practising consultants for a contemporary and evidence-based account of this sub-specialty that is relevant to their general surgical practice. It is a practical reference source incorporating the most current information on recent developments, management issues and operative procedures. The text is thoroughly referenced and supported by evidence-based recommendations wherever possible, distinguishing between strong evidence to support a conclusion, and evidence suggesting that a recommendation can be reached on the balance of probabilities. This is a title in the Companion to Specialist Surgical Practice series whose eight volumes are an established and highly regarded source of information for the specialist general surgeon. The Companion to Specialist Surgical Practice series provides a current and concise summary of the key topics within each major surgical sub-specialty. Each volume highlights evidence-based practice both in the text and within the extensive list of references at the end of every chapter. An expanded authorship team across the series includes additional European and World experts with an increased emphasis on global practice. The contents of the series have been extensively revised in line with recently published evidence. All the chapters reflect the multidisciplinary approach to the subject with up-to-date information on cytopathology, assays of hormones, localisation techniques, anaesthetic requirements, genetic implications and, of course, histopathology and adjuvant treatments. Minimally invasive approaches continue to be promoted and developed throughout the book. The text has a closer emphasis on practical and pragmatic approaches to clinical scenarios.
Front Cover 1
Endocrine Surgery: A COMPANION TO SPECIALIST SURGICAL PRACTICE 4
Copyright 5
Contents 6
Contributors 8
Series Editors' preface 10
Editor's preface 12
Evidence-based practice in surgery 14
Chapter 1: Parathyroid disease 16
Part 1. Parathyroid disease, syndromes and pathophysiology 16
Introduction 16
Embryology and anatomy 16
Calcium and parathyroid hormone (PTH) regulation 17
Primary hyperparathyroidism 18
Incidence 18
Clinical manifestations 18
Diagnosis 18
Normocalcaemic hyperparathyroidism 19
Hypercalcaemic crisis 20
Surgical indications 23
Imaging and localisation 24
Ultrasound (US) 24
Computed tomography (CT) 26
Magnetic resonance imaging (MRI) 26
Thallium-201–technetium-99 m pertechnetate scan (Tl–99mTc scan) 26
Technetium-99 m sestamibi scan (sestamibi scan) 27
Parathyroid angiography and venous sampling for PTH 29
Pathology 29
Adenoma 30
Double adenoma 30
Hyperplasia 30
Carcinoma 30
Secondary hyperparathyroidism (SHP) 31
Pathogenesis 31
Hypocalcaemia and hyperphosphataemia 31
Decreased synthesis of calcitriol 31
Bony resistance to PTH 31
Changes in PTH set point 31
Aluminium intoxication 31
Presentation 32
Osseous lesions 32
Pruritus 32
Metastatic calcification 32
Calciphylaxis 32
Treatment 32
Tertiary hyperparathyroidism 32
References 33
Part 2. Operative strategy for themanagement of parathyroid disease 36
Primary hyperparathyroidism 36
Conventional open parathyroidectomy 36
Basic principles of parathyroid surgery 36
Management of surgical procedure 37
The search for superior parathyroid (P IV) 37
The search for inferior parathyroid (P III) 38
Evaluation of the initial bilateral exploration 38
Continuation of the exploration 39
The parathyroidectomy 40
Solitary parathyroid adenoma (Fig. 1.12) 40
Sporadic multiglandular disease 40
Familial hyperparathyroidism 41
Primary hyperparathyroidism in MEN1 41
Primary hyperparathyroidism in MEN2A 41
Parathyroid carcinoma 42
Parathyroidectomy associated with thyroid excisions 42
Overall results of conventional open parathyroidectomy 42
Minimally invasive parathyroidectomy (MIP) 43
Unilateral neck exploration 43
Open minimally invasive parathyroidectomy (OMIP) 43
Minimally invasive radio-guided parathyroidectomy (MIRP) 44
Endoscopic parathyroidectomy 44
MIP in the broader context 45
Intraoperative parathyroid hormone assay (ioPTH) 46
Re-operation for persistent or recurrent primary hyperparathyroidism (PHP) 46
Analysis of causes of failure 46
Management 46
Confirmation of the diagnosis 46
Case history 46
Preoperative evaluation 47
Methods of re-operation 47
The posterolateral approach (‘back-door’ approach) 48
The thyrothymic approach (‘front-door’ approach) 48
Revision of the transverse cervicotomy 48
Mediastinal approaches 48
Other focused approaches 48
Additional procedures 48
Results 48
Secondary hyperparathyroidism (SHP) 49
Hyperparathyroidism secondary to compensatory stimulation of parathyroid hormone 49
Surgical strategies 49
Perioperative care 50
Persistent and recurrent SHP 50
Lithium-induced hyperparathyroidism 51
Tertiary hyperparathyroidism 51
References 52
Chapter 2: The thyroid gland 56
Background 56
Embryology, surgical anatomy and physiology 56
Embryology 56
Thyroid anatomy 56
Recurrent laryngeal nerve and external branch of superior laryngeal nerve anatomy 56
Parathyroid anatomy 57
Thyroid physiology 57
Clinical history and examination 58
Investigation of the thyroid 58
Blood tests 59
Thyroid function tests 59
Thyroid antibodies 59
Thyroglobulin antibody 59
Thyroid peroxidase antibody 60
TSH receptor antibody 60
Biomarkers of malignant disease 60
Thyroglobulin 60
Calcitonin 60
Carcinoembryonic antigen 60
Imaging studies 60
Ultrasonography 60
Nuclear medicine studies 60
Computed tomography 60
Tissue diagnosis 61
Incidental thyroid pathology 61
Surgical pathologies of the thyroid 62
Benign conditions 62
Benign goitre 62
Causes of multinodular goitre 63
Iodine deficiency 63
Genetics 63
Goitrogens 63
Gender 63
Drugs 63
Pathogenesis 63
Management of benign MNG 63
Thyroid cysts 63
Malignant conditions 64
Molecular biology of thyroid cancers 64
Papillary thyroid carcinoma 64
Follicular thyroid carcinoma 64
Differentiated thyroid cancers (PTC and FTC) 64
Risk factors 64
Pathology 65
Papillary thyroid carcinoma 65
Follicular thyroid carcinoma 65
Staging 66
Work-up 66
Management of DTC 67
Surgery of DTC 67
Extent of thyroidectomy 67
Contraindications to total thyroidectomy 68
Lymph node dissection 68
Adjuvant treatments 69
Follow-up 69
Poorly differentiated thyroid cancer (PDTC) 69
Medullary thyroid carcinoma 69
Pathology 69
Clinical features 70
Diagnosis 70
Treatment 70
Prognosis 71
Follow-up 71
Anaplastic thyroid carcinoma 71
Other malignancies 71
Primary thyroid lymphoma 71
Squamous cell carcinoma 72
Metastatic carcinoma to the thyroid 72
Hyperthyroidism 72
Causes 72
Clinical features 72
Investigations 72
Diagnosis of thyrotoxicosis 72
Determination of aetiology 73
End-organ effects 74
Management 74
Symptomatic management 74
Management – Graves' disease 74
131 I 74
ATD 74
Management – TMNG 74
Management – TA 74
Surgical indications 74
Operative strategy 74
Preoperative considerations 74
Operative considerations 75
Postoperative considerations 76
Thyroiditis 76
Subacute thyroiditis (de Quervain's thyroiditis) 76
Autoimmune thyroiditis (Hashimoto's thyroiditis) 76
Riedel's thyroiditis 76
Acute suppurative thyroiditis 76
Postpartum thyroiditis 76
Surgery of the thyroid 77
Unilateral total thyroid lobectomy (hemithyroidectomy) 77
Preparation 77
Exposure 77
Mobilisation 77
RLN and parathyroid glands 78
Total thyroidectomy 79
Retrosternal goitre 79
Recurrent goitre 79
Neuromonitoring 79
Sutureless thyroidectomy 79
Minimally invasive and robotic surgery 79
Complications of thyroidectomy 80
Recurrent laryngeal nerve injury 80
External branch of superior laryngeal nerve injury 80
Hypoparathyroidism 80
Recurrent hyperthyroidism 80
Thyroid crisis/storm 80
Haemorrhage/airway obstruction 80
Miscellaneous 81
References 81
Chapter 3: The adrenal glands 85
Anatomy 85
Blood supply and lymphatic drainage 85
Nerve supply 85
Microscopic anatomy 85
Embryology 86
Physiology 86
Adrenal medulla 86
Catecholamine synthesis and metabolism 86
Catecholamine physiological effects 87
Adrenal cortex 87
Mineralocorticoids 87
Glucocorticoids 88
Sex steroids 88
Adrenal incidentaloma 88
Case study 1 88
Definition and incidence 88
Aetiology 88
Investigation 89
Biochemistry 89
Biopsy 89
Imaging 89
Management 90
Case study 1 (discussion) 90
Adrenocortical carcinoma 91
Case study 2 91
Incidence and aetiology 91
Clinical features 91
Biochemistry 91
Imaging 91
Diagnosis and staging 92
Treatment 92
Surgery 92
Medical 92
Prognosis 92
Case study 2 (discussion) 93
Phaeochromocytoma and paraganglioma 93
Case study 3 93
Incidence and aetiology 93
Clinical presentation 95
Biochemical diagnosis 95
Imaging 95
Medical management 96
Surgical management 97
Case study 4 97
Malignant phaeochromocytoma 97
Phaeochromocytoma in pregnancy 97
Case study 3 (discussion) 98
Case study 4 (discussion) 99
Cushing's syndrome 99
Case study 5 99
Definition and aetiology 99
Clinical features 99
Biochemical diagnosis 99
ACTH-dependent Cushing's syndrome 101
Imaging 101
ACTH-independent Cushing's syndrome 102
Management 102
ACTH-dependent Cushing's syndrome 102
ACTH-independent Cushing's syndrome 102
Case study 5 (discussion) 103
Primary hyperaldosteronism 103
Case study 6 103
Definition and aetiology 103
Biochemical diagnosis 103
Imaging 104
Management 104
Case study 6 (discussion) 104
Congenital adrenal hyperplasia 104
Neuroblastoma 104
Addison's disease (adrenal insufficiency) 105
Adrenalectomy 105
Open adrenalectomy 105
Anterior (transabdominal) approach 105
Lateral (retroperitoneal) approach 105
Posterior (retroperitoneal) approach 106
Laparoscopic adrenalectomy 106
Lateral (transabdominal) laparoscopic approach 106
Laparoscopic left adrenalectomy 106
Laparoscopic right adrenalectomy 107
Lateral (retroperitoneal) endoscopic approach 107
Posterior (retroperitoneal) endoscopic approach 108
Robotic adrenalectomy 108
Summary 108
References 109
Chapter 4: Familial endocrine disease: genetics, clinical presentation and management 113
Introduction 113
A brief overview of clinical endocrine genetics 113
Multiple endocrine neoplasia type 1 (MEN1) 115
Genetics 115
Presentation 116
Primary hyperparathyroidism 116
Enteropancreatic islet tumours 116
Pituitary tumours 116
Foregut carcinoids 116
Adrenocortical tumours 117
Cutaneous manifestations 117
Diagnosis 117
Management 117
Primary hyperparathyroidism 117
Enteropancreatic islet tumours 117
Pituitary tumours 119
Foregut carcinoids 119
Surveillance and screening 119
Genetic testing 119
Biochemical and radiological surveillance 119
MEN1: differential diagnosis 120
Familial isolated pituitary adenoma (FIPA) 120
Presentation 120
Management 120
Familial intestinal carcinoid 120
Multiple endocrine neoplasia type 2 121
Genetics 121
Presentation 122
Medullary thyroid cancer 122
Phaeochromocytoma 122
Primary hyperparathyroidism 122
Management 122
Medullary thyroid cancer 122
Phaeochromocytoma 123
Primary hyperparathyroidism 124
Surveillance and screening 124
Genetic testing 124
Biochemical and radiological surveillance 124
MEN2: differential diagnosis 125
Familial phaeochromocytoma/paraganglioma 125
Genetics 125
Presentation 125
Management 126
Surveillance and screening 126
Genetic testing 126
Biochemical and radiological surveillance 126
Carney–Stratakis syndrome 127
Carney triad 127
Familial hyperparathyroidism (FHP) syndromes 127
Familial isolated hyperparathyroidism (FIHP) 127
Familial hypocalciuric hypercalcaemia (FHH) and neonatal severe hyperparathyroidism (NSHP) 127
Familial hyperparathyoidism–jaw tumour syndrome (FHP-JT) 128
Management of PHP syndromes 128
Von Hippel–Lindau disease 128
Genetics 129
Presentation 130
Diagnosis 130
Treatment 130
Surveillance and screening 130
Genetic 130
Biochemical/radiological 130
Pancreatic neuroendocrine tumours in VHL disease 130
Neurofibromatosis type 1 (NF1) 131
Genetics 131
Presentation 131
Management 131
Familial non-medullary thyroid cancer syndromes 131
PTEN hamartoma tumour syndrome 131
Presentation 132
Management 132
Surveillance and screening 132
Genetic testing 132
Surveillance 133
Familial papillary thyroid cancer 133
Management 133
Familial adenomatous poylposis (FAP) 133
Genetics 133
Presentation 133
Management 133
Familial adrenocortical disease 133
Familial predisposition to adrenocortical carcinoma 133
Carney syndrome 134
Presentation 134
Management 134
Familial ACTH-independent adrenal hyperplasia 134
Familial hyperaldosteronism 135
Presentation 135
Management 135
References 136
Chapter 5: Endocrine tumours of the pancreas 140
Introduction 140
Insulinoma 140
Presentation 140
Diagnosis 142
Supervised standard fasting test 142
Nesidioblastosis 143
Management 144
Medical management of hypoglycaemia 144
Preoperative tumour localisation 144
Non-invasive imaging studies 144
Invasive localising procedures 144
Operative management 146
Open exploration 146
Resection of insulinoma 147
Insulinoma and MEN1 147
Laparoscopic surgery 148
Outcome 148
Gastrinoma 148
Patient presentation 149
Diagnosis 149
Management 149
Medical control of gastric acid hypersecretion 149
Preoperative tumour localisation 151
Non-invasive tumour-localising studies 151
Invasive tumour-localising modalities 152
Surgery for tumour eradication 152
Operative approach 152
Intraoperative manoeuvres to find the primary gastrinoma 152
Tumour resection 153
Gastrinoma and MEN1 154
Outcome 155
Non-functional pNETs 155
Other rare endocrine tumours of the pancreas 155
Malignant pNETs 156
Evaluation of metastatic disease 156
Surgical management 156
Non-surgical management 157
References 158
Chapter 6: Gastrointestinal neuroendocrine tumours 162
Introduction 162
Oesophageal NETs 163
Gastric NETs 164
Type 1: gastric NETs associated with chronic atrophic gastritis 164
Type 2: NETs associated with ZES in MEN1 patients 165
Type 3: sporadic gastric NETs 166
Gastrinoma 167
Poorly differentiated gastric neuroendocrine carcinomas 167
Clinical evaluation 167
Symptoms and patient history 167
Diagnosis 167
Treatment 168
CAG-associated type 1 gastric NETs 168
MEN1-related type 2 gastric NETs 168
Sporadic type 3 gastric NETs 169
Poorly differentiated NECs 169
Duodenal NETs 169
Gastrinomas 169
Somatostatin-rich NETs 169
Gangliocytic paragangliomas 170
Other duodenal NETs 170
Duodenal NECs 170
Pancreatic NETs 170
Jejuno-ileal (small-intestinal) NETs (midgut carcinoids) 171
Morphological features 171
Clinical symptoms 172
Carcinoid syndrome 173
Diagnosis 173
Biochemistry 173
Pentagastrin provocation test 174
Radiology 174
Computed tomography 174
Ultrasound 174
OctreoScan® 174
Positron emission tomography (PET) 174
Histology 174
Surgery 175
Surgical technique 176
Liver metastases 179
Liver surgery 179
Radiofrequency or microwave ablation 180
Liver embolisation 180
Liver transplantation 181
Prophylaxis against carcinoid crisis 181
Medical treatment 182
Radiotherapy 182
Survival 182
Appendiceal NETs 183
Atypical goblet-cell NETs 184
Colon NETs 184
Rectal NETs 184
Presentation 184
Diagnosis and immunohistochemistry 185
Treatment 186
Outcome 186
Recommendations 186
References 188
Chapter 7: Clinical governance, ethics and medicolegal aspects of endocrine surgery 193
Clinical governance 193
What is good practice? 194
Who should perform surgery on the endocrine glands? 194
The advantages of subspecialisation 195
Thyroid surgery 196
Standards 196
Outcome measures 196
Parathyroid surgery 196
Standards 196
Outcome measures 196
Adrenal surgery 196
Standards 196
Outcome measures 197
Pancreatic surgery 197
Standards 197
Outcome measures 197
Risk management 197
Staff issues 197
Communication issues 197
Protocol issues 197
Record-keeping 197
Support services 198
Audit 198
Medicolegal aspects of endocrine surgery 198
Consent 198
When things do not go smoothly 199
Handling complaints 199
Complaints that turn into litigation 199
Medical negligence 200
Duty of care 200
Breach of duty of care 200
Damage 201
Causation 201
Expert opinions 202
Ethical issues in the use of new technology in endocrine surgery 202
Conclusions 203
References 203
Chapter 8: The salivary glands 206
Introduction 206
Surgical anatomy 206
The parotid gland 206
Facial nerve 206
The submandibular gland 207
The sublingual gland 207
Investigations 207
Clinical assessment 207
Imaging 207
Fine-needle aspiration cytology 208
Sialendoscopy 209
Non-neoplastic disease of the salivary glands 209
Inflammatory conditions 209
Acute viral inflammation 209
Acute suppurative sialadenitis 210
Chronic inflammatory conditions 210
Mycobacterium tuberculosis 210
Atypical tuberculosis 210
Cat-scratch disease 210
Actinomycosis 211
Sarcoidosis 211
Sjögren's syndrome 211
Human immunodeficiency virus 212
Sialolithiasis 212
Treatment 212
Interventional sialendoscopy 213
Non-inflammatory conditions 213
Sialadenosis/sialosis 213
Salivary gland cysts 213
Post-radiotherapy xerostomia 213
Neoplastic disease 213
Benign epithelial neoplasms 214
Pleomorphic adenoma 214
Warthin's tumour 215
Other benign epithelial neoplasms 215
Management of benign epithelial neoplasms 215
Recurrent benign epithelial neoplasms 216
Benign non-epithelial neoplasms 216
Malignant epithelial neoplasms 216
Mucoepidermoid carcinoma 216
Adenoid cystic carcinoma 216
Acinic cell carcinoma 217
Polymorphous low-grade adenocarcinoma 217
Carcinoma ex-pleomorphic adenoma 217
Management of epithelial malignancies 217
Malignant non-epithelial neoplasm 217
Metastatic disease to the major salivary glands 217
Surgical principles 218
Parotid surgery 218
Partial parotidectomy 218
Deep lobe parotidectomy/total parotidectomy with facial nerve preservation 220
Radical parotidectomy 220
Extended radical parotidectomy 220
Parapharyngeal space tumours 220
Submandibular gland surgery 220
Minor salivary gland surgery 221
Surgical complications 221
Intraoperative complications 221
Facial nerve palsy 221
Frey's syndrome 221
Other postoperative complications 222
References 222
Index 226
Parathyroid disease
William B. Inabnet, III, James A. Lee and Barnard J.A. Palmer
Part 1
Parathyroid disease, syndromes and pathophysiology
III William B. Inabnet, James A. Lee and Barnard J.A. Palmer
Introduction
Hyperparathyroidism is a disease characterised by elevated serum calcium and inappropriately elevated parathyroid hormone (PTH) levels, which occurs with a prevalence of 3 per 1000 in the general population.1 The modern era of treating parathyroid disease began in 1925, when Mandl performed the first parathyroidectomy in a patient with severe bone disease. Early in the history of hyperparathyroidism, patients presented with advanced clinical disease, including fractures, skeletal deformities, kidney stones and kidney failure. The discovery of the peptide PTH in the early 1970s, coupled with the development of a chemical analyser to measure calcium, permitted the biochemical diagnosis of hyperparathyroidism much earlier in the disease course.2
During this era, bilateral neck exploration was the standard approach, resulting in a cure rate ranging from 92% to 96% when performed by a skilled surgical team.3,4
Over the last 20 years, the treatment of hyperparathyroidism has experienced a dramatic change with the development of new technology to permit accurate preoperative localisation of abnormal glands, and intraoperative confirmation of the completeness of parathyroid resection.
Embryology and anatomy
In order to successfully diagnose and treat disorders of the parathyroid glands, a keen understanding of parathyroid embryology and anatomy is essential. The parathyroid glands are small, brownish-tan glands located in the space around the thyroid gland. During the fifth week of foetal development, the inferior parathyroid glands arise from the dorsal aspect of the third pharyngeal pouch.5 Following development of the thymus from the ventral aspect of the third pharyngeal pouch, the inferior parathyroid glands and thymus descend in a caudal and medial direction to rest in the inferior neck and thorax respectively. The superior parathyroid glands arise from the dorsal wing of the fourth pharyngeal pouch and descend in a caudal direction with the thyroid gland.5
Because of the longer pathway of descent, the inferior parathyroid glands have a higher variability of location compared with the superior parathyroid glands, an observation that is important during parathyroid surgery.
In an autopsy series of 503 human subjects, Akerstrom et al. showed that four parathyroid glands were present in 84% of cases, whereas 3% of patients had only three glands and 13% had supernumerary glands.6 The presence of missed hyperfunctioning supernumerary glands is an important but infrequent cause of persistent hyperparathyroidism and should be considered in all cases of persistent disease. In 80% of cases, the location of the inferior and superior glands is symmetrical when compared with the glands on the contralateral side of the neck.6 The superior parathyroid glands are most commonly found immediately superior to the junction of the recurrent laryngeal nerve and the inferior thyroid artery and can be located inside the thyroid gland in 0.2% of cases.6
Approximately 50% of inferior parathyroid glands are located in the vicinity of the inferior pole of the thyroid gland and about 30% are found in the thyrothymic ligament.6
Calcium and parathyroid hormone (PTH) regulation
The parathyroid glands play a central role in regulating serum levels of calcium through a complex feedback loop involving PTH, serum ionised calcium levels and vitamin D. The key organ systems involved in this process include the parathyroid glands, gastrointestinal tract, kidneys and skin. Although multiple factors influence parathyroid function, it is now clear that calcium is the single most potent stimulator of PTH release. Calcium-sensing receptors (CSRs), which are located on the surface of the parathyroid chief cells and are coupled with a G-protein receptor, are able to detect minuscule changes in serum levels of extracellular ionised calcium.7,8 When serum levels of calcium decrease the CSRs are activated, thereby stimulating the synthesis and release of PTH.9 In primary hyperparathyroidism (PHP), the set point of the CSRs is adjusted upwards, probably through a mutation of unknown aetiology, causing the parathyroid chief cell to ‘believe’ that serum calcium levels are low when in fact they are not. As a result of this alteration in the CSR set point, the parathyroid chief cell increases production of PTH, ultimately leading to hypercalcaemia. Calcium-sensing receptors are also present in other tissues such as the kidneys and gastrointestinal tract, where calcium homeostasis is influenced.8,10,11 In the kidney, the CSRs regulate renal calcium excretion and influence the transepithelial movement of water and other electrolytes.8 In the gastrointestinal tract, CSRs are present in the gastrin-secreting G cells and acid-secreting parietal cells, thereby providing a molecular link between hypercalcaemia and acid hypersecretion.10 These facts also underscore the complexity of calcium homeostasis in influencing cellular function throughout the body.
PTH is an intact 84-amino-acid peptide with amino and carboxy terminals.12 Production of PTH begins in the endoplasmic reticulum of the parathyroid chief cells as a 115-amino-acid molecule, which undergoes a series of cleavages before being released from the cytoplasm as the biologically active (1–84)PTH molecule. The circulating (1–84)PTH molecule, which has a half-life of 3–5 minutes in patients with normal renal function, is initially cleaved in the liver, yielding an inactive C-terminal fragment, which is ultimately cleared by the kidneys.12,13 The N-terminal fragment is the part of the peptide that is responsible for the biological activity of PTH in peripheral tissues.
PTH acts directly on the kidneys, bone and gastrointestinal tract to activate several intracellular second messengers, including cyclic AMP and calcium.14,15 In the kidneys, PTH increases serum calcium levels by acting on the renal tubule to increase resorption of calcium and to increase the hydroxylation of 25-hydroxyvitamin D to the biologically active 1,25-dihydroxyvitamin D.15 PTH also stimulates the renal tubular secretion of phosphate and bicarbonate. In the bone, PTH acts on osteoblasts and osteoclasts to increase bone turnover, thereby providing a large source of calcium for the extracellular space.16
Vitamin D is a fat-soluble vitamin that is prevalent in dairy products. After being absorbed by the gastrointestinal tract, it is hydroxylated in the liver to become 25-hydroxyvitamin D, which in turn is hydroxylated in the kidneys to become 1,25-dihydroxyvitamin D. The latter plays an important role in calcium homeostasis by increasing the resorption of phosphorus in the kidneys and increasing the absorption of calcium from the gastrointestinal tract. Calcitonin, which is synthesised by the parafollicular C cells of the thyroid gland, acts as the physiological antagonist to PTH. Calcitonin decreases serum levels of calcium by decreasing bone turnover and in fact can be used to treat patients in hypercalcaemic crisis.17
Primary hyperparathyroidism
Incidence
Early in the history of PHP, patients presented with manifestations of severe hypercalcaemia and advanced disease, but the true incidence of hyperparathyroidism was not known due to the inability to routinely measure serum calcium levels. The development of the automated serum chemical analyser and the practice of widespread biochemical screening permitted the detection of mild increases in serum calcium levels, thereby allowing earlier recognition of abnormalities in calcium homeostasis.
Multiple factors influence the incidence of PHP, including the region of the world under evaluation, the nutritional status of the studied population, iatrogenic factors and the availability of routine biochemical screening.
In the 1970s, there was a dramatic fivefold increase in the incidence of PHP, largely due to the ‘catch-up’ effect of identifying patients who had PHP prior to the development of the automated calcium analyser.1 During the 1980s, the incidence of PHP in North America actually decreased as the impact of the ‘catch-up’ effect levelled off.18
The number of patients with a history of irradiation to the head and neck region for benign disorders decreased in the 1980s, which may also have contributed to the decreased incidence of PHP, as head and neck irradiation is a known risk factor for parathyroid hypersecretion.
PHP occurs more frequently in women than men, but the overall incidence increases with age in both sexes. In North America, the incidence of PHP in the general population is 4.3 per 1000, whereas in Europe the incidence is 3 per 1000.1,18 In women aged between 55 and 75 years, the incidence of PHP is 21 per 1000.1 Possible explanations for the increased incidence with age include the lower rate of biochemical screening in patients less than 50 years of age and the increased use of bone density...
| Erscheint lt. Verlag | 21.6.2013 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Chirurgie |
| Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie | |
| ISBN-10 | 0-7020-4971-9 / 0702049719 |
| ISBN-13 | 978-0-7020-4971-2 / 9780702049712 |
| Haben Sie eine Frage zum Produkt? |
PDF (Adobe DRM)Größe: 16,6 MB
Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
EPUB (Adobe DRM)Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: EPUB (Electronic Publication)
EPUB ist ein offener Standard für eBooks und eignet sich besonders zur Darstellung von Belletristik und Sachbüchern. Der Fließtext wird dynamisch an die Display- und Schriftgröße angepasst. Auch für mobile Lesegeräte ist EPUB daher gut geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
aus dem Bereich
