Intraoperative Parathyroid Hormone Monitoring in Patients with Recognized Multiglandular Primary Hyperparathyroidism

Background  

Intraoperative parathyroid hormone (IOPTH) monitoring reliably predicts cure of primary hyperparathyroidism (PHPT) due to single-gland disease. However, its utility in PHPT caused by multiple-gland disease (MGD) is still debated, for both detection and prediction of adequate resection. Our hypothesis is that once MGD is encountered during an operation, more stringent criteria for determining adequate resection can improve cure rates.     

Inframanubrial Parathyroid Glands in Patients with Primary Hyperparathyroidism: Alternatives to Sternotomy

Deep inframanubrial parathyroid tumors have traditionally been excised through a median sternotomy. With the advent of minimally invasive surgical access, we chose to examine the treatment options and outcomes of patients with inframanubrial mediastinal parathyroid tumors. Patients with primary hyperparathyroidism seen at a university medical center over a 12-year period were retrospectively reviewed. The utility of localization studies, methods of treatment, complications, and outcomes were examined in patients with a parathyroid tumor located in the mediastinum inferior to the manubrium. Patients with parathyroid adenomas located at the thoracic inlet were excluded. Sixteen patients with inframanubrial mediastinal tumors were treated during the study period. Altogether, 81% of the patients had undergone at least one prior neck exploration for primary hyperparathyroidism. Preoperative calcium and parathyroid hormone levels were 12.4 ± 0.36 mg/dl and 273 ± 70 pg/ml, respectively. Localization studies identified mediastinal parathyroid adenomas in the following locations: anterior mediastinum (n = 8), middle mediastinum (n = 7), posterior mediastinum (n = 1). Mediastinal computed tomography and technetium-sestamibi scans demonstrated the best sensitivity, 92% and 85%, respectively. Seven patients underwent successful excision of the mediastinal adenoma by transcervical mediastinal exploration with the Cooper retractor. The other patients underwent angiographic ablation (n = 4), anterior mediastinotomy (n = 3), video-assisted thoracoscopy (VATS) (n = 1), and VATS plus thoracotomy (n = 1). The mean hospital stay for the study group was 2.9 ± 0.7 days. The complication rate was 25%. All patients were normocalcemic after a mean follow-up of 15 ± 7 months. Most inframanubrial mediastinal parathyroid tumors can be successfully managed without median sternotomy.     

4D Parathyroid CT as the Initial Localization Study for Patients with De Novo Primary Hyperparathyroidism

Background

Preoperative localization of parathyroid tumors of primary hyperparathyroidism (pHPT) is required for minimally invasive parathyroidectomy (MIP). Parathyroid four-dimensional computed tomography (4DCT) has mainly been used as an adjunct to other imaging modalities in the remedial setting. 4DCT was evaluated as the initial localization study in de novo patients with pHPT.

Materials and Methods

A total of 87 consecutive patients underwent parathyroidectomy for pHPT from August 2008 to November 2009. 4DCT was introduced as the preferred imaging modality instead of sestamibi with SPECT (SeS) in April 2009. Results of the imaging studies [4DCT, SeS, and ultrasonography (US)], operative and, pathologic findings, and biochemical measurements were evaluated.

Results

In this study, 84% of patients (73 of 87) underwent an US, 59.8% (52 of 87) a SeS, and 38.0% (33 of 87) had a 4DCT. 4DCT had improved sensitivity (85.7%) over SeS (40.4%) and US (48.0%) to localize parathyroid tumors to the correct quadrant of the neck (P < 0.005) as well as to localize (lateralize) the parathyroid lesions to one side of the neck (93.9% for 4DCT vs. 71.2% for US and 61.5% for SeS; P < 0.005). 4DCT correctly predicted multiglandular disease (MGD) in 85.7% (6 of 7) patients, whereas US and SeS were unable to detect MGD in any case. All patients achieved cure based on intraoperative parathyroid hormone (PTH) measurements and normalization of intact PTH and S-Ca during follow-up.

Conclusions

4DCT provides significantly greater sensitivity than SeS and US for precise localization of parathyroid tumors of pHPT. Additionally, it correctly predicted MGD in a majority of patients.     

Development of a Formula to Predict Parathyroid Carcinoma in Patients with Primary Hyperparathyroidism

Background

Cure of parathyroid carcinoma (PC) requires initial en bloc resection, including resection of all tumor-bearing tissue, with hemithyroidectomy and dissection of the central lymph node compartment. Unfortunately, no reliable preoperative criteria have yet been assessed to indicate a high likelihood of PC. Thus, the aim of the present study was to develop a formula to indicate preoperatively the presence of PC.

Methods

A prospective database of 1,363 patients with primary hyperparathyroidism (pHPT) was screened for patients with PC. Age, gender, surgical procedures, laboratory data, and follow-up results were evaluated and compared to a group of patients with benign pHPT. Based on preoperative serum calcium (Ca) and parathyroid hormone (PTH) levels, as well as patients’ age at the time of diagnosis, a formula was developed by a multivariate logistic model that estimates the individual risk for PC.

Results

Between 1987 and 2008, 19 patients with PC were identified. Ca (3.8?±?0.3 vs 2.9?±?0.3 mmo/l; p?=?0.0002) and PTH levels (1,250?±?769 vs 194?±?204?pg/ml; p?=?0.0030) were significantly higher in patients with PC than in those with benign pHPT. Patients with PC were also significantly younger than patients with benign pHPT (48.9?±?12.1 vs 59.1?±?13.8?years; p?<?0.05). With a ≥5?% probability that a given patient suffered from PC, the sensitivity and specificity to identify the disease were 100 and 30?%, respectively, with the new Ca, PTH, and age based logarithmic formula.

Conclusions

The new logarithmic formula can be used to calculate the individual risk for PC. If the calculated individual risk exceeds 5?%, en bloc resection seems to be justified to provide long-term cure in case of PC.     

Preoperative Localization of Parathyroid Adenomas Using 99mTc-MIBI Scintigraphy in Patients with Hyperparathyroidism

Background Technetium (Tc) 99m methoxyisobutyl isonitrile (_99mTc-MIBI) has recently been introduced for parathyroid imaging, as well as for myocardial imaging. We studied the usefulness of _99mTc-MIBI scintigraphy for preoperative localization of abnormal parathyroid glands.
Methods The usefulness of _99mTc-MIBI scintigraphy for detection of hyperfunctional parathyroid lesions was evaluated in 5 patients with primary hyperparathyroidism. The results of localizing the abnormal glands by using _99mTc-MIBI were compared with those obtained by using thallium (Tl) 201-technetium (Tc) 99m (_2ulTI-_99mTc) subtraction scintigraphy, computed tomography, and ultrasonography.
Results The delayed (2 hours) imaging of _99mTc-MIBI scintigraphy was highly useful for accurate localization of the abnormal parathyroid lesions. The diseased glands were detected in all cases where _99mTc-MIBI scintigraphy was used, and using _99mTc-MIBI scintigraphy provided more information than did computed tomography, ultrasonography, or ₂₀₁Tl-_99mTc subtraction scintigraphy. Conclusion: This method is simple and essential for detecting hyperfunctioning parathyroid glands, especially those with small or ectopic lesions. This technique should be widely applied as a localizing diagnostic method for hyperparathyroidism.     

Surgeon-Performed Ultrasound for Preoperative Localization of Abnormal Parathyroid Glands in Patients with Primary Hyperparathyroidism

Background The introduction of portable ultrasound equipment enables surgeons to perform ultrasound examinations in a clinic setting. This study was undertaken to evaluate surgeon-performed ultrasound (SP-US) in patients with primary hyperparathyroidism (PHPT). Methods Between July 2003 and March 2004, 65 patients with PHPT were evaluated with SP-US and 48 of these patients underwent parathyroid surgery. Among this group of 48 evaluable patients, 47 had preoperative imaging with technetium-99m sestamibi scanning (MIBI), and 12 had an additional ultrasound examination at an external radiology department (RP-US). Results All patients were cured of PHPT and the operative findings were used to determine the true status of the parathyroid glands of each patient. Twenty-four (50%) patients had concomitant thyroid nodules which were identified by SP-US, and 4 (8.3%) patients had simultaneous thyroid operations, 2 of which were for thyroid cancer. Considering data for all patients, SP-US had significantly higher sensitivity than MIBI or RP-US (60% vs. 46%, P = 0.013, and 60% vs. 11%, P = 0.004 respectively). Among the patients with a single adenoma, SP-US, MIBI, and RP-US had sensitivities of 83%, 63%, and 13% respectively. The specificities of all three imaging techniques were uniformly high and were not significantly different from each other. Conclusions Surgeon-performed ultrasound is an accurate modality for localizing abnormal parathyroid glands in patients with PHPT, with results that compare favorably with other parathyroid imaging modalities.     

Preoperative Serum Osteocalcin may Predict Postoperative Elevated Parathyroid Hormone in Patients with Primary Hyperparathyroidism

Background  

Persistent postoperative elevation of parathyroid hormone (POePTH) following successful parathyroidectomy for primary hyperparathyroidism (PHPT) is presumed to result from bone remineralization. Predicting which patients may need treatment is difficult. This study investigated whether preoperative serum osteocalcin (OC), a bone turnover marker involved in mineralization, can predict POePTH.     

Indian Primary Hyperparathyroidism Patients with Parathyroid Carcinoma do not Differ in Clinicoinvestigative Characteristics from Those with Benign Parathyroid Pathology

Introduction No foolproof preoperative diagnostic indicators of parathyroid carcinoma (PC) exist in absence of nonskeletal metastases. Palpable parathyroid tumor, advanced skeletal and renal manifestations, and very high serum calcium and parathyroid hormone levels are considered strong predictors. Most of these features are common in Indian primary hyperparathyroidism (PHPT) patients although only few have PC. The aim of this study was to identify dependable clinicoinvestigative predictors of PC in Indian PHPT patients. Materials and Methods Clinical, biochemical, radiological, and densitometric attributes of 100 PHPT patients who underwent successful parathyroidectomy (1990–2004) were studied. Various parameters of patient groups with parathyroid adenoma (n = 84), primary hyperplasia (n = 12), and carcinoma (n = 4) were compared using ANOVA, with P value < 0.05 considered significant. Results Mean age of patients was 37.4 years, with no difference in the 3 groups (P = 0.92). Patients in 3 groups had comparably severe bone disease; 36 had coexistent renal disease. Two patients with PC and 27 (32%) with adenoma had palpable parathyroid tumor. None of the biochemical parameters predicted malignant pathology. Mean tumor weight (milligram) in carcinoma patients (15,080 ± 5,638.02) was significantly higher than those with adenoma (5,724 ± 1,257.9) (P = 0.002). Postoperative course and recovery in carcinoma patients were similar to those with adenoma. In follow-up (mean: 33 months), none of the adenoma patients were found to have persistent/recurrent PHPT attributable to missed PC. Conclusion Indian patients with parathyroid adenoma, hyperplasia, and carcinoma were not found to differ in their clinical, biochemical, and pathological characteristics except for significantly higher tumor weight in the carcinoma group.     

Parathyroid Hormone Content Distinguishes True Normal Parathyroids from Parathyroids of Patients with Primary Hyperparathyroidism

p < 0.001) for TN parathyroid glands; however, it was not true for glands (grossly normal or otherwise) in patients with HPT. Patient groups were similar with regard to mean patient age and intracellular PTH mRNA levels. Hypercalcemic patients were similar with regard to preoperative serum calcium and PTH levels. NA parathyroids, adenomas, and hyperplasias are different from TN parathyroids with regard to their PTH content. PTH mRNA was similar across all groups. The relation between intracellular PTH mRNA and PTH was significantly absent in patients with HPT compared with TN glands. Furthermore, we have found that PTH content of normal parathyroid in patients with adenoma is similar to that of hyperplastic and adenoma tissues. These data suggest that the PTH content of parathyroid tissues may be of use in differentiating normal from abnormal parathyroids.     

Sensitivity and Utility of Parathyroid Scintigraphy in Patients with Primary Versus Secondary and Tertiary Hyperparathyroidism

Introduction Parathyroid scintigraphy (PS) may be used to localize hyperactive parathyroid glands preoperatively. Performance of PS in the setting of secondary and tertiary hyperparathyroidism (HPT) is not well quantified. The performance of PS in secondary/tertiary HPT versus primary HPT may reflect physiologic as well as radiopharmaceutical kinetic differences between multigland hyperplasia versus adenoma. The aim of this study was to review the performance of PS in secondary/tertiary HPT with a comparison to that for primary HPT. Moreover, we evaluated (1) the sensitivity of PS in detecting enlarged glands, and (2) PS detectability as a function of gland weight. Methods We performed a retrospective review of the Mayo Clinic database from 2000 to 2004. We identified 40 patients with secondary or tertiary HPT as well as a matched control group of 40 patients with primary HPT who had had preoperative PS and underwent parathyroid surgery. Results Parathyroid scintigraphy correctly localized all enlarged glands in 88% of patients in the primary HPT group. PS correctly identified both the number and locations of all hyperplastic glands in only 28% of the secondary/tertiary HPT patients. PS failed to identify one enlarged gland in 23% of the patients and two or more enlarged glands in 40% of the patients. PS correctly detects the largest gland in 88% of the patients with secondary and tertiary HPT. The mean gland weight detectable by PS was 612 ± 120 mg for primary HPT. In secondary/tertiary HPT, glands detected by PS had a mean weight of 950 ± 109 mg, whereas the mean weight was 276 ± 34 mg for undetected glands (P < 0.002). Conclusions Parathyroid scintigraphy is a sensitive study for localizing parathyroid glands preoperatively in primary HPT patients. Its sensitivity is low in secondary and tertiary HPT patients. Thus PS has limited value as a preoperative localization study in secondary/tertiary HPT patients.     

Thyroid Cancer Detection with Dual-isotope Parathyroid Scintigraphy in Primary Hyperparathyroidism

Background  

Thyroid cancer cells have been shown to take up ^99mTc-sestamibi. The role for ^99mTc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer.     

Initial Parathyroid Surgery in 606 Patients with Renal Hyperparathyroidism

Background  

The aim of the present study was to evaluate the outcome of different surgical procedures for patients on permanent dialysis who underwent initial parathyroidectomy for renal hyperparathyroidism (rHPT).     

Bilateral Internal Jugular Venous Sampling for Parathyroid Hormone Determination in Patients with Nonlocalizing Primary Hyperparathyroidism

Background  

Focused parathyroidectomy (FP) is offered to 60% to 70% of patients presenting to our unit with primary hyperparathyroidism (PHPT). A recent report identified bilateral internal jugular venous sampling (BIJVS) as a useful tool for localization of parathyroid adenomas in patients with scan-negative PHPT. The purpose of this study was to evaluate the utility of this approach in a clinical setting.     

Stepwise Approach for Parathyroid Localisation in Primary Hyperparathyroidism

World Journal of Surgery - Primary hyperparathyroidism (PHPT) is a relatively common condition in surgical practice. Availability of localisation studies has shifted the treatment from bilateral...     

Preoperative Imaging for Parathyroid Localization in Primary Hyperparathyroidism

Background : We retrospectively studied the results of diagnostic imaging using 3 different modalities to determine their usefulness for preoperative localization of the parathyroid, and whether accurate preoperative localization information could be used to modify the surgical approach for parathyroidectomy in patients with primary hyperparathyroidism.
Methods : Images of 37 parathyroid adenomas or hyperplasias in 35 patients with primary hyperparathyroidism were obtained using ultrasonography, computed tomography, and subtraction scintigraphy (using thallium 201 [thallous chloride] and either iodine 123 or technetium 99m pertechnetate [^99mTcO₄]).
Results : Approximately three fourths of the adenomas or hyperplasias were successfully identified by ultrasound (76.7%) and computed tomography (76.4%), even when the weight of the tumor was less than 500 mg. However, subtraction scintigraphy was of limited use (61.3% successfully identified). A combination of these modalities gave excellent results for detecting adenomas and hyperplasias, leading to an accurate prediction rate of 96.0%.
Conclusion : We conclude that using the combination of these 3 imaging modalities is very useful for the detection of parathyroid adenomas and hyperplasias, and that with such accurate localization information, the unilateral approach alone, or even simple excision of the parathyroid tumors might be feasible, enabling less invasive surgical treatment.     

In Vitro Parathyroid Hormone Release in Patients with Secondary Hyperparathyroidism

Background: The purpose of this study was to determine the precise endocrim. characteristics of parathyroid function in secondary hyperparathyroidism (sHPT).
Methods: We examined the effects of extracellular ionized calcium (Ca²⁺) varying from 0.5 to 2.0 mM on parathyroid hormone (PTH) release in parathyroid cell suspensions using a mid-regional PTH assay. Cells were obtained from 26 patients with sHPT who were divided into two groups according to the type of hyperplasia they exhibited, either nodular (n=16) or diffuse [n= 10). For compdrison, we also analyzed data from nine patients with primary hyperparathyroidism (pHPT; adenomas).
Results: Significant in vitro suppression of PTH release by Ca²⁺ was observed in the majority of subjects, regardless of the histologic abnormality. The pHPT group exhibited no significant relationship between clinical and in vitro data. In contrast, in the sHPT group (taken as a whole), suppression of PTH release by Ca²⁺ exhibited a plateau at a total serum calcium concentration of 2.5 mmol/L, and a parathyroid gland weight of 2 g.
Conclusions: These findings suggest that there is a curvilinear relationship in sHPT, but not pHPT, between the in vitro calcium sensitivity of parathyroid cells and total serum calcium, as well as gland weight. The in vitro calcium sensitivity in sHPT remains constant when the total serum calcium concentration exceeds 2.5 mmol/L, or when the gland weight exceeds 2 g.     

25-Hydroxyvitamin D Status Does Not Affect Intraoperative Parathyroid Hormone Dynamics in Patients with Primary Hyperparathyroidism

Background  

Deficiency of 25-hydroxyvitamin D (25OHD) is a stimulus for the secretion of parathyroid hormone (PTH). During surgery for primary hyperparathyroidism, 25OHD deficiency may artificially elevate PTH, decreasing the sensitivity of intraoperative PTH (ioPTH) measurements.