Hemithyroidectomy is the preferred initial operative approach for an indeterminate fine needle aspiration biopsy diagnosis.

BACKGROUND: Fine needle aspiration biopsy represents the critical initial diagnostic test used for evaluation of thyroid nodules. Our objectives were to determine the cytological distribution, the utility of clinicopathologic characteristics for predicting malignancy and the true proportion of cancer among individuals who presented with indeterminate cytology and had undergone thyroid surgery for suspicion of cancer. METHODS: We retrospectively reviewed 1040 consecutive primary thyroid operations carried out over an 8-year period at a tertiary care endocrine referral centre. Follicular neoplasm (FN), Hürthle cell neoplasm (HN), neoplasms suspicious for but not diagnostic of papillary carcinoma (IP) and neoplasms with cellular atypia (IA) were reviewed. RESULTS: In all, 380 individuals presented with cytologically indeterminate thyroid nodules. Of these, 252 (66%) patients had FN, 47 (12%) HN, 44 (12%) IP, 26 (7%) IA and 11 (4%) had mixed diagnoses. Biopsied lesions were found to be malignant on pathological evaluation in 102 (27%) patients: 49 (19%) with FN, 11 (23%) HN, 28 (64%) IP and 9 (35%) with IA. Hemithyroidectomy was adequate definitive treatment in 196 of 225 (87%) patients with FN and 39 of 42 (93%) with HN. Significant associations with a cancer diagnosis were identified for smaller tumour size in patients with FN (p = 0.004) and right thyroid lobe location in patients with IP (p = 0.012), although these factors were nonsignificant in the corrected analyses for multiple comparisons. CONCLUSION: In a review of the experience at a Canadian centre, 4 operations were carried out to identify each cancer, and hemithyroidectomy was the optimal initial and definitive surgical approach for most patients.

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

BACKGROUND: The aim of this study was to evaluate the influence of patient and adenoma characteristics on (99m)Tc-methoxy isobutyl isonitrile (MIBI) scan performance in individuals diagnosed with primary hyperparathyroidism (PHP). METHODS: Records of patients undergoing parathyroidectomy for PHP over 6 years at a single center were reviewed. RESULTS: The overall true-positive (TP) rate for (99m)Tc-MIBI scans was 56%. Adenomas sized 1.9 to 3.5 cm were more likely to have TP scans than 0.3-cm to 1.8-cm adenomas (74% vs 40%, P < .001). Preoperative ionized calcium levels between 1.49 and 1.72 mmol/L were more likely to have TPs than levels between 1.27 and 1.48 mmol/L (65% vs 47%, P < .05). No single class of medication was shown to significantly effect TP rates. A decrease in TP rate was observed for larger adenomas in patients on >or=1 medication (74% vs 65%, P = .05). CONCLUSIONS: In PHP, (99m)Tc-MIBI scan positivity is most related to adenoma size and preoperative ionized calcium level.

Intact parathyroid hormone measurement 1 hour after thyroid surgery identifies individuals at high risk for the development of symptomatic hypocalcemia.

BACKGROUND: There is currently no consensus regarding the utilization of intact parathyroid hormone (iPTH) for predicting postthyroid surgery hypocalcemia. The objective of this study was to determine a threshold value for the 1-hour postoperative iPTH level that can identify those patients at significantly increased risk for the development of symptomatic hypocalcemia. METHODS: A prospective study of 21 individuals undergoing either total or completion thyroid operations was performed. One-hour postoperative iPTH levels were drawn along with ionized calcium at 6 hours postoperatively and at 7 am the following morning. Symptoms of hypocalcemia were recorded. RESULTS: Of the 21 patients recruited into the study cohort, there were 18 individuals that developed hypocalcemia (4 symptomatic and 14 asymptomatic) and 3 that remained normocalcemic. The mean iPTH level 1 hour postoperatively was significantly different when comparing the normocalcemic, asymptomatic hypocalcemic, and symptomatic hypocalcemic patient groups (6.50 pmol/L versus 3.76 pmol/L versus 0.7 pmol/L, respectively; P = .007). An iPTH level

The cost-effectiveness of three strategies for the surgical treatment of symptomatic primary hyperparathyroidism.

INTRODUCTION: Modern surgical approaches to the treatment of primary hyperparathyroidism [unilateral neck exploration (UNE) and minimally invasive parathyroidectomy (MIP)] have become commonplace in recent years. However, the cost-effectiveness of these strategies has been questioned since the effectiveness of the gold standard, bilateral neck exploration (BNE), is well established. The objective of our study was to determine the incremental cost effectiveness of UNE and MIP compared with BNE for treatment of primary hyperparathyroidism (HPT). METHODS: Patients presenting to a tertiary endocrine surgical center for treatment of HPT over a 38-month period were included in the study. The primary measure of effectiveness was the rate of postoperative complications (hypocalcemia and paresthesias) observed in our cohort. A decision analytic model was constructed to determine the incremental cost-effectiveness ratios (ICERs) of the UNE and MIP strategies compared with the BNE strategy. Deterministic and probabilistic sensitivity analyses were conducted to evaluate uncertainty around model-based estimates of costs and effectiveness. RESULTS: A total of 94 patients (56 BNEs, 19 UNEs, and 19 MIPs) provided estimates of mean costs (BNE = $4524, UNE = $4784, MIP = $4961) and success rates (BNE = 0.91, UNE = 0.86, MIP = 0.93) for each treatment arm. The gold standard BNE strategy dominated the UNE strategy (lower cost, higher effectiveness) under most model formulations. The MIP strategy had an ICER of $28,439 per complication avoided, which is likely to be above societal willingness to pay to avoid primarily minor postoperative complications. CONCLUSION: Our results suggest that within our institution, and in several different model formulations, bilateral neck exploration remains the cost-effective strategy for the treatment of primary hyperparathyroidism.

Utility of intraoperative parathyroid hormone measurement in predicting postparathyroidectomy hypocalcemia.

OBJECTIVE: To evaluate the role of a standardized intraoperative parathyroid hormone (PTH) assay in predicting postoperative hypocalcemia following parathyroidectomy for primary hyperparathyroidism. STUDY DESIGN: Prospective series of 66 patients undergoing unilateral or bilateral parathyroidectomy between January 2004 and June 2005. SETTING: Tertiary care centre in Vancouver, British Columbia. METHODS: Preoperatively, ionized calcium and PTH levels were recorded. A standardized intraoperative PTH assay was used to measure PTH levels on all patients at the following times: just prior to initial incision (Ti), just prior to adenoma excision (T0), and 5 and 10 minutes after excision (T5 and T10, respectively). Calcium levels were drawn at 8 and 16 hours postoperatively. Clinically significant hypocalcemia was defined as a symptomatic patient or a serum ionized calcium < or = 1.1 mmol/L. MAIN OUTCOME MEASURES: Postoperative hypocalcemia following parathyroidectomy. RESULTS: The incidence of postoperative hypocalcemia was 12% (8 of 66). There was no significant correlation between postoperative hypocalcemia and any of the evaluated factors, including intraoperative values of PTH (all p > .05). The percentage change between ioPTH at Ti and at T10 was, however, significantly associated with the development of postoperative hypocalcemia (odds ratio = 3.47 for a 10% decline, p = .03). CONCLUSIONS: Percentage change in intraoperative PTH levels between the initial incision and at 10 minutes post-parathyroid adenoma excision is a significant predictor of postoperative hypocalcemia following parathyroidectomy for primary hyperparathyroidism.

Anaplastic thyroid carcinoma: expression profile of targets for therapy offers new insights for disease treatment.

BACKGROUND: Anaplastic thyroid cancer is an endocrine malignancy. Its rare and rapidly lethal disease course has made it challenging to study. Little is known regarding the expression by anaplastic tumors of molecular targets for new human anticancer agents that have been studied in the preclinical or clinical setting. The objective of this work was to evaluate the expression profile of anaplastic thyroid tumors for molecular targets for treatment. METHODS: Of the 94 cases of anaplastic thyroid cancers diagnosed and treated in British Columbia, Canada over a 20-year period (1984-2004), 32 cases (34%) had adequate archival tissue available for evaluation. A tissue microarray was constructed from these anaplastic thyroid tumors and immunohistochemistry was utilized to evaluate expression of 31 molecular markers. The markers evaluated were: epidermal growth factor receptor (EGFR), HER2, HER3, HER4, ER, PR, uPA-R, clusterin, E-cadherin, beta-catenin, AMF-R, c-kit, VEGF, ILK, aurora A, aurora B, aurora C, RET, CA-IX, IGF1-R, p53, MDM2, p21, Bcl-2, cyclin D1, cyclin E, p27, calcitonin, MIB-1, TTF-1, and thyroglobulin. RESULTS: A single tumor with strong calcitonin expression was identified as a poorly differentiated medullary carcinoma and excluded from the study cohort. The mean age of the anaplastic cohort was 66 years; 16 patients (51%) were females, and the median patient survival was 23 weeks. A wide range in molecular marker expression was observed by the anaplastic thyroid cancer tumors (0-100%). The therapeutic targets most frequently and most strongly overexpressed by the anaplastic tumors were: beta-catenin (41%), aurora A (41%), cyclin E (67%), cyclin D1 (77%), and EGFR (84%). CONCLUSIONS: Anaplastic thyroid tumors exhibit considerable derangement of their cell cycle and multiple signal transduction pathways that leads to uncontrolled cellular proliferation and the development of genomic instability. This report is the first to comprehensively evaluate a panel of molecular targets for therapy of anaplastic thyroid cancer and supports the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors, which may offer new hope for individuals diagnosed with this fatal thyroid malignancy.

Normocalcemic parathyroid carcinoma: an unusual clinical presentation.

BACKGROUND: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and may be associated with significant disease related morbidity and mortality. Preoperative diagnosis remains a challenge, which may jeopardize appropriate and successful patient treatment. CASE PRESENTATION: We report a case of parathyroid carcinoma diagnosed in a 60-year-old woman that presented with a tender nodule located at the left lower thyroid pole and had been present for several years. Ultrasound examination revealed a 2.7 x 1.6 x 2.7 cm mass within the lower left lobe of the thyroid with cystic and solid areas. Lab measurement of the intact PTH level revealed it to be three times the upper limit of normal and the serum calcium level was within normal limits. A left thyroid lobectomy and isthmusectomy was carried out. Histopathological evaluation was diagnostic for a parathyroid carcinoma. At greater than two years of follow-up, the patient has had no evidence of disease recurrence and her serum PTH and calcium levels have remained within normal. CONCLUSION: Parathyroid carcinoma is a rare endocrine tumor which must be considered in the differential diagnosis of a nodular thyroid mass. En bloc resection remains the treatment of choice for this malignancy. Disease prognosis is influenced by the extent of the initial resection, the presence of metastases, and adequate long-term follow-up.

Detecting and defining hypothyroidism after hemithyroidectomy.

BACKGROUND: The incidence of hypothyroidism after hemithyroidectomy for benign thyroid disease remains uncertain. This study examines the incidence, natural history, and the factors contributing to hypothyroidism after hemithyroidectomy. METHODS: A retrospective review of patients undergoing hemithyroidectomy over 37 months was performed. The incidence of postoperative hypothyroidism was based on thyrotropin values and clinical symptoms. The relationship between hypothyroidism and lymphocytic infiltration of the removed gland was investigated using stepwise logistic regression. RESULTS: Twelve of 66 patients (18%) became biochemically hypothyroid postoperatively. Four of the 12 patients (33%) subsequently became euthyroid without intervention. Of the remaining 8 patients, 4 (50%) had significant lymphocytic infiltration in the resected gland compared with 10 (19%) of the 54 euthyroid patients. Lymphocytic infiltration was associated with hypothyroidism but was age dependent. CONCLUSIONS: A minority of patients become hypothyroid after hemithyroidectomy. Some patients with biochemical hypothyroidism will become euthyroid without intervention. The impact of lymphocytic infiltrate on hypothyroidism after hemithyroidectomy is age dependent.

Selective unilateral parathyroid exploration: an effective treatment for primary hyperparathyroidism.

BACKGROUND: Unilateral neck exploration (UNE) is a well-recognized approach in the treatment of primary hyperparathyroidism (PHP). The objective of this study was to review the success of an approach involving UNE guided by preoperative sestamibi (SM) scanning. METHODS: All data were gathered by retrospective chart review. All patients undergoing surgery for the treatment of primary hyperparathyroidism at a tertiary referral center over a 3-year period were included in the study cohort. RESULTS: Fifty-two of 80 patients (65%) had an SM scan consistent with a solitary adenoma and were eligible for a UNE, with 57.5% (46/80) undergoing a UNE. Seventy-seven of 80 (96.3%) patients were normocalcemic after initial neck exploration. UNE was curative in 50 of 52 (96.2%) UNE eligible patients and required less operative time than bilateral neck exploration (mean, 60 versus 87 minutes). CONCLUSION: Selective unilateral neck exploration, guided by preoperative SM scanning, is an effective surgical approach for the management of primary hyperparathyroidism.