Open access peer-reviewed chapter

Role of Elastography in the Evaluation of Parathyroid Disease

Written By

Dana Amzar, Laura Cotoi, Andreea Borlea, Calin Adela, Gheorghe Nicusor Pop and Dana Stoian

Submitted: 13 December 2021 Reviewed: 17 June 2022 Published: 18 July 2022

DOI: 10.5772/intechopen.105923

From the Edited Volume

Elastography - Applications in Clinical Medicine

Edited by Dana Stoian and Alina Popescu

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Abstract

Primary hyperparathyroidism is a prevalent disease of the parathyroid glands and the third most common endocrinopathy, especially among postmenopausal women. Secondary hyperparathyroidism is a compensatory response to hypocalcemic states due to chronic renal disease, vitamin D deficiency and malabsorption syndromes, and other chronic illnesses. Elastography can be an effective tool in localizing and identifying parathyroid lesions, whether it is a parathyroid adenoma or hyperplastic parathyroid secondary to chronic kidney disease, by differentiating between possible parathyroid lesions and thyroid nodules, cervical lymph nodes, or other anatomical structures. No current guidelines recommendations are available and no established general cutoff values on the elasticity of parathyroid lesions. We have conducted several prospective studies on primary and secondary hyperparathyroidism, using ultrasound imaging and elastography, shear wave, and strain elastography to better identify the parathyroid lesions and improve the preoperative localization and diagnostic. The results were encouraging, allowing us to determine cutoff values that are different for lesions from primary hyperparathyroidism and secondary hyperparathyroidism and comparing them with normal thyroid tissue and surrounding muscle tissue.

Keywords

  • elastography
  • shear wear elastography
  • primary hyperparathyroidism
  • secondary hyperparathyroidism
  • hypercalcemia
  • parathormone
  • vitamin D

1. Introduction

Advancements in the medical field improved diagnostic methods, increasing the incidence of various endocrine diseases [1, 2]. Hyperparathyroidism is a common endocrine disorder, commonly as primary hyperparathyroidism. As incidence it is the third endocrinopathy after type 2 diabetes mellitus and thyroid disease [3].

When discussing primary hyperparathyroidism, parathyroid adenoma being quoted as the most common cause of primary hyperparathyroidism, parathyroid hyperplasia and parathyroid carcinoma follow [4, 5, 6].

Secondary hyperparathyroidism is a prevalent complication of chronic kidney disease, with high prevalence among patients on renal replacement therapy [7, 8].

Nowadays, primary hyperparathyroidism is mostly diagnosed in asymptomatic forms, in premenopausal women mostly, by active screening, with high serum parathormone (PTH) concentrations, and consequently high serum calcium concentrations [1, 4, 5, 6, 9, 10, 11].

Secondary hyperparathyroidism is prevalent among the chronic kidney cohort, determined by the disturbances of the phosphor-calcic metabolism. Prevalence cited in the specialty literature displays high numbers among patients receiving dialysis—of 54% in the United States and Europe—43.8% in France, 46.8% in Russia, and 42.9% in the United Kingdom [7].

The pathophysiological mechanism of primary hyperparathyroidism (PHPT) shows a loss of the homeostatic control of parathormone synthesis and secretion pathway, determining an increased secretion of parathomone and/or marked proliferation of cells with normal levels of PTH. Single adenomas present a monoclonal origin, suggesting that the tumors derive from a single abnormal cell [12], while hyperplastic parathyroid tumor usually presents polyclonal origins from a genetic point of view [1].

On the other hand, secondary hyperparathyroidism (sHPT) has a multifactorial and complex mechanism driven by hypocalcaemia, vitamin D deficiency, hyperphosphatemia, and high levels of fibroblast growth factor. In this case, sHPT could be amended by treating the underlying affection, chronic renal failure, or vitamin D deficiency. However, chronical stimulation of parathyroid glands can become autonomous, resulting in persistent tertiary hyperparathyroidism [4, 13, 14].

Regardless of the etiology of hyperparathyroidism, surgery represents a legitimate, validated, and corrective treatment in both primary and secondary hyperparathyroidism. Minimally invasive parathyroidectomy (MIP) is considered as a preferred approach current recommendation, thus the requirement to correctly identify the number and localization of affected parathyroid glands in preoperative evaluation, ultrasonography being the most cost-efficient method [15, 16, 17, 18, 19].

Given the positive features of ultrasonography, such as the noninvasive character, high resolution in real time, reproducibility, easiness in manipulation, inoffensive to children and pregnant women, and the absence of X-Ray exposure or administration of contrast agents, making it most accessible, reliable, and cost-efficient imaging technique for identifying pathological parathyroid glands [20, 21].

Elastography is a validated, complementary method to ultrasonography, labeled as “palpation imaging,” providing qualitative and quantitative information on the studied tissue such as anatomical architecture and modifications in tissue stiffness [20, 22, 23, 24]. Endorsed as a marker of pathological states in many clinical fields, contributing to the positive identification, differential diagnosis, and ultimately to the therapeutic management, establishing its role in endocrinology for both thyroid and parathyroid evaluation [25, 26], hepato-gastroenterology [20, 27, 28, 29], senology [30, 31], urology [32, 33, 34], and otorhinolaryngology [35].

Two basic principles described for ultrasound elastography: “determination of the strain or deformation of a tissue due to a force (static elastography) and analysis of the propagation speed of a shear wave (shear wave elastography)” [36]. Literature studies have obtained various parameters from these elastography techniques that characterize a modification of a tissue. Three major groups are described using those parameters:

  • qualitative criteria obtained from elastograms, which are maps, presented in gray scales or color, depending on the manufacturer, displaying the distribution of elasticities. They are available on most ultrasound machines, regardless of the technique used. A rapport can be determined between the width of tissue on B-mode and elastography.

  • semiquantitative criteria are estimation of deformation ratios or elasticity ratios between different regions of interest (ROI).

  • quantitative criteria possible by using the shear wave technique, determining the propagation speed of the shear wave. It represents a dynamic evaluation containing multiple subtypes:

  1. transient elastography (TE) giving numerical values of the elasticity index, not being able to provide ultrasonographic imagines

  2. point shear-wave elastography (pSWE)

  3. shear-wave elastography

The last two methods include two-dimensional shear wave elastography and three dimensional shear wave elastography, determining numerical values of the elasticity index and providing color maps [20]. The numerical value data are calculated in Young modulus in m/s or kPa [36].

Strain elastography (SE) is a quasi-static elastographic method first implemented on ultrasound systems. It necessitates an external pressure to induce the deformation of the underlying tissue, or the deformation can be generated by acoustic radiation force impulse (ARFI). The most recent elastographic technologies can use endogenous stress such as muscle contractions or vascularization beam movements [20, 37, 38].

It can determine qualitative evaluation by adding elastograms (color maps) on conventional 2 B mode and, depending on the manufacturer, it can offer real-time elastography, where the refresh rate is equal to that in gray scale or single-image display with the mean relative hardness over a time loop [20].

Shear wave elastography induces shear waves in targeted tissues using acoustic radiation force and ultrasound imaging techniques to track the propagating shear waves. The shear waves induce a perpendicular oscillation to the direction of the wave propagation, expressed by shear modulus G and measured by shear wave speed (cS), which can be then further recorded in m/s or converted by using the Young’s modulus E in kilopascals (kPa). The wave speed is then spatially mapped and directly related to the local stiffness of the evaluated tissue. This manner allows real-time monitoring of shear wave deformation in 2D and measures the shear wave speed or Young’s modulus E and generates quantitative elastograms [2, 22, 39].

Elastography was used in both primary and secondary hyperparathyroidism, with an important clinical impact, proven in our previous studies [11, 25, 40, 41, 42]. Is has been proven to accurately predict the parathyroid tissue when compared with thyroid or muscle tissue.

This chapter aims to identify the characteristics of parathyroid adenomas in primary hyperparathyroidism and the attributes of hyper-plastic parathyroid glands in patients with chronic kidney on renal replacement therapy and to identify if the elastography can add value to the presurgical identification and differential diagnosis.

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2. Ultrasound and elastographic evaluation of parathyroid disease

2.1 2B-ultrasonography evaluation

Gray scale ultrasound (US) has become a very accessible imaging technique in the endocrinology field, especially for thyroid and parathyroid evaluation, becoming the gold standard in these domains. The noninvasive character, the low cost, the repeatability, and especially the real-time assessment are some of the many advantages of this imagistic technique [43, 44].

The ultrasound evaluation of both thyroid and parathyroid glands involves a large ultrasound framework. Anatomical structures must be well observed and identified both in longitudinal and transverse modes [23, 45, 46]. Additional auxiliary techniques, including the rotation of the head to improve the ultrasound framework on the neck structures or swallowing, could improve the correct identification of anatomical structures and of ectopic parathyroid glands [45].

The sensitivity of ultrasound identification of parathyroid tumors varies from 70 to 80% [47] with higher positive identification for parathyroid hyperplasia 30–90% [48], but precision is dependent on the location and size of the tumor [16], by body habitus and gland morphology, and by the experience of the evaluator [46]. Increased false-positive ultrasound results are caused by structures mimicking parathyroid adenomas such as thyroid nodules, lymph nodes, muscles, vessels, and esophagus [16].

2.1.1 Adding color Doppler mode

Parathyroid adenomas typically present a peripheral vascular rim and an abnormally increased blood flow than the thyroid gland [49]. Therefore, by adding color Doppler mode in the ultrasound evaluation can increase the accuracy and sensitivity of ultrasound by 54% [50].

2.2 Ultrasound elastography: description and method

Elastography can be a helpful complementary imaging technique in the evaluation of parathyroid disease, adding additional information on tissue stiffness.

Neoplastic, fibrous, or atherosclerotic transformation in tissues is translated by tissue stiffness in elastographic evaluation [38]. The development of neoplastic tissue can be identified even in early stages, as from the physiopathological point of view, we can have an increased production of connective tissue, changes in cell density, and increased blood flow, all these changes determining a change in the tissue matrix, thus a change in the elasticity of the tissue [2]. Elastography can identify the differences between benign and malignant tissues from the early development of the disease, offering high sensitivity and resolution for deep-situated structures [51].

Elastography evaluates tissue stiffness by applying an external stress and calculating the distortion degree. The distortion in elastography is obtained by applying external pressure, manually or via ultrasound transducer. In acoustic radiation force impulse (ARFI), the distortion is induced by using crossing deformation, with converged ultrasound beams or by emitting of short duration focused acoustic beam that will generate shear waves that diffuse transversally through the tissue [52]. It thus determines qualitative information about tissue stiffness through color maps and color codes and quantitative information through numerical values [38].

An elastographic evaluation follows a 2B-mode ultrasound evaluation of the parathyroid glands. It can be performed in all patients; it is cost-efficient and adds valuable information. The elastography module is available on multiple ultrasound machines such as Aixplorer Mach 30 machine (SuperSonic Imagine, France), Philips, Fujifilm, Hitachi Preirus (Hitachi Medical Corporation, Tokyo, Japan) machine.

Elastography on the parathyroid is performed using a linear, high-resolution transducer of 15–4, respectively, 18–5 MHz chosen depending on the clarity of the image, profound parathyroid glands being evaluated with 15–4 probe, obtaining better images. The patient was examined in a supine position with neck hyperextension, maintaining regular superficial breathing. The following parathyroid parameters are to be evaluated—localization, form, parathyroid dimensions, and total volume of the gland.

Two elastographic procedures will be discussed in the chapter—2D shear wave elastography and real-time elastography.

The procedure depends on the type of elastography performed, for example, for shear wave elastography, the examiner must maintain a precise adherence for minimal 6 seconds to the probe on the examined area, with careful attention not to apply any manual compression, permitting the transducer to induce the acoustic vibrations in the parathyroid tissue. After image stabilization, a real-time elastogram will overlap on the B-mode image, obtaining an elastogram or color map (Figure 1). Afterimage stabilization, quantitative measurements can be performed on a frozen image.

Figure 1.

(a) 2B-mode ultrasound evaluation of parathyroid adenoma, with complementary color Doppler mode; (b) Elastogram of parathyroid adenoma overlying B mode image and color map of tissue elasticity, with Q-box on the region of interest and quantitative evaluation [53] .

Quantitative information, described as the elasticity index (EI) obtained on the frozen elastogram image, using a quantification box (Q-box), placed in the regions of interest (ROI). After software computing evaluates the mean SWE, minimum SWE, maximum SWE, and standard deviation, the elasticity parameters are displayed. All measurements are numerically expressed in kilopascals (kPa). As there is no scale setting recommended for the parathyroid examination, we recommend using a thyroid scale (0–100 kPa).

Another elastographic technique that requires external pressure in order to induce a deformation of the examined tissue that is further quantified by the machine software. This method is called real-time elastography (RTE) or strain elastography (SE). The examiner must apply controlled external pressure, usually manually pressure, which determines a mechanical deformation. An elastographic map is overlayed on the 2B greyscale that is displayed as a color map (red for liquid, green for soft tissue, blue for hard tissue), permitting the examined to obtain qualitative information about tissue stiffness for the examined area (Figure 2) [38].

Figure 2.

Ultrasound evaluation and strain elastography of parathyroid adenoma [54].

Semiquantitative values can be obtained using strain elastography by comparing tissue strain in the region of interest (ROI) of the targeted tissue with another adjacent tissue, calculating a strain ratio (SR) ratio.

2.3 Strain elastography

The experience with strain elastography on parathyroid disease is primarily focused on parathyroid adenomas as parathyroid hyperplasia is more difficult to evaluate with this form of elastography [54]. The evaluation scale used to evaluate parathyroid lesions is the Rago criteria, frequently used for thyroid pathology. Rago criteria [38, 55], described for thyroid pathology, especially nodular goiter, was used to assess the qualitative strain elastography evaluation, as it follows: a score 1 means that the elasticity in the whole lesion is soft tissue, a score 2 means that the tissue is mostly soft, a score 3 is defined by soft tissue in the peripheral part of lesion, a score 4 implies that the examined lesion is entirely stiff, and a score 5 involves stiffness that exceeds beyond the examined lesion’s margins, infiltrating in the enclosing tissues.

The leading disadvantage of this qualitative technique is the depth of the evaluated tissue or lesion, determining an incomplete, unusable, and uninterpretable color map for higher depths. Most of the parathyroid adenomas evaluated in the paper previously published were of score 1 according to the Rago criteria (Figure 3) [25].

Figure 3.

Color map with strain elastography with Hitachi machine showing a score 1 on Rago criteria [54].

The first study conducted evaluated strain elastography on primary hyperparathyroidism on 20 consecutives patients evaluating qualitative and semiquantitative values. Out of the total 20 cases, two parathyroid adenomas could not be evaluated and for the rest a score 1 according to the Rago criteria was found [25].

The size and localization of the parathyroid adenoma were also quantified, so on ultrasound evaluation, the mean parathyroid adenoma dimensions were 0.776 ± 0.50 cm, the maximum size found was 2.46 cm, and the minimum was 0.34 mm. Most of the parathyroid adenomas were found near the right superior thyroid lobe (nine adenomas), three were located near the right inferior thyroid lobe, three were located near the left superior lobe, and five near the left inferior lobe. As for ultrasound appearance 13 parathyroid adenomas had cystic appearance (65%), 5 parathyroid adenomas homogeneously solid and hypoechoic appearance (25%), and 2 adenomas had a mixed appearance (10%)—mostly cystic and one with an elongated shape.

Semiquantitative information was also achieved using strain elastography, by comparing tissue strain the parathyroid adenoma parenchyma and thyroid or muscle tissue. No significant differences were found between the strain ratio determined using SE for the parathyroid adenoma and the thyroid tissue (nine out of twenty cases) with a mean SR of 1.465 ± 1.458, respectively, strain ratio of the parathyroid adenoma compared with the strain ratio of the thyroid tissue with autoimmune disease (11 out of 20 cases) with a mean SR = 1.656 ± 1.746, p = 0.481 [25].

Other literature studies have compared the elasticity of parathyroid pathology using strain elastography, identifying that parathyroid adenomas appear as stiff lesions (median SR = 3.56) and parathyroid hyperplasia has a lower stiffness and a higher elasticity score (median SR = 1.49) [56].

A study based on another type of elastographic evaluation–Elastoscan Core Index (ECI) evaluating parathyroid adenomas and lymph nodes found that the ECI index was significantly higher in malignant lesions than in benign lesions. They concluded that combining ECI index with conventional US, particularly with shape and vascularization, can improve the differentiation of parathyroid lesions from lymph nodes and thyroid nodules [57].

2.4 Shear-wave elastography

We conducted several studies on primary and secondary hyperparathyroidism, comparing the results to evaluate the differences between the two clinical entities, as the pathophysiological mechanism is quite different.

Our first study [25] (previously published) evaluated the values of shear wave elastography on primary hyperparathyroidism. Twenty consecutive patients with primary hyperparathyroidism presenting a solitary adenoma were included. The parathyroid tissue was compared with thyroid and muscle tissue, as normal parathyroid adenomas cannot be evaluated using ultrasonography. The best parameter identified for evaluating parathyroid adenomas was mean SWE, with the highest specificity, sensitivity, and accuracy. The results are displayed in Table 1 [25].

SWE-min PTX/TSWE-mean PTX/TSWE-max PTX/TSWE-min PTX/MSWE-mean PTX/MSWE-max PTX/M
Area under curve (AUC) value0.9570.9500.7650.9980.9970.955
Specificity85%90.0%70.0%95.0%95.0%80.0%
Sensitivity95%95.0%80.0%100%100%100%
PPV86.4%90.5%72.7%95.2%95.2%83.3%
NPV94.4%94.7%77.8%100%100%100%
Accuracy90.0%92.5%75.0%97.5%97.5%90.0%
p value<.0.001<0.001<0.001<0.001<0.001<0.001
Cut-off value<3.14 kPa<7.28 kPa<9.14 kPa<5.32 kPa<10.47 kPa<15.16 kPa

Table 1.

Sensitivity, specificity, ROC curve for measured elastographic index SWE-min, SWE-max, and SWE-mean for primary hyperparathyroidism.

Statistical analysis has found significant difference between parathyroid elasticity (kPa) compared with thyroid and muscle elasticity (p < 0.001).

A second study [40] (previously published) was conducted on patients on renal replacement therapy with consequential secondary hyperparathyroidism. A cohort of 120 patients was evaluated, founding 59 with secondary parathyroid hyperplasia. A total of 97 hyperplastic parathyroid glands were evaluated, comparing normal thyroid and muscle tissue with hyperplastic parathyroid tissue. Statistical differences were found in this cohort and identified the best parameter to evaluate the elasticity of parathyroid tissue and the cut-off values (Table 2) [40].

SWE min PTX/TSWE mean PTX/TSWE max PTX/TSWE min PTX/MSWE mean PTX/MSWE max PTX/M
AUC value0.9430.9400.8580.9570.9490.882
Specificity86.6%90.7%75.3%95.9%90.7%84.5%
Sensitivity94.8%94.8%83.5%86.6%93.8%78.4%
PPV87.6%91.1%77.1%95.9%91%83.5%
NPV94.4%94.6%82.0%87.7%93.6%79.6%
Accuracy90.7%92.26%79.4%91.2%91.75%81.45%
Cutoff value< 6.02 kPa< 9.74 kPa< 15.3 kPa< 7.94 kPa< 9.98 kPa< 17.3 kPa

Table 2.

Sensitivity, specificity, AUROC for measured SWE min, SWE max, and SWE mean for secondary hyperparathyroidism [40].

After analyzing the two cohorts, a natural question has appeared—are there any differences between primary and secondary hyperparathyroidism on elastographic evaluation?

The third study answered this question—evaluating a total of 68 patients divided into two groups of 27 patients diagnosed with primary and 41 patients diagnosed with secondary hyperparathyroidism (Figures 4 and 5).

Figure 4.

Elastograms using 2D SWE. In image A – Elastogram overlaying gray scale ultrasound of a right inferior parathyroid adenoma; In image B – Elastogram overlaying gray scale image of a right inferior parathyroid hyperplasia in secondary hyperparathyroidism [41].

Figure 5.

Elasticity index evaluation for parathyroid and thyroid tissue. In image A – Elastographic evaluation of a right inferior parathyroid adenoma from primary hyperparathyroidism; In image B – Elastograohic evaluation of a left inferior parathyroid hyperplasia from secondary hyperparathyroidism [41].

The baseline characteristics of the primary and secondary hyperparathyroidism study are presented in Table 3 [41].

CharacteristicsPrimary hyperparathyroidismSecondary hyperparathyroidismp-value
Male-to-female ratio2/2522/19<0.001
Age (years)61 [48.67]58 [50–65.5]0.763
Parathormone (PTH) (pg/ml)160.6 [115.0–206.3]1117 [785.95–1407]<0.001
Serum phosphorus (mg/dl)2.60 [2.30–3.12]6.00 [5.15–7.77]<0.001
Total serum calcium (mg/dl)10.50 [10.10–11.40]9.00 [8.35–9.35]<0.001
Serum vitamin D (ng/ml)21.33 [15.55–25.52]35.80 [24.20–44.70]<0.001
Parathyroid volume (ml)0.120 [0.068–0.240]0.251 [0.109–0.332]0.107
Maximum diameter (mm)8.30 [6.20–12.00]9.50 [7.25–11.75]0.543
Dialysis years5.10 [4.00–8.10]NA
Kt/v1.350 [1.30–1.46]NA

Table 3.

Baseline characteristics of patients evaluated with primary and secondary hyperparathyroidism.

When comparing the results of the two studied lots, we found statistically significant differences in sex distribution between the two lots (p < 0.001, Fischer-exact Test).

Keeping the different pathophysiology pathways for primary and secondary hyperparathyroidism in mind, we conducted diagnostic tests to evaluate the elastographic differences between the two types of hyperparathyroidism [41].

A statistically significant difference (p < 0.001) was found when comparing the results of SWE-mean parathyroid tissue between primary and secondary hyperparathyroidism, with higher values for the secondary hyperparathyroidism group (Figure 6).

Figure 6.

Shear wave differences between mean value SWE for primary hyperparathyroidism and secondary hyperparathyroidism. [41].

There are multiple research studies on the elastographic evaluation of primary hyperparathyroidism, but this method is less approached for secondary hyperparathyroidism.

Different threshold values for parathyroid adenomas have been established by various authors in the field of primary hyperparathyroidism, depending on the elastography techniques used. By using shear wave virtual touch imaging quantification, higher values have been found for parathyroid adenomas (2.16 ± 0.33 m/s) compared with parathyroid hyperplasia (1.75 ± 0.28 m/s), identifying a cutoff value superior to 1.92 m/s for parathyroid adenomas [44]. Another study presented their results between the elastographic differences between thyroid and parathyroid tissue, using the same elastograohic method as the previous. Their conclusion was that the elastographic index of parathyroid adenomas is lower than of the thyroid tissue, presenting a shear wave velocity of 2.01 m/s, respectively 2.77 m/s [58].

Another representative study performed an analysis using the ARFI imaging 2D SWE, comparing parathyroid adenomas with malignant and benign thyroid pathology. They have identified that parathyroid adenomas present a higher elasticity index than benign thyroid pathology (3.09 ± 0.75 m/s versus SWV of 2.20 ± 0.39 m/s) and an even higher elasticity than malignant thyroid lesions with a mean SWV of 3.59 ± 0.43 m/s [59].

In the 2D SWE elastography field, a study conducted on parathyroid adenomas and benign thyroid nodules has identified that parathyroid adenomas present a significantly lower elasticity index than benign thyroid nodules (mean SWE 5.2 ± 7.2 kPa, respectively mean SWE of 24.3 ± 33.8 kPa) [60]. The results are similar with our conclusion using the same elastographic method.

Some elastographic studies on parathyroid hyperplasia have been published, but they not focused on patients with chronic kidney disease on hemodialysis. There are currently no other threshold values for secondary hyperparathyroidism, apart those presented [40, 41].

2.5 Strain versus shear-wave elastography

Strain elastography is a very useful elastographic technique that requires external pressure in order to produce deformation of subjacent tissue that has been validated in the field of thyroid and breast evaluation.

Even if strain elastography can be without any doubt a very useful qualitative tool by using the color mapping, 2D-SWE elastography can offer a better identification of parathyroid tissue.

There are certain limitations of the elastography in the evaluation of parathyroid glands, the most important is the difficulty in evaluating ectopic and supranumerary parathyroid glands, especially when located in the thymus or posterior mediastinum. When using elastography, a low value, near to zero could indicate the presence of a liquid lesion or a depth lesion, inaccessible to the linear probe. It is very important to verify the signal intensity, to distinguish between liquid lesions and depth lesion, and to opt for a linear probe with lower frequencies is available. Another limitation to consider is that the trachea or the carotid movement could generate artifacts, in this case, elastographic noise can be decreased by increasing the gain. One of the most important aspects in the elastographic evaluation is the external pressure applied to the probe that can produce false-positive values. This is a limitation because it is operator-dependent, less present in shear-wave elastography than in strain elastography. Another aspect to be considered is the choice of the elastography scale, as there is no recommendation for parathyroid evaluation, we have used in our studies a scale between 0 and 100 kPa.

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3. Conclusions

The clinical implications of elastography in the evaluation of primary or secondary hyperparathyroidism are undeniable. As a complementary method to conventional ultrasonography, elastography is a simple, noninvasive, repeatable, and reproducible method that can improve diagnosis and preoperative evaluation of the patient with either primary or secondary hyperparathyroidism.

Even if there are certain limitations to the technique, such as operator experience and some techniques are more operator-dependent that others, we have to take in mind that it is a complementary technique and that is noninvasive, highly reproducible, easy to manipulate, presents a high resolution in real time, it is harmless to children and pregnant women with absence of X-ray exposure or need of contrast agents, making it a very accessible and cost-efficient imaging technique for complementary evaluation of parathyroid disease.

We have found significant differences between primary and secondary hyperparathyroidism, identifying a cutoff elastographic value for parathyroid adenomas below 5.96 kPa [41].

One of the essential questions of the studies has been answered, the following question was to determine a general cutoff value for parathyroid tissue. Thus, we have considered into analysis both parathyroid adenomas and parathyroid hyperplasia values, permitting us to establish a mean SWE cutoff value for parathyroid tissue below 9.58 kPa [41].

Further studies could help establish the elastographic differences between pathological parathyroid tissue and thyroid nodules. Current literature studies had determined that there is a major difference between malignant and benign thyroid nodules, the first being stiffer than the ladder. Furthermore, benign thyroid nodules present a higher elasticity index than normal thyroid tissue. We can imagine that if parathyroid tissue should be compared with benign or malignant thyroid tissue, a significant elasticity difference should be found.

Elastography is a proven and validated method in many clinical areas and recognized by the current guideline, including thyroid disease [61, 62]. It most certainly presents a major role in the localization of the parathyroid disease as useful tool for both qualitative, but mainly quantitative evaluation of parathyroid tissue. Significant elastographic differences between parathyroid adenoma and parathyroid hyperplasia have been identified, but in both cases, the parathyroid tissue is significantly lower than the healthy thyroid tissue and the surrounding muscle tissue.

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Acknowledgments

We would like to thank all our contributors—Prof Dr. Ioan Sporea, Prof Dr. Adalbert Schiller, and Dr. Oana Schiller for the guidance and for allowing us to conduct our studies in their services.

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Conflict of interest

The authors declare no conflict of interest.

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Notes

The current chapter represents a summary of our experience with the elastography techniques applied in the field of parathyroid disease. Six papers were published on this subject. Images and statistical values were previously published in our studies.

References

  1. 1. Bilezikian JP, Cusano NE, Khan AA, Liu J-M, Marcocci C, Bandeira F. Primary hyperparathyroidism. Nature Reviews Disease Primers. 2016;2:16033
  2. 2. Barr RG, Nakashima K, Amy D, Cosgrove D, Farrokh A, Schafer F, et al. WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 2: Breast. Ultrasound in Medicine and Biology. 2015;41(5):1148-1160
  3. 3. Hindié E, Ugur Ö, Fuster D, O’Doherty M, Grassetto G, Ureña P, et al. 2009 EANM parathyroid guidelines. European Journal of Nuclear Medicine and Molecular Imaging. 2009;36(7):1201-1216
  4. 4. Mizamtsidi M, Nastos C, Mastorakos G, Dina R, Vassiliou I, Gazouli M, et al. Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: Old knowledge with new tricks. Endocrine Connections. 2018;7(2):R56-R68
  5. 5. Kebebew E, Clark OH. Parathyroid adenoma, hyperplasia, and carcinoma: Localization, technical details of primary neck exploration, and treatment of hypercalcemic crisis. Surgical Oncology Clinics of North America. 1998;7(4):721-748
  6. 6. Rahbari R, Holloway AK, He M, Khanafshar E, Clark OH, Kebebew E. Identification of differentially expressed microRNA in parathyroid tumors. Annals of Surgical Oncology. 2011 Apr;18(4):1158-1165. DOI: 10.1245/s10434-010-1359-7. Epub 2010 Nov 18. PMID: 21086055; PMCID: PMC3449317
  7. 7. Hedgeman E, Lipworth L, Lowe K, Saran R, Do T, Fryzek J. International burden of chronic kidney disease and secondary hyperparathyroidism: A systematic review of the literature and available data. International Journal of Nephrology. 2015;2015:184321. DOI: 10.1155/2015/184321. Epub 2015 Mar 31. PMID: 25918645; PMCID: PMC4396737
  8. 8. Jean G, Lafage-Proust MH, Souberbielle JC, Lechevallier S, Deleaval P, Lorriaux C, et al. Severe secondary hyperparathyroidism in patients on haemodialysis is associated with a high initial serum parathyroid hormone and beta-CrossLaps level: Results from an incident cohort. PLoS One. 2018;13(6):1-15
  9. 9. Bandeira F, Griz L, Chaves N, Carvalho NC, Borges LM, Lazaretti-Castro M, et al. Diagnosis and management of primary hyperparathyroidism - a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and metabolism. Arquivos Brasileiros de Endocrinologia e Metabologia. 2013;57(6):406-424
  10. 10. Eufrazino C, Veras A, Bandeira F. Epidemiology of primary hyperparathyroidism and its non-classical manifestations in the City of Recife. Brazil. Clin Med Insights Endocrinol Diabetes. 2013;6:69-74
  11. 11. Cotoi L, Stoian D. Ultrasonographic and Elastographic diagnostic of parathyroid lesions – A literature review. Austin Journal of Endocrinology and Diabetes. 2019;6(2-2019):1068
  12. 12. Arnold A, Staunton CE, Kim HG, Gaz RD, Kronenberg HM. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. England Journal of Medicine. 1988 Mar 17;318(11):658-662. DOI: 10.1056/NEJM198803173181102. PMID: 3344017
  13. 13. Arrangoiz R, Cordera F, Lambreton F, De LEL, Moreno E. Current thinking on primary hyperparathyroidism. JSM Head and Neck Cancer Cases and Reviews. 2016;1(August):1-15
  14. 14. Allgrove J. Parathyroid disorders. American Family Physician. 2001;11(5):357-363. ISSN 0957-5839, DOI: 10.1054/cupe.2001.0206
  15. 15. Gasser RW. Clinical aspects of primary hyperparathyroidism: Clinical manifestations, diagnosis, and therapy. Wiener Medizinische Wochenschrift (1946). 2013;163(17-18):397-402
  16. 16. Mariani G, Gulec S, Rubello D, Boni G, Puccini M, Pelizzo MR, et al. Preoperative localization and radioguided parathyroid surgery. Journal of Nuclear Medicine. 2003;44(9):1443-1458
  17. 17. Lorenz K, Bartsch DK, Sancho JJ, Guigard S, Triponez F. Surgical management of secondary hyperparathyroidism in chronic kidney disease—A consensus report of the European Society of Endocrine Surgeons. Langenbeck’s Archives of Surgery. 2015;400(8):907-927
  18. 18. Korosi A. Practice guidelines for chronic kidney disease. Annals of Internal Medicine. 2004 Jun 1;140(11):934; author reply 934-5. DOI: 10.7326/0003-4819-140-11-200406010-00025. PMID: 15172915
  19. 19. Russo D, Battaglia Y. Clinical significance of FGF-23 in patients with CKD. International Journal of Nephrology. 2011;2011:1-5
  20. 20. Bamber J, Cosgrove D, Dietrich CF, Fromageau J, Bojunga J, Calliada F, et al. EFSUMB guidelines and recommendations on the clinical use of ultrasound elastographypart 1: Basic principles and technology. Ultraschall in der Medizin. 2013;34(2):169-184
  21. 21. Park AY, Son EJ, Han K, Youk JH, Kim JA, Park CS. Shear wave elastography of thyroid nodules for the prediction of malignancy in a large scale study. European Journal of Radiology. 2015;84(3):407-412
  22. 22. Gennisson JL, Deffieux T, Fink M, Tanter M. Ultrasound elastography: principles and techniques. Diagnostic and Interventional Imaging. 2013 May;94(5):487-495. DOI: 10.1016/j.diii.2013.01.022. Epub 2013 Apr 22. PMID: 23619292
  23. 23. Parameter AP. AIUM practice Parameter for the performance of a thyroid and parathyroid ultrasound examination. Journal of Ultrasound in Medicine. 2016;35(9):1-11
  24. 24. Cosgrove D, Barr R, Bojunga J, Cantisani V, Chammas MC, Dighe M, et al. WFUMB guidelines and recommendations on the clinical use of ultrasound Elastography: Part 4. Thyroid. Ultrasound in Medicine and Biology. 2017;43(1):4-26
  25. 25. Cotoi L, Amzar D, Sporea I, Borlea A, Navolan D, Varcus F, et al. Shear wave Elastography versus strain Elastography in diagnosing parathyroid adenomas. International Journal of Endocrinology. 2020;2020:1-11
  26. 26. Stoian D, Ivan V, Sporea I, Florian V, Mozos I, Navolan D, et al. Advanced ultrasound application – Impact on presurgical risk stratification of the thyroid nodules. Therapeutics and Clinical Risk Management. 2020;16:21-30
  27. 27. Sporea I, Lie I. Shear wave elastography. Ultraschall Medicine. 2012 Aug;33(4):393-394. PMID: 23045734
  28. 28. Bota S, Herkner H, Sporea I, Salzl P, Sirli R, Neghina AM, Peck-Radosavljevic M. Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver International. 2013 Sep;33(8):1138-1147. DOI: 10.1111/liv.12240. Epub 2013 Jul 16. PMID: 23859217
  29. 29. Garra BS. Elastography: history, principles, and technique comparison. Abdominal Imaging. 2015 Apr;40(4):680-697. DOI: 10.1007/s00261-014-0305-8. PMID: 25637125
  30. 30. Stoian D, Timar B, Craina M, Bernad E, Petre I, Craciunescu M. Qualitative strain elastography-strain ratio evaluation-an important tool in breast cancer diagnostic. Medical Ultrasonography. 2016;18(2):195-200
  31. 31. Youk JH, Gweon HM, Son EJ. Shear-wave elastography in breast ultrasonography: The state of the art. Ultrasonography. 2017;36(4):300-309
  32. 32. Correas JM, Tissier AM, Khairoune A, Khoury G, Eiss D, Hélénon O. Ultrasound elastography of the prostate: State of the art. Diagnostic and Interventional Imaging. 2013;94(5):551-560
  33. 33. Rus G, Faris IH, Torres J, Callejas A, Melchor J. Why are viscosity and nonlinearity bound to make an impact in clinical elastographic diagnosis? Sensors (Switzerland). 2020;20(8):1-35
  34. 34. Rus G, Melchor JM, Faris I, Callejas A, Riveiro M, Molina F, et al. Mechanical biomarkers by torsional shear ultrasound for medical diagnosis. The Journal of the Acoustical Society of America. 2018;144:1747. DOI: 10.1121/1.5067744
  35. 35. Bhatia KS, Cho CC, Tong CS, Yuen EH, Ahuja AT. Shear wave elasticity imaging of cervical lymph nodes. Ultrasound in Medicine and Biology. 2012 Feb;38(2):195-201. DOI: 10.1016/j.ultrasmedbio.2011.10.024. Epub 2011 Dec 16. Erratum in: Ultrasound Med Biol. 2012 Oct;38(10):1849. PMID: 22178167
  36. 36. Franchi-Abella S, Elie C, Correas JM. Ultrasound elastography: Advantages, limitations and artefacts of the different techniques from a study on a phantom. Diagnostic and Interventional Imaging. 2013;94(5):497-501
  37. 37. Monpeyssen H, Tramalloni J, Poirée S, Hélénon O, Correas JM. Elastography of the thyroid. Diagnostic and Interventional Imaging. 2013;94(5):535-544
  38. 38. Stoian D, Bogdan T, Craina M, Craciunescu M, Timar R, Schiller A. Elastography: A new ultrasound technique in nodular thyroid pathology. In: Ahmadzadehfar H, editor. Thyroid Cancer-Advances in Diagnosis and Therapy [Internet]. London: IntechOpen; 2016 [cited 2022 Jul 10]. DOI: 10.5772/64374. Available from: https://www.intechopen.com/chapters/51576
  39. 39. Sigrist RMS, Liau J, El Kaffas A, Chammas MC, Willmann JK. Ultrasound elastography: Review of techniques and clinical applications. Theranostics. 2017;7:1303-1329
  40. 40. Cotoi L, Borcan F, Sporea I, Amzar D, Schiller O, Schiller A, et al. Shear wave elastography in diagnosing secondary hyperparathyroidism. Diagnostics. 2019;9(4):1-16
  41. 41. Amzar D, Cotoi L, Sporea I, Timar B, Schiller O, Schiller A, et al. Shear wave Elastography in patients with primary and secondary hyperparathyroidism. Journal of Clinical Medicine. 2021;10(4):697
  42. 42. Cotoi L, Amz D, Sporea I, Borlea A, Schiller O, Schiller A, et al. Parathyroid Elastography — Elastography evaluation algorithm. Timişoara Medicală. 2020;2020(1):1-16
  43. 43. Ruchała M, Szczepanek E. Endokrynologia polska. Endokrynologia Polska. 2010;61(3):330-344
  44. 44. Polat AV, Ozturk M, Akyuz B, Celenk C, Kefeli M, Polat C. The diagnostic value of shear wave elastography for parathyroid lesions and comparison with cervical lymph nodes. Medical Ultrasonography. 2017;19(4):386-391
  45. 45. Sung JY. Parathyroid ultrasonography: The evolving role of the radiologist. Ultrasonography. 2015;34(4):268-274
  46. 46. Kunstman JW, Kirsch JD, Mahajan A, Udelsman R. Parathyroid localization and implications for clinical management. Journal of Clinical Endocrinology and Metabolism. 2013;98(3):902-912
  47. 47. Geatti O, Shapiro B, Orsolon PG, Proto G, Guerra UP, Antonucci F, Gasparini D. Localization of parathyroid enlargement: experience with technetium-99m methoxyisobutylisonitrile and thallium-201 scintigraphy, ultrasonography and computed tomography. European Journal of Nuclear Medicine. 1994 Jan;21(1):17-22. DOI: 10.1007/BF00182301. PMID: 8088281
  48. 48. Casara D, Rubello D, Pelizzo M, Shapiro B. Clinical role of 99mTcO4/MIBI scan, ultrasound and intra-operative gamma probe in the performance of unilateral and minimally invasive surgery in primary hyperparathyroidism. European Journal of Nuclear Medicine. 2001;28(9):1351-1359
  49. 49. Rickes S, Sitzy J, Neye H, Ocran KW, Wermke W. High-resolution ultrasound in combination with colour-Doppler sonography for preoperative localization of parathyroid adenomas in patients with primary hyperparathyroidism. Ultraschall in der Medizin. 2003 Apr;24(2):85-89. DOI0: 10.1055/s-2003-38667. PMID: 12698372
  50. 50. Lane MJ, Desser TS, Weigel RJ, Jeffrey RB Jr. Use of color and power Doppler sonography to identify feeding arteries associated with parathyroid adenomas. American Journal of Roentgenology. 1998 Sep;171(3):819-823. DOI: 10.2214/ajr.171.3.9725323. PMID: 9725323
  51. 51. Dietrich CF, Barr RG, Farrokh A, Dighe M, Hocke M, Jenssen C, et al. Strain Elastography - how to Do it ? Authors introduction to Elastography what Elastography techniques are used ? Definition of color coding, why ? Strain-based Elastography – How does it work ? Technical principles of tissue Elastography. Ultrasound International Open. 2017;3:E137-E149
  52. 52. G C, D M. Strain Elastosonography of thyroid nodules: A new tool for malignancy prediction? Overview of literature. Endocrinology & Metabolic Syndrome. 2016;5(3):12-15
  53. 53. Cotoi L, Amzar D, Sporea I, Borlea A, Navolan D, Varcus F, et al. Shear wave Elastography versus strain Elastography in diagnosing parathyroid adenomas. Borretta G, editor. International Journal of Endocrinology [Internet] 2020;2020:3801902. DOI: 10.1155/2020/3801902
  54. 54. Cotoi L, Amzar D, Sporea I, Borlea A, Navolan D, Varcus F, et al. Shear wave elastography versus strain elastography in diagnosing parathyroid adenomas. International Journal of Endocrinology. 2020 Mar 17;2020:3801902. DOI: 10.1155/2020/3801902. PMID: 32256571; PMCID: PMC7103049
  55. 55. Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: New developments in ultrasound for predicting malignancy in thyroid nodules. Journal of Clinical Endocrinology and Metabolism. 2007;92(8):2917-2922
  56. 56. Ünlütürk U, Erdoğan MF, Demir O, Culha C, Güllü S, Başkal N. The role of ultrasound elastography in preoperative localization of parathyroid lesions: a new assisting method to preoperative parathyroid ultrasonography. Clinical Endocrinology (Oxf). 2012 Apr;76(4):492-498. DOI: 10.1111/j.1365-2265.2011.04241.x. PMID: 21955171
  57. 57. Isidori AM, Cantisani V, Giannetta E, Diacinti D, David E, Forte V, et al. Multiparametric ultrasonography and ultrasound elastography in the differentiation of parathyroid lesions from ectopic thyroid lesions or lymphadenopathies. Endocrine. 2017 Aug;57(2):335-343. DOI: 10.1007/s12020-016-1116-1. Epub 2016 Oct 5. PMID: 27709473
  58. 58. Azizi G, Piper K, Keller JM, Mayo ML, Puett D, Earp KM, et al. Shear wave elastography and parathyroid adenoma: A new tool for diagnosing parathyroid adenomas. European Journal of Radiology. 2016;85(9):1586-1593
  59. 59. Batur A, Atmaca M, Yavuz A, Ozgokce M, Bora A, Bulut MD, et al. Ultrasound elastography for distinction between parathyroid adenomas and thyroid nodules. Journal of Ultrasound in Medicine. 2016;35(6):1277-1282
  60. 60. Stangierski A, Wolinski K, Ruchala M. Shear wave elastography in the diagnostics of parathyroid adenomas–new application of the method. Endocrine. 2018;60(2):240-245
  61. 61. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegeds L, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European thyroid association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Journal of Endocrinological Investigation. 2010;33(5 SUPPL):1-50
  62. 62. Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard Ba G, et al. Guidelines for the management of thyroid cancer. Clinical Endocrinology (Oxf). 2014 Jul;81(Suppl 1):1-122. DOI: 10.1111/cen.12515. PMID: 24989897

Written By

Dana Amzar, Laura Cotoi, Andreea Borlea, Calin Adela, Gheorghe Nicusor Pop and Dana Stoian

Submitted: 13 December 2021 Reviewed: 17 June 2022 Published: 18 July 2022