Minimally Invasive Radioguided Parathyroidectomy

Serum calcium >12.0 mg/dL

24-h Urinary calcium >400 mg/day

Episode of life-threatening hypercalcemia

Creatinine clearance decreased by ≥30 %


Age <50 years

Osteitis fibrosa cystica


Neuromuscular symptoms

Preoperative Evaluation

In addition to the usual preoperative history, physical examination, risk stratification, and appropriate medical optimization, several other factors must be taken into consideration prior to surgery. The surgeon must be certain that the patient does, in fact, have 1° HPT and not some other condition that may mimic 1° HPT, such as severe vitamin D deficiency (increased PTH with normal or low calcium) or familial hypocalciuric hypercalcemia (FHH). In one series, nearly 20 % of patients referred for parathyroidectomy were incorrectly diagnosed with 1° HPT [28].

In cases of proven biochemical 1° HPT, vitamin D deficiency, renal failure, heart failure, and morbid obesity, among others, may compromise the utility of adjunctive modalities, including preoperative localization imaging studies and intraoperative PTH measurements. Consideration of the findings obtained from any adjunct studies must be made in the context of the patient’s comorbidities.

Preoperatively, the surgeon must assess for the presence of any voice or swallowing complaints and appropriately pursue evaluation of these. Any neck surgery may lead to subjective difficulty with swallowing and/or voice changes, especially early postoperative period. Due to the anatomic proximity of the parathyroid glands to the recurrent laryngeal nerves, it is prudent to examine vocal cord motion prior to surgery, using either laryngeal mirror examination or flexible fiber-optic laryngoscopy.

Options for Anesthesia

General anesthesia is the usual choice during MIRP, but monitored anesthesia care (MAC) with regional anesthesia (i.e., cervical block) are well-described alternatives that may also be used. In the hands of an experienced, high-volume MIRP surgeon, cases involving a localized, solitary adenoma may routinely be completed in less than 30 min. Patients with significant medical comorbidities who are otherwise unfit for general anesthesia may benefit from MAC with regional anesthesia [29]. Reliable and consistent provision of anesthesia by experienced providers is very important for a local/MAC technique to be successful.

MIRP in Specific Patient Populations

MIRP in Pediatric Patients

Primary hyperparathyroidism is rare in children, with an incidence of 2–5 per 100,000 [30]. As in the adult population, the underlying cause of 1° HPT in the pediatric population is most commonly a solitary parathyroid adenoma, accounting for 80 % of cases. Multi-gland hyperplasia is the cause in 16.5 %, double adenomas are identified in less than 1 %, and 2.6 % appeared to have normal gland histology [31]. Parathyroid carcinoma is exceedingly rare in children, accounting for far less than 1 % of cases of 1° HPT [32]. Severe neonatal hyperparathyroidism is a separate disease process and its features and management are beyond the scope of this section and are described in Chap. 19 [33].

Management of pediatric 1° HPT is similar to that in adults, but with consideration given to two points [34]. First, children are more likely than adults to have a parathyroid adenoma in an ectopic location. Second, up to 50 % of cases of multi-gland hyperplasia are related to one of the multiple endocrine neoplasia (MEN) syndromes or familial non-MEN hyperparathyroidism. The increased incidence of multi-gland disease in children is nearly completely accounted for by the number of familial cases [35]. In children who do not have a personal or family history of a hereditary endocrinopathy, MIRP is considered to be a viable surgical option, though it has not specifically been studied in this group.

In patients of all ages, accurate preoperative localization is the key to avoiding bilateral neck exploration. In children, ultrasound and 99mTc-sestamibi SPECT were found to be accurate in 79 % and 86 %, respectively—similar figures as in adults [2, 31]. In those cases where ultrasound is non-localizing, studies that offer greater anatomic detail, such as 99mTc-sestamibi SPECT, SPECT-CT, or 4D CT, may be especially useful due to a higher incidence of ectopic parathyroid adenomas in children.

MIRP in Elderly Patients

Elderly patients may be less likely to be referred for surgery and more likely to decline surgery for 1° HPT due to perceived risks of surgery. Several studies have clearly demonstrated the quality-of-life benefits, cost-effectiveness, and safety of MIRP in older patients [7, 3538], although a single (though much larger volume) study found a higher rate of complications in elderly patients [39]. The notable difference between these findings may be explained by the volume of parathyroid surgery performed by the surgeons whose patients were included in each study. Those patients who underwent surgery with a high-volume parathyroid surgeon tended to have shorter operative times and fewer complications than those who underwent surgery with a low-volume parathyroid surgeon [39].

MIRP in Pregnancy

Primary hyperparathyroidism poses a unique set of risks in pregnancy and surgery remains the definitive treatment. In this situation, the advantages of a minimally invasive procedure, including shorter operative time and potentially avoiding general anesthesia, are apparent. While some have advocated that the optimal timing for parathyroidectomy is early in the second trimester, this fact may be less important in the context of the danger of untreated hyperparathyroidism in pregnancy. The first goal remains localization of the diseased gland(s) with minimal or no radiation exposure to the fetus. Ultrasound is the most commonly recommended first-line study for parathyroid localization during pregnancy [4042]. MRI and other techniques, such as needle aspiration with measurement of PTH levels of aspirate, have been described as alternatives in the context of a non-localizing ultrasound [42]. The use of sestamibi-based imaging and intraoperative 99mTc-sestamibi administration and gamma probe measurements are considered by many to be ill-advised during pregnancy [40, 41], while others have described alternative 99mTc-sestamibi dosing protocols for that may not portend significant risk to the developing fetus [43].

MIRP in Obese Patients

Obesity complicates nearly all aspects of minimally invasive surgery. In addition to the increased risk associated with anesthesia, obesity worsens the diagnostic capability of preoperative localization imaging studies and adds significant technical difficulty to the surgical procedure. High BMI may also prolong the half-life of PTH, thereby compromising the utility of intraoperative PTH monitoring [44]. Postoperatively, obesity impacts dosing requirements for oral calcium, placing these patients at higher risk for symptomatic hypocalcemia [45, 46].

Imaging and Localization

Details of technical considerations pertaining to the various choices for imaging the parathyroid glands are discussed elsewhere in this text and are beyond the scope of this section. Since preoperative localization of the offending parathyroid adenoma is practically the sine qua non of minimally invasive radioguided parathyroidectomy, selected modalities will be briefly discussed with an emphasis placed on efficacy and shortcomings of each one. An overview of relevant imaging modalities may be found in Table 17.2.

Table 17.2
Summary of parathyroid localization studies







• Inexpensive

• Portable units are available

• Often located in offices where patients with 1° HPT are routinely followed (i.e. endocrinology)

• Highly dependent upon the experience of the operator

• Ultrasonographically “silent” anatomic locations, i.e. retro-esophageal groove or the mediastinum

• Multinodular thyroid disease

• Patients with a short or thick neck

• Limited sensitivity for small parathyroid adenomas

• Limited sensitivity for multi-gland parathyroid disease


• Sensitivity: 70–96 %

• Specificity: 50–100 %

• Accuracy: 86.2–98 %


• May be useful for imaging of pregnant patients

• Useful for identification of ectopic parathyroid glands

• Expensive

• Limited sensitivity for small parathyroid adenomas

• High-resolution machines are not available in many smaller facilities


• Sensitivity: 64–89 %

• Specificity: 75–89 %

• Accuracy: 64–84 %

Planar Scintigraphy

• Simple to interpret

• Useful for identification of ectopic parathyroid glands

• Limited sensitivity for small parathyroid adenomas

• Limited anatomic information

• Time-consuming to perform

6.7–7.8 mSv

• Sensitivity: 54–88.2 %

• Specificity: 87.8 %

• Accuracy: 88.0 %


• Improved localization and anatomic information compared to planar scintigraphy

• Limited sensitivity for small parathyroid adenomas

• Limited sensitivity for multi-gland parathyroid disease

6.7–7.8 mSv

• Sensitivity: 74–87 %

• Specificity: 84 %

• Accuracy: 83.4–94 %


• Further improvement of localization and anatomic information beyond SPECT

• Large dose of radiation

• Limited sensitivity for small parathyroid adenomas

• Limited sensitivity for multi-gland parathyroid disease

18.4 mSv

• Sensitivity: 84.4–86 %

• Specificity: 89.4–90.4 %

• Accuracy: 78–88.8 %


• Improved localization of ectopic parathyroid adenomas

• Useful for identification of multi-gland parathyroid disease

• Can detect parathyroid glands as small as 3 mm

• Large dose of radiation

• Time-sensitive imaging protocol; technical errors can render results useless

• False positives may be seen with vitamin D deficiency and multi-gland parathyroid disease

10.4–13.8 mSv

• Sensitivity: 92.1 %

• Specificity: 95.6 %

• Accuracy: 88.2–94.7 %


• May accurately localize lesions that were not identified using ultrasonography and/or sestamibi imaging

• Lower radiation dose than SPECT/CT and 4D CT

• Expensive

• Requires specialized facilities and equipment

5.2–6.7 mSv

• Sensitivity: 81–89 %

• Specificity: 78 %

• Accuracy: 80 %

Selection of preoperative localization studies depends largely on surgeon’s choice and available technologies [47]. In the past, bilateral neck exploration for 1° HPT was routinely performed without any preoperative imaging. Successful localization of the offending lesion(s) helps the surgeon to utilize a smaller skin incision (improved cosmesis), avoid unnecessary bilateral neck exploration, decrease operative time and associated costs, and reduce the rate of complications while maintaining success rates that are similar to bilateral neck exploration [2, 6].

There is no perfect imaging study for localization of diseased parathyroid glands. Over time, new techniques have emerged as evolutions of older techniques. Dual-phase (or multi-phase) imaging studies, which rely on perfusion and washout of radionuclides or intravenous contrast, have offered some improvement in differentiation of parathyroid tissue from surrounding structures. In an effort to improve reliability of preoperative localization, it is the practice of some surgeons to routinely pursue two imaging studies that show concordance in location of the parathyroid adenoma.


Ultrasonography is the most commonly utilized imaging tool in the evaluation of the parathyroid disease. It does not involve radiation exposure, it is inexpensive compared to other pertinent modalities, and it is widely available, including in many clinics where patients are seen for 1° HPT. The efficacy of parathyroid ultrasonography is highly dependent upon the experience of the user. High-resolution ultrasound units with color Doppler capability allow the operator to identify the polar feeding vessel to the adenomatous parathyroid gland and to assess vascularity. Parathyroid adenomas tend to have peripheral vascularity and are typically hypervascular compared to most thyroid nodules [48, 49].

In cases of 1° HPT due to a solitary adenoma, sensitivity, specificity, and positive predictive value of ultrasonography have been reported as 70–96, 50–100, and 90–98 %, respectively [49]. In patients with co-existent nodular thyroid disease, the sensitivity of ultrasonography has been reported to be diminished to 64 % [49, 50]. Multi-gland disease is correctly imaged using ultrasonography with success rates ranging from 10 to 50 % for multiple hyperplastic glands and 10–35 % for double adenomas [2].

The efficacy of ultrasonography for preoperative parathyroid adenoma localization has notable limitations in several groups of patients [49]:

  • Patients with multinodular thyroid disease

  • Patients with a short and/or thick neck

  • Patients with parathyroid adenoma(s) in “sonographically silent” areas, most commonly the retroesophageal groove or mediastinum

  • Patients with parathyroid gland(s) that are only minimally enlarged

  • Patients with multi-gland parathyroid disease

Some surgeons routinely use ultrasonography in the operating room to confirm the findings of preoperative localization studies and mark the patient prior to sterile prep and incision [51].

Parathyroid Scintigraphy

Various methods of parathyroid scintigraphy have been used for preoperative adenoma localization. A trend seen in several imaging modalities for parathyroid pathology, multiple images are obtained at different times after administration of either contrast or a radionuclide, and the kinetics of perfusion of the parathyroid glands may help the interpreter to identify the parathyroid gland(s) of interest. One of the early applications of this rationale was 201Tl thallous chloride and 99mTc (technetium) pertechnetate dual-isotope scintigraphy, which was later replaced by dual-phase planar (DPP) scintigraphy using technetium-99 m sestamibi (Tc-99 m MIBI), which was more accurate [52]. In the case of 99mTc-sestamibi, the radionuclide becomes concentrated within the mitochondria of the metabolically hyperactive, adenomatous parathyroid glands. While the radionuclide tends to “wash out” of structures such as the thyroid gland and lymph nodes relatively quickly, it persists within the parathyroid tissue of clinical interest for longer time periods, allowing scintigraphic localization [16, 53].


99mTc-sestamibi single-photon emission computerized tomography (SPECT) is a definite advancement, offering improved sensitivity and anatomic information compared to conventional parathyroid scintigraphy. Despite these facts, the sensitivity of SPECT is lacking in the detection of smaller adenomas (<250 mg) and multi-gland disease [54, 55].


SPECT/CT is a fusion study performed using 99mTc-sestamibi as the radionuclide and either a hybrid SPECT/CT gamma camera or software methods to assimilate the SPECT information with CT imaging. No difference in diagnostic accuracy has been noted between dual acquisition or software image fusion [56]. This study may be obtained as a single- or dual-phase study, with the first measurement being obtained at 5–15 min and the second measurement being obtained at 60–120 min after administration of the radionuclide. In dual-phase studies, the first portion will often include a diagnostic CT, while the delayed portion includes a nondiagnostic CT. The CT portion of the delayed imaging is necessary to ensure proper anatomic superimposition of the gamma imaging. While the second CT is a nondiagnostic, lower radiation study, it still adds to the overall radiation burden to the patient.

In an effort to quantify the improved localization for the additional radiation burden of the second part of this study, a comparison was made between the early phase of the SPECT/CT fusion by itself and the dual-phase study. Sensitivity, specificity, and accuracy were 84.8 %, 89.6 %, and 78 %, respectively, for dual-phase SPECT/CT. In comparison, early-phase SPECT/CT was found to have a sensitivity, specificity, and accuracy of 84.4, 89.4, and 76 %. These values were not significantly different for the study group of 75 patients, a finding which may prompt further evolution of this imaging technique [57].

Despite the proven advantages of fusion SPECT/CT, various forms of planar scintigraphy and SPECT are still used in the medical community. Investigation of this has identified a significantly higher rate of successful localization in high-volume parathyroid imaging centers (defined as centers annually performing more than 30 sestamibi scans for parathyroid localization) compared to low-volume centers. In the review of these cases, the authors noted that many of the patients with non-localizing studies obtained in the low-volume centers had undergone older imaging protocols [58].

4D Computerized Tomography

The accuracy of 4D computerized tomography (4D CT) in correctly localizing a parathyroid adenoma has been reported within the range from 88.2 to 94.7 % [47, 5962]. Accurate identification of previously non-localizing parathyroid adenomas is of particular interest, and 4D CT has shown some promise in the pursuit of this, with successful identification of more than half of parathyroid lesions that failed to localize using ultrasonography and sestamibi [63]. In a direct comparison of imaging modalities, the overall diagnostic accuracy of 4D CT was found to be 94.7 %, as compared to 88.8 % for SPECT/CT and 86.2 % for ultrasonography (p < 0.01). Additionally, this study found 4D CT to have advantages in sensitivity, specificity, positive predictive value, and negative predictive value over the other two modalities [62]. Despite its accuracy in successful localization of a solitary parathyroid adenoma, the sensitivity and accuracy of 4D CT are somewhat compromised in cases of multi-gland disease [59, 61, 63].

One important concern that has been raised with 4D CT is the radiation exposure associated with dual-phase CT. The calculated effective radiation dose exposure from 4D CT varies based on equipment and imaging protocol and has been reported to be 10.4–13.8 mSv. While this radiation dose is greater than that of 99mTc-sestamibi-SPECT (7.8 mSv), it is less than the dose obtained from hybrid sestamibi-SPECT (18.4 mSv) [47, 64].

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has the advantages of the avoidance of ionizing radiation and excellent delineation of soft-tissue structures. In comparison to ultrasonography, MRI offers more adequate imaging of the mediastinum in the case of an ectopic adenoma. Typical characteristics for a parathyroid adenoma as seen on a gadolinium-contrasted MRI are T2 hyperintensity with contrast enhancement. Specialized MRI techniques, such as fat suppression, are available to meet specific clinical needs. In the case of parathyroid analysis, suppression of surrounding fat in the tracheoesophageal groove or mediastinum can help to make the gland more apparent than it would otherwise be. Even with the use of these techniques, the sensitivity and specificity of MRI in accurate diagnosis of diseased parathyroid glands are 84–89 % and 75–89 %, respectively [65].

4D contrasted MRI is a recently described parathyroid imaging tool. Multiparametric MR perfusion studies were found to accurately localize diseased parathyroid glands in 96 % of cases, and offered reliable differentiation of parathyroid glands from both thyroid tissue and lymph nodes [66]. To date, there has been no head-to-head comparison of 4D CT to 4D MRI described.

Despite the cost and diagnostic shortcomings of MRI as a tool for parathyroid localization, it may be the follow-up study of choice (after non-localizing ultrasonography) in clinical situations where avoidance of radiation exposure is particularly important, such as small children or pregnant women. Additionally, MRI may be an adjuvant worth considering in patients who have undergone previous neck surgery and did not localize using sestamibi-SPECT, as MRI may identify more than half of lesions that are missed by sestamibi in these patients [65].

Positron Emission Tomography

Positron emission tomography (PET) and PET-CT hybrid imaging studies have been used with great clinical success, particularly in the clinical staging of cancer, posttreatment cancer surveillance, and localization of unknown primary malignant tumors. The CT portion of a hybrid PET-CT is typically non-contrasted and the images are of greater slice thickness than those of diagnostic CT imaging studies, leading to a lower radiation dose. PET imaging may be performed using several tracers, including 5-fluorodeoxyglucose (18F-FDG), 11C-methionine, and 18F-fluorocholine (18F-FC). Up to this point, 18F-FDG has failed to demonstrate sufficient sensitivity and accuracy to justify its use for parathyroid disease localization [67, 68]. 11C-methionine has shown some (very limited) utility, but it is not readily accessible for widespread use [69]. 18F-FC-PET/CT typically finds its use as a diagnostic tool in patients with prostate and hepatocellular carcinoma, but parathyroid adenomas have been incidentally noted in several patients. In patients who either failed to localize using conventional methods or had discordant findings on two conventional studies, 18F-FC-PET/CT was found to accurately localize diseased parathyroid glands in more than 80 % of cases [51, 69].

Combined Imaging Modalities

Various combinations of preoperative localization techniques have been utilized in an effort to improve the success rate of MIRP. For example, the sensitivity of the combined findings of ultrasonography and SPECT/CT was 84 %, which was greater than the individual sensitivity of either study by itself [51]. In cases when concordance of findings is seen on these two imaging studies, some have advocated that intraoperative parathyroid hormone measurements are unnecessary [70, 71].

Surgical Adjuncts

Endoscopic Visualization and Magnification

Endoscopic techniques can allow for excellent visualization of the operative field while maintaining surgical access through a very small incision (15–20 mm). Magnification of structures up to 20× may be realized using an endoscope, while telescopic loupes generally offer 5.5–8.0× and conventional loupes usually offer 2.5–3.5× [72].

Intraoperative Radionuclide Guidance

Intraoperative nuclear mapping for parathyroid disease was first described by Martinez et al. in 1995 [11] and more definitively demonstrated by Norman and Politz in 2009 [17] to be effective in discriminating adenomatous parathyroid glands from other tissue types. 99mTc-sestamibi has a proclivity for localization within the mitochondria of hypermetabolic parathyroid tissue, such as that found within a parathyroid adenoma. A 20–25 mCu dose of 99mTc-sestamibi is administered intravenously 1.5–3 h prior to surgery. During the interim time period, planar scintigraphy imaging may be obtained, but is not necessary. After this time period, the radionuclide will sequester within the tissue of interest and, after the target gland is removed, a handheld gamma probe may be used to measure ex vivo radioactivity (counts per second) of the specimen in order to confirm with a high degree of accuracy that it is, in fact, a parathyroid adenoma. Gamma probe radioactivity measurements are a far more accurate predictor of cure than size, mass, or cellularity of the removed gland (p < 0.0001) [17]. It is fundamentally important to recognize that the gamma probe is not a “divining rod” that is placed into the surgical wound to point out the parathyroid adenoma—it is only useful for measurement of radioactivity once the specimen or a biopsy is excised.

Specimen radioactivity counts may only be meaningfully interpreted when expressed as a proportion of background radioactivity. In order to create this meaningful value, several measurements are systematically obtained using the gamma probe. It is the author’s practice to have a member of the operating room staff available to document these measurements so they can later be formally recorded as part of the patient’s medical record. In order to avoid confusion, an automated stamper is used to make 3 × 5 index cards with blank spaces for the pertinent values routinely obtained during MIRP (see Fig. 17.1).


Fig. 17.1
Example of layout for 3 × 5″ index card stamp or printout for documentation during MIRP

In patients with a localizing sestamibi scan, gamma probe measurements showing radioactivity more than 20 % of the background have been clearly shown to be a reliable indicator of successful removal of a parathyroid adenoma. In the hands of high-volume parathyroid surgeons, the use of handheld gamma scintigraphy portends excellent results without identification of other glands, use of intraoperative frozen sections, or use of intraoperative PTH measurements [13]. A prospective study of 5000 patients undergoing treatment following this protocol found a successful cure in more than 99 % of patients. In all failures, a contralateral second adenoma was later identified as the cause. Analysis of counts and correlation to cure rate found radioactivity measures to be a more reliable indicator of cure than histology. Correlation of radioactivity counts to histologic findings definitively demonstrated the utility and reliability of this technique, with adenomas showing 57 ± 38 % of background counts, hyperplastic parathyroid glands showing 16 ± 4 % of background counts, normal parathyroid glands showing 4 ± 0.1 % of background counts, and fat and lymph nodes always showing less than normal parathyroid glands [17].

Intraoperative Frozen Section Analysis

Microscopic analysis of a diseased parathyroid gland shows hypercellularity for both parathyroid hyperplasia and parathyroid adenoma. The main utility of frozen sections is to confirm that tissue is, in fact, parathyroid tissue in cases where this is unclear to the surgeon on gross examination. While this may be useful in select cases, up to a 94 % concordance between surgeon’s gross examination and frozen section results has been noted [73], and the use of radionuclide gamma counts and intraoperative PTH measurement have allowed for more rapid and cost-effective confirmatory testing during parathyroid surgery in the majority of situations.

Intraoperative Parathyroid Hormone Measurement

In an effort to confirm biochemical cure of 1° HPT during MIRP, intraoperative PTH (IOPTH) levels may be measured prior to termination of the procedure. This is particularly useful in cases of multi-gland disease that were not identified preoperatively. If PTH levels remain inappropriately elevated after removal of the presumed offending parathyroid adenoma, the case is converted to bilateral neck exploration in an effort to identify other pathologic-appearing parathyroid glands.

This technique was first described in 1990 [74, 75] and has evolved since that time [7679]. IOPTH testing is useful due to the relatively short half-life of intact PTH (~3–4 min), allowing measurement of a new steady-state PTH level shortly after removal of the offending gland. Two IOPTH levels are measured, one at 10 min after removal of the adenoma and another at 20 min. One of the most widely accepted standards are the modified Miami criteria (MMC), defined as an IOPTH value that is less than 50 % of the preoperative PTH value AND within the normal range [74, 77, 8083].

The MMC have shown a sensitivity and specificity of 88 % and 22 %, respectively, for successful cure of 1° HPT [84]. A 10-year prospective study on the use of IOPTH in previously unexplored parathyroidectomy cases found a 93.4 % cure rate [85].

Drawbacks of IOPTH measurement include the time spent waiting on results and the potential for unnecessary bilateral neck exploration if PTH levels fail to decrease appropriately despite removal of a solitary offending gland. Commonly cited reasons for persistently elevated PTH after successful extirpation of a parathyroid adenoma are vitamin D deficiency [86, 87], renal dysfunction [78], and large body mass index (BMI) [44]. In vitamin D-deficient patients, the PTH levels decrease after removal of the adenoma, but may not satisfy the MMC. Renal excretion accounts for ~20–30 % of PTH clearance, leading to prolonged half-life of PTH. By measuring IOPTH at 15 and 25 min (instead of 10 and 20 min), 95 % of patients with chronic renal insufficiency successfully met the MMC.

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Aug 28, 2017 | Posted by in OTOLARYNGOLOGY | Comments Off on Minimally Invasive Radioguided Parathyroidectomy
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