Preoperative High-Resolution Ultrasound for the Assessment of Malignant Central Compartment Lymph Nodes in Papillary Thyroid Cancer.

BACKGROUND: The identification and removal of malignant central compartment lymph nodes (MCLN) is important to minimize the risk of persistent or recurrent local disease in patients with papillary thyroid cancer (PTC). While the diagnostic accuracy of preoperative ultrasound for the assessment of lateral compartment node metastases is well recognized, its role in the identification of central compartment node metastases in patients with PTC is less established. This study delineates the utility of high-resolution ultrasound (HUS) for the assessment of MCLN in patients with PTC. METHODS: A retrospective chart review was performed of 227 consecutive patients who underwent total thyroidectomy for biopsy-proven PTC by a single endocrine surgeon in an academic tertiary care center between 2004 and 2014. Preoperative sonographic results were compared to postoperative pathology reports to determine the accuracy of HUS for the assessment of MCLN. Statistical analysis also included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: HUS identified abnormal central compartment nodes in 51 (22.5%) patients. All 227 patients underwent a careful central compartment node exploration. One hundred and four (45.8%) patients had MCLN identified by surgery, of whom 65 (62.5%) had a negative preoperative central compartment HUS. The sensitivity and specificity of preoperative HUS for the assessment of MCLN were 0.38 and 0.90, respectively. The PPV and NPV were 0.76 and 0.63, with an accuracy of 0.66. CONCLUSION: Preoperative HUS is quite specific for the identification of MCLN in patients with PTC. The present findings emphasize, however, that a negative HUS does not obviate the need for careful exploration of the central compartment to minimize the risk of persistent or recurrent local disease.

No Need to Abandon Focused Unilateral Exploration for Primary Hyperparathyroidism with Intraoperative Monitoring of Intact Parathyroid Hormone.

BACKGROUND: We investigated the rate of persistent and recurrent hyperparathyroidism after focused unilateral exploration (UE) with intraoperative monitoring of intact parathyroid hormone (IOPTH). STUDY DESIGN: A prospective cohort of 915 patients with primary hyperparathyroidism (PHP) underwent parathyroid surgery by a single surgeon from January 2003 to September 2013. A total of 556 patients with at least a single positive preoperative localization by ultrasound (US) and/or sestamibi scan (STS) underwent UE with IOPTH. The criterion for completion of surgery was an IOPTH fall of 50% from the highest intraoperative level and into the normal range 5 to 10 minutes after resection of the localized gland. RESULTS: Fifteen patients had either persistent or recurrent PHP, yielding a 2.7% (95% CI 1.6% to 4.4%) overall recurrence rate based on the refined Wilson method with continuity correction. Four patients had persistent PHP. Three of these patients were cured with reoperation, and the fourth patient was followed nonoperatively. Eleven patients had recurrent PHP, with 5 corrected by surgery and 6 patients followed nonoperatively. The mean postoperative serum calcium (Ca) level was 9.4 mg/dL over a mean follow-up interval of 44.0 months. Preoperative localization rates by each localization study were: US 74.3% (n = 413), STS 86.9% (n = 483), and US and STS 71.4% (n = 397). There was no difference in the preoperative study that localized the hyperfunctional parathyroid gland in recurrent vs nonrecurrent patients by the Fisher's exact test (US, p =1.00; STS, p =0.65; US and STS, p =1.00). CONCLUSIONS: The low rate of recurrent PHP after focused unilateral exploration with IOPTH suggests that this procedure should not be abandoned.

The utility of 4-dimensional computed tomography for preoperative localization of primary hyperparathyroidism in patients not localized by sestamibi or ultrasonography.

BACKGROUND: To determine the sensitivity and clinical application of 4-dimensional computed tomography (4D CT) for the localization of patients with primary hyperparathyroidism when ultrasonography (US) and sestamibi scans (STS) are negative. METHODS: We compiled a database of 872 patients with primary hyperparathyroidism who underwent parathyroid operation by a single surgeon from January 2003 to September 2013. Seventy-three patients who failed to have positive localization by US or STS were identified. Thirty-six underwent operation without a preoperative 4D CT, and 37 underwent operation after 4D CT. RESULTS: In patients not localized by US or STS, 4D CT was 89% sensitive in localizing an abnormal parathyroid gland when reviewed blindly by a radiologist specializing in endocrine localization studies, yielding a positive likelihood ratio of 0.89 and positive predictive value of 74%. Sensitivity, positive likelihood ratio, and positive predictive value for correct gland lateralization were 93%, 0.93, and 80%. The average size of parathyroid glands removed after preoperative localization by 4D CT was 404 mg and 0.57 cm3 (SD = 280, 0.64), compared with 259 mg and 0.39 cm3 (SD = 166, 0.21) in patients not localized by 4D CT. A focused, unilateral exploration was performed in 38% of patients with preoperative localization by 4D CT compared with 19% of patients without 4D CT (χ2 = 3.0, P = .041). CONCLUSION: 4D CT provided a positive localization in a clinically substantial number of patients not able to be localized by US or STS, which enabled an increased rate of successful, focused, unilateral operations compared with patients who did not undergo a 4D CT.

Image-guided ablation of postsurgical locoregional recurrence of biopsy-proven well-differentiated thyroid carcinoma.

PURPOSE: To evaluate the clinical outcomes of ultrasound-guided percutaneous radiofrequency (RF) ablation and percutaneous ethanol injection (PEI) as salvage therapy for locoregional recurrence after resection of well-differentiated thyroid carcinoma. MATERIALS AND METHODS: There were 42 locoregional, biopsy-proven, papillary and follicular thyroid carcinoma lesions (0.5-3.7 cm) treated, 21 with RF ablation and 21 with PEI. Of treated lesions, 35 were located in the lateral compartments, and 7 were located in the central compartment. Data points in the retrospective analysis, determined beforehand by the investigators, were progression at the ablation site, serum thyroglobulin levels before and after the procedure, and procedural complications. RESULTS: Average follow-up after RF ablation was 61.3 months and after PEI was 38.5 months. No progression was detected in the region of ablation for any of the lesions treated with RF ablation. Local progression was detected 4-11 months after ablation in 5 of the 21 lesions treated with PEI, 3 in the lateral compartment and 2 in the central compartment; all of the lesions were successfully retreated with repeat PEI, RF ablation, or surgery. Permanent vocal cord paralysis occurred after one RF ablation procedure of a lateral compartment supraclavicular node. There were no complications after PEI. CONCLUSIONS: This case series provides long-term follow-up evidence of the safety and efficacy of ultrasound-guided RF ablation and PEI for control of locoregional recurrence of well-differentiated thyroid carcinoma after surgery.

Level VI lymph node dissection does not decrease radioiodine uptake in patients undergoing radioiodine ablation for differentiated thyroid cancer.

BACKGROUND: In patients with well-differentiated thyroid cancer, the incidence of pathologic central compartment lymph node metastases is reported to be approximately 50%. Recently level VI lymph node dissection has been advocated as a means of reducing recurrence rates in these patients, even if there are no clinically apparent nodal metastases. This study investigates whether level VI lymph node dissection decreases the percent radioiodine uptake when patients undergo radioiodine ablation. METHODS: All thyroid cancer patients entered into the endocrine surgery database at a tertiary care center from 2006 to 2010 were reviewed. Those treated with radioactive iodine were analyzed with respect to performance of a central compartment lymph node dissection and the percent uptake of radioiodine ((131)I) on the preablation scan at 72 h. RESULTS: There were 277 patients with well-differentiated thyroid cancer who underwent radioiodine ablation. In all, 75% were female, and the mean age was 47.7 years. A total of 87 patients underwent total thyroidectomy and level VI lymph node dissection (TT + LVIND). The mean number of level VI nodes resected was 6 (1-27), and 60.9% of patients had nodal metastases. Altogether, 190 had a total thyroidectomy (TT) only, and the median number of nodes resected was 0 (0-10). The percent uptake of radioiodine on the preablation scan was 0.93% in patients who had undergone TT + LVIND and 1.2% in those with TT alone (p = 0.17). The median number of radioactive foci noted within the thyroid bed was two in both groups (p = 0.64). The mean preablation thyroglobulin levels, measured after thyroxine withdrawal or thyrogen stimulation, were 4.0 ng/ml in the TT + LVIND group versus 4.7 ng/ml in the TT group (p = 0.07). The average ablative dose of (131)I was 111.8 mCi in the dissection group and 98.5 mCi in the TT-only group. CONCLUSIONS: There is no evidence that uptake of (131)I is reduced by performance of a central neck dissection in patients with well-differentiated thyroid cancer. Preablation thyroglobulin levels were not altered by level VI lymph node dissection.

Dynamic MDCT for localization of occult parathyroid adenomas in 26 patients with primary hyperparathyroidism.

OBJECTIVE: The objective of our study was to evaluate the accuracy of dynamic contrast-enhanced 4D MDCT in the preoperative identification of parathyroid adenomas in patients with primary hyperparathyroidism (PHPT) and a history of failed surgery or unsuccessful localization on standard imaging. MATERIALS AND METHODS: Thirty-four patients with PHPT underwent 4D CT. Retrospective blinded review of the 4D CT examinations was performed by three radiologists for the presence and location of a suspected parathyroid adenoma or adenomas. At the time of the study, 25 patients underwent surgical exploration after 4D CT. Twenty patients had solitary parathyroid adenomas, two patients had two adenomas resected, two patients did not have an adenoma, and one patient had mild four-gland hyperplasia. One patient did not have PHPT on repeat serum biochemistry. Surgical and pathology reports, adenoma enhancement, and biochemical and clinical follow-up were reviewed. Data were compared with 4D CT interpretations and interobserver reliability was calculated. RESULTS: The mean sensitivity and specificity of the three readers for the precise CT localization of adenomas was 82% (range, 79-88%) and 92% (range, 75-100%), respectively. Overall interobserver reliability was excellent (κ = 0.70; range, κ = 0.60-0.79). All adenomas resected at surgery showed a biochemical response and clinical response. The mean densities of the confirmed adenomas were 41, 128, 138, and 109 HU at 0, 30, 60, and 90 seconds, respectively. Level II lymph nodes identified in 10 patients showed significantly less enhancement at 30 (p = 0.0001) and 60 (p = 0.006) seconds compared with surgically proven adenomas. CONCLUSION: Occult parathyroid adenoma shows characteristic early enhancement. In this subset of patients, 4D CT may improve surgical outcomes and decrease morbidity.

Normalization of 2-week postoperative parathyroid hormone values in patients with primary hyperparathyroidism: four-gland exploration compared to focused-approach surgery.

BACKGROUND: Elevation of parathyroid hormone (PTH) levels is commonly seen in patients with primary hyperparathyroidism (PHPT) who have undergone parathyroidectomy. This study evaluates differences in 2-week postoperative PTH levels in patients having focused-approach surgery versus four-gland exploration. METHODS: Over 6 years, patients at Rhode Island Hospital (RIH) and the Cleveland Clinic (CCF) who had PHPT and underwent localization studies suggestive of single adenoma were analyzed. At RIH patients underwent focused-approach surgery, and at CCF routine four-gland exploration was performed. Postoperative calcium supplementation was routine at RIH and selective at CCF. RESULTS: There were 308 patients at RIH and 370 at CCF. They were similar in age (59.2 +/- 13.0 years at RIH and 60.4 +/- 12.9 years at CCF), and sex (76.9 and 80.0% female at RIH and CCF, respectively). The mean preoperative serum calcium measured 10.9 +/- 0.7 mg/dl at RIH and 11.1 +/- 0.7 mg/dl at CCF (P < 0.001). Preoperative PTH values were similar, measuring 143.8 +/- 104.8 pg/ml in the focused-approach group (RIH) and 157.6 +/- 150.3 pg/ml in the four-gland exploration group (CCF). Preoperative 25-hydroxyvitamin D (vitamin D-25) levels were 24.1 +/- 12.0 ng/ml at RIH and 27.4 +/- 10.6 ng/ml at CCF; and the prevalence of vitamin D-25 deficiency (level <20 ng/ml) was 43.9% at RIH and 27% at CCF (P = 0.017). The proportion of patients whose intraoperative PTH value dropped by >or=50% prior to completion of surgery was 95.0% at RIH and 95.5% at CCF. The total gland weight resected per patient was 942 mg at RIH versus 1,394 mg at CCF (P = 0.003). The 2-week postoperative serum PTH was >65 pg/ml in 18.8% at RIH and in 38.7% at CCF (P < 0.001). The 2-week postoperative serum calcium values dropped to 9.2 +/- 0.6 mg/dl at RIH and to 9.5 +/- 0.8 mg/dl at CCF (P < 0.001). The incidence of multigland disease was 5.8% at RIH and 21.9% at CCF (P

Does failure to perform prophylactic level VI node dissection leave persistent disease detectable by ultrasonography in patients with low-risk papillary carcinoma of the thyroid?

BACKGROUND: There is controversy regarding the need for prophylactic level VI central node dissection in patients with low-risk papillary thyroid carcinoma (PTC). This study focuses on the incidence of persistent level VI nodal disease in low-risk PTC without prophylactic central node dissection. METHODS: PTC was known at the time of thyroidectomy in 304 of the 761 patients who had initial thyroid surgery from 2001 to 2007. Therapeutic level VI node dissection was performed for suspicious or positive nodes. A prophylactic central node dissection was not done if suspicious nodes were not identified. All patients had a high-resolution ultrasonography, and almost all patients had a suppressed serum thyroglobulin level 4-6 months after thyroidectomy. RESULTS: A total of 112 of 304 patients (37%) had a therapeutic level VI node dissection. A prophylactic central node dissection was not performed in the remaining 192 patients. One hundred and sixty-one of the 192 patients (84%) were low risk. Biopsy-proven persistent disease was identified at the 4-6-month postoperative ultrasonography in only 3 of the 161 low-risk patients (1.8%). The suppressed serum thyroglobulin level was increased in these 3 patients and 2 additional patients. CONCLUSION: Failure to perform a prophylactic central node dissection in low-risk PTC resulted in both a very low incidence of persistent level VI nodal disease and elevated suppressed thyroglobulin 4-6 months after thyroidectomy.

Limited value of adrenal biopsy in the evaluation of adrenal neoplasm: a decade of experience.

OBJECTIVE: To determine the value of percutaneous adrenal biopsy in the evaluation of adrenal neoplasm. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: All adult patients undergoing image-guided adrenal biopsy from 1997 to 2007. Main Outcome Measure Biopsy sensitivity for malignancy. RESULTS: There were 163 biopsies performed on 154 patients. Mean (SD) age was 66 (12.5) years. Eighty-eight biopsies (53.4%) were performed in patients with a prior diagnosis of cancer. Forty-five (26.4%) were performed when imaging study results suggested previously undiagnosed cancer with a simultaneous adrenal metastasis. Thirty (20.2%) were performed for isolated adrenal incidentalomas. Rates of positive biopsy results in these 3 groups were 70.6%, 69.0%, and 16.7%, respectively. Prebiopsy evaluation for pheochromocytoma was performed in less than 5% of patients with established or suspected nonadrenal malignancies and 32% of patients with incidentalomas. In patients with isolated adrenal incidentaloma, a radiology report recommended biopsy 33% of the time for characteristics inconsistent with benign adenoma. Benign incidentalomas measured mean (SD) 4.2 (2.1) cm (range, 1.4-10.7 cm), and malignancies measured mean (SD) 9.3 (3.3) cm (range, 5.3-14 cm) (P < .05). All incidentalomas 5 cm or less (n = 18) were benign. There were 4 false-negative biopsy results: 3 adrenocortical carcinomas and 1 pheochromocytoma. CONCLUSIONS: Biopsy is unhelpful in patients with isolated adrenal incidentaloma. Despite atypical radiographic findings, all nonfunctioning nodules 5 cm or less were benign. The negative predictive value is unacceptably low and cannot be relied on to rule out malignancy. The value of biopsy remains the diagnosis of metastatic carcinoma in patients with a nonadrenal primary malignancy, proven by the more than 70% positive rate in this group.

Primary hyperparathyroidism: is there an increased prevalence of renal stone disease?

OBJECTIVE: Parathyroid adenomas cause hypercalcemia and are culprits in the development of renal stone disease. With serum assays available, early detection of parathyroid tumors is possible. We performed this retrospective review to determine whether the prevalence of nephrocalcinosis and nephrolithiasis is still increased in patients with primary hyperparathyroidism compared with those not affected by the disorder in view of the early detection of parathyroid adenomas. MATERIALS AND METHODS: We retrospectively reviewed the renal sonograms of 271 patients with surgically proven primary hyperparathyroidism. All patients had undergone renal imaging within 6 months before parathyroid surgery. Our control group consisted of 500 age-matched subjects who had right upper quadrant sonograms obtained for various reasons. RESULTS: Nineteen (7.0%) of the 271 patients with primary hyperparathyroidism had renal stones, and eight (1.6%) of the 500 subjects in the control group had stones. Pearson's chi-square analysis showed that this difference in prevalence is significant (p < 0.0001). CONCLUSION: Our results showed a fourfold increased prevalence of asymptomatic renal stone disease in patients with surgically proven primary hyperparathyroidism compared with subjects not affected by the disorder. The National Institutes of Health consensus conference on asymptomatic primary hyperparathyroidism recommended that patients with renal stone disease undergo parathyroid surgery. These patients should undergo surgery even if they have minimal or no elevation of the total serum calcium value and no other metabolic manifestations of hyperparathyroidism. The finding of nephrocalcinosis or nephrolithiasis is, therefore, a significant finding in evaluating patients for parathyroid surgery. Routine imaging of the kidneys is necessary when primary hyperparathyroidism is documented.

Use of the round ligament of the liver to decrease pancreatic fistulas: a novel technique.

BACKGROUND: The reported pancreatic anastomosis fistula rate for pancreaticoduodenectomy, distal pancreatectomy, or enucleation is 2% to 27%. We hypothesized that reinforcement with a vascular pedicle would decrease the number of fistulas. We report a novel technique: the use of the round ligament of the liver to reinforce the pancreatic anastomosis after resection. STUDY DESIGN: Patients undergoing resection from January 1, 2000 until August 8, 2005, at a tertiary referral center, were followed in a retrospective cohort study. The round ligament of the liver was disconnected from the abdominal wall, from the umbilicus to the liver. After pancreatic resection, it was sutured to the anastomosis or closure. A pancreatic fistula was defined as follows: Jackson-Pratt (JP) drainage>50 mL/d, after the fifth postoperative day, with amylase>3 times the serum level; reexploration for a fistula; postoperative pseudocyst; or death from sepsis with a presumed fistula. RESULTS: In 95 patients, we were able to mobilize the round ligament and use it as a vascular pedicle. The overall fistula rate for the series was 5.3% (5 of 95) and for pancreaticoduodenectomy it was 8.8% (5 of 57). There were no fistulas within the distal pancreatectomy and enucleation group (n=38). Importantly, there was no mortality from pancreatic fistula in the studied patients and no need for operative intervention for a fistula. CONCLUSIONS: We present a novel technique to prevent pancreatic fistula. Although randomized trials are necessary, it appears that the use of the round ligament as a vascular pedicle for reinforcing the pancreatic anastomoses and resections results in a very low number of pancreatic fistulas.

Re-operative neck surgery for well-differentiated thyroid cancer of follicular origin.

This review focuses on the pathologic criteria for completion thyroidectomy in well differentiated thyroid cancer as well the diagnosis and treatment of recurrent disease. The roles of ultrasound in the diagnosis of a cervical recurrence, its value in determining the extent of lymph node dissection in the lateral compartment, and the importance of intra-operative ultrasound in re-operative thyroid surgery are discussed.

Radiofrequency ablation and percutaneous ethanol injection treatment for recurrent local and distant well-differentiated thyroid carcinoma.

OBJECTIVE: To assess the long-term efficacy of radiofrequency ablation (RFA) and percutaneous ethanol (EtOH) injection treatment of local recurrence or focal distant metastases of well-differentiated thyroid cancer (WTC). BACKGROUND: RFA and EtOH injection techniques are new minimally invasive surgical alternatives for treatment of recurrent WTC. We report our experience and long-term follow-up results using RFA or EtOH ablation in treating local recurrence and distant focal metastases from WTC. METHODS: Twenty patients underwent treatment of biopsy-proven recurrent WTC in the neck. Sixteen of these patients had lesions treated by ultrasound-guided RFA (mean size, 17.0 mm; range, 8-40 mm), while 6 had ultrasound-guided EtOH injection treatment (mean size, 11.4 mm; range, 6-15 mm). Four patients underwent RFA treatment of focal distant metastases from WTC. Three of these patients had CT-guided RFA of bone metastases (mean size, 40.0 mm; range, 30-60 mm), and 1 patient underwent RFA for a solitary lung metastasis (size, 27 mm). Patients were then followed with routine ultrasound, I whole body scan, and/or serum thyroglobulin levels for recurrence at the treatment site. RESULTS: No recurrent disease was detected at the treatment site in 14 of the 16 patients treated with RFA and in all 6 patients treated with EtOH injection at a mean follow-up of 40.7 and 18.7 months, respectively. Two of the 3 patients treated for bone metastases are free of disease at the treatment site at 44 and 53 months of follow-up, respectively. The patient who underwent RFA for a solitary lung metastasis is free of disease at the treatment site at 10 months of follow-up. No complications were experienced in the group treated by EtOH injection, while 1 minor skin burn and 1 permanent vocal cord paralysis occurred in the RFA treatment group. CONCLUSIONS: RFA and EtOH ablation show promise as alternatives to surgical treatment of recurrent WTC in patients with difficult reoperations. Further long-term follow-up studies are necessary to determine the precise role these therapies should play in the treatment of recurrent WTC.

Reassessment of parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism after 2 preoperative localization studies.

HYPOTHESIS: For patients with primary hyperparathyroidism and patients with 2 localization studies showing the same single location of parathyroid disease, use of intraoperative parathyroid hormone (IOPTH) measurement does not significantly increase the success of minimally invasive parathyroidectomy. DESIGN: Retrospective cohort study. SETTING: Experience of 2 academic centers over 5 years (at Brigham and Women's Hospital, Boston, Mass) and almost 4 years (at Rhode Island Hospital, Providence). PATIENTS: A total of 569 patients with primary hyperparathyroidism who underwent technetium Tc 99m sestamibi (MIBI) parathyroid imaging and neck ultrasonography (US). MAIN OUTCOME MEASURES: Incidence of correct prediction of location and extent of disease. RESULTS: In 322 patients (57%), MIBI and US imaging identified the same single site of disease. In 319 (99%) of these 322 patients, surgical exploration confirmed a parathyroid adenoma at that site, and the IOPTH levels normalized on removal. In 3 (1%) of the 322 patients, IOPTH measurement identified unsuspected additional disease. In 3 (1%) of the remaining 319 patients, IOPTH-guided removal of a single adenoma failed to correct hypercalcemia. Therefore, the failure rate of surgery in patients with positive MIBI and positive US imaging was 1% with IOPTH measurement and 2% without IOPTH measurement (P = .50). In 201 (35%) of the 569 patients, only 1 of the 2 studies recognized an abnormality or the studies disagreed on location. In these cases, either MIBI imaging or US imaging (if MIBI imaging was negative) failed to predict the correct site or extent of disease in 76 (38%) of the 201 patients (P<.001 vs concordant studies). CONCLUSIONS: In primary hyperparathyroidism, concordant preoperative localization with MIBI and US imaging is highly accurate. Use of IOPTH measurement in these cases adds only marginal benefit. When only 1 of the 2 studies identifies disease or the studies conflict, however, IOPTH measurement remains essential during minimally invasive parathyroidectomy.

Risk for malignancy of thyroid nodules as assessed by sonographic criteria: the need for biopsy.

OBJECTIVE: To correlate sonographic and color Doppler characteristics of thyroid nodules with the results of sonographically guided fine-needle aspiration biopsy to establish the relative importance of these features in predicting risk for malignancy. METHODS: We retrospectively analyzed the sonographic features of 34 malignant and 36 benign thyroid nodules with respect to size, echogenicity, echo structure, shape, border, calcification, and internal vascularity. Individual features and combinations of features were analyzed for their correlation with benign or malignant disease. A comparative analysis of several authors' previously proposed methods for distinguishing between benign and malignant nodules using sonographic criteria was also performed to determine their sensitivity and specificity in predicting nodule disease within our study data. RESULTS: Nodule size ranged from 0.8 to 4.6 cm in greatest dimension (mean, 1.96 cm; SD, 0.877 cm). The prevalence of malignancy in our study population was estimated to be nearly 5.33%. Intragroup comparison of sonographic features among benign and malignant nodules resulted in identification of intrinsic calcification as the only statistically significant predictor of malignancy (35.3% sensitive and 94.4% specific; P < .005). Presence of a "snowstorm" pattern of calcification was 100% specific for malignancy. Echogenicity, echo structure, shape, border classification, and grade of internal vascularity did not show any significant difference between benign and malignant nodules in this study. Various combinations of features previously suggested to be significant predictors of malignancy were also analyzed and shown to have very little sensitivity or specificity in predicting benign or malignant disease among nodules in our study population. CONCLUSIONS: This study indicates that the presence of intrinsic microcalcification is the only statistically reliable criterion on which to base increased suspicion for malignancy in thyroid nodules. Our results indicate the need for biopsy in determining further workup. All nodules that show the presence of intrinsic microcalcification should undergo biopsy, particularly if calcifications have a snowstorm appearance on sonography.