**2. Anatomy of the parathyroid glands**

Parathyroid glands differ in shape and size. Typically four glands are present and are located adjacent to the dorsal surface of the thyroid lobes-two upper and two lower pairs. Normal glands tend to be flat and oval and normal measurements are 3 × 5 × 7 mm [5]. The combined weight of all parathyroid glans is 90–130 mg and the superior glands are smaller than the inferior [6, 7]. Autopsy series demonstrate that four glands are found in 91% in subjects, five glands in 4%, and three glands in 5% [8]. Approximately 5% of humans have supernumerary (more than four) parathyroid glands [9]. Supernumerary glands are most commonly found within the thymus. Although gland distribution may deviate widely, the superior parathyroid glands, originating from the fourth pharyngeal pouch, are commonly found along the posterior surface of the upper two-thirds of the thyroid gland (92%). The inferior parathyroid glands have a more variable distribution than the superior ones. They originate from the third pharyngeal pouch together with the thymus. They migrate caudally until they reach the lower pole of the thyroid gland and 17% of them touch the inferior border of the thyroid gland, 26% are within the superior horn of the thymus, and 2% are in the mediastinal thymus [10]. The variable anatomic distribution makes the inferior glands more difficult to locate than the superior ones. Histologically parathyroid glands are made of chief, oxyphillic and transient oxyphillic cells mixed with fat tissue. Chief cells produce PTH. The oxyphillic cells which are rich of mitochondria are with poorly defined function [11].

## **3. Noninvasive parathyroid imaging**

The normal parathyroid glands cannot be visualized. The lack of the perfect imaging method for precise localization of parathyroid adenomas had led to search

**47**

*Parathyroid Scintigraphy*

(

*DOI: http://dx.doi.org/10.5772/intechopen.90341*

99mTc-sestamibi or 99mTc-tetrofosmin.

**4. Parathyrod scintigraphy**

only of the parathyroid glands [16].

for an alternative imaging techniques. Ultrasonography (US) is one of the most widely used procedures. Because of the great anatomic variations of the parathyroid glands, their small sizes, the presence of more than one abnormal gland and the higher frequency of concomitant morphological changes of the thyroid gland, US proved to be specific but with low sensitivity. The success of US is highly operator dependent [12]. Rapid spiral thin-slice CT scanning of the neck and mediastinum with evaluation of axial, coronal and sagittal views can add much to the search for elusive parathyroid tissue [13]. MRI can also identify abnormal parathyroid tissue, but it is time consuming and expensive. It is also less sensitive than other modalities. It can nonetheless be useful when the search with the other noninvasive approaches has been unsuccessful. PET/CT can be used, but like MRI, it is expensive and does not have the kind of experiential basis that make it attractive. There are limiting data for using PET/CT in parathyroid imaging. PET with 18F-fluorodeoxyglucose

18F-FDG) was used with varying success. One study showed that 18F-FDG РЕТ was more sensitive but less specific than 99mTc-sestamibi SPECT [14]. Others reported very low sensitivity for detecting abnormal parathyroid glands [15]. Using РЕТ with 11C-methionine in parathyroid examination has been studied in some patients but because of the very short half-life of 11C-methionine, only 20 min its use is limited only to nuclear medicine centers located near to a cyclotron. There is a general consensus that the most sensitive and specific imaging modality, especially when it is combined with single-photon emission CT (SPECT) is the scintigraphy with

Historically, the success of scintigraphy had been compromised by the failure of finding a pharmaceutical agent with specific topic accumulation in parathyroid glands and their close proximity to the thyroid gland. That is why to find a reliable method to differentiate both glands on scintigraphy was crucial. This was first achieved by a combined use of two radionuclides with different uptake in the thyroid and parathyroid cells. The latter allowed to perform a subtraction of the obtained images of both glands and to visualize only the abnormal parathyroid gland, but this proved to be time consuming and with greate radiation exposure to the patients. The first widely used radionuclide for detecting hyperfunctioning parathyroid glands during the 80s was 201Thallium chloride (201Tl). 201Tl chloride accumulates equally in thyroid and parathyroid cells. To make differentiation possible, its application was followed by an injection of 99mTc pertechnetate, with predominant thyroid uptake. Then 99mTc pertechnetate thyroid images were digitally subtracted from the images obtained with 201Tl chloride to allow visualization

Introduced in clinical practice by Coakley et al. [17], the 99mTc-sestamibi scintigraphy significantly increased the role of preoperative scintigraphy in patients with hyperparathyroidism. Firstly used as a cardiotropic agent this radionuclide showed increased accumulation in a variety of benign and malignant tumors. 99mTc-sestamibi consists of lipophilic cationic molecules. After being intravenously injected these molecules distribute throughout the body accordingly to the local blood supply and by passive diffusion through cell's membrane accumulate intracellularly into the mitochondria [18, 19]. Normally 99mTc-sestamibi distributes in parotid and submandibular salivary glands, thyroid gland, the heart and the liver, but not in normal parathyroid glands. Visualization of parathyroid adenomas and hyperplastic parathyroid glands depends on the presence of oxyphillic cells, which are rich of mitochondria. The cells of parathyroid adenomas have plenty of

#### *Parathyroid Scintigraphy DOI: http://dx.doi.org/10.5772/intechopen.90341*

*Medical Isotopes*

men, in a ratio of approximately 3:1. PHPT occurs predominantly in individuals in their middle years with a peak incidence between ages 50 and 60 years and can reach 4 cases per 1000 persons in women after their 60s. At the time of diagnosis, most patients with PHPT do not have classic symptoms like osteitis fibrosa cystica, nephrocalcinosis, nephrolithiasis or other signs associated with the disease. Symptomatic PHPT is now exception rather than the rule, with more than threefourths of patients having no symptoms making detected changes of the blood values of calcium, phosphorus and parathyroid hormone (PTH) to be the only reason for diagnosis [1, 2]. By far, the most common lesion found in patients with PHPT is the solitary parathyroid adenoma, occurring in 85–90% of patients, while in the rest 10–15% primary hyperplasia of the parathyroid glands is present [3]. In the past the standard surgical approach for PHPT was the bilateral four-gland parathyroid exploration with the removal of each gland which showed changes macroscopically. While in most of the patients with PHPT only one parathyroid gland is being affected, the above mentioned surgical approach is inappropriate in all cases. Unilateral approaches are appealing in a disease in which only a single gland is involved. So nowadays, the currently most widely used surgical approach is the minimally invasive parathyroidectomy which is connected with less postsurgical complications and shortens the time of operation [4]. To be successful this procedure needs to rely on a precise preoperative localization of the abnormal parathyroid glands. That is, why preoperative parathyroid imaging gained so large importance. The rationale for locating abnormal parathyroid glands prior to surgery

is that they can be notoriously unpredictable in their location.

Parathyroid glands differ in shape and size. Typically four glands are present and are located adjacent to the dorsal surface of the thyroid lobes-two upper and two lower pairs. Normal glands tend to be flat and oval and normal measurements are 3 × 5 × 7 mm [5]. The combined weight of all parathyroid glans is 90–130 mg and the superior glands are smaller than the inferior [6, 7]. Autopsy series demonstrate that four glands are found in 91% in subjects, five glands in 4%, and three glands in 5% [8]. Approximately 5% of humans have supernumerary (more than four) parathyroid glands [9]. Supernumerary glands are most commonly found within the thymus. Although gland distribution may deviate widely, the superior parathyroid glands, originating from the fourth pharyngeal pouch, are commonly found along the posterior surface of the upper two-thirds of the thyroid gland (92%). The inferior parathyroid glands have a more variable distribution than the superior ones. They originate from the third pharyngeal pouch together with the thymus. They migrate caudally until they reach the lower pole of the thyroid gland and 17% of them touch the inferior border of the thyroid gland, 26% are within the superior horn of the thymus, and 2% are in the mediastinal thymus [10]. The variable anatomic distribution makes the inferior glands more difficult to locate than the superior ones. Histologically parathyroid glands are made of chief, oxyphillic and transient oxyphillic cells mixed with fat tissue. Chief cells produce PTH. The oxyphillic cells which are rich of mitochondria are with poorly defined function [11].

The normal parathyroid glands cannot be visualized. The lack of the perfect imaging method for precise localization of parathyroid adenomas had led to search

**2. Anatomy of the parathyroid glands**

**3. Noninvasive parathyroid imaging**

**46**

for an alternative imaging techniques. Ultrasonography (US) is one of the most widely used procedures. Because of the great anatomic variations of the parathyroid glands, their small sizes, the presence of more than one abnormal gland and the higher frequency of concomitant morphological changes of the thyroid gland, US proved to be specific but with low sensitivity. The success of US is highly operator dependent [12]. Rapid spiral thin-slice CT scanning of the neck and mediastinum with evaluation of axial, coronal and sagittal views can add much to the search for elusive parathyroid tissue [13]. MRI can also identify abnormal parathyroid tissue, but it is time consuming and expensive. It is also less sensitive than other modalities. It can nonetheless be useful when the search with the other noninvasive approaches has been unsuccessful. PET/CT can be used, but like MRI, it is expensive and does not have the kind of experiential basis that make it attractive. There are limiting data for using PET/CT in parathyroid imaging. PET with 18F-fluorodeoxyglucose ( 18F-FDG) was used with varying success. One study showed that 18F-FDG РЕТ was more sensitive but less specific than 99mTc-sestamibi SPECT [14]. Others reported very low sensitivity for detecting abnormal parathyroid glands [15]. Using РЕТ with 11C-methionine in parathyroid examination has been studied in some patients but because of the very short half-life of 11C-methionine, only 20 min its use is limited only to nuclear medicine centers located near to a cyclotron. There is a general consensus that the most sensitive and specific imaging modality, especially when it is combined with single-photon emission CT (SPECT) is the scintigraphy with 99mTc-sestamibi or 99mTc-tetrofosmin.
