Parathyroid Gland Disorders: Controversies and Debates

392 Pages·2022·16.375 MB·English

by  Mahmoud F. Sakr

Parathyroid
Gland Disorders
Controversies and Debates
Mahmoud F. Sakr
123
Parathyroid Gland Disorders
Mahmoud F. Sakr
Parathyroid Gland
Disorders
Controversies and Debates
Mahmoud F. Sakr
Faculty of Medicine
University of Alexandria
Alexandria, Egypt
ISBN 978-3-031-07417-2 ISBN 978-3-031-07418-9 (eBook)
https://doi.org/10.1007/978-3-031-07418-9
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2022
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To my dear students and colleagues
Preface
In this authored book, we aim at emphasizing established concepts, displaying the
ongoing arguments, controversies, challenges, and debates on diagnosis and treat-
ment of different parathyroid gland disorders with a view of clarifying some uncer-
tainties, making suggestions to resolve others, and establishing strategies to reach
therapeutic success.
This book, with 107 images and 1673 references, will provide a valuable source
of knowledge and reference for all specialists and trainees entrusted with the care of
patients suffering from parathyroid gland diseases. It includes 18 chapters, namely,
historical review, embryology of the parathyroid gland, surgical anatomy of the
parathyroid gland, histology of the parathyroid gland, physiology of the parathyroid
gland, calcium: why is it important?, hyperparathyroidism (HPT), osteitis fibrosa
cystica, hypothyroidism, metabolic syndromes of parathyroid failure, hungry bone
syndrome, post-thyroidectomy hypocalcemia (incidence and risk factors, clinical
presentation, prevention), parathyroid transplantation, parathyroid cancer, intra-
operative tools in parathyroidectomy, and parathyroidectomy.
It is my collective hope that head and neck surgeons, dentists, maxillofacial sur-
geons, orthopedic surgeons, endocrinologists, oncologists, pediatricians, and clini-
cians of other specialties will find this book to be a useful and indispensable resource
as they face the most challenging of parathyroid gland disorders to help provide
individual patients with the best possible outcome.
Alexandria, Egypt Mahmoud F. Sakr
vii
Acknowledgments
I would like to thank all those who helped and encouraged me during the writing,
editing, and revision of this book. I would like to express my appreciation and grati-
tude to my wife and children for their continuous support and unconditioned love.
ix
Contents
1 Parathyroid Glands: Historical Review . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Parathyroid Gland Discovery and Anatomy . . . . . . . . . . . . . . . . . . 1
1.3 Parathyroid Function and Relation to Calcium . . . . . . . . . . . . . . . . 2
1.4 Evolution of Parathyroid Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.5 Hyperparathyroidism (HPT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.6 Parathyroid Hormone (PTH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.7 Technological Advances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2 Embryology of the Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.1 Embryogenic Origin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.1.1 Parathyroid Gland (PTG) Organogenesis . . . . . . . . . . . . . . 14
2.1.2 Molecular Regulators of Initial Parathyroid
Specification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.1.3 Differentiation and Survival of Parathyroids: Gcm2 . . . . . . 17
2.2 Thymus–Parathyroid Connection . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2.1 Do the Thymus and Parathyroids Have Overlapping
Functions? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.3 Stability of Parathyroid Fate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.4 Parathyroid Hormone and Related Protein . . . . . . . . . . . . . . . . . . . 19
2.4.1 Parathyroid Hormone (PTH) . . . . . . . . . . . . . . . . . . . . . . . . 19
2.4.2 Parathyroid Hormone-Related Protein (PTHrP) . . . . . . . . . 19
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3 Surgical Anatomy of the Parathyroid Glands . . . . . . . . . . . . . . . . . . . . 23
3.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.2 Recognizing Parathyroid Glands and their Number . . . . . . . . . . . . 23
3.2.1 Recognizing the Parathyroid Glands (PTGs) . . . . . . . . . . . 23
3.2.2 Number of Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . 24
3.3 Location of Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
3.3.1 Superior Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . . . 26
3.3.2 Inferior Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . . . 27
3.3.3 Variations in Location/Ectopic Glands . . . . . . . . . . . . . . . . 27
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xii Contents
3.3.4 Surgical Implications of Variations in Number
and Location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.4 Vascular Supply and Innervation . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4.1 Arterial Supply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4.2 Venous Drainage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4.3 Lymphatic Drainage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4.4 Innervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4 Histology of the Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4.1 Gross Appearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4.2 Microscopic Appearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4.2.1 Stroma (Capsule and Trabeculae) . . . . . . . . . . . . . . . . . . . . 33
4.2.2 Parenchyma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.3 Immunohistochemical (IHC) Features . . . . . . . . . . . . . . . . . . . . . . . 37
4.4 Electron Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
5 Physiology of the Parathyroid Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
5.1 Basic Biology of Calcium Homeostasis . . . . . . . . . . . . . . . . . . . . . 39
5.1.1 Plasma Levels of Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . 39
5.2 Absorption and Excretion of Calcium and Phosphorus . . . . . . . . . . 40
5.3 Key Components of Calcium Homeostasis . . . . . . . . . . . . . . . . . . . 41
5.3.1 Parathyroid Hormone (PTH) . . . . . . . . . . . . . . . . . . . . . . . . 41
5.3.2 Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.3.3 Calcitonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6 Calcium: Why Is It Important? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
6.2 Properties of Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
6.2.1 Solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
6.2.2 Binding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
6.2.3 Calcium Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
6.2.4 Bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6.3 Functions of Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6.3.1 Structure of Bone and Teeth . . . . . . . . . . . . . . . . . . . . . . . . 50
6.3.2 Cell Signaling/Muscle Contraction . . . . . . . . . . . . . . . . . . . 50
6.3.3 Microbiological Functions/Regulation of Protein
Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.4 Dietary and Pharmacological Uses of Calcium . . . . . . . . . . . . . . . . 51
6.4.1 Disease Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
6.4.2 Disease Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
6.5 Food Sources and Recommended Dietary Allowance . . . . . . . . . . . 59
6.5.1 Food Sources of Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . 59
6.5.2 Calcium Supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Contents xiii
6.6 Abnormal Serum Levels of Calcium . . . . . . . . . . . . . . . . . . . . . . . . 61
6.6.1 Calcium Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
6.6.2 The Recommended Dietary Allowance (RDA) . . . . . . . . . 62
6.6.3 Calcium Excess—Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
6.7 The Linus Pauling Institute Recommendations . . . . . . . . . . . . . . . . 70
6.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
7 Hyperparathyroidism (HPT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
7.2 Surgical Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
7.2.1 Classification of Hyperparathyroidism (HPT) . . . . . . . . . . 81
7.2.2 Hyperparathyroidism: Sporadic or Familial? . . . . . . . . . . . 82
7.3 Primary Hyperparathyroidism (PHPT) . . . . . . . . . . . . . . . . . . . . . . 82
7.3.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
7.3.2 Etiology of “PTH” Overproduction . . . . . . . . . . . . . . . . . . 83
7.3.3 Surgical Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
7.3.4 Clinical Picture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
7.3.5 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
7.3.6 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
7.3.7 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
7.4 Secondary Hyperparathyroidism (SHPT) . . . . . . . . . . . . . . . . . . . . 123
7.4.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
7.4.2 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
7.4.3 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
7.4.4 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
7.4.5 Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
7.4.6 Clinical Picture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
7.4.7 Evaluation/Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
7.4.8 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
7.4.9 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
7.4.10 Pertinent Studies and Ongoing Trials . . . . . . . . . . . . . . . . . 129
7.4.11 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
7.5 Tertiary Hyperparathyroidism (THPT) . . . . . . . . . . . . . . . . . . . . . . 130
7.5.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
7.5.2 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
7.5.3 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
7.5.4 Risk Factors and Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . 132
7.5.5 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
7.5.6 Clinical Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
7.5.7 Investigations/Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
7.5.8 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
7.6 Familial HPT in “Men” Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . 136
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136