**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.

*Role of Elastography in the Evaluation of Parathyroid Disease DOI: http://dx.doi.org/10.5772/intechopen.105923*

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].

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].

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].

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**).

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

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].

*Role of Elastography in the Evaluation of Parathyroid Disease DOI: http://dx.doi.org/10.5772/intechopen.105923*


#### **Table 1.**

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


#### **Table 2.**

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

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**).

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

#### **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].*

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.

*Role of Elastography in the Evaluation of Parathyroid Disease DOI: http://dx.doi.org/10.5772/intechopen.105923*


#### **Table 3.**

*Baseline characteristics of patients evaluated with primary and secondary hyperparathyroidism.*

#### **Figure 6.**

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

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.

## **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.
