Role of Elastography in the Evaluation of Parathyroid Disease

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

### **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 [4–6].

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, 4–6, 9–11].

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 [15–19].

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, 22–24]. 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, 27–29], senology [30, 31], urology [32–34], 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.


b.point shear-wave elastography (pSWE)

c. 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, 40–42]. 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.
