Predictors of accuracy in preoperative parathyroid adenoma localization using ultrasound and Tc-99 m-Sestamibi: A 4-quadrant analysis

Purpose

To compare the accuracy of preoperative parathyroid adenoma localization in patients with primary hyperparathyroidism (pHPT) due to a single adenoma using a detailed 4-quadrant analysis and to identify patient and tumor characteristics associated with accurate preoperative localization.

Materials and Methods

Retrospective review of 203 patients who underwent parathyroidectomy for pHPT due to a single adenoma between 2008 and 2011. Results from preoperative ultrasound and Tc-99 m-sestamibi were compared to operative findings to determine accuracy of localization studies. Associations between clinicopathologic features and accurate preoperative adenoma localization were evaluated.

Results

Ultrasound was performed on 198 patients, sestamibi on 177 patients, and both on 172 patients. Accurate localization occurred significantly more often for ultrasound than sestamibi (63% vs. 41%, P < 0.001). For ultrasound, accurate localization was found in patients with larger or heavier adenomas, those with adenomas located inferiorly, patients not having a reoperative procedure, and patients with higher post-operative serum calcium levels. For sestamibi, greater adenoma size or weight, adenomas located inferiorly, and patients with associated thyroid cancer on pathology were most predictive of accurate preoperative localization.

Conclusions

Our results provide evidence that ultrasound is more accurate in localizing parathyroid adenomas in patients with pHPT due to a single adenoma when compared to sestamibi scan using 4-quadrant location analysis and may be the preferred preoperative imaging modality in these patients. No significant preoperative patient factors were associated with accurate localization by ultrasound or sestamibi, but adenoma size, weight, and location in an inferior position were predictive of accurate preoperative localization.     

Primary hyperparathyroidism--case report and review of the literature

We present case report of primary hyperparathyroidism treated surgically as well as a review of literature concerning this subject. The disease of not well known etiology presents with elevated parathormon levels and hypercalcemia. Primary hyperparathyroidism which states 85% percent of all kinds of hyperparathyroidism is usually parathyroid adenoma, in 11-15% glandular hyperplasia and in 1-4% parathyroid cancer. Clinical symptoms are muscle weakness and fatigue, nephrolithiasis, occasionally peptic ulcers, pancreatitis, hypertension. Laboratory test reveal increased level of PTH, hypercalcemia, elevated alkaline phosphatase levels and decreased phosphorus levels. Diagnostic imaging techniques such as ultrasonography, MRI or CT have sensitivity about 52-75%. Highest sensitivity in localization of ectopic parathyroid adenoma has sestamibi scintigraphy with technetium-99. Skeleton x-rays show typical changes in distal parts of bones and osteopenia. Treatment of choice is surgical excision of adenoma. Normalization of PTH and calcium levels after surgery and improvement of renal, musculoskeletal and circulatory system function could be achieved in 95%. Most common complications are recurrent laryngeal nerve injury, hypo- or hyperparathyroidism, bleeding or stridor.     

Preoperative localization of parathyroid adenomas: ultrasonography,sestamibi scintigraphy,or both?

Minimal access techniques are increasingly used to remove parathyroid adenomas. Such surgery depends on accurate preoperative localization but the selection of imaging modality remains controversial. We have reviewed the accuracy of ultrasonography, sestamibi scintigraphy and their combination in 48 cases of primary hyperparathyroidism. Ultrasound had a sensitivity of 64.3% (95% confidence interval 44.1–81.4) and positive predictive value (PPV) of 100% (81.5–100) for correct lateralization. Sestamibi had a sensitivity of 83.3% (69.8–92.5) and PPV of 87.1% (73.7–95.1). The simple combination of ultrasound with sestamibi had a sensitivity of 82.1% (63.1–93.9) and a PPV of 92.0% (74.0–99.0): little different from sestamibi alone. However, if the sestamibi result was disregarded in favour of ultrasonography in discordant cases, the sensitivity reached 96.4% (81.7–99.9) and the PPV was 100% (87.2–100). These results were not dependant on a learning curve or the size of adenoma.     

Preoperative localization of parathyroid adenomas: ultrasonography, sestamibi scintigraphy, or both?

Minimal access techniques are increasingly used to remove parathyroid adenomas. Such surgery depends on accurate preoperative localization but the selection of imaging modality remains controversial. We have reviewed the accuracy of ultrasonography, sestamibi scintigraphy and their combination in 48 cases of primary hyperparathyroidism. Ultrasound had a sensitivity of 64.3% (95% confidence interval 44.1-81.4) and positive predictive value (PPV) of 100% (81.5-100) for correct lateralization. Sestamibi had a sensitivity of 83.3% (69.8-92.5) and PPV of 87.1% (73.7-95.1). The simple combination of ultrasound with sestamibi had a sensitivity of 82.1% (63.1-93.9) and a PPV of 92.0% (74.0-99.0): little different from sestamibi alone. However, if the sestamibi result was disregarded in favour of ultrasonography in discordant cases, the sensitivity reached 96.4% (81.7-99.9) and the PPV was 100% (87.2-100). These results were not dependant on a learning curve or the size of adenoma.     

Efficacy of preoperative dual-phase sestamibi scanning in hyperparathyroidism

PURPOSE: The objective of this article is to evaluate our experience with sestamibi scanning in patients with primary and secondary hyperparathyroidism. PATIENTS AND METHODS: A retrospective review of patients referred to the radiology department at the University of Kansas Medical Center for parathyroid studies between January 1, 1993, and August 1, 1998, was done. Patients included in the study were those who underwent both dual-phase technetium (Tc-99m) sestamibi scanning and subsequent parathyroidectomy at our institution (n = 34). Twenty-six patients had primary hyperparathyroidism and 8 patients had secondary hyperparathyroidism. Fifteen had previous history of neck exploration. RESULTS: Sensitivity of sestamibi scans in detection of all abnormal pathology in cases of primary hyperparathyroidism was 60% overall. Among the subset of adenoma cases, sensitivity was 82% (14/17). Among cases of primary parathyroid hyperplasia, no scan correctly localized all abnormal glands; however 60% (3/5) showed localization of at least one hyperplastic gland. Of the 2 patients with parathyroid carcinoma, in only one case was there evidence of sestamibi retention in the correct thyroid lobe. In patients with secondary hyperparathyroidism, sestamibi scanning was successful in identifying all hyperplastic tissue in only one case (sensitivity 13%). In 7 of the 8 cases of secondary hyperparathyroidism, the scan localized at least one hyperplastic gland. CONCLUSION: Sestamibi scanning is useful in the localization of abnormal pathology in cases of primary hyperparathyroidism, especially adenomas. In cases of hyperplasia, whether attributable to primary or secondary hyperparathyroidism, sestamibi imaging is less successful.     

Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT

Primary hyperparathyroidism (pHPT) is almost exclusively the result of a solitary parathyroid adenoma. In most cases, the affected gland can be surgically removed, but precise preoperative imaging is essential for adenoma localization prior to surgical intervention. In this study, we evaluated the diagnostic value of four-dimensional computed tomography (4D-CT) as a preoperative imaging tool in relation to the localization of pathologic parathyroid glands in patients with pHPT and negative sestamibi scans. This study included 43 consecutive patients with pHPT referred for parathyroidectomy at the Department of Head and Neck Surgery of Copenhagen University Hospital Rigshospitalet in 2011 and 2012. All patients had a 4D-CT performed prior to parathyroidectomy. CT localization of the suspected adenoma was correlated to the actual surgical findings and subsequent histological diagnosis was also available as references for the accuracy of this imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D-CT identified 32 solitary hyperfunctioning parathyroid glands located on the correct side of the neck (PPV 76 %) and 21 located within the correct quadrant (PPV 49 %). Unilateral resection was performed in 72 % of patients due to the localization findings of preoperative imaging. 4D-CT can, therefore, be considered an effective method for the preoperative localization of parathyroid adenomas and is an important tool in surgical intervention for patients referred to parathyroidectomy.     

Value of sestamibi scans in tertiary hyperparathyroidism

OBJECTIVES: To determine the value of preoperative Tc-sestamibi scans and the incidence of ectopic glands in tertiary hyperparathyroidism. DESIGN: Prospective, non-randomized analysis of a consecutive cohort of surgical patients from the Medical College of Georgia Thyroid/Parathyroid Center. MATERIALS AND METHODS: A consecutive series of patients with tertiary hyperparathyroidism undergoing parathyroidectomy was analyzed. Demographic data, preoperative Tc-sestamibi scintigraphy results, location of diseased glands, pre- and postoperative calcium, and parathyroid hormone levels were collected. RESULTS: Twenty-one patients underwent parathyroidectomy for tertiary hyperparathyroidism between March 2004 and September 2006. Of these 21 patients, 3 were re-operative cases for persistent hypercalcemia and each was found to have a single diseased gland. Of the 18 patients undergoing first time surgery, 15 had four-gland hyperplasia, 2 patients had single adenomas, and 1 patient had a double adenoma. Nine of the 21 patients (43%) had ectopic glands (2 of these patients had 2 ectopic glands each). The overall sensitivity of the preoperative Tc-sestamibi scintigraphy was 76% and was not significantly different when comparing patients with ectopic glands (78%) and those without (75%). CONCLUSIONS: Tc sestamibi scintigraphy has high positive predictive value and sensitivity in patients with tertiary hyperparathyroidism. Sestamibi scanning is particularly valuable in this patient population since the incidence of ectopic glands may be higher than previously recognized.     

Preoperative imaging in primary hyperparathyroidism. Role of thallium-technetium subtraction scintigraphy

Primary hyperparathyroidism, although often silent clinically, may lead to significant morbidity if it remains untreated. In more than 95% of all cases the cause is a parathyroid adenoma or glandular hyperplasia. Regression of disease follows successful surgical excision of the abnormal parathyroid gland. Recurrent or persistent hyperparathyroidism is most commonly caused by solitary adenomas, which may have an ectopic location. Preoperative localization of lesions may improve postoperative cure rates and decrease morbidity. Thallium T1 201 chloride-technetium Tc 99m pertechnetate subtraction scintigraphy was performed on 15 patients with primary hyperparathyroidism. The sensitivity and specificity for detection of abnormal glands were 90% and 95%, respectively. False-positive or false-negative results were minimize by strict adherence to a protocol and by the use of well-defined diagnostic criteria. Because of the superior sensitivity and specificity, this modality should be the primary imaging method of choice for preoperative evaluation of primary hyperparathyroidism. The relative role of other imaging modalities is also discussed.     

A case of congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma mimicking a carotid body tumor

Ectopic parathyroid adenomas can be encountered during four gland explorations, but nearly 80% of adenomas are localized with ultrasound and sestamibi imaging. Ectopic adenomas are thought to arise from abnormal migration during development. As a cervical congenital anomaly, common carotid artery agenesis is an extremely rare anomaly characterized by separate origins of the internal and external carotid arteries directly from the aortic arch. Here we present a case of a 75 year old man with primary hyperparathyroidism who was found to have congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma within the parapharyngeal space, which mimicked a carotid body tumor based on location and imaging. The successful identification and resection of the ectopic parathyroid adenoma presented here demonstrate the importance of preoperative imaging studies to allow appropriate operative planning as well as the utility of intraoperative parathyroid hormone assay in predicting cure during surgery.     

Role of microvascular density in nonlocalizing parathyroid sestamibi scans

OBJECTIVES: Sestamibi scans for localization of abnormal parathyroid glands in patients with hyperparathyroidism are widely used at many institutions. Minimally invasive parathyroid surgery demands accurate preoperative localization imaging; however, nonlocalizing sestamibi scans occur in 15% of patients with primary hyperparathyroidism. It remains unknown why some sestamibi scans fail to localize. We hypothesize that an increase in microvascular density (MVD) within an adenoma will result in rapid tracer washout and a subsequent nonlocalizing scan. This study investigates the role of MVD in sestamibi localization. STUDY DESIGN: Retrospective chart review with immunohistochemical staining and data analysis. METHODS: Medical records of 83 patients who had a sestamibi scan for evaluation of primary hyperparathyroidism and underwent initial parathyroidectomy from 2000 to 2002 were retrospectively reviewed. Patients' age, sex, preoperative imaging results, operative procedure, gland weight, and histologic findings were collected. Immunohistochemistry was performed to assess MVD. RESULTS: Of the 75 preoperative sestamibi scans used, 51 patients had a localizing scan, and 24 were nonlocalizing. Localizing sestamibi scans for primary hyperparathyroidism demonstrated a sensitivity of 94% and specificity of 85%. By identifying multiglandular hyperplasia, nonlocalizing sestamibi scans produced a sensitivity of 83%. The localizing group had a greater percentage of solitary adenomas (94%) compared with the nonlocalizing group (15.6%) (P < .001). The mean gland weight for the nonlocalizing group was less than 398 g compared with the localizing groupweight of 1,113 g (P < .001). The mean MVD for localizing scan group was 229 vessels per high-power field,and the mean for the nonlocalizing scans was 213 vessels per high-power field (P = .2). CONCLUSIONS: MVD does not predict whether sestamibi scans are localizing or nonlocalizing.     

Preoperative ultrasound is worthwhile for reoperative parathyroid surgery

OBJECTIVES/HYPOTHESIS: High-resolution ultrasound and sestamibi scanning are regarded as the first-line methods for preoperative localization of parathyroid adenomas. The utility of ultrasound in reoperative cases has been questioned because of concern that scarring will obscure normal tissue planes and vascularity that are critical to identification of an adenoma using this imaging modality. The purposes of the study were to evaluate the ability of high-resolution ultrasound to accurately localize parathyroid adenomas in the reoperative exploration and to identify any factors that influence its accuracy STUDY DESIGN: Retrospective chart review at a tertiary care academic medical center. METHODS: All patients seen in referral for parathyroid surgery between May 1994 and September 2002 underwent high-resolution ultrasound as their initial diagnostic test. Patients who subsequently underwent exploration were included in the study. Intraoperative and ultrasound findings were compared. RESULTS: One hundred forty-two patients were included, 116 without and 26 with prior exploration. The sensitivity and positive predictive value of ultrasound were 86.9% and 89.1%, respectively. These data were not significantly different in patients without (88.2% and 90%) and in patients with (80% and 84.2%) prior thyroid or parathyroid surgery. The overall accuracy was 79% with a false-negative rate of 11.3%. Thyroid nodularity was significantly more common (81.8%) in patients who had a false-positive or false-negative finding on ultrasound than in the total population (61.3%). CONCLUSION: High-resolution ultrasound is an accurate method for localizing parathyroid adenomas even in patients who have previously undergone parathyroid exploration. However, the presence of thyroid nodules can interfere with its accuracy.     

Gamma-probe localization of a parathyroid adenoma in the reoperative neck

Preoperative localization of parathyroid adenomas in patients with hyperparathyroidism currently relies on a combination of computed tomography, magnetic resonance imaging, ultrasound, (99m)Tc-sestamibi scintigraphy, and venous sampling of parathyroid hormone. No procedure is universally reliable, however, and in reoperation for missed parathyroid adenomas, development of an optimal preoperative localization strategy becomes especially problematic. We report the case of a patient with hyperparathyroidism who required reoperation for a missed parathyroid adenoma despite preoperative localization with (99m)Tc-sestamibi scintigraphy. (99m)Tc-sestamibi scintigraphy was done 2.5 hours before reoperation. On reoperation, a gamma-detecting probe (C-Track; Care Wise Medical Corporation, Morgan Hill, CA) introduced through a right neck incision was used to localize a 4-cm adenoma within 45 minutes. No significant radiation hazard existed, and no special handling of the specimen was required. The patient's hyperparathyroidism resolved within 24 hours postoperatively. Therefore, this intraoperative technique may prove to be a useful adjunct to preoperative localization studies of parathyroid adenomas, particularly in patients requiring reoperation for persistent postsurgical hyperparathyroidism.     

Otolaryngologist-head and neck surgeon-performed ultrasonography for parathyroid adenoma localization

OBJECTIVE: To demonstrate the efficacy of otolaryngologist-head and neck surgeon-performed ultrasonography (US) for the preoperative localization of parathyroid adenomas. METHODS: A retrospective chart review of all patients evaluated by office-based US for the localization of surgery-proven parathyroid adenomas from October 2004 through February 2007. RESULTS: A total of 29 patients underwent preoperative US localization. Twenty-three (79%) were females, and six (21%) were males. The age of patients ranged from 27 to 85 years of age. The size range of adenomas detected as measured by US was 0.5 to 2.7 cm. Pathology specimen measurements ranged from 0.3 to 3.4 cm. A total of 30 parathyroid adenomas were found. US identified 90% of the parathyroid adenomas to the correct side, left or right. In addition, US localized the parathyroid adenomas to the correct quadrant, superior or inferior, 83% of the time. Challenges in accurate localization were associated with patient obesity, presence of thyroid carcinoma, and multinodular thyroid disease. For comparison, sestamibi scans performed on the same patients localized the parathyroid adenoma to the correct side only 71% of the time and to the correct quadrant 61% of the time. CONCLUSIONS: Otolaryngologist-head and neck surgeon-performed US can accurately identify the location of parathyroid adenomas and is a useful tool for preoperative planning.     

Technetium Tc 99m sestamibi sensitivity in oxyphil cell-dominant parathyroid adenomas

OBJECTIVE: A subset of parathyroid adenomas contains a relative overabundance of oxyphil cells that are capable of greater technetium Tc 99m sestamibi tracer uptake and retention than other cell types. We examined whether the presence of oxyphil cells augments the sensitivity of technetium Tc 99m sestamibi preoperative localization and whether the histologic findings of a lesion could be predicted based on the adenoma mass and serum calcium and parathyroid hormone levels. DESIGN: Retrospective, single-blinded comparison of technetium Tc 99m sensitivity rates, lesion mass, and preoperative serum calcium and parathyroid hormone values of patients with chief and mixed cell-dominant adenomas and those with oxyphil-dominant parathyroid adenomas. SETTING: Tertiary care university hospital. PATIENTS: Sixty-three patients diagnosed as having a parathyroid adenoma. INTERVENTION: All patients underwent resection of a parathyroid adenoma following a preoperative technetium Tc 99m sestamibi localization study and serum calcium and parathyroid hormone level analysis. MAIN OUTCOME MEASURE: Technetium Tc 99m sensitivity rate. RESULTS: The overall technetium Tc 99m sestamibi sensitivity rate was 76.2%. The sensitivity within the chief and mixed cell-dominant (n = 52) and oxyphil cell-dominant groups (n = 11) were 71.2% and 100%, respectively (P = .04). There was no correlation between histologic findings of the lesion and its size or serum calcium and parathyroid hormone levels. CONCLUSIONS: Oxyphil cell predominance within an adenoma augments technetium Tc 99m sestamibi scan sensitivity in a statistically significant manner. The use of technetium Tc 99m sestamibi preoperative localization may therefore be differentially greater in patients with these types of lesions.     

Methylene Blue and Sestamibi: Complementary Tools for Localizing Parathyroids

Objective To determine the value and correlation between sestamibi scan and methylene blue staining for localization of parathyroid glands in patients with primary hyperparathyroidism. Study Design Nonrandomized convenience sample, followed prospectively. Methods Twenty‐three consecutive patients underwent 24 operations for primary hyperparathyroidism. All patients underwent preoperative technetium 99m–sestamibi planar scintigraphy, preoperative administration of 7.5 mg/kg methylene blue initiated within 60 minutes of surgical incision, and surgical neck exploration supervised by a single surgeon. Results All patients were cured of hypercalcemia. Sensitivity for sestamibi and for methylene blue staining was 76% and 79%, respectively. Specificity for sestamibi and for methylene blue was 98% and 93%, respectively. Agreement between sestamibi and methylene blue was 96%. Conclusions Sestamibi scanning and methylene blue staining are useful, complementary localizing tools for patients undergoing surgery for primary hyperparathyroidism. When used together, these studies decrease operative time, justify unilateral exploration in patients with parathyroid adenoma, and increase the ease of identification of hyperplastic parathyroid glands.     

Sestamibi scans and intraoperative parathyroid hormone measurement in the treatment of primary hyperparathyroidism

OBJECTIVE: To assess the value of preoperative sestamibi scanning and intraoperative parathyroid hormone (IOPTH) measurement in the treatment of patients with primary hyperparathyroidism due to multiple gland disease (MGD). DESIGN: Retrospective medical record review. SETTING: Tertiary care academic medical center. PATIENTS: The study population comprised 383 consecutive patients who underwent surgery for primary hyperparathyroidism at Long Island Jewish Medical Center, New Hyde Park, NY, between June 1, 1999, and January 31, 2002. INTERVENTIONS: Sestamibi scanning, IOPTH measurement, bilateral parathyroid exploration, and minimally invasive parathyroid surgery. MAIN OUTCOME MEASURES: Rate of postoperative persistent hyperparathyroidism. RESULTS: A total of 376 patients met the requirements for inclusion in the study. There were 275 women (73%) and 101 men (27%). Of the patients, 325 (86%) had single adenomas, 28 (7%) had double adenomas, 16 (4%) had 3 or more abnormal glands, and 1 had parathyroid cancer. There were 9 cases (2%) of persistent or recurrent hypercalcemia after surgery. Duration of follow-up ranged from 1 to 37 (median, 7) months. The sensitivity of sestamibi scanning for detecting MGD was 23%, and the positive predictive value was 63%. Using the requirement that the IOPTH level fall by 50% from the first baseline and into the normal range, MGD was distinguished from solitary adenoma in 36 (88%) of 41 cases. CONCLUSIONS: The combination of preoperative sestamibi scanning and IOPTH measurement is effective in identifying cases of MGD and allows successful minimally invasive parathyroidectomy in most patients.     

Diagnostic Value of the Preoperative Sestamibi Scan in Intraoperative Localization of Parathyroid Adenomas: A Case Study

A retrospective chart review of 43 patients who underwent technetium 99m (Tc-99m) sestamibi scans from June 1995 to January 1997 was performed. Only those who underwent subsequent parathyroid exploration with excision were included in the study. Twenty subjects (13 women and seven men) were included in the study. Ages ranged from 21 to 84 years (mean, 58 years). All patients had laboratory values and clinical findings consistent with primary hyperparathyroidism. Two patients had preoperative magnetic resonance imaging (MRI) scans (one patient with recurrent disease), and one had a preoperative computed tomography (CT) scan. The remaining patients had the sestamibi scan as the only preoperative localization study. There were 18 pathologic diagnoses of parathyroid adenoma and two of parathyroid hyperplasia. Sestamibi failed to correctly identify the location of the parathyroid lesion in two cases. In 18 cases the preoperative sestamibi scan correctly localized the lesion, a predictive value of 90%. We conclude that the Tc-99m sestamibi scan is an accurate preoperative tool that can be used as a single modality to localize parathyroid adenomas.     

Reoperation because of ectopic parathyroid adenoma with previous removal of lipothymoma. Importance of intraoperative PTH

Sometimes the surgery of hyperparathyroidism is not easy and the surgical team find difficulties to locate the pathological gland or glands. We report a case of primary hyperparathyroidism due to an ectopic parathyroid adenoma which required two interventions. First we removed what it seems an adenoma but resulted to be a lipotimoma. In the reintervention practiced one week later, having then the rapid or turbo intraoperative PTH and previous digital scintigraphy, it was possible to remove an adenoma histologically confirmed, with 3,5 cm diameter located in depth to right thyroid lobe towards the superior mediastinal straits. The postoperative evolution of the patient was satisfactory and no complications were registered.