Are preoperative sestamibi scans useful for identifying ectopic parathyroid glands in patients with expected multigland parathyroid disease?

BACKGROUND: The role of preoperative localization studies in patients with hyperparathyroidism and expected multigland disease remains poorly defined. Our study investigates the usefulness of obtaining preoperative sestamibi scans and ultrasonography of the neck in identifying ectopic glands in this group of patients. METHODS: Under Institutional Review Board approval, we performed a retrospective review of patients who underwent operation for secondary hyperparathyroidism, tertiary hyperparathyroidism, lithium-induced hyperparathyroidism, and multiple endocrine neoplasia syndrome at a tertiary institution between 2004 and 2015. We reviewed patient demographics, laboratory, radiology, pathology, and operative reports. RESULTS: Of 2,975 parathyroidectomies performed during this period, 154 operations were performed in 149 patients who met the criteria. Of the 149 patients, 82 (55.0%) had secondary, 31 (20.8%) had tertiary, 23 (15.4%) had lithium-induced HPT, and 13 (10.1%) had multiple endocrine neoplasia syndrome; 86 ectopic glands were identified in 64 patients (43.0%). Sensitivity for identification of ectopic glands was 29% for sestamibi scan and 7% for ultrasonography, while 89% of mediastinal glands were localized by sestamibi scans and thoracotomy, thoracoscopy, or sternotomy occurred in 4.7% of patients. CONCLUSION: We found a greater rate of preoperative localization of ectopic glands than reported previously. Because the sensitivity of sestamibi for identification of ectopic glands is 23.0%, the implication of missing mediastinal glands warrants preoperative imaging.

Association of BRAF V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers.

BACKGROUND: Studies have demonstrated an association of the BRAF(V600E) mutation and microRNA (miR) expression with aggressive clinicopathologic features in papillary thyroid cancer (PTC). Analysis of BRAF(V600E) mutations with miR expression data may improve perioperative decision making for patients with PTC, specifically in identifying patients harboring central lymph node metastases (CLNM). METHODS: Between January 2012 and June 2013, 237 consecutive patients underwent total thyroidectomy and prophylactic central lymph node dissection (CLND) at four endocrine surgery centers. All tumors were tested for the presence of the BRAF(V600E) mutation and miR-21, miR-146b-3p, miR-146b-5p, miR-204, miR-221, miR-222, and miR-375 expression. Bivariate and multivariable analyses were performed to examine associations between molecular markers and aggressive clinicopathologic features of PTC. RESULTS: Multivariable logistic regression analysis of all clinicopathologic features found miR-146b-3p and miR-146b-5p to be independent predictors of CLNM, while the presence of BRAF(V600E) almost reached significance. Multivariable logistic regression analysis limited to only predictors available preoperatively (molecular markers, age, sex, and tumor size) found miR-146b-3p, miR-146b-5p, miR-222, and BRAF(V600E) mutation to predict CLNM independently. While BRAF(V600E) was found to be associated with CLNM (48% mutated in node-positive cases vs. 28% mutated in node-negative cases), its positive and negative predictive values (48% and 72%, respectively) limit its clinical utility as a stand-alone marker. In the subgroup analysis focusing on only classical variant of PTC cases (CVPTC), undergoing prophylactic lymph node dissection, multivariable logistic regression analysis found only miR-146b-5p and miR-222 to be independent predictors of CLNM, while BRAF(V600E) was not significantly associated with CLNM. CONCLUSION: In the patients undergoing prophylactic CLNDs, miR-146b-3p, miR-146b-5p, and miR-222 were found to be predictive of CLNM preoperatively. However, there was significant overlap in expression of these miRs in the two outcome groups. The BRAF(V600E) mutation, while being a marker of CLNM when considering only preoperative variables among all histological subtypes, is likely not a useful stand-alone marker clinically because the difference between node-positive and node-negative cases was small. Furthermore, it lost significance when examining only CVPTC. Overall, our results speak to the concept and interpretation of statistical significance versus actual applicability of molecular markers, raising questions about their clinical usefulness as individual prognostic markers.

Lower vitamin D levels in surgical hyperparathyroidism versus thyroid patients.

Low vitamin D levels have been shown to be associated with primary hyperparathyroidism, but it is unclear whether vitamin D deficiency may be an etiologic factor in the development of primary hyperparathyroidism. To investigate this, we compared preoperative vitamin D levels of patients undergoing surgery for primary hyperparathyroidism with those of patients undergoing surgery for benign thyroid disease. With Institutional Review Board approval, data were collected prospectively on patients undergoing parathyroidectomy or thyroidectomy by one surgeon between March 2006 and July 2011. Patients were excluded if they underwent simultaneous thyroid and parathyroid surgery, had secondary or tertiary hyperparathyroidism, if no preoperative vitamin D level was measured, or if they took vitamin D supplements. Inclusion criteria were met by 219 patients who underwent parathyroidectomy and 186 patients who underwent thyroid surgery. Patient age, sex, race, and preoperative vitamin D levels (vitamin D 25-OH; normal, 32 to 100 pg/mL) were collected. Statistical analysis was performed using linear regression. Vitamin D levels were significantly lower in the parathyroid group compared with the thyroid group (23.8 vs 28.5 pg/mL; P < 0.001). This difference was also observed after adjustment for age, sex, and race with a mean difference of 4.87 pg/mL (P < 0.001). Statistically significant associations between lower vitamin D levels and patients younger than 50 years (P = 0.048), male sex (P = 0.03), and nonwhite race were identified (P < 0.001). Patients with primary hyperparathyroidism are more likely to have lower vitamin D levels than a control surgical population. Further study is needed to determine whether low vitamin D levels may be an etiologic factor associated with the development of hyperparathyroidism.

DNA copy number variations characterize benign and malignant thyroid tumors.

CONTEXT: Fine-needle aspiration (FNA) is the best diagnostic tool for preoperative evaluation of thyroid nodules but is often inconclusive as a guide for surgical management. OBJECTIVE: Our hypothesis was that thyroid tumor subtypes may show characteristic DNA copy number variation (CNV) patterns, which may further improve the preoperative classification. DESIGN: Our study cohorts included benign follicular adenomas (FAs), classic papillary thyroid carcinomas (PTCs), and follicular variant PTCs (FVPTCs), the three subtypes most commonly associated with inconclusive preoperative cytopathology. SETTING: Tissue and FNA samples were obtained at an academic tertiary referral center. PATIENTS: Cases were identified that underwent partial or complete thyroidectomy for malignant or indeterminate thyroid lesions between 2000 and 2008 and had adequate snap-frozen tissue. INTERVENTIONS: Pairs of tumor tissue and matching normal thyroid tissue-derived DNA were compared using 550K single-nucleotide polymorphism arrays. MAIN OUTCOME MEASURE: Statistically significant differences in CNV patterns between tumor subtypes were identified. RESULTS: Segmental amplifications in chromosomes (Ch) 7 and 12 were more common in FAs than in PTCs or FVPTCs. Additionally, a subset of FAs and FVPTCs showed deletions in Ch22. We identified the 5 CNV-associated genes best at discriminating between FAs and PTCs/FVPTCs, which correctly classified 90% of cases. These 5 Ch12 genes were validated by quantitative genomic PCR and gene expression array analyses on the same patient cohort. The 5-gene signature was then successfully validated against an independent test cohort of benign and malignant tumor samples. Finally, we performed a feasibility study on matched FA-derived intraoperative FNA samples and were able to correctly identify FAs harboring the Ch12 amplification signature, whereas FAs without amplification showed a normal Ch12 signature. CONCLUSIONS: Thyroid tumor subtypes possess characteristic genomic profiles that may further our understanding of structural genetic changes in thyroid tumor subtypes and may lead to the development of new diagnostic biomarkers in FNA samples.

Is BRAF mutation associated with lymph node metastasis in patients with papillary thyroid cancer?

BACKGROUND: Some have proposed using V600E BRAF mutation status to dictate the surgical management of patients with papillary thyroid cancer (PTC). However, well-designed studies examining BRAF association with aggressive clinicopathologic features of PTC, including the presence of lymph node metastases (LNM), in patients who have undergone routine central lymph node dissection (CLND), are lacking. METHODS: Under institutional review board approval, 63 patients diagnosed with PTC on fine-needle aspiration who underwent total thyroidectomy and CLND were included. BRAF mutation status was determined in fresh frozen or intraoperative fine-needle aspiration samples with a colorimetric assay. Associations between BRAF mutation status and clinicopathologic features of PTC were examined using Chi-square and multivariate logistic regression analyses. RESULTS: BRAF mutation was found to be significantly associated with race only on Chi-square analysis. BRAF mutation was not found to be significantly associated with the presence of LNM (P = .167). On multivariate analysis, only size and venous/lymphatic invasion were significantly associated with LNM. CONCLUSION: This small series underscores the prematurity in utilizing BRAF mutation status to determine the surgical management of patients with PTC, specifically whether or not to perform a CLND.

Three-gene molecular diagnostic model for thyroid cancer.

BACKGROUND: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. METHODS: Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. RESULTS: Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. CONCLUSIONS: Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

Tumor size and presence of calcifications on ultrasonography are pre-operative predictors of lymph node metastases in patients with papillary thyroid cancer.

BACKGROUND AND OBJECTIVES: Lymph node metastases in papillary thyroid cancer (PTC) are common and their presence can significantly alter the treatment for patients with PTC. We therefore sought to identify pre-operative predictors of lymph node metastases in patients with PTC. METHODS: A thyroid tumor database was queried to identify patients with a pre-operative diagnosis of PTC and underwent thyroidectomy between January 2006 and August 2009. One hundred and three patients who had a pre-operative ultrasound and had lymph nodes surgically resected were identified. Clinical factors and tumor ultrasound characteristics were recorded. The pre-operative ultrasound results, type of operation, and final pathology results were also recorded. RESULTS: Of the 103 patients, 74 (72%) were women and 29 (28%) were men with an age range of 15-78 years (median age of 43). Of the ultrasound characteristics evaluated only calcifications (P = 0.007) and size (P = 0.003) were statistically associated with positive cervical lymph nodes. None of the other demographic or clinical factors were significantly associated with lymph node metastases. CONCLUSIONS: Thyroid nodule size and presence of calcifications on ultrasound were found to have a statistically significant association with lymph node metastases in patients with PTC. This information could be used to guide the surgical management of these patients.

Telomere length is related to alternative splice patterns of telomerase in thyroid tumors.

Telomere dysfunction and aberrant telomerase expression play important roles in tumorigenesis. In thyroid tumors, three possibly inhibitory splice variants of the active full-length isoform of human telomerase reverse transcriptase (hTERT) may be expressed. These variants might regulate telomerase activity and telomere length because it is the fraction of the full-length isoform, rather than the total transcript level, that correlates with enzymatic activity. Telomerase reactivation may be critical in the early stages of tumorigenesis, when progressive telomere shortening may be limiting cell viability. The aim of this study was to investigate the relationship between telomere length and hTERT splice variant expression patterns in benign and well-differentiated malignant thyroid tumors. Telomere lengths of 61 thyroid tumors were examined by fluorescence in situ hybridization, comparing tumors with adjacent normal thyroid tissue on the same slide. Expression patterns of hTERT splice variants were evaluated by quantitative and nested RT-PCR. Telomere length was inversely correlated with percentage of full-length hTERT expression rather than with total hTERT expression levels. Short telomeres and high fractions of full-length hTERT transcripts were associated with follicular and papillary thyroid carcinomas, whereas long telomeres and low levels of full-length hTERT were associated with benign thyroid nodules. Intermediate levels of full-length hTERT and telomere length were found in follicular variant of papillary thyroid carcinomas and follicular adenomas.

Chasing "shadows": discovering the subtleties of sestamibi scans to facilitate minimally invasive parathyroidectomy.

BACKGROUND: With the advent of sestamibi scans, high-resolution ultrasonography (US), and intraoperative intact parathyroid hormone (PTH) measurements, minimally invasive parathyroidectomy (MIP) is considered the standard of care for patients with primary hyperparathyroidism (PHPT). Preoperative imaging, however, can be negative more than 20% of the time. METHODS: We chose to examine one surgeon's experience with patients who presented with PHPT and negative or indeterminate preoperative imaging from July 1993 to September 2009. A retrospective review of a parathyroid surgery database and patient records was conducted to collect the following information: patient age and sex; calcium and PTH levels; sestamibi and US results; and operative reports. Each sestamibi scan had been re-reviewed preoperatively by the surgeon with a nuclear medicine physician. The study cohort included patients with negative or indeterminate sestamibi results and a negative or no US report in which the surgeon was able to identify a "shadow" or subtlety on sestamibi and plan an MIP. RESULTS: A total of 126 patients had a negative or indeterminate sestamibi scan and a negative or no US report. "Shadows" or subtleties were found in 18 of 44 (41%) of the cases with a negative sestamibi and in 62 of 82 (76%) of cases with an indeterminate sestamibi scan. For these 80 cases a MIP was planned. In all, 7 of 80 (9%) were converted to a bilateral exploration. The remaining 46 patients underwent a planned bilateral exploration. Cure rates were comparable: 99% in the study group compared to 97% in the group who underwent a planned or converted bilateral exploration. CONCLUSIONS: With careful preoperative re-review of a negative or indeterminate sestamibi scan and the identification of subtleties in patients with a negative preoperative US scan, a successful MIP can be performed 91% of the time with a 98% cure rate.

Evaluation for concomitant thyroid nodules and primary hyperparathyroidism in patients undergoing parathyroidectomy or thyroidectomy.

BACKGROUND: Previous investigators have reported the incidence of thyroid nodules in patients with primary hyperparathyroidism; others have noted the incidence of primary hyperparathyroidism in patients who underwent thyroidectomy. It is well known that both of these entities coexist. In this article, we present a single-center experience with the incidence of concomitant thyroid nodular disease and primary hyperparathyroidism in patients who underwent parathyroidectomy or thyroidectomy. METHODS: From May 2006 to December 2007, 526 patients underwent thyroidectomy, parathyroidectomy, or both. Operations were performed by surgeons in the Johns Hopkins Endocrine Surgery Section after screening preoperatively for concomitant thyroid nodular disease or primary hyperparathyroidism. RESULTS: Among the 200 patients who underwent a parathyroidectomy, 102 (51.0%) were found to have thyroid nodular disease. Six percent of these 200 patients also had a thyroid malignancy. Of the 326 patients who were primarily seen for thyroid disease, the incidence of primary hyperparathyroidism was 3.1%. CONCLUSION: By implementing a comprehensive approach to patients who present with thyroid disease or primary hyperparathyroidism, concomitant pathology may be elucidated preoperatively. This approach will facilitate the detection of otherwise unsuspected thyroid cancer and hyperparathyroidism as well as prevent unnecessary reoperative surgery.

African Americans present with more severe primary hyperparathyroidism than non-African Americans.

BACKGROUND: Similar to other disease states, we postulated that African American patients present with more severe signs of primary hyperparathyroidism than non-African Americans. To test this hypothesis, we compared relevant preoperative laboratory values, sestamibi scan results, and intraoperative findings between African American and non-African American patients with primary hyperparathyroidism who underwent parathyroidectomy between January 2002 and May 2007. METHODS: In all, 588 patients were included and 113 (19%) were African American. A linear model was used to examine the effect of race with respect to mean differences in serum calcium, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), alkaline phosphatase (ALKP) levels, gland weight, presence of double adenomas and, sestamibi scan sensitivity. RESULTS: Adjusted for age and gender, African Americans exhibited significantly higher median calcium (11.36 [SD = 0.91] vs 11.06 [SD = 0.72] mg/dL, P < .001), iPTH (138.5 [SD = 166.03] vs 117 [73.22] pg/mL, P < .01), and ALKP (101 [SD = 57.86] vs 90.5 [SD = 29.78] U/L, P < .01) levels compared with non- African Americans. They exhibited significantly lower median serum 25(OH)D (14 [SD = 9.36] vs 23 [SD = 12.160] ng/mL, P < .001), greater gland weight (P < .001), a higher probability of double adenomas (odds ratio = 2.83, 95% confidence interval [CI], 1.36-5.88), and a higher probability of presenting with a positive sestamibi scan (odds ratio = 4.99, 95% CI = 2.44-10.19) compared with non-African Americans. CONCLUSION: African Americans present with more advanced signs of primary hyperparathyroidism than non-African Americans. These results may reflect less access to health care, surgical consultations, or other unidentified factors. These highly significant findings, however, warrant additional investigation.

Correlation of plasma 25-hydroxyvitamin D levels with severity of primary hyperparathyroidism and likelihood of parathyroid adenoma localization on sestamibi scan.

OBJECTIVES: To determine the relationship between preoperative plasma 25-hydroxyvitamin D (25[OH]D) levels and severity of primary hyperparathyroidism (PHPT) and to explore whether presurgical 25(OH)D levels could predict the likelihood of positive results on technetium Tc 99m sestamibi scintigraphy. DESIGN: Retrospective analysis. SETTING: Tertiary university referral center. PATIENTS: A total of 421 consecutive patients underwent preoperative sestamibi scintigraphy and parathyroid exploration. Patients with cholecalciferol (vitamin D) deficiency, defined as plasma levels lower than 25 ng/mL, were compared with patients having no vitamin D deficiency. We explored the relationship between 25 (OH)D levels and intact parathyroid hormone (iPTH) levels, alkaline phosphatase (ALKP) levels, adenoma weight, binary sestamibi scan results, and postoperative serum calcium levels (at 1 week and 6 months). MAIN OUTCOME MEASURES: We hypothesized that severity of hypovitaminosis D would correlate with severity of PHPT and predict the likelihood of a positive finding on sestamibi scan. RESULTS: Concentrations of iPTH and ALKP and parathyroid adenoma weight were significantly higher in patients with lower 25(OH)D levels (P < .01 for all). Patients with hypovitaminosis D had a greater percentage decrease in serum calcium levels 1 week and 6 months postoperatively (P < .05). Median 25(OH)D levels were lower in patients with positive sestamibi scan results (P < .001). CONCLUSIONS: Patients with hypovitaminosis D present with more advanced indices of PHPT. Parathyroid sestamibi scanning is more likely to show positive results for this subset of patients who may then benefit from sestamibi scan-directed surgical intervention.

A diagnostic predictor model for indeterminate or suspicious thyroid FNA samples.

BACKGROUND: The management of patients with thyroid fine-needle aspiration (FNA) specimens that are neither benign nor malignant still remains problematic. Efforts to improve their management have focused on identifying risk factors that predict malignancy. This study seeks to identify clinical and tumor characteristics that predict thyroid malignancy among patients with indeterminate or suspicious FNA and to develop a diagnostic predictor model. METHODS: The records of 639 patients with an indeterminate or suspicious thyroid FNA between January 1995 and April 2005 were reviewed. Patient and tumor characteristics were evaluated for their potential to predict malignancy in the final surgical histopathology. A diagnostic predictor model was designed based on statistically significant predictors. Patients seen between April 2005 and April 2007 were used to validate the model. RESULTS: Patient age, nodule size, and FNA cytopathology were identified as risk factors. Patients at extremes of age were at increased risk. Patients 50 years of age had the lowest risk of malignancy. For patients less than age 50, the risk increased 3% for each year decrease in age (p = 0.001). After 50, the risk increased 3.4% for each year increase in age (p = 0.016). Nodules 2.5 cm had the lowest likelihood of malignancy. For smaller nodules, the risk increased 53% per cm decrease in size (p < 0.001). For larger nodules, the risk increased 39% per cm increase (p < 0.001). Patients with FNA cytology suspicious for papillary thyroid carcinoma had the greatest risk of malignancy (p < 0.001). CONCLUSIONS: A predictor model was created using the variables age, nodule size, and FNA cytology to predict thyroid malignancy.

Differentiating alternative splice variant patterns of human telomerase reverse transcriptase in thyroid neoplasms.

BACKGROUND: Although fine-needle aspiration (FNA) biopsy of thyroid nodules is very sensitive in detecting thyroid malignancy, it remains ambiguous in 20-30% of cases. Current biomarkers for thyroid cancer lack either the sensitivity or specificity to substantially address this clinical problem. The aim of this study was to investigate the gene expression patterns of human telomerase reverse transcriptase (hTERT) alternative splice variants in benign and malignant thyroid tumors in an attempt to find a more reliable biomarker in the differential diagnosis of thyroid nodules. METHODS: One hundred and thirty-three thyroid tumors from eight histopathological tumor types were collected from patients undergoing thyroid surgery at Johns Hopkins Hospital. Gene expression patterns of hTERT alternative splice variants were investigated in the tumors by nested reverse transcriptase-PCR. Telomerase enzyme activity was evaluated in a subset of 16 samples associated with the different hTERT patterns. Association of c-myc expression and hTERT patterns was also examined. RESULTS: Malignant thyroid tumors exhibited a greater proportion of the active full-length hTERT transcript (0.57 +/- 0.15) than inactive splice variants, alpha(-) (0.13 +/- 0.02), or beta(-)/alpha(-)beta(-) deletion transcripts (0.30 +/- 0.11; p < 0.001). The opposite was observed in benign tumors, which exhibited greater proportions of beta(-)/alpha(-)beta(-) deletion transcripts (0.64 +/- 0.08) than either the full-length (0.19 +/- 0.06) or alpha(-) deletion transcripts (0.17 +/- 0.02; p < 0.001). Similar results were observed among a diagnostically challenging subset of 50 thyroid tumors that were suspicious for malignancy on FNA. Further, increased telomerase enzymatic activity was only associated with expression of the full-length hTERT isoform. In contrast, c-myc expression, which has been implicated in hTERT regulation, correlated with overall hTERT transcription without specificity for expression of the full-length isoform. CONCLUSIONS: These differences in gene expression patterns of hTERT alternative splice variants may provide a useful adjunct to FNA diagnosis of suspicious thyroid tumors.

Identification of genes differentially expressed in benign versus malignant thyroid tumors.

PURPOSE: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. EXPERIMENTAL DESIGN: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. RESULTS: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription-PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription-PCR data. CONCLUSIONS: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.

25-hydroxyvitamin D deficiency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy.

BACKGROUND: Patients with primary hyperparathyroidism who undergo minimally invasive parathyroidectomy (MIP) may have postoperative symptoms of hypocalcemia or secondary hyperparathyroidism. This study sought to identify factors predictive of these events. METHODS: Between 1998 and 2004, 190 patients with primary hyperparathyroidism underwent MIP with excision of a single adenoma. Age, gender, race, prior head and neck surgery, use of preoperative thyroid hormone or calcium-channel blockers, preoperative levels of calcium, 25-hydroxyvitamin D (25[OH]D) and intact parathyroid hormone (iPTH), the presence of osteopenia or osteoporosis, intraoperative iPTH levels, and adenoma weight were evaluated by univariate analysis as predictors of postoperative symptoms of hypocalcemia and secondary hyperparathyroidism. RESULTS: None of the following were predictors of postoperative symptoms of hypocalcemia: age, gender, race, prior head and neck surgery, preoperative medications, preoperative calcium and iPTH levels, osteopenia or osteoporosis, intraoperative iPTH levels, or adenoma weight. However, patients with postoperative symptoms of hypocalcemia had significantly lower preoperative 25[OH]D levels (P = .01). Further, higher preoperative iPTH levels (P < .01) and lower preoperative 25[OH]D levels (P = .05) were associated with secondary hyperparathyroidism postoperatively. CONCLUSIONS: A low preoperative 25[OH]D level is associated with postoperative symptoms of hypocalcemia and secondary hyperparathyroidism in patients undergoing MIP. One might consider instituting empiric calcium supplementation postoperatively in patients with low 25[OH]D levels.

Interpretation of 99mTc sestamibi parathyroid SPECT scan is improved when read by the surgeon and nuclear medicine physician together.

OBJECTIVE: Parathyroid gland localization and lateralization are important before surgery, particularly for minimally invasive parathyroidectomy (MIP) and recurrent hyperparathyroidism. We hypothesized that readings of Tc sestamibi scans with single photon emission computed tomography (SPECT) by a surgeon and nuclear medicine physician together (NMP+S) compared to a nuclear medicine physician alone (NMP alone) might affect scan interpretation accuracy. METHODS: Between May 1999 and December 2002, 127 hyperparathyroid patients had preoperative localization with sestamibi SPECT. Scans were prospectively interpreted by an endocrine surgeon and nuclear medicine physician attending together (NMP+S) and a nuclear medicine physician attending alone (NMP alone). These readings were compared to intra-operative findings, which served as the 'gold standard'. RESULTS: There were 120 patients with primary hyperparathyroidism (55 underwent MIP) and seven with secondary or tertiary hyperparathyroidism; seven patients had recurrent hyperparathyroidism. Of 127 patients, 83 had single adenomas; 27, double adenomas; 15, hyperplasia; one, MENIIA; and one, parathyroid cancer. Sensitivity and positive predictive values were 58.6% and 67.4% for NMP alone compared to 81.9% and 70.0% for NMP+S. The overall accuracy of correct localization was 45.7% vs. 60.6% (P<0.01) and of correct lateralization was 69.3% vs. 80.3% (P<0.01) for NMP alone versus NMP+S respectively. The most common finding interpreted incorrectly by NMP alone and correctly by NMP+S was an ectopic superior parathyroid adenoma in the inferior position. Ninety-eight per cent of patients were cured of their hyperparathyroidism. CONCLUSIONS: Parathyroid sestamibi SPECT scan interpretation by an endocrine surgeon reading with a nuclear medicine attending resulted in improved accuracy of gland localization and lateralization compared to a nuclear medicine attending reading alone. This improvement may be due to increased awareness of clinical factors and head-and-neck anatomy.

Using gene expression profiling to differentiate benign versus malignant thyroid tumors.

DNA microarrays allow quick and complete evaluation of a cell's transcriptional activity. Expression genomics is very powerful in that it can generate expression data for a large number of genes simultaneously across multiple samples. In cancer research, an intriguing application of expression arrays includes assessing the molecular components of the neoplastic process and utilizing the data for cancer classification (Miller LD, et al. Cancer Cell 2002;2:353-61). Classification of human cancers into distinct groups based on their molecular profile rather than their histological appearance may prove to be more relevant to specific cancer diagnoses and cancer treatment regimes. Several attempts to formulate a consensus about classification and treatment of thyroid carcinoma based on standard histopathological analysis have resulted in published guidelines for diagnosis and initial disease management (Sherman SI. Lancet 2003;361:501-11). In the past few decades, no improvement has been made in the differential diagnosis of thyroid tumors by fine needle aspiration biopsy, specifically suspicious or indeterminate thyroid lesions, suggesting that a new approach to this should be explored. Therefore, in this study, we developed a gene expression approach to diagnose benign versus malignant thyroid lesions in 73 patients with thyroid tumors. We successfully built a 10 and 6 gene model able to differentiate benign versus malignant thyroid tumors. Our results support the premise that a molecular classification system for thyroid tumors is possible, and this in turn may provide a more accurate diagnostic tool for the clinician managing patients with suspicious thyroid lesions.

Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism.

BACKGROUND: Technetium 99m ( 99m Tc)-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) is frequently used in the evaluation of patients with hyperparathyroidism. Calcium channel blockers (CACBs) may affect 99m Tc-MIBI uptake by parathyroid cells. This study examines the effect of CACB therapy on the sensitivity of 99m Tc-MIBI SPECT localization for hyperparathyroidism. METHODS: Two hundred fifty-three operated patients with hyperparathyroidism were retrospectively reviewed. The potential effect of CACB therapy on 99m Tc-MIBI scan sensitivity was examined by using logistic regression analysis. Possible confounding factors were considered. RESULTS: Among 235 patients, those with multiple endocrine neoplasia, type I (MEN-I), MEN-IIA, 4-gland hyperplasia, secondary hyperparathyroidism, and tertiary hyperparathyroidism exhibited no difference associated with CACB use. Of the remaining 198 patients with primary hyperparathyroidism, 7/30 (23%) with negative 99m Tc-MIBI SPECT scans compared to 24/168 (14%) with positive scans used CACBs. After correcting for age, gender and gland weight, the odds ratio (OR) for a negative study in patients taking CACBs was 2.88 (95% CI, 1.03-8.10; P = .045). Atherosclerosis, hypertension, diabetes mellitus, preoperative calcium and parathyroid hormone levels, and thyroid hormone use were not confounding factors. CONCLUSIONS: CACB therapy reduces the sensitivity of 99m Tc-MIBI parathyroid SPECT in patients with primary hyperparathyroidism. Further studies are required to determine the potential reversibility of this effect with termination of CACB therapy.