Atlas of Parathyroid Imaging and Pathology

This book provides a visual demonstration of normal and ectopic locations of parathyroid adenomas using different modalities in patients with PHPT and to describe parathyroid gland–related pathology. It includes several modern imaging modalities for localization of parathyroid glands and parathyroid adenomas, such as Sestamibi scan, SPECT/CT Sestamibi scan, neck ultrasound, MRI, thin-cut CT, and 4D CT scans. Written by experts in the field, chapters include pathology images corresponding to radiology imaging for some presented cases (gross and high-power view). Authors have also collected radiological images of difficult-to-localize parathyroid adenomas in ectopic (abnormal) locations. The atlas is organized by location of the adenomas in upper and lower eutopic locations followed by ectopic locations. Each case demonstrates dual or triple modalities such as US, Sestamibi scan, or SPECT/CT Sestamibi scan, thin-cut CT scan, or 4D CT performed on the same patient. A chapter on parathyroid pathology is also included to help the reader understand challenges in pathological interpretation.

Atlas of Parathyroid Imaging and Pathology serves as a valuable reference for radiologists, endocrine surgeons, head and neck surgeons, ENT surgeons, surgical oncologists, endocrinologists, pathologists, nephrologists, students, and all physicians and allayed health practitioners involved in the treatment of patients with primary, secondary, and tertiary hyperparathyroidism.

• Language: English
• Publisher: Springer
• Release date: Oct 5, 2020
• ISBN: 9783030409593

Book preview

Part IUltrasound, Sestamibi Scan, and Pathology of the Parathyroid Glands

© Springer Nature Switzerland AG 2020

A. L. Shifrin et al. (eds.)Atlas of Parathyroid Imaging and Pathologyhttps://doi.org/10.1007/978-3-030-40959-3_1

1. Parathyroid Ultrasound

Alexander L. Shifrin¹   and Pritinder K. Thind², ³

(1)

Department of Surgery, Jersey Shore University Medical Center, Neptune, NJ, USA

(2)

University Radiology Group, New Brunswick, NJ, USA

(3)

Jersey Shore University Medical Center, Department of Radiology, Neptune, NJ, USA

Keywords

UltrasoundUSUltrasonographyParathyroid ultrasoundPrimary hyperparathyroidismPHPTParathyroid glandParathyroid adenomaParathyroidectomyMinimally invasive parathyroidectomy

Introduction: Diagnosis of Hyperparathyroidism

Primary hyperparathyroidism (PHPT) develops as a result of hyperfunctioning parathyroid glands. Up to 85% of cases of primary hyperparathyroidism are due to parathyroid adenomas, while parathyroid glands hyperplasia accounts for about 10% to 15% and parathyroid carcinoma for less than 1% of cases. The prevalence of PHPT in the general population is approximately 0.1%, with a higher incidence in patients older than 60 years of age. Female patients are affected two to three times more often than male patients. Diagnosis of PHPT is established biochemically by findings of an elevated serum calcium level with concurrent elevation in serum parathyroid hormone (PTH) level, which is considered the classic form of PHPT. An elevation of serum calcium with a serum PTH level in the high normal range is called normohormonal PHPT , and an elevation of the serum PTH level with a high normal level of serum calcium is called normocalcemic PHPT . Most, up to 80% of patients are asymptomatic, so the diagnosis is established by screening blood tests for calcium and PTH levels. Based on the Fourth International Workshop and the American Association of Endocrine Surgeons (AAES) Guidelines for Definitive Management of Asymptomatic PHPT, the following are indications for surgical treatment of PHPT [1–3]:

Serum calcium 1.0 mg/dL (0.25 mmol/L) above the upper limit of normal

Presence of osteoporosis, defined by DEXA scan as BMD with a T-score of less than −2.5 at lumbar spine, total hip, femoral neck, and especially the distal third of the radius. Z-scores should be used instead of T-scores in premenopausal women and men younger than 50 years of age.

Presence of vertebral fracture by imaging studies such as x-ray, CT scan, MRI, or Vertebral Fracture Assessment (VFA) by the DEXA scan.

24-hour urine for calcium above 400 mg/d (10 mmol/d) and increased kidney stone risk by biochemical stone risk analysis

Creatinine clearance <60 cc/min

Presence of nephrolithiasis or nephrocalcinosis by x-ray, ultrasound, or CT scan

Age less than 50 years

After the diagnosis of PHPT has been established and surgical criteria have been met, then imaging studies should be obtained to localize the parathyroid adenoma, because approximately 85% of patients with PHPT will have single-gland disease, an adenoma. Parathyroid gland malignancies are rare, described in about 0.5% to 1% of patients with PHPT [4]. Ultrasonography (US) of the parathyroid glands is the first-line study of choice in localization of parathyroid adenoma. Normal parathyroid glands are not visualized on US examination because of their small size, their location posterior or attached to the thyroid gland, and most importantly, their intraparathyroidal fat content, which makes them resemble the surrounding lymph nodes. In contrast, an enlarged, hyperplastic parathyroid gland or adenoma has almost no fat content and consists of crowded, hyperplastic (mostly chief) parathyroid cells. These histological changes decrease echogenicity, making parathyroid adenoma more visible on US, where it presents as a solid, hypoechoic mass.

Principles of Ultrasound

Understanding the basic physics of US is essential in understanding how to use this technology. Ultrasound machines generate and receive US waves that are emitted from piezoelectric crystals of the transducer. Echoes directed back toward the transducer are produced as the pulse travels along a straight line through the tissues. In the most commonly used brightness-mode (B-mode) images , more reflective structures appear brighter than less reflective structures. Different grades of white and black images are produced depending on the acoustic impedance of different materials, which is based on their density. Sound speed changes with differing density of the structure. Sound travels faster through more dense structures such as fluid. Wavelength is inversely proportional to frequency: high-frequency wavelengths are shorter, and low-frequency wavelengths are longer. Deeper tissue penetration (helpful for imaging of abdominal organs) is better with a low-frequency transducer, but it carries poorer resolution. For imaging of more superficial structures such as neck organs, including the thyroid gland, parathyroid glands, and lymph nodes, penetration is better with a high-frequency transducer (with shorter wavelengths), which produces better resolution. Resolution is defined by the ability to differentiate between two points. High-frequency ultrasound has a resolution of 1–2 mm.

Ultrasound assesses the relationships between the neck structures such as parathyroid glands, thyroid gland, trachea, esophagus, vessels, lymph nodes, and muscles by assessing their echogenicity and echostructure. A normal thyroid is considered to be isoechoic (gray color). All structures that are brighter than the thyroid are considered to be hyperechoic; these include bones, arterial walls, and calcifications. Structures that appear black, or darker than the thyroid, are hypoechoic; these include the inside of vessels (blood) and fluid-filled cysts. Parathyroid gland adenoma is denser than thyroid and appears to be hypoechoic (dark gray, almost black) compared with the thyroid gland [5] (Fig. 1.1).

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Fig. 1.1

Normal thyroid and parathyroid ultrasound. A normal thyroid is considered to be isoechoic (gray color), all structures that are brighter than the thyroid (tracheal wall, bones, arterial walls, calcifications) are considered to be hyperechoic, and structures that are darker than the thyroid (inside of the vessels, fluid-filled cyst) are hypoechoic. Parathyroid gland adenoma is denser than thyroid and appears hypoechoic (dark gray, almost black) compared with the thyroid gland. (a) Transverse view of the thyroid gland. (b) Transverse view of the left thyroid lobe and parathyroid adenoma (arrow). (c) Longitudinal view of the left thyroid lobe and parathyroid adenoma (arrow). CA carotid artery, LT left thyroid lobe, RT right thyroid lobe, Tr trachea

To visualize deeper structures in the neck, the resolution can be changed to a lower frequency to increase the penetration. A 10- to 15-MHz linear US transducer is most useful in evaluation of the neck structures, including the parathyroid glands (Fig. 1.2). A curved transducer usually has a low frequency (2–5 MHz), compared with a linear transducer, which is high-frequency (7–15 MHz). Frequency is the number of cycles repeated per second and measured in hertz (Hz). Frequencies of less than 2 MHz or higher than 15 MHz are rarely used because of insufficient resolution or insufficient penetration depth in most clinical applications [6–12].

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Fig. 1.2

A 5- to 13-MHz linear ultrasound transducer

Parathyroid Ultrasound in Operative Planning

Real-time imaging is a better way to assess the parathyroid glands than static images. In planning a parathyroidectomy , the surgeon may benefit from doing his or her own US, rather than relying on a study performed by a technician. US guidance in locating a parathyroid adenoma helps the surgeon to evaluate neck structures and determine the relationship between them. Knowing the distance between a parathyroid adenoma and surrounding tissues and the proximity of the adenoma to other organs (thyroid, carotid and other vessels, trachea, esophagus) helps in preoperative planning and intraoperative search, and sometimes measuring the distance from the skin to the adenoma may give the surgeon a hint as to the depth and location of the parathyroid adenoma [6–12].

It is recommended that a designated parathyroid US always be performed prior to a parathyroidectomy for operative planning in all patients with PHPT. It is the least expensive test that can be used to localize a parathyroid adenoma, it carries no risk of radiation exposure, and, because of that, it can be performed in children and pregnant women. This type of test allows a practitioner to perform an evaluation of the thyroid gland and the parathyroid glands and to visualize the soft tissues of the neck. Designated parathyroid US performed by an endocrine surgeon has more chances to visualize a parathyroid adenoma than a study performed by a radiologist [6, 7, 10–15].

In a prospective study by Siperstein et al. [16] of 1158 patients with PHPT between 1999 and 2007, a single parathyroid adenoma was identified by surgeon-performed neck US using a 7.5-MHz curved fingerprint transducer in 80% of patients and on a Tc 99 m sestamibi scan (MIBI) in 74% of patients. Following this study, Siperstein et al. reviewed the factors contributing to negative parathyroid localization by US and MIBI scan. They found that thyroid nodules, lymph nodes, and prominent thyrothymic ligaments all impaired detection of abnormal parathyroid glands by both US and MIBI. The false positive rate for US was 6% and for MIBI scan was 29%. Based on their multivariate logistic regression analysis of preoperative and intraoperative factors affecting the localization of parathyroid adenoma in patients with PHPT, body mass index (BMI), gland size, and volume were the only independent variables affecting the detection rate for both US and MIBI scan. The probability of visualizing the gland was reported as 0.5 when the volume of the gland was greater than about 15.9 mm³. Nevertheless, parathyroid glands were detected more frequently with US than with MIBI. The sensitivity of US was better for single-gland disease than for multi-gland disease in patients with PHPT [17].

A retrospective study by Stern et al. of 410 patients who underwent a parathyroidectomy procedure for PHPT between 1996 and 2012 analyzed the accuracy of US. The study compared the preoperative ultrasound findings with the intraoperative findings and pathology reports. The US of the parathyroid adenoma was performed by specialized radiologists at various centers. The US correctly localized the adenoma in 76% of cases, with a sensitivity of 76.2% and a positive predictive value of 86.8% [18].

Based on several studies, the sensitivity of high-resolution US was reported to be between 51% and 89%, with a positive predictive value of 93.2%, when the study was interpreted by a radiologist. Surgeons performing US correctly identified a parathyroid adenoma in 74% to 90% of patients, with a sensitivity of 87% and 88% specificity [13–16]. Further research conducted by several other groups reported the sensitivity of surgeon-performed US to be between 60% and 93%, which is equivalent or superior to radiology-based US [19–22].

Accurate localization of the parathyroid adenoma helps achieve several goals through the use of a minimally invasive surgical approach. It minimizes the risk of complications secondary to more extensive exploratory surgery, it decreases postoperative pain and discomfort, it decreases surgical operative time, and it helps with obtaining the best cosmetic results.

Performing the Ultrasonography

The proper position of the patient is paramount in performing the ultrasonography (Fig. 1.3). The patient should be positioned supine, with the head in the midline position and the neck hyperextended over a shoulder roll or pillow. This position helps facilitate the movement of the neck structures up anteriorly to under the skin and cephalad from under the subclavicular location. An US for the evaluation of the neck structures is best performed by using a linear, rather than curved, transducer. A generous amount of US transmission gel is used on the transducer probe to facilitate elimination of the air-filled space between the transducer and the skin. The evaluation starts with the US probe in a transverse position and going from the cephalad direction (from the level of the hyoid bone) caudally to the level of the clavicle, slowly moving the probe for the transverse views of the neck structures (Fig. 1.4). Start from the front of the neck over each thyroid lobe, then proceed laterally over the carotid artery and jugular vein. Lastly, direct the probe slightly medially to get a view of the thyroid lobe laterally and posteriorly, to localize a retrothyroidal and retroesophageal parathyroid adenoma. When the probe is at the level of the clavicle, it can be directed under the clavicle by angulating it inferiorly to visualize the area behind the clavicle or anterior mediastinum (Fig. 1.5). Then the probe should be rotated vertically for a longitudinal view of the neck structures, going from medial to lateral, viewing the thyroid anteriorly and then the area behind the thyroid from the lateral to the medial aspect (Fig. 1.6).

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Fig. 1.3

The proper position of the patient . The patient should be positioned supine, with the head in the midline position and the neck hyperextended over a shoulder roll or pillow

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Fig. 1.4

The evaluation starts with the ultrasound probe in a transverse position and going from the cephalad direction (from the level of the hyoid bone) caudally to the level of the clavicle, slowly moving the probe for transverse views of the neck structures

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Fig. 1.5

When the probe is at the level of the clavicle, it can be directed under the clavicle by angulating it inferiorly to visualize the area behind the clavicle or anterior mediastinum

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Fig. 1.6

Then the probe should be rotated vertically for a longitudinal view of the neck structures

Evaluating a Parathyroid Adenoma

Parathyroid adenoma usually presents as a rounded, solid, hypoechoic, homogeneous mass with well-defined margins (see Fig. 1.1b, c). The adenoma is located next to or behind the thyroid gland, with no Doppler vascular flow within it, compared with the adjacent carotid artery or internal jugular vein, which will have a high-velocity flow on Doppler study (Fig. 1.7). Sometimes vascular rim vessels are seen at the periphery, with a small feeding vessel going towards the middle of the parathyroid adenoma on the Doppler flow study. In a rare occurrence, a large parathyroid adenoma can develop cystic components and appear as a large cyst. Evaluation of the parathyroid glands by US should include longitudinal (vertical) and transverse (horizontal) positioning of the probe, as well as Doppler flow. Parathyroid adenoma should be measured in all three dimensions, documenting its shape, borders, consistency (solid vs. cystic), echogenicity (usually hypoechoic), homogeneity, and location in relation to the surrounding structures. Typically, parathyroid adenomas are larger than 1 cm in size and can be readily seen on US, whereas normal glands are smaller and are rarely visible [6, 7, 12, 23].

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Fig. 1.7

Doppler flow study. Transverse view of a right inferior parathyroid adenoma (arrow) shows the absence of blood flow within the adenoma and the presence of blood flow in the right carotid artery (CA). There is a small feeding vessel with the parathyroid adenoma (arrow)

The main rule in the evaluation of parathyroid glands is to know what you are looking for. If the person performing the study is conscious of looking for a parathyroid adenoma, the likelihood of finding an adenoma and providing accurate documentation is much higher. Thus the prescription should contain clear directions to the provider obtaining the study. In other words, the prescription should not read to evaluate the neck or to evaluate the thyroid gland; the result is likely to be omission of key information on the report. More importantly, the findings of the parathyroid adenoma will be overlooked and hence not mentioned in the report. Conversely, if the provider who performs the US has clear directions to evaluate for parathyroid adenoma, the chances of finding the adenoma are much higher.

The location of the parathyroid adenoma usually is predictable, based on the embryology of the parathyroid glands. Superior parathyroid glands are derived from the fourth branchial pouch, and inferior parathyroid glands are derived from the third branchial pouch, along with the thymus. That makes it easier to evaluate the inferior parathyroid glands, for example, by looking at the thyrothymic ligament and the superior portion of the thymuses. An evaluation of superior parathyroid glands may be difficult because of the overlying thyroid gland. Looking above the thyroid lobe over the superior pole, and then positioning the ultrasound probe slightly laterally may help to evaluate the space behind the thyroid lobe. The usual location of a superior parathyroid adenoma is either behind the superior pole of the thyroid lobe and posterior to it, or behind the middle part of the thyroid lobe, as in the case of an enlarged, descended parathyroid adenoma. Sometimes it can be lateral to the superior pole or above the superior pole.

The location of an inferior parathyroid adenoma may vary. In the lower part of the neck, the anatomical location of the esophagus is posterior and to the left side of the trachea. Therefore, the left inferior parathyroid adenoma may be seen either next to the esophagus or inferior to the inferior pole of the left thyroid lobe and attached to the inferior pole. Asking the patient to swallow during the study will help in differentiating the esophagus from other neck structures during real-time US. Real-time imaging of parathyroid glands can show some findings that can help to differentiate between a thyroid nodule and the parathyroid gland. For example, it is sometimes possible to see the inferior parathyroid gland moving with pulsation of the adjacent carotid artery, with a slightly different rhythm than the thyroid gland, making it visible as a separate structure.

Parathyroid adenoma can be intrathyroidal in approximately 6% of patients [24]. A high level of suspicion and experience of the ultrasonographer can suggest the possibility of an intrathyroidal parathyroid adenoma, which usually presents as a well-circumscribed, homogeneous, rounded, hypoechoic mass within the thyroid lobe (Fig. 1.8). In the absence of other findings of an extrathyroidal parathyroid adenoma in a typical location, finding a homogeneously hypoechoic thyroid nodule with a large polar feeding artery, usually under the thyroid capsule, is suggestive of an intrathyroidal parathyroid adenoma [10]. It is usually found on the side of the thyroid lobe, with one side presenting in line with the thyroid capsule either laterally or posteriorly. In some cases, a hyperechoic rim of the thyroid capsule can be visualized between the thyroid lobe and the parathyroid adenoma.

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Fig. 1.8

Right superior intrathyroidal parathyroid adenoma. The thyroid (T) appears gray (isoechoic) on the ultrasound evaluation, compared with the darker-appearing (hypoechoic) parathyroid adenoma. (a–c) Parathyroid ultrasound showing a large, well-defined, solid, hypoechoic parathyroid adenoma (arrow) in the middle of the right thyroid lobe posteriorly. Intraoperative frozen section diagnosis and the final pathological diagnosis were consistent with parathyroid adenoma. ((a) Transverse view; (b) Logitudinal view; (c) Doppler flow study, transverse view, showing the flow surrounding the parathyroid adenoma within the right thyroid lobe. Tr trachea.) (d, e) Gross images of the parathyroid adenoma

The finding of a parathyroid cyst on US of the parathyroid glands was reported in 1–5% of neck masses. Parathyroid cysts are found by the left thyroid lobe in 31.6% of patients, and in the superior mediastinum in 19.3%. These cysts have been found to be non-functional in 61.6% of patients; they were found incidentally as a neck mass in 41.7% of patients, but compressive symptoms were reported in 20.6%. Only 17.5% of the patients with parathyroid cysts presented with hyperparathyroidism [25].

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