Limitations of technetium 99m sestamibi scintigraphic localization for primary hyperparathyroidism associated with multiglandular disease

Successful surgical treatment of primary hyperparathyroidism requires the localization and excision of the parathyroid tissue responsible for excessive parathyroid hormone secretion while ensuring that the patient will have sufficient endogenous parathyroid hormone production to maintain eucalcemia. In selecting patients with primary hyperparathyroidism for unilateral parathyroidectomy the surgeon should be able to diagnose multiglandular disease either preoperatively or intraoperatively. We performed a retrospective review of 123 patients who underwent surgical treatment for primary hyperparathyroidism to determine the potential feasibility of selecting patients for minimally invasive surgery based on preoperative imaging studies. All patients were studied preoperatively with 99m technetium-sestamibi scintigraphy. High-resolution ultrasonography was performed in 119 of these patients. All patients except one underwent bilateral cervical exploration. A patient with an intrathoracic adenoma was successfully diagnosed by scintigraphy thereby allowing treatment by a limited thoracotomy. One hundred eight patients had solitary adenomas and 15 had multiglandular disease. In none of the patients with bilateral multiglandular disease were all abnormal glands localized preoperatively. Patients in our study with primary hyperparathyroidism and multiglandular disease were underdiagnosed by preoperative imaging. A minimally invasive approach based solely on preoperative imaging studies may result in treatment failure in patients with multiglandular involvement.     

Preoperative technetium Tc 99m sestamibi SPECT imaging in the management of primary hyperparathyroidism in patients with concomitant multinodular goiter

HYPOTHESIS: Preoperative parathyroid and thyroid imaging using technetium Tc 99m sestamibi scintigraphy-single-photon emission computed tomography (Tc 99m MIBI SPECT) and technetium Tc 99m sodium pertechnetate, respectively, in patients with parathyroid adenomas and concomitant multinodular goiters enables the selection of those suitable for minimally invasive radio-guided surgery. DESIGN: One hundred thirty patients with primary hyperparathyroidism were treated surgically during a 30-month period. Forty-one of these 130 patients had an associated multinodular goiter. All patients underwent planar and SPECT parathyroid scintigraphy using Tc 99m MIBI, and thyroid scintigraphy with technetium Tc 99m pertechnetate 2 to 5 days before surgery. On the morning of surgery each patient was reinjected with Tc 99m MIBI for intraoperative localization and validation. Minimally invasive radio-guided parathyroidectomy was performed using a handheld gamma-detection device with a thyroid probe. Removed glands were submitted for histopathologic examination for comparison with the scintigraphic results. Quantitative analysis of parathyroid activity was performed. RESULTS: Minimally invasive, radioguided parathyroidectomy was successfully performed in 21 (51%) of 41 patients who had a concomitant multinodular goiter. The remaining 20 patients underwent standard neck exploratory surgery because of associated thyroid disease; 5 of them had malignant thyroid disease. Among the 41 patients planar scintigraphy correctly identified 28 adenomas (68%). Single-photon emission computed tomographic imaging identified an additional 11 adenomas for a sensitivity of 95% and a specificity of 100%. Moreover, SPECT imaging correctly identified malignant thyroid nodules in 4 of 5 patients. Technetium Tc 99m MIBI retention was noted in only 25 adenomas (61%) while the remaining adenomas demonstrated a rapid washout. The average uptake ratio of parathyroid counts to maximum thyroid activity was significantly correlated with parathyroid hormone levels before surgery (P = .04). CONCLUSIONS: Our data encourage the use of preoperative SPECT imaging of parathyroid adenomas in patients who have multinodular goiters to select those suitable for minimally invasive radioguided surgery. This technique also offers important information regarding thyroid nodules that are suspicious for malignancy. The intraoperative gamma-probe technique enables the surgeon to focus his or her search, provides instant feedback regarding the progress of the operation, reduces surgical trauma and complications, and yields better cosmetic results. Patients with higher presurgical parathyroid hormone levels may especially benefit from radioguided surgery.     

Unilateral surgery for primary hyperparathyroidism on the basis of technetium Tc 99m sestamibi and iodine 123 subtraction scanning

HYPOTHESIS: Parathyroid scanning, based on simultaneous recording of technetium Tc 99m sestamibi and iodine 123 images, is able to identify patients with multiple parathyroid gland disease and is a safe imaging technique for unilateral parathyroid surgery. DESIGN: Scintigraphic criteria of eligibility for unilateral surgery were prospectively tested against findings of conventional bilateral surgery. SETTING: Patients referred to an endocrine surgeon in a university hospital. PATIENTS: Seventy consecutive patients with primary hyperparathyroidism had dual-isotope scanning before conventional surgery. Forty-one patients had scan findings compatible with unilateral surgery, with a single focus of high intensity seen on the anterior and lateral views. The remaining 29 patients had 1 or more criteria of ineligibility: (1) scan findings pointing to multiple gland disease, (2) no well-identified focus, (3) contralateral thyroid nodule requiring surgical management, or (4) family history of hyperparathyroidism or multiple endocrine disease. MAIN OUTCOME MEASURES: Number of enlarged parathyroid glands at surgical inspection and calcemia follow-up. RESULTS: None of the 41 patients, with a single well-defined focus on the scan image, showed evidence of multiple parathyroid involvement. Each parathyroid adenoma was resected from the precise site predicted by the subtraction scan. Nine patients (13%) had surgical findings of multiple parathyroid gland disease. All 9 were ineligible based on preoperative image findings. CONCLUSIONS: Unilateral surgery can be safely offered to 60% of patients with primary hyperparathyroidism, on the basis of simultaneous (99m)Tc-sestamibi and (123)I scanning. This may reduce the length of the operation, anesthesia requirements, and hospital stay, and the risks of hypoparathyroidism and injury to the recurrent laryngeal nerve.     

Determinants of Tc-99m sestamibi SPECT scan sensitivity in primary hyperparathyroidism

Background

The aim of this study was to evaluate the influence of patient and adenoma characteristics on ^99mTc-methoxy isobutyl isonitrile (MIBI) scan performance in individuals diagnosed with primary hyperparathyroidism (PHP).

Methods

Records of patients undergoing parathyroidectomy for PHP over 6 years at a single center were reviewed.

Results

The overall true-positive (TP) rate for ^99mTc-MIBI scans was 56%. Adenomas sized 1.9 to 3.5 cm were more likely to have TP scans than 0.3-cm to 1.8-cm adenomas (74% vs 40%, P < .001). Preoperative ionized calcium levels between 1.49 and 1.72 mmol/L were more likely to have TPs than levels between 1.27 and 1.48 mmol/L (65% vs 47%, P < .05). No single class of medication was shown to significantly effect TP rates. A decrease in TP rate was observed for larger adenomas in patients on ≥1 medication (74% vs 65%, P = .05).

Conclusions

In PHP, ^99mTc-MIBI scan positivity is most related to adenoma size and preoperative ionized calcium level.     

International prospective evaluation of scintimammography with (99m)technetium sestamibi

BACKGROUND: The purpose of this study is to evaluate the efficacy of scintimammography with (99m)Technetium-Sestamibi for the diagnosis of breast cancer. METHODS: This was a multicenter prospective cohort clinical trial. A total of 1,734 women were enrolled of whom 1,243 had complete data upon study completion. RESULTS: The mean +/- standard error age of the patients is 56 +/-12 years (with a range of 19 to 94). Mammographic results were classified by the Breast Imaging Reporting and Data System (BIRADS) as 199 (16%) BIRADS 5, 149 (12%) BIRADS 4, 199 (16%) BIRADS 3, and 696 (56%) BIRADS 2 or 1. Scintimammography was positive for 322 (26%) of the patients and negative for 921 (76%). Histopathology showed malignancy for 201 (16%) of the patients. Sensitivity and specificity of scintimammography was estimated 93% and 87% respectively. A positive predictive value (PPV) of 58% with a negative predictive value of 98% were calculated. CONCLUSIONS: The present study suggests that scintimammography with (99m)Technetium-Sestamibi is highly accurate for the detection of breast cancer.     

A prospective evaluation of preoperative localization by technetium-99m sestamibi scintigraphy and ultrasonography in primary hyperparathyroidism

BACKGROUND: Ultrasonography (USG) and technetium-99m sestamibi (MIBI) scintigraphy are commonly used imaging modalities in the era of minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism (pHPT). However, their relative importance and actual contribution to MIP have not been prospectively assessed. METHODS: A total of 100 consecutive pHPT patients planning for MIP were recruited. Both USG and MIBI findings were correlated with intraoperative findings and postoperative outcome. Clinicopathologic factors were examined for potential association with a correct localizing result. RESULTS: Thirty men and 70 women (age range 13 to 93 years [median 55.5]) were included in the study. The final pathology included 98 patients with solitary adenoma and 2 patients with multiglandular disease. The sensitivities, accuracies, and positive predicted values for USG and MIBI alone were 57% vs 89%, 56% vs 85%, and 97% vs 94%, respectively. Correctly localized adenomas were significantly heavier than incorrectly localized ones. CONCLUSIONS: MIBI is preferred over USG in pHPT patients planning for MIP. Weight of adenoma appeared to be the only clinicopathologic factor determining localization accuracy.     

Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism

BACKGROUND: Delayed technetium-99m sestamibi single photon emission computed tomography (SPECT) scans were prospectively analyzed in a large series of patients with primary hyperparathyroidism. METHODS: Three hundred thirty-eight patients underwent sestamibi-SPECT and were explored. Prospective data included preoperative demographics, clinical, sestamibi, and operative findings, laboratory values, and pathologic and follow-up laboratory results from all patients. RESULTS: Between 1994 and 2000, 287 unexplored patients (85%) and 51 re-explored patients (15%) participated. The abnormal parathyroid glands excised from 336 of 338 patients included 299 single adenomas (88%) and 23 double adenomas (7%), and 14 patients had multigland hyperplasia (4%). Sestamibi SPECT correctly lateralized 349 of 400 abnormal parathyroid glands, with an overall sensitivity of 87%, an accuracy of 94%, and a positive predictive value of 86%. Precise localization occurred in 82% of the abnormal parathyroid glands. Sestamibi sensitivity was similar in unexplored (87%) and reoperative (92%) cases; two hundred eighty-six of 299 (96%) solitary adenomas, 38 of 46 (83%) double adenomas, but only 25 of 55 (45%) hyperplastic glands were identified. The mean weight of the true-positive glands (1252 +/- 1980 mg) was greater than that of the false-negative glands (297 +/- 286 mg) (P <.005). Three patients had persistent primary hyperparathyroidism, in spite of the excision of sestamibi-identified lesions in 2 cases. Follow-up indicated curative resection in 99% of the unexplored cases and 94% of the remedial cases. CONCLUSIONS: Sestamibi SPECT is highly accurate for the localization of parathyroid adenomas in unexplored and re-explored cases, where it is often the only imaging required. Its sensitivity is limited in multiglandular disease.     

Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands.

BACKGROUND. Technetium 99m sestamibi is an isonitrile radionuclide imaging agent that, when used with subtraction iodine 123 thyroid scans, has the potential for imaging abnormal parathyroid glands. METHODS. We prospectively evaluated 20 patients with hyperparathyroidism to study the efficacy of Tc 99m sestamibi and 123I subtraction radionuclide scanning for the imaging of abnormal parathyroid glands. All patients underwent neck exploration and histologic confirmation of all parathyroid glands identified. RESULTS. The solitary adenomas in 11 of 16 patients with primary hyperparathyroidism were localized with sestamibi scans. The scans in four of five patients with diffuse parathyroid hyperplasia showed bilateral localization consistent with enlarged glands. The fifth patient previously underwent a subtotal parathyroidectomy, and a fifth supernumerary gland was localized with the sestamibi scan. Four patients had hyperparathyroidism related to kidney disease. Three of these had bilateral localization of enlarged glands. The fourth patient had undergone two previous operations, and a fifth supernumerary gland was localized with the sestamibi scan. CONCLUSIONS. The preliminary data indicate that Tc 99m sestamibi in combination with 123I radionuclide scanning may be useful in the preoperative localization of abnormal parathyroid glands. This technique localized all of the solitary adenomas that were subsequently resected, and in two reoperative cases it identified the remaining solitary gland causing persistent hypercalcemia.     

Two-phase scintigraphy with technetium 99m-sestamibi in patients with hyperparathyroidism due to chronic renal failure

BACKGROUND: The objective of the current study was to study different functional and anatomic features of the hyperplastic gland and clinical and biochemical characteristics of renal hyperparathyroidism (HPT) patients and their relationship with the scintigraphic detection of parathyroid glands. METHODS: A retrospective study was performed of 40 patients with chronic renal failure (CRF) who underwent cervical surgery for HPT. Weight, histology, and localization of hyperplastic glands were recorded. Parathyroid cell proliferation was assessed by percentage of S-phase cells. Double-phase scintigraphy with technetium 99m-sestamibi and serum parathyroid intact hormone (PTHi), creatinine, calcium, and phosphate levels were performed. RESULTS: Detection of hyperplastic parathyroid glands by 99mTc-sestamibi scintigraphy was associated with the weight and inferior localization of the glands. The functionality of the glands as reflected in serum PTHi and phosphorus levels was associated with the number of glands detected. CONCLUSION: Double-phase 99mTc-sestamibi scintigraphy is of limited usefulness in patients with renal HPT. Detection of hyperplastic parathyroid glands in patients with CRF depends on the weight and inferior localization of the glands. Serum PTHi, phosphorus and creatine levels are associated with the number of glands detected by means of 99mTc-sestamibi scintigraphy.     

The utility of sestamibi scanning in the operative management of patients with primary hyperparathyroidism

BACKGROUND: The role of imaging studies before parathyroidectomy has been extensively debated and recent advances in unilateral parathyroidectomy intensify this controversy. The purpose of this study was to review the parathyroidectomy experience of a single surgeon, looking at the role of sestamibi scans and a standard postoperative care regimen. STUDY DESIGN: Retrospective review of office and hospital charts was completed on 90 patients with primary hyperparathyroidism who underwent parathyroidectomy from 1991 to 1998. Patient workup and outcomes were noted, as were results of preoperative imaging. True-positive scans visualized an abnormality ipsilateral to the adenoma found at operation. Statistics were performed using nonparametric testing and Student's t-test. RESULTS: There were 21 male and 69 female patients, with an average age of 54 years (range 29 to 81). There were zero mortalities, three morbidities (3.3%), and three patients who had persistent hypercalcemia, yielding a 96.7% success rate. Sixty-seven patients underwent preoperative sestamibi scanning, with a sensitivity of 74% and positive predictive value of 89%. Operative time in imaged patients averaged 103 +/- 49.9 minutes versus 121.5 +/- 85.9 minutes for patients without sestamibi scans. Operating time differences were not statistically significant and a preoperative sestamibi scan did not affect the success of parathyroidectomy. Discharge on postoperative day 1 was accomplished in 80% of patients and 13% were discharged the next day. There was no morbidity from hypocalcemia. CONCLUSIONS: A preoperative sestamibi scan does not improve efficacy or decrease operating time for primary hyperparathyroidism when bilateral neck exploration is performed. A postoperative care protocol including oral calcium and vitamin D supplementation allows the majority of patients to be discharged on postoperative day 1 with excellent results.     

Mammoscintigraphy with Tc-99m sestamibi in the evaluation of benign and malignant breast disease

Ninety-eight women and 3 men (age range, 16–88 years; mean 46 years) with 103 lesions underwent technetium-99m methoxyisobutylisonitrile (^99mTc-sestamibi, ^99mTc-MIBI) breast scintigraphy prior to biopsy to assess the value of this technique for the detection of breast carcinomas and for their differentiation from benign breast masses. Scans of 29 patients were ^99mTc-sestamibi-positive and 72 were ^99mTc-sestamibi-negative. Scintimammographic findings were true positive in 21 (72%) biopsy confirmed carcinomas and true negative in 65 (89%) benign lesions. ^99mTc-sestamibi scans were false-negative in 7 cases of breast cancer: 4 infiltrating ductal carcinomas and 3 infiltrating ductal with an intraductal component. There were 8 false positive scans which included 4 fibroadenomas, 2 papillomas and 2 areas of chronic inflammation. The mean size of the ^99mTc-sestamibi-positive carcinomas was 2.9 ± 1.2 cm, which contrasts to the size of ^99mTc-sestamibi-negative breast malignancies, which averaged 1.8 ± 0.6 cm (P < 0.0005). The sensitivity of using ^99mTc-sestamibi for detection of breast carcinoma was 75% and its specificity 89%. The positive and negative predictive values were 88% and 93% respectively. Interobserver agreement between the 2 independent and blinded nuclear medicine physicians was 98%. Size of tumor is a critical factor in the detection of sestamibi uptake. ^99mTc-sestamibi can help in the investigation of breast masses.     

The use of scintiangiography with technetium 99m in the diagnosis of traumatic pseudoaneurysm

Pseudoaneurysm formation is a known complication of peripheral arterial access procedures. Although standard contrast angiography has been considered the diagnostic study of choice to identify pseudoaneurysms, isotope angiography has been described as an alternative method. In this study, we examined the role of 99mTc-tagged red blood cell scans in the diagnosis of traumatic pseudoaneurysm. Forty patients underwent scans; 25 scans were reported as abnormal and 15 as normal. There were no false-negative results; one scan had false-positive results (2.5%). The presence of pseudoaneurysm among the patients with abnormal scans was verified at operation in 23 of 25 patients. The one false-positive test was verified by ultrasound. All patients with normal scans were followed up for verification. Follow-up time ranged from 2 to 28 months. Radionuclide vascular flow study appears to give information similar to that of conventional angiography. With a series false-positive rate of 2.5%, the examination has a high specificity. The 99mTc-tagged red blood cell scan is a viable alternative to conventional angiography for the diagnosis of traumatic pseudoaneurysms and is associated with less radiation and morbidity.     

Relationship between sestamibi uptake, parathyroid hormone assay, and nuclear morphology in primary hyperparathyroidism

BACKGROUND: Technetium-99m-sestamibi scanning and the intraoperative intact parathyroid hormone (iPTH) assay have permitted development of focused parathyroid techniques for treatment of primary hyperparathyroidism. The purpose of this study was to assess if any pre- and intraoperative factors (degree of sestamibi uptake and iPTH levels) were associated with postoperative results (resected gland weight and parathyroid nuclear morphology). STUDY DESIGN: We performed a retrospective analysis of 101 consecutive patients who underwent preoperative sestamibi scintigraphy and a targeted parathyroid exploration for primary hyperparathyroidism. Sestamibi uptake was graded visually on a 4-point scale of 0 (no uptake or false-negative result) to 3 (high uptake) and compared with respect to iPTH levels, gland morphology, and specimen weight. A Kruskal-Wallis test and a Pearson test were used for the statistical analysis. RESULTS: Degree of sestamibi uptake was associated with gland weight (median weight of 250 mg, 340 mg, 655 mg, 1,400 mg for grades 0, 1, 2, and 3, respectively, p < 0.001). The uptake of sestamibi was also associated with preoperative PTH levels (median PTH levels of 113, 151, 129, and 170 pg/mL for grades 0, 1, 2, and 3, respectively, p = 0.02), but not with the other parameters. The weight of resected gland(s) was associated with preoperative PTH levels (p = 0.02), and with some of the morphologic nuclear data (mean surface area (p = 0.02), maximum diameter (p = 0.01), and perimeter of the nuclei (p = 0.01). CONCLUSIONS: These data suggest that false-negative sestamibi scanning (visual score of 0) might result when hypersecreting parathyroid glands are small. Preoperative PTH level might be useful to estimate the amount of hypersecreting tissue to be resected.     

The use of 99m technetium pertechnetate to detect transplanted gastric mucosa in the dog

A surgical model of a Meckel's diverticulum with ectopic gastric mucosa was constructed in seven dogs by implanting a full-thickness patch of gastric wall into the open end of a Roux-en-Y ileoileostomy. ^99mTc Pertechnetate scintiphotography with a gamma camera consistently identified this ectopic gastric mucosa when it was 1.8 sq cm or larger. Excision of the surgical models after ^99mTc injection showed that gastric mucosal radioactive counts were 6–20 times those in the adjacent ileum. Contact radioautographs of the specimens compared to the histologic sections from which they were made demonstrated that the ^99mTc was concentrated in the mucous cells of the gastric mucosal surgace and gastric pits. ^99mTc Scintiphotography should be utilized to identify ectopic gastric mucosa in symptomatic patients, recognizing that the amount of ectopic gastric mucosa present will be one determining factor in visualization.     

Technetium-99m sestamibi scintimammography complements mammography in the detection of breast cancer

Mammography remains the technique of choice for the detection of early breast cancer. The sensitivity of mammography is 85%, but is decreased in patients with dense breasts. Sestamibi scintimammography (SCM) has been suggested as an adjunctive modality to improve the detection of breast cancer. We conducted a study to determine the impact of SCM in patient management. A prospective study was conducted in 95 patients presenting with palpable masses and/or abnormal mammography scheduled for biopsy. Injection of 20-30 mCi of technetium-99m (Tc-99m) sestamibi into a pedal vein was performed. Ten-minute images of the breast and axilla were obtained in multiple projections. The mammography and SCM were correlated with pathology and clinical findings. The median age was 44 years (range 28-86 years). The total number of lesions was 104, as eight patients had bilateral lesions and one patient had two lesions in the same breast. Fifty-nine patients presented with palpable lesions and 45 patients with nonpalpable lesions (42 with abnormal mammography only and 3 with nipple discharge). A comparison of sensitivity, specificity, positive and negative predictive values, and overall accuracy of SCM and mammography were performed. The sensitivity and specificity for SCM were 83% and 83%, respectively, and for mammography were 65%, and 72%, respectively. The sensitivity and specificity for combined SCM and mammography were 87% and 94%, respectively. The p-value for mammography versus combined SCM and mammography was 0.0003 and that for SCM versus SCM and mammography was 0.0098. There were 80 (77%) benign and 24 (23%) malignant lesions. Of the 24 malignancies, SCM missed six (25%), versus eight (33%) by mammography. In two patients (9%) SCM detected malignancy in the breast that was not visualized by mammography or found on clinical examination. Sestamibi SCM improves the sensitivity of mammography and it detects up to 9% of malignancies not detected by mammography or clinical examination. This testing could impact the management of 16,500 patients in the United States every year. More studies are needed to better define its role in breast cancer detection.