Parathyroid Tissue In Patients Research Articles

Comparing early and delayed [99mTc]Tc-MIBI SPECT/CT parathyroid scans: agreement, confidence levels, and clinical predictive factors

BackgroundParathyroid scan is an important imaging modality for localizing hyperfunctioning parathyroid tissue in patients with hyperparathyroidism. Unfortunately, whether early or delayed timing is the optimal protocol for [99mTc]Tc-MIBI SPECT/CT parathyroid remains under debate. This study aimed to evaluate the agreement and compare the confidence levels of physicians when interpreting early and delayed [99mTc]Tc-MIBI SPECT/CT parathyroid scans. Additionally, it sought to identify clinical factors that related to positive scan result. We conducted a prospective study where the early and delayed [99mTc]Tc-MIBI SPECT/CT was separately interpreted as either positive or negative. Furthermore, these interpretations were categorized based on whether they fell within more or less confidence levels of the readers and were correlated with clinical information.ResultsWe enrolled 39 patients with hyperparathyroidism with 158 possible locations of parathyroid glands. The per-location agreement between the early and delayed scans was moderate (concordant rate: 80.3%, Kappa = 0.558), and the per-patient agreement was slight (concordant rate: 71.8%, Kappa = 0.093). The confidence of interpretation was significantly higher for the delayed scans. Calcium supplementation, low serum parathyroid hormone levels, and low serum phosphate levels were associated with positive early scans. High calcium level and high parathyroid hormone levels were associated with positive delayed scans.ConclusionsOur study highlights the impact of the timing of SPECT/CT in [99mTc]Tc-MIBI parathyroid scans. The different confidence levels between early and delayed scans, along with clinical factors, imply that various factors affect parathyroid scan interpretation, and individualized scanning protocols adjusted for specific settings may be needed to optimize the successful localization of hyperfunctioning parathyroid tissue.

An essential practice summary of the new EANM guidelines for parathyroid imaging.

Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.

18F-Fluorocholine PET and 4D-CT in Patients with Persistent and Recurrent Primary Hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) can develop persistent (P-pHPT) or recurrent (R-pHPT) disease after parathyroidectomy. Before recommending reoperation, recurrence must be accurately identified because of the high risk of complications. Our study evaluates 18F-fluorocholine (18F-FCH) PET/CT and 4D-CT integrated in PET/4D-CT in patients with P-pHPT/R-pHPT. Patients with P-pHPT/R-pHPT investigated by 18F-FCH PET/4D-CT between May 2018 and March 2021 were retrospectively included. Forty-two patients were included, 37 of whom underwent 4D-CT. The sensitivity and detection rate (DR%) were 95% and 88% for 18F-FCH PET/CT and 70% and 63% for 4D-CT, respectively. PET/CT and 4D-CT were concordant in 18/24 glands and concordant and positive in 15/24 (63%) glands. Discordant results were obtained for 6/24 glands. The surgical success rate was 65%. PET/CT showed significantly higher sensitivity than 4D-CT. Dynamic CT allowed the identification of no additional glands missed by PET/CT, and the combination of the 2 techniques did not improve the sensitivity or DR%. 18F-FCH PET/CT appears to be a valuable technique to accurately detect hyperfunctioning parathyroid tissue in patients with P-pHPT/R-pHPT and is better than 4D-CT. Except for cases with doubtful locations of PET targets that may require 4D-CT for surgical guidance, standard nonenhanced 18F-FCH PET/CT can be effectively recommended in patients with P-pHPT/R-pHPT before reoperation.

18F-Fluorocholine PET/CT Is More Sensitive Than 11C-Methionine PET/CT for the Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism.

Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of 18F-fluorocholine (18F-FCH) PET/CT compared with 11C-methionine (11C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive 99mTc-sestaMIBI (99mTc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive 99mTc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by 11C-MET and 18F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. 18F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for 11C-MET PET/CT. 18F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with 11C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, 18F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by 11C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for 18F-FCH and 60% and 94%, respectively, for 11C-MET (P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for 18F-FCH and 52% and 94%, respectively, for 11C-MET (P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive 99mTc-MIBI SPECT findings, 18F-FCH PET/CT performs better than 11C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients.

Persistent Calciphylaxis and Secondary Hyperparathyroidism in End Stage Renal Disease Patient Due to Ectopic Mediastinal Parathyroid Adenoma- A Case Report

Intruducion: Secondary hyperparathyroidism (SHPT) is prevalent in patients with end-stage renal disease (ESRD) with reported prevalence of 90%. SHPT treatment is usually medical. Although 5% ends up with parathyroidectomy. Indications of parathyroidectomy in ESRD patients include persistent elevation of PTH more than 800, Calcyphylaxis, Osteitis Fibrosa Cystica, and persistent anemia. Among these patients who require surgery, 5–20% present with persistent or recurrent disease and require further re-exploration and excision of parathyroid tissue. We present a case of persistent Calciphylaxis and SHPT in ESRD patient despite Parathyroidectomy which prompted diagnosing an ectopic mediastinal parathyroid adenoma. Case Presentation: 49 year-old male with ESRD for 15 years complicated with SHPT, presented due to worsening Caciphylaxis of bilateral lower extremities despite Cinacalcet, IV sodium thiosulfate, and Phosphate binder. Serum Calcium level was 9.0 mg/dl with corrected levels of 10.2 mg/dl, Phosphorus level of 9.3 with Intact PTH level 1,369 pg/ml. Ultrasound of parathyroid glands was normal. Due to failure of medical treatment, He underwent Total parathyridectomy and left arm parathyroid autograft. Intraoperative PTH level went down to 300 (less than 50%). Calciphylaxis never improved. 5 months later, Parathyroid hormone was elevated 1338 pg/ml, Calcium level 6.9 mg/dl and Phosphorus level 10.0 mg/dl. 99mTc-sestamibi parathyroid scan didn’t show any activity in thyroid gland area and no increased uptake at the autograft area. Although it showed a small focus of persistent activity in substernal area suggestive of ectopic parathyroid tissue. Patient was referred for removal of ectopic adenoma. Discussion: Persistent SHPT is identified as the persistence or recurrence of symptoms, lab abnormalities and radiologic findings within 6 months after parathyroidectomy. Pathophysiology of recurrence is not well studied but one theory suggests that in SHPT, altered Calcium-phosphate hemostasis leads to hyperplasia of parathyroid tissue including ectopic and supernumerary tissue. This aforementioned altered hemostasis continues even after parathyroidectomy and cause hyperplasia and hyperfunction of the residual parathyroid tissue left accidentally by seeding within surgical site or implanted autograft or It can present with ectopic adenoma, even if they were undetected prior to or in the first intervention. Ectopic parathyroid tissue is an uncommon etiology of persistent or recurrent secondary hyperparathyroidism, it is reported in many cases where it was missed at initial workup. Prevalence reported up to 14% in patients with persistent SHPT. It is warranted further investigations to look for ectopic parathyroid tissue in patients with ESRD who present with recurrent or persistent secondary hyperparathyroidism after total parathyroidectomy with reimplantation.

Performance of F-18 Fluorocholine PET/CT for Detection of Hyperfunctioning Parathyroid Tissue in Patients with Elevated Parathyroid Hormone Levels and Negative or Discrepant Results in conventional Imaging.

ObjectiveOur aim was to assess the diagnostic performance of F-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in detecting hyperfunctioning parathyroid tissue (HPT) in patients with elevated parathyroid hormone levels with negative or inconclusive conventional imaging results and to compare the findings with those obtained using technetium-99m sestamibi (MIBI) scintigraphy and neck ultrasonography (US).Materials and MethodsImages of 105 patients with hyperparathyroidism who underwent FCH PET/CT, dual-phase MIBI parathyroid scintigraphy (median interval: 42 days), and neck US were retrospectively analyzed. The gold standard was histopathological findings for 81 patients who underwent parathyroidectomy and clinical follow-up findings in the remaining 24 patients. Sensitivities, positive predictive values (PPVs), and accuracies were calculated for all imaging modalities.ResultsAmong the 81 patients who underwent parathyroidectomy, either parathyroid adenoma (n = 64), hyperplasia (n = 9), neoplasia (n = 4), or both parathyroid adenoma and hyperplasia (n = 1) were detected, except 3 patients who did not show HPT. Of the 24 (23%) patients who were followed-up without operation, 22 (92%) showed persistent hyperparathyroidism. FCH PET/CT showed significantly higher sensitivity than MIBI scintigraphy and US in detection of HPT (p < 0.01). Sensitivity, PPV, and accuracy of FCH PET/CT were 94.1% (95/101), 97.9% (95/97), and 92.4% (97/105), respectively. The corresponding values for MIBI scintigraphy and US were 45.1% (46/102), 97.9% (46/47), and 45.7% (48/105) and 44.1% (45/102), 93.8% (45/48), and 42.9% (45/105), respectively. Among the 35 patients showing negative MIBI scintigraphy and neck US findings, 30 (86%) showed positive results on FCH PET/CT. FCH PET/CT could demonstrate ectopic locations of HPT in 11 patients whereas MIBI and US showed positive findings in only 6 and 3 patients, respectively.ConclusionFCH PET/CT is an effective imaging modality for detection of HPT with the highest sensitivity among the available imaging techniques. Therefore, FCH PET/CT can be recommended especially for patients who show negative or inconclusive results on conventional imaging.

Incremental Value of Sestamibi SPECT/CT Over Dual-Phase Planar Scintigraphy in Patients With Primary Hyperparathyroidism and Inconclusive Ultrasound.

Background: We evaluated the incremental value of [99mTc]sestamibi single photon-emission computed tomography (SPECT)/computed tomography (CT) over planar imaging for localization of abnormal parathyroid tissue in patients with primary hyperparathyroidism.Methods: Forty-six patients with biochemical evidence of hyperparathyroidism and inconclusive ultrasound underwent sestamibi dual-phase planar scintigraphy and SPECT/CT for preoperative localization of parathyroid adenoma. Imaging findings were compared with histopathological data. Decision tree analysis was performed to evaluate the value of SPECT/CT over planar scintigraphy for classifying patients with or without hyperfunctioning parathyroid tissue. The added value of SPECT/CT was also evaluated by decision curve analysis.Results: Planar scintigraphy was positive for presence of hyperfunctioning parathyroid in 52% of patients, with sensitivity of 63% and specificity of 100%. SPECT/CT was positive in 80% of patients with sensitivity of 97% and specificity of 100%. At decision tree analysis, after an initial split on planar imaging results, no further split was performed in patients with positive results, while those with negative results were further stratified by SPECT/CT. At decision curve analysis, the model including SPECT/CT was associated with the highest net benefit compared to the model including only planar technique and to a strategy considering that all patients should be treated.Conclusion: Sestamibi SPECT/CT provides incremental value over dual-phase scintigraphy in preoperative localization of hyperfunctioning parathyroid tissue in subjects with inconclusive ultrasound. Hybrid technique allows a better identification of pathological lesion to perform minimally invasive surgery and showed the highest net benefit, improving selection of surgical approach.

Intraoperative Parathyroid Autofluorescence Detection in Patients with Primary Hyperparathyroidism.

Intrinsic near-infrared (NIR) autofluorescence of the parathyroid gland may improve intraoperative gland identification without the need for contrast agent injection. Compared with patients undergoing surgery for thyroid disease, identification of pathologic parathyroid tissue in patients with hyperparathyroidism is essential. This study analyzed the utility of a novel real-time autofluorescence imaging system in patients with primary hyperparathyroidism enrolled in a prospective feasibility clinical trial. Data on patients undergoing surgery for primary hyperparathyroidism by two experienced endocrine surgeons were prospectively collected. Intraoperative imaging was performed with a handheld NIR device, and images were captured for analysis. The collected data included the surgeon's confidence in parathyroid identification, both with ambient light and use of NIR imaging, as well as how the imaging affected the surgical procedure. Images were quantified by Image J software, with autofluorescence reported as mean values ± SD. From 2017 to 2018, 59 consecutive patients with a diagnosis of primary hyperparathyroidism underwent resection of 69 parathyroid glands. Use of NIR imaging increased the intraoperative confidence of parathyroid identification (on a scale of 0-5) from an average of 4.1 to an average of 4.4 (+0.3, p = 0.003), all of which were confirmed pathologically. The addition of autofluorescence helped to identify the parathyroid gland in 12 patients (20%), and to rule out other soft tissue as not parathyroid in an additional 9 patients (15%). The mean autofluorescence for the parathyroid in situ (75.9 ± 21.3) was significantly greater than that for the thyroid (61.1 ± 17.4) or soft tissue (53.3 ± 19.2) (p < 0.001 for both). The mean absolute difference in parathyroid versus background thyroid autofluorescence was +15.2 (range, 2.4-53.1). This is the first prospective trial to examine the utility of parathyroid autofluorescence for identifying glands exclusively in patients with parathyroid disease. Intraoperative identification and localization of parathyroid glands by real-time, NIR imaging using their intrinsic autofluorescence is feasible and may provide a useful adjunct during parathyroid surgery.

Parathyroid autotransplantation in thyroid surgery.

Careful parathyroid gland dissection and in situ preservation was the time-honored approach to prevent parathyroid failure after total thyroidectomy. The relative success of parathyroid autotransplantation of hyperplastic parathyroid tissue in patients with renal or hereditary hyperparathyroidism did popularize the use of normal parathyroid tissue autografts during thyroidectomy to prevent permanent hypoparathyroidism. Proof of autograft function in this setting, however, is controversial. This narrative review aims at reviewing critically the current status of parathyroid autotransplantation during total thyroidectomy. It is also meant to analyze from the historical, methodological, and clinical points of view the claimed benefit of normal parathyroid gland autotransplantation. A focus is placed on the prevention of permanent hypoparathyroidism by parathyroid autotransplantation. Liberal parathyroid autotransplantation was proposed in the mid 1970s but evidence of function is scarce. Proofs are accumulating that parathyroid autografts not only increase the rate of postoperative hypocalcemia, but may be also contribute to permanent hypoparathyroidism.

Role of Imaging Tests for Preoperative Location of Pathologic Parathyroid Tissue in Patients with Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) can be cured by parathyroidectomy, and the preoperative location of enlarged pathologic parathyroid glands is determined by imaging studies, especially cervical ultrasonography and scintigraphy scanning. The aim of this retrospective study was to evaluate the use of preoperative cervical ultrasonography and/or parathyroid scintigraphy in locating pathologic parathyroid tissue in a group of patients with PHPT followed in the same endocrine center. We examined the records of 61 patients who had undergone parathyroidectomy for PHPT following (99m)Tc-sestamibi scintigraphy scan and/or cervical ultrasonography. Scintigraphic and ultrasonographic findings were compared to histopathologic results of the surgical specimens. Ultrasonography detected enlarged parathyroid glands in 87% (48/55) of patients with PHPT and (99m)Tc-sestamibi scintigraphy in 79% (37/47) of the cases. Ultrasonography was able to correctly predict the surgical findings in 75% (41/55) of patients and scintigraphy in 72% (34/47). Of 7 patients who had negative ultrasonography, scintigraphy correctly predicted the surgical results in 2 (29%). Of 10 patients who had negative scintigraphy, ultrasonography correctly predicted the surgical results in 4 (40%). When we analyzed only patients with solitary eutopic parathyroid adenomas, the predictive positive values of ultrasonography and scintigraphy were 90% and 86%, respectively. Cervical ultrasonography had a higher likelihood of a correct positive test and a greater predictive positive value for solitary adenoma compared to (99m)Tc-sestamibi and should be used as the first diagnostic tool for preoperative localization of affected parathyroid glands in PHPT. Ca = calcium IEDE = Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione PHPT = primary hyperparathyroidism PTH = parathyroid hormone.

Combined application of ultrasound and SPECT/CT has incremental value in detecting parathyroid tissue in SHPT patients.

The goal of this study is to investigate whether combined application of ultrasound and 99mTc-sestamibi SPECT/CT had the incremental value in accurately detecting parathyroid tissue in patients with SHPT over either method alone. Sixty patients with SHPT on hemodialysis were evaluated preoperatively with parathyroid 99mTc-sestamibi SPECT/CT scintigraphy and ultrasound prior to parathyroidectomy. The sensitivity, specificity and accuracy of 99mTc-sestamibi SPECT/CT scintigraphy, ultrasound and combined application were determined respectively. The sensitivity, specificity and accuracy of ultrasound were 81% (155/192), 47% (17/36) and 82% (172/228), respectively. The sensitivity, specificity and accuracy of 99mTc-sestamibi SPECT/CT were 85% (163/192), 58% (21/36) and 89% (184/228) respectively. The accuracy of 99mTc-sestamibi SPECT/CT in the diagnosis of parathyroid tissue in patients with SHPT is significantly higher than that of ultrasound. The sensitivity, specificity and accuracy of combined application of ultrasound and 99mTc-sestamibi SPECT/CT were 93% (178/192), 61% (22/36) and 97% (200/228). The sensitivity, specificity and accuracy of combined application of ultrasound and 99mTc-sestamibi SPECT/CT were higher than those of either ultrasound or 99mTc-sestamibi SPECT/CT. The combined application of ultrasound and 99mTc-sestamibi SPECT/CT had incremental value in accurately detecting parathyroid tissue in patients with SHPT over either method alone.

Pedicled Parathyroid Autotransposition in Surgical Management of Secondary Hyperparathyroidism

Objectives: In this study, we report a new, less invasive surgical technique in managing preserved parathyroid tissue in patients with secondary hyperparathyroidism who undergo bilateral parathyroid exploration and excision of all 4 parathyroid glands. We report this technique in 4 patients and evaluate their postoperative parathyroid hormone (PTH) levels as a marker to evaluate efficacy. Methods: All 4 glands were first exposed. Superior glands are not possible to transpose and were excised while the inferior glands were mobilized on their pedicles. Once identified, the inferior glands were kept intact until it was determined which gland can be best preserved on its vascular pedicle with adequate length for transposition. This gland was then mobilized through an incision made in the strap muscles, placing it superficial and ventral to the muscles. The majority of the hyperplastic gland was then resected distal to its vascular pedicle. The portion of the gland that was preserved was secured over the strap muscle, making it easily accessible for future exploration and debulking if needed and avoiding a second operative site in the forearm. Results: Rapid intraoperative PTH assay confirmed adequate removal of hypersecreting parathyroids and was indicative of a curative outcome. All patients exhibited a greater than 90% initial reduction in the PTH level from their baseline and a sustained decrease in postoperative PTH levels well below their preoperative baselines at one month. The percentage mean reduction in PTH at longest follow-up was 94.57%. Importantly, none of the patients exhibited postoperative PTH levels indicative of hypoparathyroidism. Conclusions: None provided.

Cost-effectiveness of 99mTc-MIBI in the evaluation of thyroid nodules for malignancy: a new lease of life for an old radiopharmaceutical?

In nuclear medicine practice, physicians are often confronted with the problem that formal registration of a specific radiopharmaceutical and the indications for its use are lacking (e.g. the modern Ga-labelled somatostatin analogues). If formal registration is available, this registration often only covers a few, specific and predominantly commercially interesting indications even when the radiopharmaceutical can be applied more broadly. A good example of the latter is the case of Tc-methoxyisobutylisonitrile (MIBI). MIBI was first described in the 1980s [1, 2]. Originally developed for myocardial perfusion scintigraphy for the detection and localization of coronary artery disease, it went on to eventually achieve registration not only for this indication, but also for the assessment of global ventricular function, scintimammography for the detection of suspected breast cancer when mammography is equivocal, inadequate or indeterminate, and localization of hyperfunctioning parathyroid tissue in patients with recurrent or persistent hyperparathyroidism, both primary and secondary, and in patients with primary hyperparathyroidism scheduled to undergo initial surgery of the parathyroid glands [3]. However, for many years it has been known that MIBI scintigraphy can also be used in the diagnostic work-up of scintigraphically cold and therefore suspicious thyroid nodules in combination with fine needle biopsy (FNB) [4–12]. As Wale et al. show in this edition of the European Journal of Nuclear Medicine and Molecular Imaging [13] and Treglia et al. showed recently in a comparable meta-analysis [14], in conjunction with prior Tc-pertechnetate thyroid scintigraphy MIBI scintigraphy can achieve a very high negative predictive value ranging from 88 % to 100 % with a mean of 97 %. Furthermore, the sensitivity of MIBI scintigraphy is similarly good with an aggregate value of 96%. This indicates that a negative MIBI scan will obviate the need to surgically remove the thyroid nodule for definitive histological clarification in the large majority of patients, as the risk of malignancy in such a nodule is very low. This of course does have economic implications. Considering that the risk of missing the diagnosis of thyroid cancer is low, and a large number of, in hindsight unnecessary, comparatively expensive surgical procedures can be avoided, it is not surprising that Wale et al. are able to show that the addition of MIBI scintigraphy leads to a considerable saving in costs per patient and per cancer diagnosed while not significantly affecting life expectancy [13]. Of course, the model used by Wale et al. is a theoretical one and any model requires simplification of the sometimes complex individual situations of different patients. For example, the authors did not directly assess the life expectancy of patients scanned with MIBI, but derived these data from unrelated survival analyses of patients with thyroid cancer. This and further notable limitations of the model are mainly due to the lack of data from prospective randomized controlled trials. F. A. Verburg : F. F. Behrendt : F. M. Mottaghy :A. Heinzel Department of Nuclear Medicine, RWTH Aachen University Hospital, Pauwelsstrase 30, 52074 Aachen, Germany

Limitations of Tc99m‐MIBI‐SPECT Imaging Scans in Persistent Primary Hyperparathyroidism

BackgroundIn primary hyperparathyroidism (PHPT) the predictive value of technetium 99m sestamibi single emission computed tomography (Tc99m-MIBI-SPECT) for localizing pathological parathyroid glands before a first parathyroidectomy (PTx) is 83–100%. Data are scarce in patients undergoing reoperative parathyroidectomy for persistent hyperparathyroidism. The aim of the present study was to determine the value of Tc99m-MIBI-SPECT in localizing residual hyperactive parathyroid tissue in patients with persistent primary hyperparathyroidism (PHPT) after initial excision of one or more pathological glands.MethodWe retrospectively evaluated the localizing accuracy of Tc99m-MIBI-SPECT scans in 19 consecutive patients with persistent PHPT who had a scan before reoperative parathyroidectomy. We used as controls 23 patients with sporadic PHPT who had a scan before initial surgery.ResultsIn patients with persistent PHPT, Tc99m-MIBI-SPECT accurately localized a pathological parathyroid gland in 33% of cases before reoperative parathyroidectomy, compared to 61% before first PTx for sporadic PHPT. The Tc99m-MIBI-SPECT scan accurately localized intra-thyroidal glands in 2 of 7 cases and a mediastinal gland in 1 of 3 cases either before initial or reoperative parathyroidectomy.ConclusionsOur data suggest that the accuracy of Tc99m-MIBI-SPECT in localizing residual hyperactive glands is significantly lower before reoperative parathyroidectomy for persistent PHPT than before initial surgery for sporadic PHPT. These findings should be taken in consideration in the preoperative workup of patients with persistent primary hyperparathyroidism.

CT-MIBI-SPECT image fusion predicts multiglandular disease in hyperparathyroidism

To perform focused or minimally invasive surgery for hyperparathyroidism (HPT) exact preoperative localization is mandatory. Computed tomography-(99m)Tc-sestamibi-single photon emission computed tomography image fusion (CT-MIBI-SPECT) serves this difficult task in single gland HPT to a large extent. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT alone and CT alone in detecting abnormal parathyroid tissue in patients with multiglandular disease. CT-MIBI-SPECT image fusion for preoperative localization was performed in 30 patients with multiglandular disease. There were six patients with primary hyperparathyroidism (four MEN I syndromes and two double adenomas; one of these patients has HRPT2 gene mutation), 14 with secondary, and eight with tertiary HPT, further one patient each suffering from persistent primary and persistent secondary hyperparathyroidism. In both persistent patients only one remaining gland was left from primary surgery. The results of MIBI-SPECT, CT, and CT-MIBI-SPECT image fusion were compared in these patients. The outcome and the exact predicted positions were correlated with intraoperative findings. In five out of six patients with multiglandular primary hyperparathyroidism more than one gland was detected, thus multiglandular disease could be suspected preoperatively. Overall CT-MIBI-SPECT image fusion was able to predict the exact position of all abnormal glands per patient in 14 of 30 (46.7%) cases, whereas CT alone was successful in 11 (36.7%), and MIBI-SPECT alone just in four (13.3%) of 30 patients. Multiglandular disease in primary hyperparathyroidism can be suspected preoperatively in a high percentage of patients. Additionally, this study shows that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone in preoperative localization of all pathologic glands in patients suffering from multiglandular disease.

The Apoptotic Labeling Index of Parathyroid Tissue in Patients with the Secondary Hyperparathyroidism of End Stage Renal Disease

The Apoptotic Labeling Index of Parathyroid Tissue in Patients with the Secondary Hyperparathyroidism of End Stage Renal Disease

The False Negative Technetium-99m-Sestatnibi Scan in Patients with Primary Hyperparathyroidism: Correlation with Clinical Factors and Operative Findings

False negative (FN) results limit the efficacy of technetium-99m-sestamibi scanning for parathyroid localization. We determined the incidence of FN results and attempted to correlate it with clinical and operative findings. One hundred forty-six patients underwent parathyroidectomy; 89 had primary hyperparathyroidism (76 single adenoma and 13 multiglandular disease) and underwent sestamibi scanning. The false negative rate was 22 per cent with an overall sensitivity of 77 per cent and a positive predictive value of 99 per cent. Patients with single adenomas were more likely to have a true positive scan than those with multiglandular disease [83% vs 38%; odds ratio (OR) = 7.754, 95% confidence interval (CI) = 2.184–27.524; P ≤ 0.0001]. Inferior adenomas (90% vs 59%; OR = 6.261,95% CI = 2.037–19.243; P ≤ 0.0001) and larger adenomas (1422.3 ± 1576.2 vs 474.6 ± 193.2 g; P ≤ 0.0001) were more likely to be detected by sestamibi imaging. Patients with normal preoperative calcium levels were more likely to have an FN sestamibi scan. Sestamibi parathyroid imaging is limited by a 22 per cent FN rate and is less accurate for detecting abnormal parathyroid tissue in patients with small adenomas, multiglandular disease, superior adenomas, or preoperative normocalcemia.

In vitro accumulation of technetium-99m-sestamibi in human parathyroid mitochondria

Background. Technetium-99m-sestamibi (sestamibi) is the imaging agent of choice for preoperative parathyroid localization. The subcellular localization of sestamibi uptake in enlarged parathyroid glands in patients with hyperparathyroidism has not been determined. This study investigated the mechanism of retention of sestamibi by human parathyroid tissue. Methods. Twenty-three freshly harvested and 15 cryopreserved parathyroid glands excised from patients with primary or secondary hyperparathyroidism were analyzed for subcellular localization of Tc-99m-sestamibi. Tissues were incubated with 100 μCi of sestamibi and isolated for mitochondria by differential centrifugation, and the integrity of subcellular fractions was quantified with the mitochondrial enzyme marker, succinate dehydrogenase. Results. Ninety-two percent of sestamibi activity was associated with mitochondria. Furthermore, after adding the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), to fresh parathyroid tissues, 84.96% and 73.86% of sestamibi was released from the mitochondrial and tissue fragment components, respectively. In addition, sestamibi activity in the mitochondrial component of cryopreserved human parathyroid tissue decreased to the same amount as the CCCP-treated group. Conclusions. These data confirm that mitochondrial activity is the major component of sestamibi uptake by human parathyroid tissue in patients with hyperparathyroidism. (Surgery 2001;130:1011-8.)

Sestamibi/iodine subtraction single photon emission computed tomography in reoperative secondary hyperparathyroidism

Background: Sestamibi/iodine subtraction single photon emission computed tomography (SPECT) has been used successfully for the preoperative localization of adenomatous and hyperplastic parathyroid tissue in primary hyperparathyroidism, but the clinical usefulness of this technique in secondary hyperparathyroidism remains uncertain. The purpose of this study was to evaluate parathyroid localization that uses sestamibi/iodine subtraction SPECT in patients with secondary hyperparathyroidism before reoperative parathyroid surgery. Methods: Fourteen consecutive patients with chronic renal failure and secondary hyperparathyroidism who had previously undergone total parathyroidectomy combined with parathyroid autotransplantation in a sternocleidomastoid muscle were studied. Before reoperation, each patient received 400 μCi of sodium iodide I 123 orally and 20 to 25 mCi of technetium Tc 99m (99mTc)-sestamibi intravenously, followed by sestamibi/iodine subtraction SPECT of the neck and chest. At surgery, the location, weight, and histopathologic results of all identified parathyroid tissue were recorded. Results: At surgery, 1 hyperplastic parathyroid gland was resected from each of 13 patients; including 1 undescended gland, 6 parathyroid autotransplants, and 5 mediastinal glands. The mean weight of the resected parathyroid glands was 1707 mg (range, 85-5300 mg). Sestamibi/iodine subtraction SPECT correctly identified and localized all 13 parathyroid glands (100% sensitivity) and was negative in the 1 patient whose surgery was unsuccessful. Conclusions: The 99mTc-sestamibi/123I subtraction SPECT is able to correctly localize hyperplastic parathyroid tissue in patients with secondary hyperparathyroidism who have previously undergone parathyroid surgery and is a clinically useful study before reoperation. (Surgery 2000;128:22-8)

Subcutaneous forearm transplantation of autologous parathyroid tissue in patients with renal hyperparathyroidism

Parathyroidectomy is required in up to 5% of patients with chronic renal failure. Intramuscular transplantation of autologous parathyroid tissue in the forearm has been the traditional method of transplantation at the time of total parathyroidectomy. The removal of an intramuscular transplantation can be technically difficult should graft-dependent hyperparathyroidism (GRH) occur. This problem resulted in our initiating a study of subcutaneous transplantation with total parathyroidectomy in patients with renal failure. Twenty-six patients who were receiving dialysis therapy underwent total parathyroidectomy and subcutaneous transplantation. Parathyroid tissue was diced into 1- to 2-mm pieces, and 6 pieces were grafted into 6 subcutaneous pockets of the forearm. Intact parathyroid hormone was measured within 48 hours of operation and in the bilateral antecubital veins 1 to 24 months after the operation to assess completeness of resection and graft function, respectively. No major surgical complications occurred. Symptoms improved in 24 patients (85%). Graft failure rate was 4.3%. No GRH was observed. Follow-up was 4 to 55 months (mean, 27 months). This study indicates that the subcutaneous transplantation function is comparable to intramuscular transplantation and suggests a decreased incidence of GRH. Subcutaneous transplantation is technically easier than intramuscular transplantation and has the additional advantage of easy removal should GRH occur.