Developed in the early 1990s, sestamibi parathyroid scanning is now widely available. This imaging modality, comprised of several different nuclear scintigraphic techniques, is the most popular procedure used for parathyroid localization and is collectively the most accurate, with a sensitivity and specificity of greater than 90 % for identifying parathyroid disease. Sestamibi scanning is particularly useful for identifying ectopic disease and has been shown to be more reliable for adenoma localization in patients with lower levels of vitamin D.

Often used in conjunction with ultrasound, this combination is highly reliable, as an ultrasound can anatomically identify a possible adenoma, while a nuclear medicine scan can differentiate it functionally from a lymph node or thyroid mass.

Tc-99m sestamibi is a lipid-soluble myocardial perfusion tracer that accumulates in the mitochondria of cells. Parathyroid adenomas are very vascular and have a high concentration of oxyphilic cells, which have increased mitochondrial content, increasing their sestamibi uptake. The sestamibi isotope, which emits gamma rays, is retained longer in the parathyroid adenoma cells than the adjacent thyroid due to this increased mitochondrial content. Thus, there is focal increased uptake on early and delayed images taken with a gamma camera in an adenoma, as compared to other surrounding tissue. The two most common techniques used are subtraction imaging and dual-phase imaging. Subtraction imaging can be especially helpful if a thyroid mass is present. Dual-phase imaging is less affected by motion artifact, making it a better option for SPECT imaging.

In subtraction imaging, both a thyroid-specific radionuclide and a thyroid- and parathyroid-specific radionuclide are administered. The most commonly used thyroid-specific radionuclides are either iodine-123 (¹²³I) or Tc-99 m sodium pertechnetate. The image from the uptake of the thyroid-specific radionuclide is subtracted from the parathyroid/thyroid radionuclide (Tc-99m sestamibi) image, resulting in an estimation of parathyroid tissue uptake (Fig. 14.3).

In the dual-phase technique, visualization of parathyroid adenomas is based on differential washout. In this process, initial images are taken 10 min after intravenous infusion, and subsequent images are taken at 2–3 h after sestamibi administration, based on the kinetics of the compound. Due to retention and delayed sestamibi washout, there should be persistent sestamibi visualization in the parathyroid adenomas in the delayed images, as compared to the initial set (Fig. 14.4). Hyperparathyroid patients with double adenomas and parathyroid hyperplasia have progressively less distinct or successful localization than those with single adenomas.

Sestamibi imaging was originally performed as two-dimensional (2D) planar scanning (Fig. 14.5). Such 2D scans have in some centers been replaced by SPECT (single proton emission computed tomography) scans, which provide three-dimensional (3D) reconstruction and greater localizing information (Fig. 14.6). Furthermore, SPECT sestamibi scans have recently been fused with high-resolution, thin slice CT to localize disease even more precisely (Fig. 14.7). Several studies have found dual-phase SPECT/CT sestamibi imaging to be significantly superior to planar imaging in the detection of parathyroid lesions, especially when there is concomitant thyroid nodularity. However, other studies have found that SPECT/CT has no significant clinical value additional to that of conventional SPECT for parathyroid imaging except in locating ectopic parathyroid glands and that the additional time, radiation exposure, and expense do not justify the CT acquisition.

One of the main limitations of all variations of sestamibi scanning is the fact that, like ultrasound, it is highly operator dependent. It is most reliable for identifying large, solitary adenomas. False positives occur when there are other cell types that also have high mitochondrial content, such as Hurthle cell nodules in thyroid tissue. Also, brown fat, brown tumors, lymphoma, breast cancer, and thyroid carcinoma all have a propensity for increased uptake. False negatives often occur with adenomas with low oxyphilic count, which is seen in smaller adenomas and in multiglandular disease. False-negative sestamibi scanning has also been linked to patients with higher levels of vitamin D and lower levels of serum calcium, as well as patients with multigland disease (multiple adenomas or parathyroid hyperplasia.). Reviewing early, late, and subtraction pinhole images together with SPECT images maximizes parathyroid lesion detection accuracy. Also, the operating surgeon should review all sestamibi scans irrespective of what is reported, because there are often subtle findings that are pertinent but not reported on the formal interpretation.

Computed tomography (CT) is a second-line noninvasive imaging modality that is typically used to localize elusive parathyroid disease. Although not as sensitive as ultrasound or sestamibi scans, this imaging modality is useful for identifying ectopic disease (Fig. 14.8). It is available for use in most medical centers and can be used for guiding FNA biopsy of a lesion. In addition, it is less operator dependent than ultrasound or sestamibi imaging, and the images are easily stored in most databases.

The disadvantages of CT include its cost, exposure of the patient to radiation, and necessity for intravenous contrast. In addition, false positives are not uncommon, with lymph nodes most commonly mistaken for parathyroid adenomas. False negatives also result from parathyroid lesions being mistaken for lymph nodes.

The four-dimensional CT (4D-CT) imaging of the neck and upper mediastinum takes advantage of precise timing of contrast perfusion coordinated with acquisition of computed tomography data to identify the adenoma. It yields 3D multiphasic images, combined with the fourth or time dimension, to result in images at specified moments pre-contrast, during infusion, and 30 s after infusion. This imaging modality reveals both the anatomic location and the physiology of the lesion, by evaluating the perfusion characteristics. Parathyroid adenomas are characterized by rapid uptake of contrast with early washout of contrast. Lymph nodes are characterized by slow uptake of contrast with slow release. Thus, on the contrast-enhanced CT, a parathyroid adenoma will typically enhance earlier and more briefly than lymph nodes.

The 4D-CT has been shown in some centers to be more sensitive than ultrasound or sestamibi scan alone for precise localization of hyperfunctioning parathyroid glands, with a lateralization accuracy of 93 % and localization accuracy of 86 %. It has also been shown to be useful in localizing adenomas in the reoperative setting. The disadvantages of using this imaging modality are its cost, exposure of the patient to radiation, the necessity for contrast, and limited availability of this type of study, as compared to other imaging modalities.

The use of MRI for identification of parathyroid adenomas is mainly reserved for patients with nonlocalizing sestamibi and ultrasound studies and for previously operated patients with persistent hyperparathyroidism. MRI is also very useful for identifying ectopic disease, especially in the mediastinum (Fig. 14.9), and in cases when findings on nuclear medicine imaging and on ultrasound are discordant. Its use is limited due to its increased cost and need for expertise in interpreting the images.