Sestamibi (six methoxyisobutylisonitrile) is a monovalent lipophilic cation that diffuses passively across cell membranes and concentrates in the mitochondria. Hyperfunctional parathyroid glands have a rich supply of mitochondria that concentrate sestamibi [13]. Sestamibi scans are obtained following injection of ^99mTc-sestamibi and then again approximately 2 h later, in order to identify foci of retained radiotracer activity after thyroid gland washout [14]. Residual signal usually indicates parathyroid hyperfunction [15] (Fig. 37.2). Sestamibi scanning alone has a sensitivity of 60–80 % [16]. Sestamibi scanning is less accurate in patients with very small parathyroid adenomas, parathyroid hyperplasia, and concurrent inflammatory or neoplastic thyroid disease. Nevertheless, sestamibi scintingraphy may be advantageous in patients with ectopic or supernumerary parathyroid tumors. Excessively “hot” parathyroid sestamibi scans may preoperatively suggest a diagnosis of parathyroid carcinoma.

Sestamibi-SPECT is a three-dimensional sestamibi scan that integrates the functional form of sestamibi imaging with the surrounding anatomic structures identified by a computed tomography scan, improving the accuracy of sestamibi scanning (Fig. 37.3). In a large prospective series of 338 patients who underwent sestamibi-SPECT for primary hyperparathyroidism, the overall sensitivity of sestamibi-SPECT was 82 %, but sensitivity varied greatly with the number and pathology of affected parathyroid glands; the technique correctly identified 90 % of solitary adenomas, 73 % of double adenomas, and 45 % of multigland hyperplasia [17]. Sestamibi-SPECT appears to be more accurate and superior to sestamibi scan alone for localization of parathyroid adenomas.

4D-CT is a four-phase CT technique that offers additional information with regard to the perfusion status of potential parathyroid lesions by assessing the dynamic contrast enhancement properties of the candidate lesions [11] (Fig. 37.4). A noncontrasted phase is performed first. Iodinated contrast is then administered, and examination is performed at different intervals from the time of injection (arterial phase). Subsequent images are obtained at 30 and 60 s (washout phase). Identification of parathyroid adenomas using this technique is based on the fact that adenomas are characterized by rapid uptake and washout of contrast. Typically, parathyroid adenomas have initial low density, rapid increase in density to 60 s, followed by rapid washout of contrast [11]. 4D-CT is a promising technique for preoperative parathyroid localization, with improved accuracy. The reported sensitivity of 4D-CT for single-gland disease is as high as 94 % [18]. The addition of 4D-CT to previously negative or inconclusive ultrasound and sestamibi-SPECT is often advantageous, with a reported sensitivity of 71.8 % [12]. The major disadvantages of 4D-CT are the higher radiation exposure associated with the technique, which is of particular concerns in young patients, and the need for iodinated intravenous contrast administration. Patients with severe allergy to contrast and those with renal insufficiency may not be candidates for 4D-CT.

While MRI is an acceptable localization technique for parathyroid tumors, its utility in localizing enlarged parathyroid glands is limited by the considerable overlap between the appearance of parathyroid tissue, lymph nodes, and exophytic thyroid tissue. Parathyroid adenomas appear hypointense on T1 images and hyperintense on T2 images (Fig. 37.5). Sensitivity of MRI for enlarged parathyroid glands ranges from 43 to 82 % [19, 20]. MRI is seldom used as a primary localization imaging technique in primary hyperparathyroidism. However, it may be considered a reasonable second-line localization test for pregnant patients with primary hyperparathyroidism if a cervical ultrasound is nonlocalizing, as it offers cross-sectional imaging without radiation exposure.

Good preoperative localization of an abnormal parathyroid gland is necessary for undertaking outpatient parathyroidectomy. Surgeons should employ the various imaging studies based on the probability of accurate localization at their own institution.

In a decision tree analysis, Wang et al. examined the cost-utility of various preoperative imaging algorithms before undergoing initial parathyroidectomy for sporadic primary hyperparathyroidism—based on sensitivity and cost-effectiveness of individual imaging studies. Patients were randomized to one of five preoperative localization protocols: (1) ultrasound; (2) sestamibi-SPECT; (3) 4D-CT; (4) sestamibi-SPECT and ultrasound; and (5) sestamibi-SPECT and ultrasound and 4D-CT, if discordant (sestamibi-SPECT and ultrasound ± 4D-CT). Ultrasound was the least expensive, followed by 4D-CT; sestamibi-SPECT and ultrasound ± 4D-CT; sestamibi-SPECT; and sestamibi-SPECT and ultrasound. Sestamibi-SPECT and ultrasound ± 4D-CT were most cost-effective because of improved localization resulting in fewer bilateral surgical neck explorations. Compared to sestamibi-SPECT, ultrasound, 4D-CT, and sestamibi-SPECT and ultrasound ± 4D-CT resulted in a win–win situation costing less because of the enhanced ability to perform limited, outpatient parathyroidectomy. Based on this analysis, a cost-effective imaging algorithm can be developed for preoperative localization of parathyroid adenomas, in which cervical ultrasound should be used first. If the ultrasound is indeterminate, then a combination of 4D-CT and/or sestamibi-SPECT should be employed [21]. While we believe that this algorithm is efficient and effective in localizing abnormal parathyroid adenomas for outpatient parathyroidectomy, it is important to recognize the need for individualization in certain conditions. For example, use of 4D-CT may not be appropriate in the setting of patients with renal insufficiency or in those with significant contrast allergy. Also, 4D-CT may not be easily available at many institutions; therefore, imaging algorithms need to be optimized based on best available studies.

Surgery is the only curative treatment strategy for primary hyperparathyroidism. Parathyroidectomy is recommended for all patients with biochemically proven disease who have symptoms involving target organs, such as nephrolithiasis, severe bone disease, pancreatitis, peptic ulcer disease, and severe neurocognitive dysfunction [22, 23]. In the United States, the overwhelming majority of patients with primary hyperparathyroidism exhibit nonspecific symptoms that cannot always be easily attributed to primary hyperparathyroidism. These nonspecific symptoms include fatigue, weakness, headaches, anxiety, mental depression, and reduced neurocognitive function, such as “mental cloudiness.” Traditionally, patients presenting with these nonspecific findings were considered “asymptomatic.” However, it is reasonable to argue that the term “asymptomatic” may be a misnomer [23].

According to the Fourth International Workshop on Asymptomatic Primary Hyperparathyroidism guidelines, parathyroidectomy is indicated in asymptomatic primary hyperparathyroidism patients who are younger than 50 years, with a serum calcium level of 1 mg/dL above the normal limit, glomerular filtration rate of less than 60 mL/min, or bone density at the hip, lumbar spine, or distal radius that is more than 2.5 standard deviations below peak bone mass. Nephrolithiasis, nephrocalcinosis, or radiographic evidence of vertebral fracture are clear indications for parathyroidectomy (Table 37.1) [22].

Traditional parathyroidectomy dictates a bilateral neck exploration, with identification of all parathyroid glands, even for patients with single-gland disease. This approach proves to be effective, with cure in over 97 % of cases, when the operation is performed by experienced surgeons [10, 24]. However, a large majority of patients with primary hyperparathyroidism harbor a single abnormal parathyroid gland, prompting the concept of unilateral, or focused neck exploration if the location of the abnormal gland can be identified preoperatively. Improvements in accuracy of preoperative localization techniques coupled with the successful introduction of intraoperative rapid PTH monitoring have obviated the need for bilateral neck exploration in most cases and led to the successful development of minimally invasive parathyroidectomy or parathyroidectomy via unilateral/focused neck exploration. Currently, minimally invasive parathyroidectomy is an established approach for parathyroidectomy and has become the standard of care in the hands of experienced parathyroid surgeons for the management of sporadic primary hyperparathyroidism [10]. Published data have established that minimally invasive parathyroidectomy is equally effective to the bilateral neck exploration technique in curing primary hyperparathyroidism [9, 10, 25].

Historically, patients undergoing parathyroid surgery via bilateral neck exploration stayed in the hospital for 1–2 days. Successful implementation of minimally invasive or focused parathyroidectomy has challenged the need for such inpatient admission or even an extended overnight/23-h observation patient stay. This has led to parathyroidectomy becoming truly outpatient surgery, where patients are discharged within hours after successful completion of the operation if meeting discharge criteria.