Atlas of Sonography of Parathyroid 9811979189, 9789811979187

This comprehensive atlas covers various common and uncommon cases of parathyroid disorders encountered in the day to day

190 56 28MB

English Pages 211 [212] Year 2023

Table of contents :
Foreword
Foreword
Foreword
Foreword
Foreword
Foreword
Foreword
Foreword
Foreword
Foreword
Acknowledgements
Contents
About the Author
Abbreviations
1: Introduction to Parathyroid Sonography
1.1 Anatomy and Embryology of Parathyroid Glands
1.2 Vascular Anatomy
1.3 Nerve Relations
1.4 Microscopic Anatomy
1.5 Embryological Anatomy
1.5.1 Origin, Migration and Eutopic Locations
1.6 Calcium Metabolism and Role of Parathyroid Hormone and Calcitonin
1.7 Hyperparathyroidism
1.8 Types of Hyperparathyroidism
1.9 Clinical Symptoms of Hyperparathyroidism
1.10 Biochemical Investigations: A Practical Approach to Hypercalcaemia
1.11 Approach to Hypercalcaemia
1.12 Imaging
1.12.1 Guiding Principles of Parathyroid Imaging
1.12.2 Parathyroid Scintigraphy: Tc-99m Sestamibi SPECT and SPECT/CT
1.12.3 Four-Dimensional Computed Tomography (4D CT)
1.12.4 Ultrasound of the Neck for Localization of the Parathyroid Glands
1.12.5 Patient Positioning for Neck Ultrasound
1.12.6 Ultrasound
1.12.6.1 Transducer Selection
1.12.6.2 Ultrasound Technique
1.12.7 Key Greyscale Ultrasound Features
1.12.8 Typical Parathyroid Adenoma
1.12.8.1 Key Colour Doppler Ultrasound Features
1.12.9 Role of Spectral Doppler in Parathyroid Evaluation
1.12.10 Role of Contrast-Enhanced Ultrasound (CEUS) in Parathyroid Evaluation
1.12.11 Role of Shear Wave Elastography in Parathyroid Nodule Evaluation
1.12.12 Differential Diagnosis of an Orthotopic Parathyroid Adenoma
1.12.12.1 Lymph Node
1.12.12.2 Blood Vessel
1.12.12.3 Thyroid Nodule
1.12.12.4 Sequestrated Thyroid Tissue
1.12.12.5 Internal Jugular Vein Thrombosis
1.12.12.6 Schwannoma of the Vagus Nerve in the Neck
1.12.12.7 Carotid Body Tumour
1.13 Medical Management
1.13.1 Calcium Supplementation/Restriction
1.14 Indications for Surgery
1.14.1 Skeletal Guidelines
1.14.2 Renal Guidelines
1.14.3 Histopathology
1.14.4 Parathyroid Adenoma
1.14.5 Parathyroid Hyperplasia
1.14.6 Parathyroid Carcinoma
References
2: Sonography of a Typical Parathyroid Adenoma: Solitary Parathyroids as Seen on Ultrasound
2.1 Introduction
2.2 Case 1
2.2.1 Bio-Clinical Parameters
2.2.2 Technetium-99m Sestamibi Scan
2.2.3 Ultrasound Neck
2.2.4 Management
2.3 Case 2
2.3.1 Bio-Clinical Parameters
2.3.2 Imaging
2.3.3 Management
2.4 Case 3
2.4.1 Bio-Clinical Parameters
2.4.2 Management
2.5 Case 4
2.5.1 Clinical Details
2.5.2 Bio-Clinical Parameters
2.5.3 Technetium-99m Sestamibi Scan
2.5.4 Management
2.6 Case 5
2.6.1 Bio-Clinical Parameters
2.6.2 “Tc-99m Sestamibi” Scan Findings
2.6.3 Management
2.7 Case 6
2.7.1 Bio-Clinical Parameters
2.7.2 Ultrasound of the Neck for Parathyroid
2.7.3 Management
2.8 Case 7
2.8.1 Bio-Clinical Parameters
2.8.2 Ultrasound Neck
2.8.2.1 Findings
2.8.3 Management
2.9 Case 8
2.9.1 Bio-Clinical Parameters
2.9.2 Ultrasound Neck
2.9.3 Skeletal Survey
2.9.4 Management
2.10 Case 9
2.10.1 Bio-Clinical Parameters
2.10.2 Ultrasound Neck
2.10.3 Management
2.11 Case10
2.11.1 Bio-Clinical Parameters
2.11.2 Ultrasound Neck
2.11.3 Management
2.12 Case 11
2.12.1 Bio-Clinical Parameters
2.12.2 Management
2.13 Discussion
2.14 Management
2.15 Conclusion
References
3: Atypical Sonographic Appearances of Enlarged Parathyroids
3.1 Introduction
3.2 Changes in the Shape of Adenoma
3.2.1 Case 1
3.2.1.1 Bio-Clinical Parameters
3.2.1.2 Imaging
3.2.1.3 Ultrasound Neck
3.2.1.4 Discussion of the Neck Ultrasound Findings
3.2.1.5 Management
3.2.2 Case 2
3.2.2.1 Bio-Clinical Parameters
3.2.2.2 Imaging
3.2.2.3 Ultrasound Neck
3.2.2.4 Management
3.2.3 Case 3
3.2.3.1 Bio-Clinical Parameters
3.2.3.2 Ultrasound Neck
3.2.3.3 Discussion of the Ultrasound Findings
3.2.3.4 Management
3.2.4 Discussion
3.3 Cystic Changes in Parathyroid Lesions
3.3.1 Case 4
3.3.1.1 Bio-Clinical Parameters
3.3.1.2 Imaging
Technetium-99m Sestamibi Scan
3.3.1.3 Ultrasound Neck
3.3.1.4 Management
3.3.2 Case 5
3.3.2.1 Bio-Clinical Parameters
3.3.2.2 Management
3.3.2.3 Discussion: Parathyroid Cystic Changes and Parathyroid Cysts
3.3.3 Case 6
3.3.3.1 Bio-Clinical Parameters
3.3.3.2 Ultrasound Neck
3.3.3.3 Management
3.3.3.4 Discussion: Parathyroid Haemorrhage
3.4 Parathyroid Calcification
3.4.1 Case 7
3.4.1.1 Bio-Clinical Parameters
3.4.1.2 Ultrasound Neck
3.4.1.3 Management
3.4.1.4 Discussion: Parathyroid Calcifications
3.5 Altered Echotexture and Lobulations in Parathyroid Lesions
3.5.1 Case 8
3.5.1.1 Bio-Clinical Parameters
3.5.1.2 Imaging
3.5.1.3 Management
3.5.1.4 Discussion: Bilobed Parathyroid Adenoma
3.5.2 Case 9
3.5.2.1 Bio-Clinical Parameters
3.5.2.2 Ultrasound Neck
3.5.2.3 Management
3.5.3 Case 10
3.5.3.1 Bio-Clinical Parameters
3.5.3.2 Ultrasound
3.5.3.3 Management
3.5.4 Case 11
3.5.4.1 Bio-Clinical Parameters
3.5.4.2 Ultrasound Neck Findings
3.5.4.3 Management
3.6 Discussion
3.7 Conclusion
References
4: Sonography of Large Parathyroid Adenomas
4.1 Introduction
4.2 Case 1
4.2.1 Bio-Clinical Parameters
4.2.2 Technetium-99m Sestamibi Scan
4.2.3 Ultrasound Neck Findings
4.2.4 Management
4.3 Case 2
4.3.1 Bio-Clinical Parameters
4.3.2 Ultrasound Neck
4.3.2.1 Findings
4.3.3 Management
4.3.4 Discussion
4.4 Case 3
4.4.1 Bio-Clinical Parameters
4.4.2 Findings: Technetium-99m sestamibi scan
4.4.3 Ultrasound Neck
4.4.3.1 Findings
4.4.4 Management
4.5 Case 4
4.5.1 Bio-Clinical Parameters
4.5.2 Technetium-99m Parathyroid scan
4.5.3 Ultrasound Neck
4.5.4 Management
4.6 Case 5
4.6.1 Bio-Clinical Parameters
4.6.2 99m-Tc Parathyroid Scan
4.6.3 Findings
4.6.4 Ultrasound Neck
4.6.5 Management
4.7 Case 6
4.7.1 Bio-Clinical Parameters
4.7.2 Ultrasound Neck
4.7.2.1 Findings
4.7.3 Management
4.8 Case 7
4.8.1 Bio-Clinical Parameters
4.8.2 Ultrasound Neck
4.8.2.1 Findings
4.8.3 Management
4.9 Case 8
4.9.1 Bio-Clinical Parameters
4.9.2 Ultrasound Neck
4.9.2.1 Findings
4.9.3 Management
4.10 Discussion
References
5: Role of Ultrasound in Evaluation of Ectopic Parathyroid Glands
5.1 Introduction
5.2 Case 1
5.2.1 Bio-Clinical Parameters
5.2.2 Ultrasound Neck
5.2.2.1 Findings
5.2.3 Management
5.3 Case 2
5.3.1 Bio-Clinical Parameters
5.3.2 Management
5.4 Case 3
5.4.1 Bio-Clinical Parameters
5.4.2 Ultrasound Neck
5.4.3 Management
5.5 Case 4
5.5.1 Bio-Clinical Parameters
5.5.2 Ultrasound Neck
5.5.2.1 Findings
5.5.3 Management
5.6 Case 5
5.6.1 Bio-Clinical Parameters
5.6.2 Ultrasound Neck
5.6.3 Management
5.7 Case 6
5.7.1 Bio-Clinical Parameters
5.7.2 Ultrasound Neck
5.7.3 Management
5.8 Case 7
5.8.1 Bio-Clinical Parameters
5.8.2 Ultrasound Neck
5.8.2.1 Findings
5.8.3 Management
5.9 Case 8
5.9.1 Bio-Clinical Parameters
5.9.2 Ultrasound Neck
5.9.2.1 Findings
5.9.3 Management
5.10 Case 9
5.10.1 Bio-Clinical Parameters
5.10.2 Ultrasound Neck
5.10.2.1 Findings
5.10.3 Management
5.11 Case 10
5.11.1 Bio-Clinical Parameters
5.11.2 Ultrasound Neck
5.11.2.1 Findings
5.11.3 Management
5.12 Case 11
5.12.1 Bio-Clinical Parameters
5.12.2 Ultrasound Neck
5.12.2.1 Findings
5.12.3 Management
5.13 Case 12
5.13.1 Bio-Clinical Parameters
5.13.2 Ultrasound Neck
5.13.2.1 Findings
5.14 Discussion
5.14.1 Ectopic Parathyroids Along the Thymo-thymic Tract
5.14.2 Intrathyroidal Parathyroids
References
6: Sonographic Technique and Tips to Localize Tiny Parathyroids
6.1 Introduction
6.1.1 Management
6.2 Case 1
6.2.1 Bio-Clinical Parameters
6.2.2 Ultrasound Neck
6.2.3 Management
6.3 Case 2
6.3.1 Bio-Clinical Parameters
6.3.2 Ultrasound Neck
6.3.2.1 Findings
6.3.3 Management
6.4 Case 3
6.4.1 Bio-Clinical Parameters
6.4.2 Ultrasound Neck
6.4.3 Management
6.5 Case 4
6.5.1 Bio-Clinical Parameters
6.5.2 Ultrasound Neck
6.5.2.1 Findings
6.5.3 Management
6.6 Case 5
6.6.1 Bio-Clinical Parameters
6.6.2 Ultrasound Neck
6.6.2.1 Findings
6.6.3 Management
6.7 Case 6
6.7.1 Bio-Clinical Parameters
6.7.2 Ultrasound Neck
6.7.3 Management
6.8 Discussion
References
7: Sonography of Dual and Multiple Parathyroid Adenomas in Sporadic Primary Hyperparathyroidism
7.1 Introduction
7.1.1 Management
7.2 Case 1
7.2.1 Bio-Clinical Parameters
7.2.2 Ultrasound Neck
7.2.2.1 Findings
Right Inferior Parathyroid Gland
Left Superior Parathyroid Gland
Left Inferior Parathyroid Gland
7.2.3 Management
7.3 Case 2
7.3.1 Bio-Clinical Parameters
7.3.2 Ultrasound Neck
7.3.2.1 Findings
Left Inferior Parathyroid
Right Superior Parathyroid
Right Inferior Parathyroid
7.3.3 Management
7.4 Discussion
References
8: Role of Sonography in Hyperparathyroidism in Chronic Kidney Disease and Post-Renal Transplant Recipients
8.1 Introduction
8.2 Pathophysiology of Hyperparathyroidism in Renal Disease
8.2.1 Management
8.3 Case 1
8.3.1 Clinical Details
8.3.1.1 Bio-Clinical Parameters
8.3.1.2 Ultrasound Neck
Findings
Right Inferior Parathyroid
Right Superior Parathyroid
Left Superior Parathyroid
Left Inferior Parathyroid
8.3.2 Management
8.4 Case 2
8.4.1 Bio-Clinical Parameters
8.4.2 Ultrasound Neck
8.4.2.1 Right Inferior Parathyroid
8.4.2.2 Left Inferior Parathyroid
8.4.3 Management
8.5 Case 3
8.5.1 Bio-Clinical Parameters
8.5.2 Ultrasound Neck
8.5.3 Management
8.6 Case 4
8.6.1 Bio-Clinical Parameters
8.6.2 Ultrasound Neck
8.6.2.1 Findings
Right Superior Parathyroid
Right Inferior Parathyroid
Left Superior Parathyroid
8.6.3 Management
8.7 Case 5
8.7.1 Bio-Clinical Parameters
8.7.2 Ultrasound Neck
8.7.2.1 Findings
Right Superior Parathyroid
Right Inferior Parathyroid
Left Superior Parathyroid
Left Inferior Parathyroid
8.7.3 Management
8.8 Case 6
8.8.1 Bio-Clinical Parameters
8.8.2 Ultrasound Neck
8.8.2.1 Findings
Left Inferior Parathyroid
Left Superior Parathyroid
Right Inferior Parathyroid
Right Superior Parathyroid
8.8.3 Management
8.9 Case 7
8.9.1 Bio-Clinical Parameters
8.9.2 Ultrasound Neck
8.9.3 Management
8.10 Case 8
8.10.1 Bio-Clinical Parameters
8.10.2 Discussion: Altered Echotexture of parathyroid nodules
8.10.3 Management
8.11 Case 9
8.11.1 Bio-Clinical Parameters
8.11.2 Ultrasound Neck
8.11.2.1 Findings
Left Superior Parathyroid
Left Inferior Parathyroid
Right Inferior Parathyroid
8.11.3 Management
8.12 Conclusion
References
9: Sonography Findings in Parathyroid Carcinoma and Heterogenous Parathyroids
9.1 Introduction
9.2 Case 1
9.2.1 Bio-Clinical Parameters
9.2.2 Ultrasound Neck
9.2.3 Management
9.2.4 Post Operative Histopathology Findings
9.3 Case 2
9.3.1 Bio-Clinical Parameters
9.3.2 Ultrasound
9.3.3 Management
9.4 Case 3
9.4.1 Bio-Clinical Parameters
9.4.2 Ultrasound
9.4.2.1 Findings
9.4.3 Management
9.5 Discussion
References
10: Ultrasound Evaluation of Parathyroid Adenoma with Co-Existent Thyroid Pathology
10.1 Introduction
10.2 Case 1
10.2.1 Bio-Clinical Parameters
10.2.1.1 Findings
10.2.2 Ultrasound Neck
10.2.3 Management
10.2.4 Discussion
10.3 Case 2
10.3.1 Bio-Clinical Parameters
10.3.2 Ultrasound Neck
10.3.3 Management
10.4 Case 3
10.4.1 Bio-Clinical Parameters
10.4.2 Ultrasound Neck
10.4.3 Management
10.4.4 Discussion
10.5 Case 4
10.5.1 Bio-Clinical Parameters
10.5.2 Ultrasound Neck
10.5.3 Management
10.5.4 Discussion
References
11: Ultrasound Essentials in MEN Syndromes and Familial Hyperparathyroidism
11.1 Introduction
11.2 Case 1
11.2.1 Bio-Clinical Parameters
11.2.2 Ultrasound Neck
11.2.2.1 Findings
11.2.3 Discussion
11.2.4 Management
11.3 Case 2
11.3.1 Bio-Clinical Parameters
11.3.2 Ultrasound Neck
11.3.2.1 Findings
Right Superior Parathyroid
Right Inferior Parathyroid
Left Superior Parathyroid
Left Inferior Parathyroid
11.3.3 Management
11.4 Case 3
11.4.1 Bio-Clinical Parameters
11.4.2 Ultrasound Neck
11.4.2.1 Findings
Right Inferior Parathyroid
Right Superior Parathyroid
Left Inferior Parathyroid
Left Superior Parathyroid
11.4.3 Management
11.5 Case 4
11.5.1 Bio-Clinical Parameters
11.5.2 Ultrasound Neck
11.5.2.1 Findings
Right Superior Parathyroid
Right Inferior Parathyroid
Left Superior Parathyroid
Left Inferior Parathyroid
11.5.3 Management
11.6 Discussion
11.7 Case 5
11.7.1 Bio Clinical Parameters
11.7.1.1 Radiograph of Both Hands and Skull
Findings
11.7.1.2 99m-Technetium Parathyroid Scan
11.7.2 Ultrasound Neck
11.7.3 Management
11.8 Case 6
11.8.1 Bio Clinical Parameters
11.8.2 Ultrasound Neck
11.8.2.1 Findings
11.8.3 Management
11.9 Case 7
11.9.1 Bio Clinical Parameters
11.9.2 Ultrasound Neck
11.9.2.1 Right Inferior Parathyroid
11.9.2.2 Left Inferior Parathyroid
11.9.3 Management
11.9.4 Discussion
11.9.4.1 MEN1
11.9.4.2 MEN2
References
12: Essentials of Surgical Perspectives of Parathyroid Surgery
12.1 Indications for Exploration
12.2 Surgical Strategy and Approach to Exploration
12.3 Technique of Parathyroidectomy
12.3.1 Positioning of the Patient
12.3.2 Exploration of the Neck
12.3.3 Minimally Invasive Techniques
12.3.4 Closure of the Incision
12.3.5 Postoperative Care
References
Afterword

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Atlas of Sonography of Parathyroid Alka Ashmita Singhal Foreword by Ambrish Mithal SS Baijal Deepak Sarin K K Handa Kulbir Ahalawat

123

Atlas of Sonography of Parathyroid

Alka Ashmita Singhal

Atlas of Sonography of Parathyroid

Alka Ashmita Singhal Division of Radiology & Nuclear Medicine Medanta The Medicity Gurugram, Haryana, India

This work contains media enhancements, which are displayed with a “play” icon. Material in the print book can be viewed on a mobile device by downloading the Springer Nature “More Media” app available in the major app stores. The media enhancements in the online version of the work can be accessed directly by authorized users. ISBN 978-981-19-7918-7 ISBN 978-981-19-7919-4 (eBook) https://doi.org/10.1007/978-981-19-7919-4 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Foreword

It is indeed an honour for me to write about Dr Alka Singhal’s “Atlas of Sonography of Parathyroid”. The last two decades have witnessed remarkable changes in the diagnosis and management of parathyroid disorders. In the early days it used to be said that the only way to locate the parathyroid gland is to locate an expert surgeon! With the advent of superior imaging techniques and minimally invasive surgery there has been a paradigm shift in our approach to parathyroid surgery. Expert ultrasonologists are now able to successfully localize parathyroid adenomas in the majority of cases. The key word here is “expert” as not all ultrasonologists are able to perform this job with the same degree of dexterity. I have been associated with Dr Alka Singhal for more than a decade. During this period she has been an invaluable asset to the parathyroid team. Her ability to pick up adenomas which are not localized by other techniques is amazing. I depend almost totally on her for the localization of parathyroid adenomas. It is most appropriate that she is bringing out this highly informative Atlas to share her rich experience in this field, so that all can benefit from it. I am certain that this book will be very useful and widely quoted. Endocrinology and Diabetology Max Healthcare (PAN Max) New Delhi, India

Ambrish Mithal

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Foreword

The science of imaging has advanced remarkably in the last three decades turning radiologists into the new hidden heroes of the modern-day medicine. A good image coupled with the telescopic eye of a proficient sonologist is the key to many complex clinical puzzles. Ultrasonography has proven to be one of the most handy and practical devices in elucidating various challenging clinical enigmas. My own case shall serve as corroborative evidence. Following an episode of renal colic I was detected with hypercalcaemia, raised parathormone and host of debilitating symptoms. Exploration for a parathyroid tumour began with sonography of the neck which was reported normal (due to the observer error). As luck would have it, a second review imaging by Dr Alka Singhal, known for her expertise in the niche area of thyroid and parathyroid glands, spotted the enlarged parathyroid gland and a thyroid nodule. What followed was a well-delineated surgery which ended the long tale of my misery. My personal experience has reinforced my confidence in the deftness of Dr Alka Singhal. Her astute skills, expertise and laser sharp eye for detecting the cloistered pathology in these tiny and mostly benign glands (thyroid and parathyroid) must have solved many such jigsaw puzzles. Her in-depth knowledge of this demarcated area has blossomed into this atlas that comprises many priceless sonographic images of her patients. I am sure that this novel atlas will do full justice in depicting several diverse entities pertaining to the parathyroid and the thyroid glands. It shall serve as a quick reckoner and ready resource for learners in this alcove of

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imaging. This unique collection is definitely poised to grab the attention of interested readers and beginners. I congratulate her and wish Dr Alka great success in this endeavour. Dermatology, Venereology and Leprology Lady Hardinge Medical College and Associated Hospitals, Sucheta Kriplani and Kalawati Saran Children Hospital Delhi, India

Vibhu Mendiratta

Foreword

Building a good parathyroid treatment team requires several key ingredients. The radiologist’s role in this is crucial, given the enormous variability in the exact location of the parathyroid glands. A reliable localizing study can greatly simplify a focused parathyroidectomy. On the other hand, a misleading report can send you on a wild goose chase extending from mandible to diaphragm and still be unsuccessful. I am a Head & Neck specialist trained in India and the United States, with particular interest in surgery of the parathyroid glands. I have been performing these operations for 20 years now, summing to about 400 cases. I first met Dr Alka Singhal when she attended our presentation, made in our hospital, about our budding parathyroid programme. At the time, the programme was pioneered by Endocrinology and our department. We had recently started our Head & Neck Surgery department and were keen to develop this aspect of our craft. Dr Singhal would prove an invaluable asset, as an experienced sonologist with manifest interest in pursuing imaging of the parathyroid glands. Over the past 10 years, we have developed a relationship of mutual admiration and respect. She has single-handedly conducted ultrasounds on over 500 patients with parathyroid disease and published extensively on the same. We have interacted over virtually every case to discuss feedback and potential improvements. Her continuing eagerness to better our work and its outcomes would inspire any medical professional. Despite the availability of other imaging modalities in our institute, including the Sestamibi and 4D CT scan, the ultrasound remains our most reliable test. We have published extensively arguing

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for this stance, and I strongly believe it comes down to the woman behind the machine. This appears to be a worldwide trend; different institutes rely on different localizing studies depending on the expertise of their own professionals. The ultrasound’s biggest advantage lies in its affordability and availability. The additional information it provides about the thyroid gland allows surgeons to plan appropriate neck surgery of the central compartment in a single sitting. In a country like ours, where patients often struggle to cover the expenses of such operations, minimizing the number of tests needed to safely plan an effective surgery is of utmost importance. This textbook extensively covers ultrasound-based imaging of the parathyroid glands and has lovely images collected over the last decade to supplement the text. I believe Dr Singhal’s book will aid sonologists who are intrigued by this application of radiology and hope it will help many more to develop interest and expertise in this area. Head and Neck Oncology Surgery Medanta, The Medicity Gurgaon, NCR Delhi, India

Deepak Sarin

Foreword

Parathyroid disorders have always been an enigma for the clinicians owing to its variable presentation and different management approaches. These disorders are frequently encountered by general physicians, endocrinologists, ENT and head and neck surgeons, nephrologists and gastroenterologists. Correct diagnosis of hyperparathyroidism and appropriate localization of the abnormal glands are imperative for the success of the treatment, radiology being the first and foremost tool to be used for the appropriate management. Dr Alka Ashmita Singhal is a renowned radiologist with special interest in parathyroid and thyroid disorders. She has a vast experience in the diagnosis of parathyroid lesions on ultrasonography that she has gathered over her experience of 10 years at Medanta - The Medicity. She has innumerable publications to her credit and has mentored a number of master courses on the diagnosis of thyroid and parathyroid lesions. Personally, I feel her radiological assessment is at par with all other investigation modalities for this disorder and helps us tremendously during surgical procedures. It is of paramount importance while dealing with difficult situations like multi-gland parathyroids, ectopic locations, parathyroid carcinomas and parathyroid along with multi-nodular thyroids. Her book on Atlas of Sonography of Parathyroid is an excellent tool describing a spectrum of parathyroid disorders ranging from primary hyperparathyroidism to hyperparathyroidism in special situations like chronic kidney disease, paediatric population, pregnancy, and associated thyroid nodules. It aims at building the foundation of diagnosing the disease and focuses on the management as per the specific case. It is a perfect condensation of her

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unparalleled expertise on this topic that she has gracefully decided to share with the rest of the medical fraternity. With different chapters on individual scenarios this book covers almost all aspects of parathyroid disorders. I strongly feel that this book is a “must read” and will be of immense help to all ENT and head and neck surgeons, endocrinologists, radiologists and other clinicians interested in this field in understanding the disease better and will be of great value in clinical decision making. Head and Neck Oncology Department Medanta - The Medicity Gurgaon, India

Kanika Rana

Foreword

I have known Dr Alka as a fellow colleague in our department of Medanta Division of Radiology and Nuclear Medicine at Medanta Medicity for the past 11 years. She has had a great passion and dedication for neck ultrasound, and she has been contributing significantly to the localization of parathyroid nodules in hyperparathyroidism on ultrasound imaging. This has been a very valuable skill in our tertiary care hospital and a golden asset in pregnancy with hyperparathyroidism cases where other investigations are contraindicated. This textbook of Atlas of Sonography of Parathyroid is a comprehensive compilation of state-of-the-art ultrasound images and video clips of parathyroid adenoma in various clinical scenarios. Both greyscale and colour Doppler ultrasound images and video clips are included. It is a great resource material for all interested in doing parathyroid ultrasound as to how to localize the abnormal parathyroid with the tips and the tricks and the challenges during the parathyroid ultrasound. Best wishes to all the readers. Medanta, The Medicity Gurgaon, NCR Delhi, India

Kulbir Ahlawat

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Foreword

I was delighted when I received a request from Dr Alka Singhal to write a foreword to this book because, for many years, I have admired her incredible work in the field of hyperparathyroidism. We are witnessing a rise in primary hyperparathyroidism cases in India, predominantly the asymptomatic form. As an endocrinologist, the single most challenge which I face during evaluation of such cases is localization of parathyroid nodule responsible for hypersecretion of parathyroid hormone. MIBI parathyroid scan and USG neck are the two main modalities in localization of parathyroid nodule. USG neck if performed by an expertise has much higher specificity and sensitivity than MIBI scan. Our endocrinology department is fortunate to have Dr Alka’s expertise which has been proven in recently published studies from our centre where Dr Alka Singhal performed USG neck in nearly 200 primary hyperparathyroidism cases and showed superiority of USG neck over MIBI scan in localization. Not only endocrinologists, but also head and neck surgeons rely upon Dr Alka’s expertise and experience in pre-op localization of parathyroid nodule translating into high surgical success rates. Her passion towards her work and willingness to help patients are commendable. Whenever I ask her for an urgent ultrasound of my patients, she manages to take her time through her busy schedule and goes out of the way to do the needful. She is not only an excellent radiologist but also a very kind, compassionate and joyful person by heart. Looking through this magnificent atlas, I am absolutely amazed at Dr Alka’s talent. Through this book she has shared her experience and knowledge in the field of hyperparathyroidism in minutest detail. She has compre-

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Foreword

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hensively covered all forms of hyperparathyroidism including primary, tertiary, sporadic, familial, ectopic and challenging cases. It is a mine of information for all radiologists, endocrinologists and head and neck oncosurgeons. In short Dr Alka’s book is unique and surely a work to treasure for anyone who is interested in the field of parathyroid disorders. So read it, enjoy it and learn from it. Thank you Dr Alka for producing such a master work. Division of Endocrinology and Diabetes Medanta - The Medicity Gurgaon, India

Parjeet Kaur

Foreword

Imaging plays a pivotal role in the management of parathyroid gland pathologies. Ultrasound imaging is now accepted as the first investigation in the workup strategy of patients with suspected hyper-functioning parathyroid glands. The strategic location of the parathyroid gland, and there being four of them, requires a high level of expertise of the radiologist. In addition the anatomical variations and aberrant location further add to the complexity of the imaging of parathyroid glands. Hence the need of the hour is to have an up to date, comprehensive resource for easy referral. This Atlas of Sonography of Parathyroid provides an extensive review of the subject. Dr Alka Ashmita Singhal’s compendium provides more than adequate detailing of the ultrasound imaging techniques of parathyroid backed up by excellent images. Her passion and interest for ultrasound imaging of the neck supported by numerous presentations and publications make her the most appropriate expert to author a textbook on this subject. I am sure that this book will be useful to radiologists in training as well as in practice and should become an essential reference textbook in departments that offer teaching and training. It would also be a very useful reference to head and neck surgeons. I recommend this book to all physicians who treat patients with parathyroid disease. Radiology and Imaging Medanta, The Medicity Gurgaon, NCR Delhi, India

Sanjay Saran Baijal

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Foreword

Name of book – Atlas of Parathyroid Ultrasound. Author – Dr Alka Ashmita Singhal As a young, practicing thoracic surgeon in Sir Ganga Ram Hospital, I was diagnosed with a thyroid malignancy early on in my career. As irony would have it, being a part of the medical field didn’t help. It didn’t deter the enervating and daunting task of hunting down the best treatment. I scoured through the entire country as staging was uncertain to end my search at Medanta. I was referred to Dr Singhal who was able to accurately stage it after which I received the necessary treatment. As fate would have it, in 2 years, I returned to Medanta and, wistfully so, started working alongside her. The neck has unparalleled mobility, but its anatomy contains 7 vertebrae, 32 muscles, 13 lymph node stations, 3 glands, the oesophagus as well as the airway—that’s a lot of action in a comparatively small area. With the dearth of radiologists in the country specializing in head and neck radiology, I have personally referred countless patients to Dr Singhal for ultrasound of the neck and they have always been pleased with the consistently impeccable results. With a comprehensive body of work and an exhaustive repository of professional accomplishments, Dr Singhal is the best suited to fill in spaces in the community that can only come from her polished experience in the field. A recipient of Bharat Ratna Dr Radhakrishnan Gold Medal Award in 2019 for excellence in the field of radiology, Dr Singhal is an ex-alumnus of UNSW in Sydney where she sought Fellowship in Medical Ultrasound. She then moved to Rockville, USA, for Fellowship in Musculoskeletal and Doppler/Vascular Ultrasound. With countless authored articles and publications in international journals to her name, what amazes me is her unparalleled professional experience xix

Foreword

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spanning over 30 years, detecting over 600 parathyroid nodules and countless thyroid nodules. Hopefully, future generations will be able to benefit from such knowledge and experience. Can’t think of anyone better suited to pen down this book. Brighton, MA, USA

Sarav Shah

Foreword

It is my great pleasure to write about the great work Dr Alka Singhal is doing in the field of imaging for parathyroid localization. As we know with the advent of localization studies mainly USG and sestamibi scan, surgeons can do focused parathyroidectomy with much lesser morbidity. USG has the advantage of not only indicating the culprit parathyroid but also helping in exact location of parathyroid in relation to surrounding structures as well as detecting ectopic locations. But it is operator dependent and requires a lot of experience and skill. Dr Alka is one of the best in the field and many a time has solved the problem for us especially in cases of discordance. I wish her all the very best and extend my heartiest congratulations for this fabulous book on parathyroid imaging. This book will certainly be very useful for all stakeholders involved in hyperparathyroidism management. Max Superspeciality Hospital Vaishali and Patparganj Delhi, India

Sowrabh Kumar Arora

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Foreword

It is my pleasure to write a forward for the Atlas of Sonography of Parathyroid written by Dr Alka Singhal, Associate Director, Department of Radiology, Medanta The Medicity, Gurugram. She is a very accomplished radiologist with focus on ultrasound imaging of the head and neck area. Parathyroid is a very important yet neglected area which has been covered extensively in this book. The broad topics covered include basics of parathyroid sonography, parathyroid adenomas, ultrasound for ectopic parathyroids, sonographic techniques to localize tiny parathyroids, sonography to localize parathyroids in primary hyperparathyroidism, ultrasound evaluation of parathyroids with coexisting thyroid disease, parathyroid carcinoma USG evaluation and ultrasound essentials in MEN syndromes and familial hyperparathyroidism. The last chapter is on surgical perspectives of parathyroid surgery. There are very few good books on ultrasound in parathyroid. This book is likely to fill that gap. I recommend this book for those in training and the experienced head and neck surgeon, radiologist, and endocrinologist. Department of ENT and Head Neck Surgery Medanta Medicity Gurugram, India

K. K. Handa

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Acknowledgements

I am really grateful to Dr Deepak Sarin, Director and Head of Head and Neck Oncosurgery Department at Medanta, for his constant referral, guidance and feedback, inspiring me to do more and more and dwell into finer and finer details and come up with the best possible diagnosis for the patients and to support them to full recovery. My immense gratitude to Dr Ambrish Mithal, Chairman of the Division of Endocrinology and Diabetes at Medanta, for all his excellent recommendations and trust in my work. My heartfelt gratitude to Dr Naresh Trehan, Chairman and Managing Director at Medanta Medicity Hospital, Gurgaon, Delhi, India, for opening up a fantastic multispeciality tertiary hospital with great integrated departments across all clinical specialties and with various centres across the country and globe serving millions restore their perfect health. I am highly grateful to Dr S Baijal, Chairman Medanta Division of Radiology and Nuclear Medicine, and the entire interventional radiology team for their fantastic and very targeted tissue sampling enabling the most accurate diagnosis. My deepest thanks to the Radiology Department for all its state-of-the-art diagnostic ultrasound imaging equipment with the latest technological advances enabling ease of acquiring all the required diagnostic information for each patient. I am incredibly grateful to my nuclear medicine colleagues for all their fantastic correlation across all the various imaging modalities and constant guidance and feedback, enabling the best possible diagnosis for the benefit of all patients. I sincerely thank the entire radiology equipment in ultrasound, computed tomography, magnetic resonance imaging and nuclear medicine and all my technicians and support staff across all the various modalities for always encouraging me and promptly supporting me with all the required information. I am incredibly grateful to the entire Medanta Cytopathology and Histopathology team for their great analysis, categorization and final diagnosis of tissue, enabling deep experiential learning and laying the foundation of knowledge for future generations. My deepest gratitude to dear God almighty for giving me a fantastic work opportunity with the most fabulous work colleagues and clinicians across endocrinology, nephrology, internal medicine, ENT, medical and surgical oncology, and wellness with their excellent referral base and expertise, empowering me in my diagnostic work and research. xxv

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I am immensely grateful to the Medanta Information Technology for their phenomenal technical support enabling retrieving the required information so easily, quickly and conveniently at all times empowering my research, analysis and publication. My immense heartfelt thanks to the Medanta Graphic Designing team for their constant support in editing and labelling all the diagnostic images and videos and presenting them in a format enabling easy viewership and understanding for all our readers. My deepest gratitude to them for making things so easy and possible for me. I am grateful for the vast array of technological tools available to me, such as computers, laptops, mobile phones, and the internet, as well as devices such as paper, pen, and printer, which enabled me to conduct research, write my research and analysis, and organize and format it in a manner that is suitable for publication. I am grateful to my mother and my brothers for always inspiring me and empowering me to focus on my very own dreams and aspirations of writing and expressing the immense knowledge and experiential learning over many years and publishing the textbook, wherein the treasure of knowledge is made available for the benefit of humanity for all the generations to come. I am grateful to my family, my husband and my mother-in-law for always showering their love and blessings on me, enabling me to fulfil my dreams. I am grateful to my father and my father-in-law for bestowing their divine heavenly blessings upon me at all the times, guiding and strengthening me to focus and concentrate to achieve my dreams and goals in life. My heartfelt thanks to my son Anish for his phenomenal strength of love and bonding and immense joy given to me at all times, enlightening and rejuvenating me with the spark needed to see the excellent outcomes and work towards them. My deepest thanks to my daughter Isha, an angel in my life blessing me with great love and strength and joy and inspiring me to get going, put in my very best and be determined for fantastic outcomes. My deepest thanks to my supporters at home Mariam and Mansi for addressing all the domestic chores and managing the functioning of my home very efficiently and smoothly, enabling me to focus and concentrate on my publications. I sincerely thank all my extended family and friends for their best wishes and inspiration. I extend my sincere thanks to all my support nursing staff, front office staff, transport team and all my patients for their trust and faith in me. My deepest thanks to all my teachers and mentors at school, college and all walks of life for all their eternal guidance, teachings and support. I am grateful to all my teachers and professors in medical college and school life for all their teachings and valuable guidance and instilling in me the strength and confidence to achieve results beyond my imagination and unravel and create new possibilities in life. My sincere gratitude to my parents for giving me birth to an excellent upbringing, education and values to empower me to provide the best diagnostics in the given scenario for every patient. My most profound appre-

Acknowledgements

Acknowledgements

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ciation to my body, all my body parts and their harmonious working together, my intelligence and all the five elements such as earth, water, air, fire and space for making my inside and outside world beautiful with perfect harmony and balance, and enabling me to perform, imbibe, analyse and share my knowledge with all around me. I am grateful to all the patients I scanned for supporting me with their health stories and life experiences due to hyperparathyroidism. I am grateful to my patients for sharing their challenges of life and vague symptoms and the significant improvement in lifestyle post-treatment, inspiring and highlighting the great need to share the knowledge, primarily to diagnose tiny parathyroid nodules that often are undetectable on other imaging modalities, thus guiding focussed surgery. I aim to empower everyone involved in thyroid and parathyroid ultrasound to make scanning, diagnosing, and detecting a parathyroid a joyful experience full of accomplishment. This is my intention for each and every reader. This is my intention for you.

Contents

1 Introduction to Parathyroid Sonography�� 1 1.1 Anatomy and Embryology of Parathyroid Glands�� 2 1.2 Vascular Anatomy �� 2 1.3 Nerve Relations�� 2 1.4 Microscopic Anatomy�� 3 1.5 Embryological Anatomy �� 3 1.5.1 Origin, Migration and Eutopic Locations �� 3 1.6 Calcium Metabolism and Role of Parathyroid Hormone and Calcitonin �� 3 1.7 Hyperparathyroidism�� 4 1.8 Types of Hyperparathyroidism�� 4 1.9 Clinical Symptoms of Hyperparathyroidism�� 4 1.10 Biochemical Investigations: A Practical Approach to Hypercalcaemia�� 5 1.11 Approach to Hypercalcaemia�� 6 1.12 Imaging �� 6 1.12.1 Guiding Principles of Parathyroid Imaging�� 6 1.12.2 Parathyroid Scintigraphy: Tc-99m Sestamibi SPECT and SPECT/CT�� 7 1.12.3 Four-Dimensional Computed Tomography (4D CT)�� 7 1.12.4 Ultrasound of the Neck for Localization of the Parathyroid Glands�� 8 1.12.5 Patient Positioning for Neck Ultrasound�� 9 1.12.6 Ultrasound�� 9 1.12.7 Key Greyscale Ultrasound Features�� 10 1.12.8 Typical Parathyroid Adenoma�� 11 1.12.9 Role of Spectral Doppler in Parathyroid Evaluation �� 13 1.12.10 Role of Contrast-Enhanced Ultrasound (CEUS) in Parathyroid Evaluation�� 13 1.12.11 Role of Shear Wave Elastography in Parathyroid Nodule Evaluation�� 13 1.12.12 Differential Diagnosis of an Orthotopic Parathyroid Adenoma�� 13

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1.13 Medical Management�� 15 1.13.1 Calcium Supplementation/Restriction�� 15 1.14 Indications for Surgery�� 16 1.14.1 Skeletal Guidelines �� 16 1.14.2 Renal Guidelines�� 16 1.14.3 Histopathology�� 17 1.14.4 Parathyroid Adenoma�� 17 1.14.5 Parathyroid Hyperplasia�� 17 1.14.6 Parathyroid Carcinoma �� 17 References�� 17 2 Sonography of a Typical Parathyroid Adenoma: Solitary Parathyroids as Seen on Ultrasound�� 21 2.1 Introduction�� 21 2.2 Case 1�� 21 2.2.1 Bio-Clinical Parameters�� 21 2.2.2 Technetium-99m Sestamibi Scan�� 21 2.2.3 Ultrasound Neck �� 22 2.2.4 Management�� 22 2.3 Case 2�� 23 2.3.1 Bio-Clinical Parameters�� 23 2.3.2 Imaging �� 23 2.3.3 Management�� 25 2.4 Case 3�� 25 2.4.1 Bio-Clinical Parameters�� 25 2.4.2 Management�� 25 2.5 Case 4�� 26 2.5.1 Clinical Details�� 26 2.5.2 Bio-Clinical Parameters�� 27 2.5.3 Technetium-99m Sestamibi Scan�� 27 2.5.4 Management�� 27 2.6 Case 5�� 28 2.6.1 Bio-Clinical Parameters�� 28 2.6.2 “Tc-99m Sestamibi” Scan Findings�� 28 2.6.3 Management�� 29 2.7 Case 6�� 30 2.7.1 Bio-Clinical Parameters�� 30 2.7.2 Ultrasound of the Neck for Parathyroid�� 30 2.7.3 Management�� 30 2.8 Case 7�� 31 2.8.1 Bio-Clinical Parameters�� 31 2.8.2 Ultrasound Neck �� 31 2.8.3 Management�� 32 2.9 Case 8�� 32 2.9.1 Bio-Clinical Parameters�� 32 2.9.2 Ultrasound Neck �� 32 2.9.3 Skeletal Survey �� 32 2.9.4 Management�� 33

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2.10 Case 9�� 35 2.10.1 Bio-Clinical Parameters�� 35 2.10.2 Ultrasound Neck �� 35 2.10.3 Management�� 36 2.11 Case10�� 36 2.11.1 Bio-Clinical Parameters�� 36 2.11.2 Ultrasound Neck �� 36 2.11.3 Management�� 38 2.12 Case 11�� 38 2.12.1 Bio-Clinical Parameters�� 38 2.12.2 Management�� 38 2.13 Discussion �� 39 2.14 Management�� 41 2.15 Conclusion�� 41 References�� 41 3 Atypical Sonographic Appearances of Enlarged Parathyroids �� 43 3.1 Introduction�� 43 3.2 Changes in the Shape of Adenoma �� 43 3.2.1 Case 1�� 43 3.2.2 Case 2�� 44 3.2.3 Case 3�� 46 3.2.4 Discussion �� 47 3.3 Cystic Changes in Parathyroid Lesions�� 48 3.3.1 Case 4�� 48 3.3.2 Case 5�� 48 3.3.3 Case 6�� 50 3.4 Parathyroid Calcification�� 53 3.4.1 Case 7�� 53 3.5 Altered Echotexture and Lobulations in Parathyroid Lesions�� 55 3.5.1 Case 8�� 55 3.5.2 Case 9�� 56 3.5.3 Case 10�� 59 3.5.4 Case 11�� 59 3.6 Discussion �� 61 3.7 Conclusion�� 62 References�� 62 4 Sonography of Large Parathyroid Adenomas�� 63 4.1 Introduction�� 63 4.2 Case 1�� 63 4.2.1 Bio-Clinical Parameters�� 63 4.2.2 Technetium-99m Sestamibi Scan�� 63 4.2.3 Ultrasound Neck Findings�� 63 4.2.4 Management�� 64

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4.3 Case 2�� 66 4.3.1 Bio-Clinical Parameters�� 66 4.3.2 Ultrasound Neck �� 66 4.3.3 Management�� 67 4.3.4 Discussion �� 67 4.4 Case 3�� 67 4.4.1 Bio-Clinical Parameters�� 68 4.4.2 Findings: Technetium-99m sestamibi scan �� 68 4.4.3 Ultrasound Neck �� 68 4.4.4 Management�� 68 4.5 Case 4�� 70 4.5.1 Bio-Clinical Parameters�� 70 4.5.2 Technetium-99m Parathyroid scan�� 70 4.5.3 Ultrasound Neck �� 70 4.5.4 Management�� 70 4.6 Case 5�� 71 4.6.1 Bio-Clinical Parameters�� 71 4.6.2 99m-Tc Parathyroid Scan �� 71 4.6.3 Findings�� 72 4.6.4 Ultrasound Neck �� 72 4.6.5 Management�� 72 4.7 Case 6�� 73 4.7.1 Bio-Clinical Parameters�� 73 4.7.2 Ultrasound Neck �� 74 4.7.3 Management�� 74 4.8 Case 7�� 75 4.8.1 Bio-Clinical Parameters�� 75 4.8.2 Ultrasound Neck �� 75 4.8.3 Management�� 77 4.9 Case 8�� 77 4.9.1 Bio-Clinical Parameters�� 77 4.9.2 Ultrasound Neck �� 77 4.9.3 Management�� 77 4.10 Discussion �� 78 References�� 79 5 Role of Ultrasound in Evaluation of Ectopic Parathyroid Glands�� 81 5.1 Introduction�� 81 5.2 Case 1�� 81 5.2.1 Bio-Clinical Parameters�� 82 5.2.2 Ultrasound Neck �� 82 5.2.3 Management�� 83 5.3 Case 2�� 83 5.3.1 Bio-Clinical Parameters�� 83 5.3.2 Management�� 84 5.4 Case 3�� 84 5.4.1 Bio-Clinical Parameters�� 84 5.4.2 Ultrasound Neck �� 84 5.4.3 Management�� 84

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5.5 Case 4�� 85 5.5.1 Bio-Clinical Parameters�� 85 5.5.2 Ultrasound Neck �� 85 5.5.3 Management�� 86 5.6 Case 5�� 86 5.6.1 Bio-Clinical Parameters�� 86 5.6.2 Ultrasound Neck �� 86 5.6.3 Management�� 87 5.7 Case 6�� 88 5.7.1 Bio-Clinical Parameters�� 88 5.7.2 Ultrasound Neck �� 88 5.7.3 Management�� 88 5.8 Case 7�� 89 5.8.1 Bio-Clinical Parameters�� 90 5.8.2 Ultrasound Neck �� 90 5.8.3 Management�� 90 5.9 Case 8�� 92 5.9.1 Bio-Clinical Parameters�� 92 5.9.2 Ultrasound Neck �� 92 5.9.3 Management�� 93 5.10 Case 9�� 93 5.10.1 Bio-Clinical Parameters�� 94 5.10.2 Ultrasound Neck �� 94 5.10.3 Management�� 95 5.11 Case 10�� 95 5.11.1 Bio-Clinical Parameters�� 95 5.11.2 Ultrasound Neck �� 95 5.11.3 Management�� 95 5.12 Case 11�� 96 5.12.1 Bio-Clinical Parameters�� 96 5.12.2 Ultrasound Neck �� 97 5.12.3 Management�� 98 5.13 Case 12�� 98 5.13.1 Bio-Clinical Parameters�� 98 5.13.2 Ultrasound Neck �� 98 5.14 Discussion �� 100 5.14.1 Ectopic Parathyroids Along the Thymo-thymic Tract�� 100 5.14.2 Intrathyroidal Parathyroids �� 101 References�� 101 6 Sonographic Technique and Tips to Localize Tiny Parathyroids �� 103 6.1 Introduction�� 103 6.1.1 Management�� 104 6.2 Case 1�� 104 6.2.1 Bio-Clinical Parameters�� 104 6.2.2 Ultrasound Neck �� 105 6.2.3 Management�� 105

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6.3 Case 2�� 105 6.3.1 Bio-Clinical Parameters�� 105 6.3.2 Ultrasound Neck �� 106 6.3.3 Management�� 106 6.4 Case 3�� 107 6.4.1 Bio-Clinical Parameters�� 107 6.4.2 Ultrasound Neck �� 107 6.4.3 Management�� 109 6.5 Case 4�� 109 6.5.1 Bio-Clinical Parameters�� 109 6.5.2 Ultrasound Neck �� 109 6.5.3 Management�� 110 6.6 Case 5�� 110 6.6.1 Bio-Clinical Parameters�� 110 6.6.2 Ultrasound Neck �� 110 6.6.3 Management�� 111 6.7 Case 6�� 111 6.7.1 Bio-Clinical Parameters�� 111 6.7.2 Ultrasound Neck �� 111 6.7.3 Management�� 112 6.8 Discussion �� 112 References�� 112 7 Sonography of Dual and Multiple Parathyroid Adenomas in Sporadic Primary Hyperparathyroidism�� 115 7.1 Introduction�� 115 7.1.1 Management�� 115 7.2 Case 1�� 115 7.2.1 Bio-Clinical Parameters�� 116 7.2.2 Ultrasound Neck �� 116 7.2.3 Management�� 116 7.3 Case 2�� 118 7.3.1 Bio-Clinical Parameters�� 118 7.3.2 Ultrasound Neck �� 118 7.3.3 Management�� 119 7.4 Discussion �� 120 References�� 120 8 Role of Sonography in Hyperparathyroidism in Chronic Kidney Disease and Post-Renal Transplant Recipients�� 121 8.1 Introduction�� 121 8.2 Pathophysiology of Hyperparathyroidism in Renal Disease�� 121 8.2.1 Management�� 122 8.3 Case 1�� 122 8.3.1 Clinical Details�� 122 8.3.2 Management�� 122

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8.4 Case 2�� 123 8.4.1 Bio-Clinical Parameters�� 123 8.4.2 Ultrasound Neck �� 123 8.4.3 Management�� 125 8.5 Case 3�� 125 8.5.1 Bio-Clinical Parameters�� 125 8.5.2 Ultrasound Neck �� 125 8.5.3 Management�� 127 8.6 Case 4�� 127 8.6.1 Bio-Clinical Parameters�� 127 8.6.2 Ultrasound Neck �� 127 8.6.3 Management�� 128 8.7 Case 5�� 128 8.7.1 Bio-Clinical Parameters�� 129 8.7.2 Ultrasound Neck �� 129 8.7.3 Management�� 129 8.8 Case 6�� 132 8.8.1 Bio-Clinical Parameters�� 132 8.8.2 Ultrasound Neck �� 132 8.8.3 Management�� 133 8.9 Case 7�� 133 8.9.1 Bio-Clinical Parameters�� 133 8.9.2 Ultrasound Neck �� 134 8.9.3 Management�� 134 8.10 Case 8�� 135 8.10.1 Bio-Clinical Parameters�� 135 8.10.2 Discussion: Altered Echotexture of parathyroid nodules�� 135 8.10.3 Management�� 136 8.11 Case 9�� 136 8.11.1 Bio-Clinical Parameters�� 136 8.11.2 Ultrasound Neck �� 136 8.11.3 Management�� 136 8.12 Conclusion�� 137 References�� 138 9 Sonography Findings in Parathyroid Carcinoma and Heterogenous Parathyroids�� 139 9.1 Introduction�� 139 9.2 Case 1�� 139 9.2.1 Bio-Clinical Parameters�� 140 9.2.2 Ultrasound Neck �� 140 9.2.3 Management�� 140 9.2.4 Post Operative Histopathology Findings�� 141 9.3 Case 2�� 142 9.3.1 Bio-Clinical Parameters�� 142 9.3.2 Ultrasound�� 142 9.3.3 Management�� 143

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9.4 Case 3�� 144 9.4.1 Bio-Clinical Parameters�� 144 9.4.2 Ultrasound�� 145 9.4.3 Management�� 145 9.5 Discussion �� 146 References�� 146 10 Ultrasound Evaluation of Parathyroid Adenoma with Co-Existent Thyroid Pathology�� 147 10.1 Introduction�� 147 10.2 Case 1�� 147 10.2.1 Bio-Clinical Parameters�� 147 10.2.2 Ultrasound Neck �� 148 10.2.3 Management�� 148 10.2.4 Discussion �� 148 10.3 Case 2�� 150 10.3.1 Bio-Clinical Parameters�� 150 10.3.2 Ultrasound Neck �� 150 10.3.3 Management�� 152 10.4 Case 3�� 152 10.4.1 Bio-Clinical Parameters�� 152 10.4.2 Ultrasound Neck �� 152 10.4.3 Management�� 152 10.4.4 Discussion �� 152 10.5 Case 4�� 153 10.5.1 Bio-Clinical Parameters�� 153 10.5.2 Ultrasound Neck �� 154 10.5.3 Management�� 154 10.5.4 Discussion �� 154 References�� 156 11 Ultrasound Essentials in MEN Syndromes and Familial Hyperparathyroidism�� 157 11.1 Introduction�� 157 11.2 Case 1�� 158 11.2.1 Bio-Clinical Parameters�� 158 11.2.2 Ultrasound Neck �� 158 11.2.3 Discussion �� 158 11.2.4 Management�� 159 11.3 Case 2�� 159 11.3.1 Bio-Clinical Parameters�� 160 11.3.2 Ultrasound Neck �� 160 11.3.3 Management�� 160 11.4 Case 3�� 162 11.4.1 Bio-Clinical Parameters�� 162 11.4.2 Ultrasound Neck �� 162 11.4.3 Management�� 164

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11.5 Case 4�� 164 11.5.1 Bio-Clinical Parameters�� 164 11.5.2 Ultrasound Neck �� 165 11.5.3 Management�� 165 11.6 Discussion �� 167 11.7 Case 5�� 167 11.7.1 Bio Clinical Parameters�� 167 11.7.2 Ultrasound Neck �� 169 11.7.3 Management�� 169 11.8 Case 6�� 169 11.8.1 Bio Clinical Parameters�� 169 11.8.2 Ultrasound Neck �� 169 11.8.3 Management�� 169 11.9 Case 7�� 171 11.9.1 Bio Clinical Parameters�� 171 11.9.2 Ultrasound Neck �� 171 11.9.3 Management�� 171 11.9.4 Discussion �� 172 References�� 174 12 Essentials of Surgical Perspectives of Parathyroid Surgery�� 177 12.1 Indications for Exploration �� 177 12.2 Surgical Strategy and Approach to Exploration�� 178 12.3 Technique of Parathyroidectomy�� 178 12.3.1 Positioning of the Patient�� 178 12.3.2 Exploration of the Neck�� 179 12.3.3 Minimally Invasive Techniques�� 180 12.3.4 Closure of the Incision�� 180 12.3.5 Postoperative Care�� 180 References�� 181 Afterword�� 183

About the Author

Alka Ashmita Singhal a postgraduate in radiodiagnosis from Sawai Man Singh Medical College, Jaipur, affiliated to the University of Rajasthan. She has worked in Sydney, Australia, and in Toronto, Canada, in the field of ultrasound imaging. She is presently the associate director, Medanta Division of Radiology and Nuclear Medicine at Medanta the Medicity Hospital, Gurgaon, Delhi NCR, India. Dr Singhal is a regular invited faculty for her pioneering work on the art of localizing the tiny parathyroid nodules on ultrasound and for a precise thyroid and neck lymph node ultrasound assessment. She has more than 50 peer-reviewed international publications and has delivered numerous oral and poster presentations in various international meetings related to radiology and head and neck, thyroid, and parathyroid imaging. She is a member of the Indian Society of thyroid Surgeons (ISTS) and International Federation of Head and Neck oncology (IFHNO). She is a leading Thyroid, Parathyroid, and Neck ultrasound imaging professional and is sought after for expert further ultrasound opinion in challenging cases. Member of IRIA, ICRI, RSNA, ECR, and BISI she is a reviewer of many leading international journals and has reviewed over 400 articles. She was invited as a Scientific Chairperson in 2019 by both European Congress of Radiology, Vienna, Austria, and Radiological Society of North America, Chicago, USA, for a session on neck-thyroid and parathyroid imaging. She is a recipient of Bharat Ratna Dr Radhakrishnan Gold Medal Award 2019 for her outstanding achievements in the areas of medicine and research particularly in the field of radiology and radiodiagnosis by the Global Economic Progress and Research Association, New Delhi.

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Abbreviations

1,25-(OH)2D 1,25-dihydroxycholecalciferol 18F FDG 18F-fluorodeoxyglucose (18F-FDG) 25-OHD 25-hydroxyvitamin D3 4D-CT Four-dimensional computed tomography 99mTc Technetium 99m BMD Bone mineral density Ca Calcium CI Confidence interval CKD Chronic kidney disease CT Computed tomography Dexa Dual-energy X-ray absorptiometry DOTANOC Ga-68 DOTA-NOC EUS Endoscopic ultrasound FDA Food and Drug Administration FHH Familial hypocalciuric hypercalcemia FNA Fine needle aspiration HPT-JT Hyperparathyroidism-jaw tumour syndrome IOPTH Intraoperative parathyroid hormone monitoring Lymphoma (GCB type) Germinal centre B-cell mCi Millicurie MEN Multiple endocrine neoplasia MEN1 Multiple endocrine neoplasia type 1 (MEN1) MEN2 Multiple endocrine neoplasia type 2 (MEN2) mEq/L Milliequivalents per litre (mEq/L) mg/dL Milligrams per decilitre (mg/dL) MGD Multiglandular disease MIBI Methoxyisobutyl isonitrile MIVAP Minimally invasive video-assisted parathyroidectomy mm Millimetre mmol/L Millimoles per litre (mmol/L) MRI Magnetic resonance imaging PET Positron emission tomography pg/mL Picograms per millilitre (pg/mL) PHPT Primary hyperparathyroidism PTH Parathyroid hormone RLN Recurrent laryngeal nerve

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xlii

S. PTH SHPT SPECT

Serum parathyroid hormone Secondary hyperparathyroidism Single-photon emission computerized tomography Tc Technetium Tc 99m Technetium-99m (99mTc) THPT Tertiary hyperparathyroidism T-score The T-score is a comparison of a person’s bone density with that of a healthy 30-year-old of the same sex US Ultrasound VFA Vertebral Fracture Assessment VIT D Vitamin D WHO World Health Organization Z-score The Z-score is a comparison of a person’s bone density with that of an average person of the same age and sex

Abbreviations

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Introduction to Parathyroid Sonography

The prevalence of hypercalcaemia across the globe is approximately 1–2%. The two most common causes of hypercalcaemia are hyperparathyroidism and malignancy-associated hypercalcaemia and together account for 90% of cases (Sadiq et al. 2021). The prevalence of parathyroid- dependent hypercalcaemia and hyperparathyroidism is 0.2–0.8% in the general population and increases with age. There is significant morbidity associated due to the hidden nature of the disease with a large number of subclinical cases. The varied clinical presentation and vague and subtle symptoms are often unreported and often only surface after the clinical diagnosis is established. Hyperparathyroidism is one of the leading causes of secondary osteoporosis, leading to increased fracture risk and traumatic complications. Recurrent renal calculi and pancreatitis amount to a significant number of cases presenting with acute abdomen. Peptic ulcer disease may at times be the first manifestation of hyperparathyroidism. Less often, psychiatric symptoms often alert to the presence of underlying hyperparathyroidism. Vague symptoms of fatigue and aches and pain may be present for years and are only revealed on clinical evaluation, though they significantly compromise the lifestyle and well-being of the patient. While clinical diagnosis is often hidden for a long time, once established, imaging diagnosis and localization of abnormal parathyroids is still a challenge in most developing countries across the globe.

The definitive management of primary hyperparathyroidism (PHPT) is parathyroidectomy, to remove one or more of the abnormal parathyroids. Surgical approach is focused parathyroidectomy or bilateral neck exploration. As per the guidelines of the American Association of Endocrine Surgeons (Wilhelm et al. 2016), parathyroidectomy is indicated for all patients with symptomatic PHPT, when serum calcium levels are more than 1 mg/dL above the normal limits, regardless of the presence or absence of objective symptoms, evidence of renal impairment and osteoporosis. Parathyroidectomy is recommended when the age at first diagnosis is less than 50 years. Other indications of parathyroidectomy are neurocognitive and/or neuropsychiatric symptoms that are attributable to PHPT. Parathyroidectomy is not recommended when there is any contraindication to surgery or anaesthesia, and ethanol ablation or medical management with annual biochemical evaluation and bone DEXA scan is recommended in these cases. An accurate preoperative localization of the enlarged parathyroid glands in hyperparathyroidism significantly contributes to management outcomes. Various imaging modalities are employed, as we shall discover in this textbook, the commonest and the most easily available and convenient modality being ultrasound. Ultrasound scanning techniques are operator dependent, and localization of abnormal parathyroid glands on ultrasound still remains a diagnostic challenge for most ultrasound

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 A. A. Singhal, Atlas of Sonography of Parathyroid, https://doi.org/10.1007/978-981-19-7919-4_1

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professionals. The aim of writing this parathyroid ultrasound atlas is to strengthen the operator skill and the required knowledge for improving the outcomes and sensitivity and specificity of parathyroid localization. As per available literature, in most experienced hands, the sensitivity and localization accuracy of localization of parathyroid nodules in hyperparathyroidism are 98% and 93% (Kaur et al. 2016). The commonest cause of primary hyperparathyroidism is usually a single parathyroid adenoma seen in 89% cases, hyperplasia in 6% cases, multiple adenomas in 4% cases and, rarely, a parathyroid carcinoma in 1% cases (Johnson et al. 2007). The atlas includes various cases of hyperparathyroidism with their clinical presentation, biochemical parameters and imaging findings correlated with surgical findings and management outcomes. The purpose of this ultrasound atlas of parathyroid is to empower each and every reader with the art of diagnosing and localizing the abnormal parathyroid nodules on ultrasound in cases of hyperparathyroidism. Thank you for choosing to read the book.

1.1 Anatomy and Embryology of Parathyroid Glands Parathyroid glands are paired endocrine glands, usually four in number, two superior parathyroids and two inferior parathyroids. These can be found to be located in eutopic locations or ectopic locations. The parathyroid glands are eutopic in location in approximately 84% cases and are found juxta-thyroid, commonly embedded along the posterior surface of the corresponding lobe of thyroid (Phitayakorn and McHenry 2006). Normal parathyroid glands are small, flattened or oval glands, being smaller than the size of a pea, measuring between 2 and 5 mm in diameter and weighing between 30 and 50 mg (Yao et al. 2004). Rarely, parathyroid glands may be only three or more than four, when supernumerary parathyroids are seen (Andrade et al. 2014).

1 Introduction to Parathyroid Sonography

1.2 Vascular Anatomy In majority of cases, the arterial supply of both the superior and the inferior parathyroids is from the inferior thyroid artery, which runs along the posterior surface of the thyroid. Inferior thyroid artery is a branch of the thyrocervical trunk. The parathyroids are also supplied by the superior thyroid artery branches or from an anastomosis between the superior and inferior thyroid artery or by the thyroid ima artery. Venous drainage is into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into the internal jugular vein, and the inferior thyroid vein drains into the brachiocephalic vein. Lymphatic vessels from the parathyroid gland drain into the paratracheal and deep cervical lymph nodes. The ectopic parathyroid glands in the mediastinum are supplied by the branches of the internal thoracic artery, mainly the thymic branch. The most characteristic finding of the vascular supply of parathyroids is that the polar feeding artery reaches the pole of the parathyroid gland and then divides there either in a fork pattern with sub-branches or as an arc and then branches supply the entire gland. This vascular pattern is unique and is being used as a very useful tool in identifying the parathyroids on colour Doppler ultrasound and contrast computed tomography scan. It helps in the differential diagnosis of parathyroid nodules from cervical lymph nodes, thyroid nodules and other abnormalities in the area.

1.3 Nerve Relations The parathyroid glands are supplied by vasomotor sympathetic nerves derived from thyroid branches of the cervical ganglia. The recurrent laryngeal nerve runs along the posterior surface of the thyroid and lies close to the posterior surface of the thyroid and adjacent parathyroids and is an important challenge at surgery.

1.6 Calcium Metabolism and Role of Parathyroid Hormone and Calcitonin

1.4 Microscopic Anatomy The parathyroid glands are composed of chief cells or the principal cells and parenchymal fat cells enclosed within a thin fibrous capsule (Brown and Limaiem 2021). The chief cells are often arranged in cords or nests interspersed with the rich capillary network. The chief cells are abundant, polygonal in shape, measuring 6–8 μm, with central round nuclei and are responsible for the production of parathyroid hormone. Few oxyphil cells packed with mitochondria are seen. The colour of the parathyroid glands is pinkish and varies from yellow to red-brown based on the amount of fat content and the vascularity. With increasing age, the amount of fat content in the parathyroid glands increases, and this is determined on a cellular level by the increase in the number of yellow parenchymal fat cells.

1.5 Embryological Anatomy 1.5.1 Origin, Migration and Eutopic Locations The superior parathyroids and the lateral anlagen of the thyroid arise from the fourth branchial (pharyngeal) pouch. As the parathyroid glands travel along the line of their respective pharyngeal pouches from the angle of the mandible to the mediastinum, any aberrations can lead to the ectopic locations of the parathyroid glands anywhere along this median line. The upper (superior) parathyroid glands descend in the line of the fourth pharyngeal pouch with the thyroid, and the lower (inferior) parathyroids descend in the line of the third pharyngeal pouch along with the thymus. The superior parathyroids, being closely related to the thyroid, descend minimally, and their locations are relatively constant. The normal juxta-thyroid location of the superior parathyroid glands is posterior to the upper or middle third of the thyroid lobe. The inferior parathyroid glands are typically located within 1 cm radius of the lower pole of the correspond-

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ing thyroid, usually posterior or postero-medial or postero-lateral to the lower pole of the thyroid. Any parathyroid glands that are not juxta-thyroid or adjacent to the thyroid gland are classified as ectopic parathyroids, and these may be located above or below the thyroid gland in the neck or located in the mediastinum. Supernumerary parathyroid glands result from the separation of the parathyroid anlage when the glands pull away from the pharyngeal pouch during the embryological branchial complex phase. Supernumerary glands are often associated with thymus, and often, thymectomy is performed in cases of MEN1 and persistent hyperparathyroidism.

1.6 Calcium Metabolism and Role of Parathyroid Hormone and Calcitonin Parathyroid hormone is the central factor for calcium homeostasis and can be aptly called as the calcium thermostat of the body. Its coordinated actions on the bones, kidney and intestine work together to increase the flow of calcium into the extracellular fluid and raise the serum calcium levels. Normal serum calcium levels range from 8.6 to 10.3 mg/dL (equivalent to 2.2–2.6 mmol/L and 4.4–5.2 mEq/L). Primary hyperparathyroidism is characterized by hypercalcaemia with elevated or inappropriately normal parathyroid hormone levels. Calcitonin is a peptide hormone secreted by the parafollicular C cells of the thyroid in response to high serum calcium levels. It lowers serum calcium levels by inhibiting osteoclastic activity in the bones and increasing the kidneys’ urinary excretion. The exact physiological role of calcitonin is uncertain. The complete absence of calcitonin post-total thyroidectomy patients requires no replacement, and no major effects on calcium metabolism are seen in patients with very high calcitonin levels, such as in patients with medullary thyroid carcinoma. Synthetic calcitonin hormone is used in the treatment of osteoporosis (Muñoz-Torres et al. 2004).

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1.7 Hyperparathyroidism Hyperparathyroidism is a bio-clinical spectrum accompanied with hypercalcaemia and elevated serum parathyroid hormone levels or inappropriately normal parathyroid hormone levels. It causes significant morbidity and mortality primarily due to manifestations of resultant prolonged hypercalcaemia. Hyperparathyroidism occurs when one or more of the parathyroid glands release too much parathyroid hormone, elevating the serum calcium levels. With hypercalcaemia (serum calcium levels more than 10.3 or 10.5 mg/dL), an intact PTH level of greater than 25 pg/mL is considered abnormal, assuming a normal range of 10–65 pg/mL (Goldstein 1990).

1.8 Types of Hyperparathyroidism Primary hyperparathyroidism (HPT) occurs due to an intrinsic abnormality in the parathyroid glands (adenoma, hyperplasia or carcinoma), leading to hypersecretion of the parathyroid hormones. Rarely, parathyroid cysts may be functional and hypersecretory leading to hyperparathyroidism (Bhatia et al. 2020; Khan et al. 2012). Primary hyperparathyroidism may be seen as a sporadic disorder or as part of genetic syndromes such as MEN 1 and MEN 2a, MEN 4, and hereditary hyperparathyroidism jaw tumour syndrome (HPT-JT). Non-syndromic hereditary PHPT is seen in familial isolated primary hypercalcinaemia and neonatal severe hyperparathyroidism (Sung 2015). Secondary hyperparathyroidism results due to any factor outside of the parathyroid glands which causes enlargement of the parathyroid glands and increased secretion of parathyroid hormone, the two common causes being renal insufficiency (eGFR of 10.3 mg/dL) has widespread effects on the body involving the gastrointestinal, renal, skeletal, neuromuscular and cardiovascular

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systems. The two most common causes of hypercalcaemia are PHPT and malignancy accounting for 80–90% of cases. Out of these, PHPT accounts for most of the cases in ambulatory patients, and malignancy accounts for most of the patients in hospital admissions (Guilmette and Sadow 2019). The various laboratory parameters used for the differential diagnosis of hypercalcaemia are serum calcium, parathyroid hormone, chloride, phosphorus, serum 25-OHD, 1,25(OH)2D and urinary calcium. Intact PTH assay is essential in the cases of renal insufficiency. Malignancy is usually clinically evident by the time it has led to lead to significant hypercalcaemia. Serum parathyroid hormone levels are suppressed in cases of hypercalcaemia due to malignancy and are elevated in cases of hypercalcaemia due to PHPT. Broadly speaking, patients with hypercalcaemia due to malignancy have much higher serum calcium levels and have more symptoms due to hypercalcaemia as compared to those with benign causes of hyperparathyroidism (Mirrakhimov 2015). The presence of long- standing asymptomatic hypercalcaemia is more suggestive of PHPT. The degree of hypercalcaemia in PHPT is mild (usually less than 11 mg/dL) unless it is due to parathyroid carcinoma, where severe hypercalcaemia is seen. The serum parathyroid hormone levels may be either low or normal or elevated (range 25–65 pg/ mL). Urine calcium levels are elevated (>100 mg/ dL) in primary hyperparathyroidism. Urinary calcium levels when low (14 mg/dL

1.11 Approach to Hypercalcaemia The first step is to confirm hypercalcaemia, by correcting for albumin or by doing ionized calcium levels. Corrected calcium = (4.0 g/ dL − [plasma albumin]) 0.8 + [serum calcium]). In PHPT, PTH levels are high or inappropriately normal (i.e. not suppressed despite hypercalcaemia). Diagnosis of normocalcaemic PHPT requires the exclusion of other causes of secondary elevation of PTH. Familial hypocalciuric hypercalcaemia should be considered in patients with long-standing hypercalcaemia, urinary calcium levels less than 100 mg/24 h and a calcium-to-creatinine clearance ratio less than 0.01. In 3–5% of patients, PHPT occurs as a component of an inherited syndrome, with specific types including familial isolated PHPT, multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), hyperparathyroidism-jaw tumour syndrome (HPT-JT) and familial hypocalciuric hypercalcemia (FHH). Genetic counselling should be performed for patients younger than 40 years with PHPT and multigland disease (MGD) and considered for those with a family history or syndromic manifestations. Multigland disease affects approximately 15% of patients with PHPT and should be routinely considered in preoperative planning. In patients with asymptomatic PHPT, abdominal imaging should be performed for the detection of nephrocalcinosis or nephrolithiasis.

Bone mineral density should be measured at the lumbar spine, hip and distal radius, preferably using DXA. Bone loss on DXA in PHPT is typically greatest at the forearm (one-third distal radius site), as this site is comprised primarily of cortical bone, and least at the lumbar spine, composed primarily of trabecular bone. BMD should routinely be obtained at three sites: lumbar spine, hip and distal third of the radius. Examination should occur within 2 years prior to initial surgical evaluation. Lithium-associated PHPT occurs in up to 15% of long-term users, with increased rates of MGD. Thiazide diuretics, which can uncover mild PHPT, are associated with hypercalcaemia that may be secondary to a reduction in urine calcium excretion, increased intestinal calcium absorption or metabolic alkalosis from diuretic use.

1.12 Imaging The standard parathyroid imaging modalities include ultrasound (US), sestamibi scanning and more recently four-dimensional computed tomography (4D CT).

1.12.1 Guiding Principles of Parathyroid Imaging 1. For any patient, the diagnosis of PHPT is biochemical. Imaging has no demonstrated utility in confirming or excluding the diagnosis.

1.12 Imaging

2. The decision to operate is not based on imaging findings, and imaging results should not be used to select patients for surgical referral. Patients with negative imaging remain candidates for parathyroidectomy given the high rate of false negative imaging, especially in cases of MGD. 3. A number of studies have reported that when patients with negative results have imaging repeated at high-volume centres, the sensitivity of localization improves to as high as 92%. 4. Imaging is obtained after deciding to proceed with parathyroidectomy and is performed for the purpose of operative planning. 5. Parathyroid imaging is significantly less accurate in the setting of MGD. Since thyroid disease occurs in 30–51% of patients with PHPT, adequate preoperative evaluation of the thyroid is critical. Low-lying superior glands, especially those in the retroesophageal/retrotracheal positions, may not be visible due to their depth and impeded sound transmission through gas-containing structures like the oesophagus or trachea. Similarly, inferior parathyroid glands low in the thyrothymic ligament and mediastinum may be obscured by overlying bone. Normal parathyroid glands are typically not visible due to their small size (2–3 mm). Meta-analyses have demonstrated a sensitivity of 76% (95% confidence interval [CI] 70–81%) to 79% (95% CI 77–80%), while single-institution series have reported sensitivity as high as 82. However, the sensitivity drops considerably to 35% (95% CI 30–40%) in the setting of MGD. Ultrasound of the neck is recommended to localize parathyroid disease and assess for concomitant thyroid pathology. Parathyroid fine needle aspiration (FNA) should be reserved for difficult cases of localization such as intrathyroidal parathyroids and reoperative cases. Preoperative parathyroid (FNA) is not recommended except in unusual, difficult cases of PHPT and should not be performed if parathyroid cancer is suspected (Rania et al. 2019). This technique has 82% sensitivity and 100% specificity when the PTH levels in the sample washout are higher than the serum PTH levels.

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1.12.2 Parathyroid Scintigraphy: Tc-99m Sestamibi SPECT and SPECT/CT Technetium-99m sestamibi scan is a gold standard examination for localization of the abnormal parathyroids in patients with hyperparathyroidism. Various protocols adopted are single-phase dual-isotope subtraction imaging, dual-phase single-isotope imaging or a combination of the two to obtain planar or tomographic views. In SPECT/CT (single-photon emission computed tomography), the functional information obtained by the radiotracer (technetium-99m) is fused with anatomical information on planar CT images and helps in an effective three-dimensional localization (Eslamy and Ziessman 2008) (Fig. 1.1a–c). Hence, SPECT imaging provides three- dimensional information that helps give better anatomic detail. The technique is especially helpful in identifying posteriorly located low-lying superior adenomas that are typically obscured by thyroid uptake. This modality can be performed with an attenuated CT component to reduce radiation exposure. The main benefits of sestamibi imaging include the ability to assess for deep cervical and ectopic glands (including in the mediastinum), a relatively low exposure to ionizing radiation and ability to assess for function of autotransplanted tissue to the forearm or elsewhere. The metaanalysis of Ruda et al. using studies of Tc-99m sestamibi scintigraphy in the setting of PHPT calculated the sensitivity for detecting solitary adenomas at 88% (95% confidence interval, 87–89%). However, sensitivities for the detection of both hyperplasia and double adenomas were low, calculated at 44% (95% confidence interval, 41–48%) and 30% (95% confidence interval, 2–62%), respectively https://www.ajronline.org/ doi/10.2214/AJR.06.0938.

1.12.3 Four-Dimensional Computed Tomography (4D CT) Typically, parathyroid adenomas demonstrate rapid uptake and washout of contrast compared to the thyroid and adjacent tissue. 4D CT has a

1 Introduction to Parathyroid Sonography

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a

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Fig. 1.1 (a–c) Nuclear scintigraphy with methoxyisobutylisonitrile (technetium-99m sestamibi scan or MIBI scan) in an 18-year-old male, diagnosed with acute pancreatitis with PHPT (serum calcium 11.2 mg/dL and serum PTH 199.1 mg/dL). Early images were taken at 30 min and delayed images taken at 2 h post-injection of tracer. Images are zoomed in for the area of interest. Early

images show uniform uptake of the tracer by the thyroid gland and the salivary glands, with increased uptake along the upper pole of the left thyroid (arrow). Delayed images show retention of the tracer along the left thyroid upper pole (arrow), suggestive of left superior parathyroid adenoma. (c) Corresponding ultrasound image showing typical left superior parathyroid adenoma

high sensitivity and specificity for lateralizing (85% and 94%) and predicting the exact location of diseased glands (66% and 89%) in patients with previously negative sestamibi scans (Matthews et al. 2017). Magnetic Resonance Imaging (MRI) is typically reserved for cases of difficult localization, such as for reoperative parathyroid surgery, or for patients who cannot be exposed to ionizing radiation, such as pregnant patients.

1.12.4 Ultrasound of the Neck for Localization of the Parathyroid Glands Normal parathyroid glands are not visualized on current ultrasound imaging. Parathyroid glands abnormally enlarged due to an adenoma or hyperplasia or carcinomatous changes can be detected on high-resolution ultrasound imaging of the neck. Ultrasound is a convenient and bedside

1.12 Imaging

modality without any harmful effects of ionizing radiation and is used to localize parathyroid nodules in hyperparathyroidism. Ultrasound imaging has an integral role in the diagnosis and has the potential to diagnose all the eutopic and ectopic parathyroids in the neck region. In many parts of the world, ultrasound imaging is the preferred first line of investigation, because of its lower cost, ease of availability, non-invasive nature and without any effects of ionizing radiation. There have been significant advances in the ultrasound technology with enhanced transducer sensitivities and capabilities which have contributed to improved diagnostic outcomes. Ultrasound technology is dependent on the operator and the equipment sensitivity and settings. Ultrasound examination begins with careful evaluation of the clinical information provided by the referring physician and by the patient. A detailed scrutiny of the clinical records and available previous imaging is done. Note is made of the serum calcium and serum parathyroid hormone levels. A brief evaluation for any associated factors such as vitamin D deficiency or chronic renal disease or any other history to suggest a familial predisposition is done.

1.12.5 Patient Positioning for Neck Ultrasound The patient is positioned in supine position with a pillow placed underneath the shoulders to slightly hyperextend the neck. This position gives wide exposure of the neck. The examination may be performed with the patient in sitting position; however, I prefer to do it in supine position as it gives great exposure and stabilizes the patient and is perhaps more comfortable for both the patient and the operator. A common pitfall is inadequate exposure of the scan area and limited evaluation of the neck structures. The ultrasound scan area includes all the area superiorly from underneath the mandibles and extending inferiorly up to the clavicles including the suprasternal area and the suprasternal notch. Great care is required in choosing appropriate ultrasound machine settings, starting from transducer selection, exami-

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nation presets, and selecting the most optimum two-dimensional and colour Doppler settings. Experience of the operator significantly contributes to the diagnostic outcomes.

1.12.6 Ultrasound Previously as in 1990, neck ultrasound was done using the standoff technique with a water-based gel, or an inflated water balloon was placed over the anterior neck along and scanned with the low- frequency 3–5 MHz curvilinear transducer. Currently, we are living in an era of great state-of- the-art ultrasound equipment that have a very high sensitivity for the diagnostic evaluation of superficial neck structures. Today, modern transducers with very high frequencies are available and can directly scan the neck and provide excellent resolution. The shape of the transducers commonly used for neck area is usually a linear transducer; however, curvilinear or round-shaped transducers are utilized in select cases. Appropriate machine settings along with appropriate transducer selection must be adopted to get the maximum diagnostic outcome of the ultrasound procedure.

1.12.6.1 Transducer Selection The choice of the transducer depends upon the area being scanned. The principle of ultrasound imaging recommends use of the highest transducer frequency possible for the required depth of penetration in any organ of the body. We can begin the scanning with a millihertz linear transducer of frequency range 4–9 MHz, increasing or decreasing the transducer frequency to achieve the required depth of penetration and to maximize the resolution. The currently available linear transducer frequencies vary with different manufacturers and range between 5 and 14 MHz and 5 and 18 MHz and can be as high as up to 24 MHz. The size of the footprints of currently available linear ultrasound transducers is 39–40 mm, and smaller footprint transducers of 23–26 mm are available which allow adequate contact along the narrow cervices or along the bony or cartilaginous surfaces such as paratracheal region and sternal notch.

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1 Introduction to Parathyroid Sonography

1.12.6.2 Ultrasound Technique A thorough ultrasound scanning is done starting from either superior to inferior or inferior to superior depending on operator preference. Scanning begins from the thoracic inlet and the base of the origins of the common carotid artery and going upwards up to the level of carotid bifurcation and beyond; scanning is done on both the sides in longitudinal and transverse planes and going in oblique plans as required. Superiorly, the area around the angle of the mandible and the submandibular region is evaluated to look for the undescended parathyroid glands and inferiorly, the scan is extended up to the sternal angle. The transducer’s frequency might require adjustment using the millihertz frequency option or by changing the transducer itself. Using the deglutition technique by asking the patient to swallow during the ultrasound procedure might help in visualizing the inferior glands better in cases of enlarged thyroid or in inferiorly located ectopic parathyroid glands. In all cases, a detailed evaluation of the complete thyroid gland is done to look for any diffuse thyroid abnormalities or any discrete focal thyroid nodules, and if any abnormality is detected, the findings are documented in the ultrasound reporting. Evaluation of cervical lymph nodes and all other neck structures is included as well.

of the thyroid and parathyroid glands may be affected and pose a diagnostic challenge. 4. Atypical parathyroids may present with cystic changes, calcifications and rarely haemorrhage in a parathyroid cyst. 5. In cases of multiglandular parathyroid hyperplasia in cases of chronic renal disease, the parathyroid nodules are often seen to be isoechoic or lesser hypoechoic in relative comparison to a typical parathyroid adenoma seen in cases of primary hyperparathyroidism.

1.12.7 Key Greyscale Ultrasound Features

1. Most parathyroid adenomas larger than a centimetre size are easily demonstrated on ultrasound by an experienced professional. The challenge appears specifically in smaller, lesser than centimetre-sized nodules where sestamibi and other imaging modalities are often equivocal. Ultrasound is a highly sensitive technique and, when applied well in appropriate clinical settings, has the potential to diagnose most of the parathyroid nodules in the neck. Ultrasound combined with technetium- 99m scan has a diagnostic sensitivity of 99% and a specificity of 98% (Singhal et al. 2020). 2. Demonstration of the polar feeding vessel at a pole of the parathyroid nodule is an excellent clue and increases the diagnostic confidence in all these cases.

Parathyroid adenomas are homogeneously hypoechoic relative to the thyroid gland (Rumack et al. 2011). 1. However, in ectopic parathyroid adenomas, there may not be adjacent thyroid parenchyma visualized in the same ultrasound frame of view for comparison. 2. In cases of coexistent thyroiditis or multinodular goitre, the criteria of comparison with the adjacent thyroid parenchyma may not be applicable due to altered echotexture of the background thyroid parenchyma itself. 3. In cases of large thyroids causing anatomical distortion, the relative anatomical orientation

A thin echogenic thyroid capsule separating the thyroid gland from the adjacent parathyroid adenoma is appreciable on high-resolution ultrasound and is seen as a thin white line (Fig. 1.2). 1. Heterogeneous parathyroids or parathyroid carcinoma may be suspected when the plane of cleavage between the parathyroid and the adjacent parathyroid is merging, and the capsule is not well defined. The presence of chaotic vessels on colour Doppler may be seen in these cases. Parathyroid adenomas vary in size from subcentimetre-sized nodules to as large as 6–10 cm.

1.12 Imaging

a

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Fig. 1.2 (a–d) A 52-year-old male with PHPT (serum calcium, 12.9 mg/dL; parathyroid hormone (PTH), 451.0 pg/mL). Longitudinal and transverse ultrasound scans with colour Doppler showing a hypoechoic nodule (thin arrow) measuring 20 mm × 8 mm × 9 mm located

inferior to the lower part of the right thyroid suggestive of right inferior parathyroid adenoma. Note the characteristic polar feeding vessel (arrow) entering the parathyroid nodule at its superomedial aspect and then branching to supply the gland

1.12.8 Typical Parathyroid Adenoma

capsule or poles of the thyroid gland. These lesions often account for false positives on sestamibi scan as well. 3. The colour Doppler settings on ultrasound must always be adjusted with an adequate filling of a vessel in the field of view for correct interpretation of the ultrasound findings. In the neck area, the vessels commonly selected are the carotid vessels for adjusting the Doppler settings and optimization techniques.

1.12.8.1 Key Colour Doppler Ultrasound Features On colour Doppler, parathyroid adenomas are hypervascular lesions. 1. After identification of a possible parathyroid adenoma, colour Doppler settings are turned on the machine. Most parathyroid adenomas show significantly increased vascularity relative to the thyroid gland. However, being a relative phenomenon, this phenomenon may be obscured in cases of coexistent thyroiditis or Graves’ disease where the thyroid gland itself shows profound vascularity. 2. Thyroid abnormalities such as thyroid follicular adenomas also show significantly increased vascularity on colour Doppler and may mimic a parathyroid adenoma when present in a strategic location close to the

A typical polar feeding vessel is seen leading to a pole of the parathyroid adenoma and characteristically branching as a fork into two vessels, and further sub-branches arise to supply the whole of the parathyroid gland. 1. This polar feeding artery is usually a branch of the inferior thyroid artery or from the superior thyroid artery or their anastomosis or very rarely from the thyrocervical trunk.

1 Introduction to Parathyroid Sonography

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2. This signature identification of the polar feeding vessel is a hallmark in the identification of a parathyroid nodule and, when demonstrated, clearly differentiates it from other differential possibilities of a lymph node or a parathyroid nodule. 3. The demonstration of this feature is dependent on the expertise of the ultrasound operator and the equipment settings. 4. This feature is noted in all ectopic parathyroids, including intrathyroidal parathyroids, and its demonstration in these cases is supportive in identification and differential diagnosis. Parathyroid adenomas are seen to have an arc rim vascularity on colour Doppler. The arc rim is a result of the sub-branches arising from the polar feeding artery and supplying the gland. 1. The presence of an arc rim vascularity is another peculiar feature of a parathyroid ade-

noma (Fig. 1.3) and contrasts well and helps differentiation from a lymph node with its intrinsic hilar vascularity pattern. 2. Appropriate Doppler gain settings are required for the demonstration of the arc rim vascularity, and the Doppler gain neither too less nor excessive. Too less Doppler gain will not demonstrate the feature adequately, and too excessive gain will cause overfilling and obscure the colour flow information and lead to flash artefacts. Adjacent thyroid parenchyma may show increased vascularity, seen as an asymmetric area of increased vascularity in the thyroid adjoining the parathyroid gland. 1. The thyroid parenchyma located just adjoining the juxta-thyroid parathyroid nodule may show increased vascularity relative to the other parts of the thyroid gland. 2. This area can be a clue to locate and trace the hidden underlying parathyroid adenoma during an ultrasound examination.

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Fig. 1.3 (a–d) Longitudinal sonogram with colour Doppler in a patient with PHPT showing a well-defined ovoid homogeneously hypoechoic nodule measuring 26 × 9 × 6 mm located below the lower pole of the left thyroid gland, suggestive of left inferior parathyroid nod-

ule. The nodule is seen to project inferiorly below the lower pole of the left lobe thyroid. On colour Doppler, characteristic peripheral arc rim vascularity and polar feeding vessel are noted in the nodule

1.12 Imaging

1.12.9 Role of Spectral Doppler in Parathyroid Evaluation Studies have been conducted to document the correlation of the resistive index of the parathyroid adenoma, the volume of adenoma and serum parathyroid hormone concentration. The mean resistive index of parathyroid adenoma is 0.69 +0.12. A strong negative correlation exists between the resistive index and serum PTH levels, suggesting a relation between the perfusion of the parathyroid adenoma and the serum PTH levels (Mohammadi et al. 2013).

1.12.10 Role of Contrast-Enhanced Ultrasound (CEUS) in Parathyroid Evaluation The available data on the role of contrast ultrasound for parathyroid adenomas is limited; however, it appears to be a promising adjuvant in diagnosing parathyroid adenomas, especially intrathyroidal ectopic parathyroids, and for localization or confirmation and follow-up with ethanol ablation of the parathyroids (Vestergaard and Thomsen 2011). CEUS has a role in differentiating between lymph nodes and parathyroid adenomas and in challenging cases of dual parathyroid adenomas (Karakas et al. 2012; Uller et al. 2011; Parra Ramírez et al. 2019).

1.12.11 Role of Shear Wave Elastography in Parathyroid Nodule Evaluation The role of shear wave elastography as an adjunct tool to contribute to the diagnosis is under research (Stangierski et al. 2018). Ultrasound elastography objectively evaluates the tissue’s stiffness by measuring the elasticity. The principle of elastography is based on the fact that softer tissues have a higher likelihood of being compressible due to an external force as compared to harder tissues or in other words, the softer tissues offer lesser resistance to deforma-

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tion. A study proposed by Cakir et al. suggests that parathyroid adenomas are relatively stiffer as compared to parathyroid hyperplasia which are soft on ultrasound imaging. The parathyroid nodules are generally softer than the solid thyroid nodules (Cakir et al. 2019).

1.12.12 Differential Diagnosis of an Orthotopic Parathyroid Adenoma 1.12.12.1 Lymph Node Ultrasound appearances of a typical inflammatory lymph node may be of similar shape and echotexture and, when found located strategically in juxta-thyroid areas, may mimic a parathyroid adenoma; however, the presence of a fatty echogenic hilum on B mode contrasts that with a typical smooth homogeneous hypoechoic appearance of a parathyroid adenoma. On colour Doppler, an inflammatory lymph node shows the characteristic hilar vascularity (Fig. 1.4). 1.12.12.2 Blood Vessel An hypoechoic or an almost anechoic appearance of a blood vessel located predominantly at the poles of the thyroid may mimic a thin flattened parathyroid adenoma; however, on careful evaluation, continuity as a vessel can be easily demonstrated and further confirmed with the application of colour Doppler, which shows filling of the lumen of the blood vessel with colour. 1.12.12.3 Thyroid Nodule Thyroid nodules on ultrasound imaging may mimic parathyroid adenomas and do account for the false positives seen on ultrasound. The thyroid nodules can be intrinsic or exophytic. Intrinsic thyroid nodules, such as benign follicular adenomas, show significant vascularity and may cause confusion when located close to the capsule or with intrathyroidal parathyroids. Exophytic thyroid nodules are simply nodules that are protruding out of the normal contour of the thyroid outline. At times, there may be a nodular lesion just bulging the thyroid, which may

1 Introduction to Parathyroid Sonography

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a

b

c

Fig. 1.4 (a–c) Longitudinal sonogram with colour Doppler of a level II lymph node showing a well-defined ovoid hypoechoic lymph node with echogenic hilum and characteristic central or hilar vascularity (arrow)

apparently appear to be extrathyroidal and may mimic a parathyroid adenoma; however, on closer inspection, the lesion is often located within the thyroid capsule. Common examples are the tubercle of Zuckerkandl along the posterior surface of the thyroid and exophytic thyroid nodules. On colour Doppler, these are thyroid tissue, and the characteristic flow pattern of parathyroid adenoma is not seen.

1.12.12.4 Sequestrated Thyroid Tissue Sequestrated thyroid tissue or an accessory thyroid nodule is a developmental abnormality where ectopic nests of thyroid tissue are seen along the path of descent of the thyroid, mainly in the anterior neck in the midline or submandibular or parotid gland locations (Mace et al. 2011). 1.12.12.5 Internal Jugular Vein Thrombosis The internal jugular vein is identified in the neck just lateral to the carotid vessels, and when

thrombus is present, it may be seen to be dilated and demonstrate hypoechoic heterogeneous echoes with or without partial flow seen within. The ultrasound appearances depend on the age of the thrombus and whether the thrombus is partial or complete. Further on tracing the area in longitudinal plane, the identification of continuity with a vessel lumen can be identified (Driver and Kendall 2010; Lee and Siddiqui 2021). Associated collateral draining veins may be observed. Mild pain or probe tenderness may be noted in the area.

1.12.12.6 Schwannoma of the Vagus Nerve in the Neck Schwannomas are benign encapsulated tumours originating from the Schwann cells of the peripheral nervous system. A vagus nerve schwannoma in the neck may mimic an ectopic parathyroid nodule. On ultrasound imaging, these appear as well-defined solid ovoid heterogeneous mass lesions in the carotid triangle, splaying the internal jugular vein and

1.13 Medical Management

the common carotid artery (Man and Chau 2018; Le Corroller et al. 2009). On careful high-resolution ultrasound, the continuity of the lesion with the nerve can be demonstrated. Mild vascularity may be seen; however, no cystic changes or calcifications are seen.

1.12.12.7 Carotid Body Tumour Carotid body tumour also known as carotid body paraganglioma arises from the paraganglion cells of the carotid body. It appears as a well-defined solid heterogeneous hypoechoic mass lesion typically splaying the carotid bulb and the internal and external carotid arteries (Fig. 1.5). It shows significantly increased vascularity on colour Doppler, and based on the circumferential contact with the internal carotid artery, Shamblin’s classification is used to grade the tumour (Hoang et al. 2019).

a

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1.13 Medical Management 1.13.1 Calcium Supplementation/ Restriction The Food and Nutrition Board at the Institute of Medicine recommends an intake of 1000– 1200 mg of calcium daily (between diet and supplements) for adults >18 years, although PHPT patients are often erroneously advised to restrict their calcium intake. Prior to parathyroidectomy, patients with PHPT who are vitamin D deficient can safely begin vitamin D supplementation to restore the Vitamin D levels to ≥20 ng/mL (50 nmol/L). However, restoring vitamin D in deficient patients should not delay the appropriate definitive surgical management of PHPT. The goals of medical treatment include correction of the hypovolemic state, promotion of

b

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Fig. 1.5 (a–c) Carotid body tumour in a 43-year-old female presenting with headache and hypertension. Longitudinal sonogram with colour Doppler at the level of

carotid bifurcation showing a heterogeneous hypoechoic mass lesion located within the carotid bulb and splaying the carotid vessels (arrow)

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renal calcium excretion and inhibition of accelerated bone resorption. In patients with a precipitating intercurrent illness, the underlying problem must be identified and treated. Initial management should be intravenous administration of isotonic saline, based on the degree of hypovolaemia and the comorbidities; one approach suggests 3–4 L of normal saline for 24 h, followed by 2–3 L/24 h, until adequate urine output is established. Once the hypovolaemia has been corrected, loop diuretics such as furosemide are utilized to block calcium reabsorption and promote calciuresis. Thiazide diuretics enhance calcium reabsorption and are contraindicated in the management of severe hypercalcaemia. Restoration of euvolaemia does not treat the underlying pathophysiology of the hypercalcaemic crisis, which is excessive mobilization of calcium from bone. The use of intravenous bisphosphonates can be effective in lowering serum calcium levels, but is slow in onset and not used in non-cancer hypercalcaemia. The effect of calcitonin is relatively short- lived and is most effective in combination with bisphosphonates. Cinacalcet is an oral calcimimetic agent that activates the calcium-sensing receptor on parathyroid cells, increasing sensitivity to extracellular calcium to lower PTH and serum calcium levels. Cinacalcet has been shown to reduce and even normalize serum calcium levels in patients with PHPT, who may maintain normocalcaemia over a prolonged period of time. However, cinacalcet has not been studied in patients with parathyroid crisis. It should be noted that in order to reduce calcium significantly, markedly higher doses (up to 90 mg twice daily) than the 30 mg twice daily currently FDA-approved for patients with PHPT may be required. In patients with PHPT and severe hypercalcaemia, medical management should be seen as a “bridge” to expeditious parathyroidectomy for definitive management (Ameerudden and He 2011; Khoury and Carmichael 2011).

1 Introduction to Parathyroid Sonography

1.14 Indications for Surgery Parathyroidectomy is indicated, and is the preferred treatment, for all patients with symptomatic PHPT. The threshold value for the serum calcium above which surgery is recommended remains >1 mg/dL (>0.25 mM/L) above the upper limit of normal.

1.14.1 Skeletal Guidelines Surgery is recommended for peri- or postmenopausal women and men age 50 and older who have a T-score of −2.5 or less at the lumbar spine, femoral neck, total hip or distal 1/3 radius. In premenopausal women and in men under 50, the Z-score of ≤−2.5 is recommended as the cut- point below which surgery is advised. • Fracture: If a vertebral fracture is present by X-ray or vertebral fracture assessment (VFA), surgery is recommended, even if there is no prior documentation.

1.14.2 Renal Guidelines • Renal function: a creatinine clearance of 400 mg/day), a more complete urinary biochemical stone profile should be considered. In the presence of abnormal findings indicating increased calcium-containing stone risk and marked hypercalciuria, a guideline for surgery is met. • Age under 50 continues to be an evidence- based guideline for surgery.

References

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• Parathyroidectomy is indicated when the clinical or biochemical evidence is consistent with parathyroid carcinoma. • Parathyroidectomy is recommended for patients with neurocognitive and/or neuropsychiatric symptoms that are attributable to PHPT.

arranged within a delicate capillary network. Lobules may be seen within the adenoma. Parathyroid lipoadenomas have more than 50% adipocytes in the adenoma.

Changes in specific endpoints during monitoring that should lead to parathyroid surgery

Parathyroid hyperplastic glands are usually round to oval and vary from red to brown. The cut surface is usually homogeneous. It is characteristically chief cell hyperplasia and is a proliferative disorder involving all the four or more parathyroid glands. As the process is insidious and progressive, variable sizes of the different parathyroids are seen. On histopathology, the nodule is composed of sheets, cords or an acinar arrangement of parenchymal cells with reduced stromal fat. These nodules may be separated by fibrotic bands and septa, mimicking a fibrous capsule. Degenerative cystic changes and haemorrhage are seen less often.

• An increase in serum calcium >1 mg/dL (0.25 mmol/L) above the upper limit of normal. • A reduction in BMD that is significantly decreased over the baseline measurement and a T-score that falls below −2.5 at that site. If the patient demonstrates a progressive reduction in BMD that exceeds the least significant change at any site and the T-score falls to between −2.0 and −2.5, the physician may opt to recommend surgery, although guidelines have not been strictly met. The occurrence of a fragility fracture. The occurrence of a kidney stone. A reduction in creatinine clearance to