Cervical ultrasound demonstrating a right inferior parathyroid adenoma (a) Transverse view; (b) Longitudinal view
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 . 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 . Residual signal usually indicates parathyroid hyperfunction  (Fig. 37.2). Sestamibi scanning alone has a sensitivity of 60–80 % . 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 scan following injection of 99mTc-sestamibi, and then again approximately 2 h later; a focus of retained radiotracer activity is seen after thyroid gland washout in the left inferior position denotes a left infra-thyroidal parathyroid adenoma
Sestamibi-Single Photon Emission Computed Tomography (Sestamibi-SPECT)
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 . Sestamibi-SPECT appears to be more accurate and superior to sestamibi scan alone for localization of parathyroid adenomas.
Sestamibi with SPECT scan with superimposed images of three planes screen capture demonstrating a right-sided parathyroid adenoma
Four-Dimensional Computed Tomography (4D-CT)
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  (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 . 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 % . The addition of 4D-CT to previously negative or inconclusive ultrasound and sestamibi-SPECT is often advantageous, with a reported sensitivity of 71.8 % . 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.
4D-CT scan demonstrating a right inferior parathyroid adenoma
Magnetic Resonance Imaging (MRI)
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.
MRI of the neck demonstrating hyperintense uptake in a left-sided parathyroid adenoma on T2-weighted imaging
Algorithm for Preoperative Localization
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 . 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 .
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) .
The Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (2013) and the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (2008) guidelines for surgical management of asymptomatic primary hyperparathyroidism patients
Patient age (years)
Serum calcium (> normal limit)
< −2.5 at any site
Previous fragility fracture
24-h urinary calcium
>400 mg/day and increased stone riskf
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 . 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.
In general, patients with single-gland parathyroid adenomas are considered to be the best candidates for outpatient parathyroidectomy. Patients with indeterminate preoperative parathyroid localization studies, multigland disease, familial primary hyperparathyroidism, multiple endocrine neoplasia type 1 or 2A, poorly localized recurrent disease, suspected parathyroid carcinoma, or those who are considered for concurrent total thyroidectomy may not be candidates for the procedure, given the potential for higher likelihood of having postoperative complications and requiring serial laboratory calcium checks or aggressive calcium supplementation in the immediate postoperative period [9, 24].
Choice of Anesthesia
Outpatient parathyroidectomy can be performed under superficial regional cervical block with sedation, or general anesthesia with endotracheal intubation or laryngeal mask.
The superficial cervical block should be complemented by intravenous sedation with fentanyl and/or midazolam in order to minimize patient anxiety, while maintaining consciousness of the patient such that the patient can phonate upon request to allow the surgical team to assess the integrity of the recurrent laryngeal nerve. The superficial cervical block is performed by the surgeon after the patient has been positioned and mild sedation has been administered by the anesthesiologist. Usually, 10 cc of 1 % lidocaine with/out epinephrine (1:100,000) is administered (1) posterior and deep to the ipsilateral sternocleidomastoid muscle at Erb’s point (Fig. 37.6a); (2) along the entire anterior border of the ipsilateral sternocleidomastoid muscle (Fig. 37.6b); and then (3) using a combination of 1 % lidocaine with/out epinephrine mixed with 0.5 % marcaine in a 1:1 ratio along the anterior line of the neck incision in the dermis and under the platysma (Fig. 37.6c). Care should be taken not inject the local analgesic agent intravascularly . Before proceeding to injecting analgesic to the contralateral side, one must assess the patient’s voice and cough, thereby assuring that the ipsilateral vagus nerve or phrenic nerve have not been anesthetized inadvertently. If the cervical block inadvertently involves both vagus nerves, bilateral vocal cord paresis and breathing problems can result, and this potential airway emergency should be avoided at all costs. Certainly, bilateral cervical blocks can be performed to facilitate bilateral exploration, but great caution should be employed to intermittently assess the integrity of recurrent laryngeal nerve function and the patient’s airway.
Superficial cervical block for outpatient parathyroidectomy . 10 cc of 1 % lidocaine is administered (a) posterior and deep to the ipsilateral sternocleidomastoid muscle at Erb’s point; (b) along the entire anterior border of the ipsilateral sternocleidomastoid muscle; (c) a combination of 1 % lidocaine mixed with 0.5 % bupivicaine in a 1:1 ratio injected along the anterior line of the neck incision in the dermis and under the platysma muscle
Data have demonstrated that superficial cervical block may provide significant advantages with regard to the immediate postoperative recovery. In a study of 177 consecutive primary hyperparathyroidism patients who underwent minimally invasive parathyroidectomy, patients who experienced surgery under cervical block (41 %) vs. general anesthesia had better pain control, required less narcotic pain medications, and were less likely to experience nausea or vomiting postoperatively . Surgeon-performed superficial cervical block with monitored sedation/anesthetic care is effective and advantageous in the setting of outpatient parathyroidectomy for well-suited patients, such as those who are motivated, with normal thyroid glands or small goiters, and who have no significant contraindications to sedation (such as severe chronic obstructive pulmonary disease). General anesthesia is an acceptable alternative for outpatient parathyroidectomy for patients who do not fit criteria for superficial cervical block with sedation.
Before commencement of surgery, preparation for adequate blood draws for intraoperative rapid PTH monitoring should be done. A large intravenous line (16–18 gauge) is inserted in an adequate forearm vein. A blood pressure cuff can be placed on the ipsilateral arm above the intravenous line and inflated when blood draws are desired for PTH monitoring, thereby acting as a tourniquet. Arterial line placement for blood draws is most often unnecessary. A first, baseline intraoperative rapid PTH level should be obtained prior to the skin incision. The patient is placed in the “beach chair” neck extension position (or “sniffing position”), and the neck is prepped and draped. Sedation and the surgeon-performed superficial cervical block are then undertaken as described above. A 2–4 cm Kocher midline incision in a natural skin crease is performed, allowing access to both sides of the neck if that should become necessary during the procedure.
A focused, ipsilateral exploration is then undertaken based on the preoperative imaging studies. The strap muscles are divided in the midline raphe, and the thyroid is medially retracted to allow visualization of the paratracheal area. The culprit parathyroid gland is found and carefully dissected out, assuring that its capsule is not violated, thus avoiding any risk of implantation of parathyroid cells in the neck; its vascular supply is clipped or ligated, and the parathyroid adenoma should be removed intact. The ipsilateral recurrent laryngeal nerve must be protected and preserved. Once the parathyroid gland is resected, intraoperative rapid PTH samples are drawn by the anesthesia team via the intravenous line, at time 0 min post-resection, and every 5 min thereafter for a total of 15 min. The patient’s incision can be closed while waiting for the intraoperative PTH results. The procedure is concluded if the PTH drops by 50–65 % from the baseline PTH levels into the normal range, usually within 10–15 min after removal of the hyperfunctioning parathyroid gland . Older patients may have longer PTH half-lives; therefore, additional samples may need to be drawn. The 50 % drop in serum PTH levels into the normal range is a reliable test for documentation of successful identification and resection of the offending parathyroid glands; however, a more aggressive drop of >60–65 % has been proposed recently to improve the rate of missed multigland disease [27–32]. The patient is then observed in the recovery room for a few of hours to assure they do not have nausea or neck swelling suggestive of an expanding hematoma.