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Background Childhood papillary thyroid carcinoma (CPTC), despite bilateral thyroidectomy (BT), nodal dissection and radioiodine remnant ablation (RRA), recurs within neck nodal metastases (NNM) in 33% within 20 postoperative years. These NNM are usually treated with re-operation or further radioiodine. Ethanol ablation (EA) may be considered when numbers of NNM are limited. Patients and Methods We studied long-term results of EA in 14 patients presenting with CPTC during 1978-2013 and having EA for NNM during 2000-18. Cytologic diagnoses of 20 NNM (median diameter 9mm; median volume 203 mm3) were biopsy-proven. EA was performed during two outpatient sessions under local anesthesia; total volume injected ranged from 0.1-2.8cc (median 0.7). All were followed regularly by sonography and underwent volume recalculation and intra-nodal Doppler flow measurements. Successful ablation required reduction in both NNM volume and vascularity. Results Post-EA, patients were followed for 5-20 years (median 16). There were no complications, including post-procedure hoarseness. All 20 NNM shrank (mean by 87%) and Doppler flow eliminated in 19/20. After EA, 11 NNM (55%) disappeared on sonography; 8/11 before 20 months. Nine ablated foci were still identifiable after median of 147 months; only one identifiable 5mm NNM retained flow. Median serum Tg post-EA was 0.6 ng/ml. Only one patient had a rise in Tg attributed to lung metastases. Conclusions EA of NNM in CPTC is effective and safe. Our results suggest that for CPTC patients, who do not wish further surgery and are uncomfortable with active surveillance of NNM, EA represents a minimally invasive outpatient management option.

Objective To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence rates (TRR) after potentially curative bilateral thyroidectomy (BT) in low-risk adult papillary thyroid carcinoma (APTC) patients, we compared postoperative outcomes in 1836 pTNM stage I APTC patients having BT alone with 832 having BT+RRA during two consecutive 25-year periods. Methods The THEN cohort (consecutively managed during 1966–1990) comprised 809 patients (36% having BT+RRA) and the NOW cohort (1991–2015) comprised 1859 patients (29% BT+RRA). Analyses of differences in occurrence rates between BT alone and BT+RRA patients were performed with SAS software. Results During 1966–1990, when RRA rates rose ten-fold, 20-year CSM after BT alone was 0.6% and after BT+RRA was 1.2% (P = 0.66); during 1991–2015, when RRA rates progressively fell, no PTC deaths occurred in 1859 patients. In the THEN cohort, RRA did not significantly improve TRR at local, regional, or distant sites (P > 0.1), when compared to BT alone. RRA in NOW cohort was administered to 49% of node-positive (pN1) patients and 17% of node-negative (pN0/NX) patients (P < 0.0001); TRR therefore, were examined separately for pN0/NX and pN1 patients. In 1157 pN0/NX cases, 20-year locoregional TRR were 3.1% after BT and were higher (P = 0.049) at 8.6% after BT+RRA. In four pN1 groups, stratified by metastatic nodal burden, RRA did not significantly reduce the locoregional TRR observed after BT with curative intent (P > 0.5). Conclusions In a 5-decade experience, RRA administered postoperatively to stage I APTC patients did not reduce either CSM or TRR and should probably not be indicated when such patients undergo potentially curative BT.

OBJECTIVE: Systematic approach to myelolipoma remains poorly defined. We aimed to describe clinical course of myelolipoma and to identify predictors of tumor growth and need for surgery. METHODS: We conducted a retrospective study of consecutive patients with myelolipoma. RESULTS: A total of 321 myelolipomas (median size, 2.3 cm) were diagnosed in 305 patients at median age of 63 years (range, 25-87). Median follow-up was 54 months. Most myelolipomas were incidentally detected (86%), whereas 9% were discovered during cancer staging, and 5% during workup of mass effect symptoms. Thirty seven (12%) patients underwent adrenalectomy. Compared to myelolipomas

BACKGROUND: Excluding a pheochromocytoma is important when a patient presents with an incidentally discovered adrenal mass. However, biochemical testing for pheochromocytoma can be cumbersome, time consuming, or falsely positive. Our objective was to determine if unenhanced computed tomography (CT) imaging alone can be used to rule out pheochromocytoma. METHODS: We performed a retrospective study of all patients with a pathologically confirmed pheochromocytoma and unenhanced CT imaging who were treated at the Mayo Clinic between 1998 and 2016. Additionally, we performed a systematic review and meta-analysis of original studies published after 2005 with patients who had adrenal masses, more than 10 patients with pheochromocytomas, and reported attenuation on unenhanced CT imaging in Hounsfield units (HU). RESULTS: In the Mayo cohort, we identified 186 patients and 199 pheochromocytomas with unenhanced CT imaging. The mean unenhanced CT attenuation was 35±9 HU (range, 15–62), and only 15 tumors had attenuation ≤20 HU. The systematic review identified 26 studies (1,217 tumors), and 23 studies provided a mean unenhanced CT attenuation. The overall mean unenhanced CT attenuation across the studies was 35.6 HU (95% CI, 22.0–49.1 HU). A cutoff of >10 HU had a 100% sensitivity (95% CI, 1.00–1.00) for pheochromocytoma with low heterogeneity between the 21 qualified studies (I(2)=0%). Sensitivity for pheochromocytoma was 100% and 99% for an unenhanced CT attenuation cutoff of >15 and >20 HU. CONCLUSIONS: Biochemical testing may not be required to exclude pheochromocytoma if an incidental adrenal mass has low attenuation (

BACKGROUND Patients with persistent or recurrent Cushing disease (CD) after prior transsphenoidal surgery require further treatment to reduce the disease's metabolic consequences. OBJECTIVE To assess patient outcomes after stereotactic radiosurgery (SRS) for persistent or recurrent CD from adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas and propose a management algorithm. METHODS Retrospective review of 38 patients without prior radiation treatment having SRS for ACTH-secreting pituitary adenomas from 1990 to 2015. Favorable outcome was defined as biochemical remission and tumor growth control. Patients were evaluated separately if they underwent bilateral adrenalectomy (Adx). RESULTS Twenty patients (53%) were treated with Adx and SRS (median margin dose, 25 Gy) and 18 patients (47%) received SRS alone (median margin dose, 22.5 Gy). Median follow-up after SRS was 76 mo. Of patients undergoing Adx, 18/20 (90%) had a favorable outcome. Two patients (10%) had tumor growth requiring additional treatment. A favorable outcome was achieved in 13/18 patients (72%) having SRS alone (median, 14 mo; interquartile range, 8-23). Five patients (28%) required additional treatment due to persistent hypercortisolemia (n = 4) or hypercortisolemia and tumor growth (n = 1). Favorable outcomes were more frequent in the Adx and SRS group at 1 yr (100% vs 33%; P

Objectives To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. Methods A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). Results Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. Conclusion Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rate after bilateral lobar resection (BLR).There were 2952 low-risk adult papillary thyroid cancer (LRAPTC) patients (with MACIS scores6) who underwent potentially curative BLR during 1955-2014. During 1955-1974, 1975-1994, and 1995-2014, RRA was administered in 3%, 49%, and 28%. Statistical analyses were performed using SAS software.During 1955-1974, the 20-year CSM and TR rates after BLR alone were 1.0% and 6.8%; rates after BLR+RRA were 0% (P=.63) and 5.9% (P=.82). During 1975-1994, post-BLR 20-year rates for CSM and TR were 0.3% and 7.5%; after BLR+RRA, rates were higher at 0.9% (P=.31) and 12.8% (P=.01). When TR rates were examined separately for 448 node-negative and 317 node-positive patients, differences were nonsignificant. In 1995-2014, post-BLR 20-year CSM and TR rates were 0% and 9.2%; rates after BLR+RRA were higher at 1.4% (P=.19) and 21.0% (P.001). In 890 pN0 cases, 15-year locoregional recurrence rates were 3.4% after BLR and 3.7% after BLR+RRA (P=.99). In 740 pN1 patients, 15-year locoregional recurrence rates were 10% higher after BLR+RRA compared with BLR alone (P=.01). However, this difference became nonsignificant when stratified by numbers of metastatic nodes.RRA administered to LRAPTC patients during 1955-2014 did not reduce either the CSM or TR rate. We would therefore not recommend RRA in LRAPTC patients undergoing BLR with curative intent.

Background Currently acceptable management options for patients with adult papillary thyroid microcarcinoma (APTM) range from immediate surgery, either unilateral lobectomy or bilateral lobar resection, to active surveillance (AS). An alternative minimally invasive approach, originally employed for eliminating neck nodal metastases, may be ultrasound-guided percutaneous ethanol ablation (EA). Here we present our experience of definitively treating with EA 15 patients with APTM. Patients and Methods During 2010 through 2017, the 15 cT1aN0M0 patients selected for EA were aged 36 to 86 years (median, 45 years). Tumor volumes (n = 17), assessed by sonography, ranged from 25 to 375 mm3 (median, 109 mm3). Fourteen of 15 patients had 2 ethanol injections on successive days; total volume injected ranged from 0.45 to 1.80 cc (median, 1.1 cc). All ablated patients were followed with sonography and underwent recalculation of tumor volume and reassessment of tumor perfusion at each follow-up visit. Results The ablated patients have now been followed for 10 to 100 months (median, 64 months). There were no complications and no ablated patient developed postprocedure recurrent laryngeal nerve dysfunction. All 17 ablated tumors shrank (median 93%) and Doppler flow eliminated. Median tumor volume reduction in 9 identifiable avascular foci was 82% (range, 26%-93%). After EA, 8 tumors (47%) disappeared on sonography after a median of 10 months. During follow-up no new PTM foci and no nodal metastases have been identified. Conclusions Definitive treatment of APTM by EA is effective, safe, and inexpensive. Our results suggest that, for APTM patients who do not wish neck surgery and are uncomfortable with AS, EA represents a well-tolerated and minimally invasive outpatient management option.

The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a “logbook” for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.

INTRODUCTION: Due to the rarity of malignant insulinoma, a lack of the literature describing factors affecting outcomes exists. Our aim was to review malignant insulinoma incidence, characteristics and survival trends. METHODS: We identified all patients with malignant insulinoma in the SEER registries from 1973 to 2015. Incidence, neoplasm characteristics and factors affecting cancer-specific survival (CSS) were described. RESULTS: A total of 121 patients were identified. The crude annual overall incidence was low (range 0.0–0.27 cases per million person years). The largest proportion had localized disease (40%), while 16% had regional disease, 39% distant metastatic disease, and stage was unreported in 5%. Most neoplasms were in the body/tail of the pancreas, followed by the head of the pancreas. Grade was reported in 40% of patients; only a single patient reported as having grade IV with the remainder all grades I/II. Surgical resection was performed in 64% of patients. Within surgical patients, the median primary neoplasm size was 1.8 cm. Regional lymph nodes were examined in 57.1% of surgical patients, while 34% of examined nodes were positive. The median CSS was 183 months. On multivariable analysis, surgical resection, male sex and absence of metastatic disease were associated with superior survival. CONCLUSION: While the greatest proportion of patients with malignant insulinoma present with localized disease, regional lymph node involvement was found in 34% of whose nodes were tested. Further studies are needed to assess the role of lymph node dissection in improving survival and preventing recurrence given the observed frequency of lymph node involvement.

Background Care for patients with thyroid nodules is complex and multidisciplinary, and research demonstrates variation in care. The objective was to develop clinical guidelines and quality metrics to reduce unwarranted variation and improve quality. Methods Multidisciplinary expert consensus and modified Delphi approach. Source documents were workflow algorithms from Kaiser Permanente Northern California and Cancer Care of Ontario based on the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Results A consensus-based, unified preoperative, perioperative, and postoperative workflow was developed for North American use. Twenty-one panelists achieved consensus on 16 statements about workflow-embedded process and outcomes metrics addressing safety, access, appropriateness, efficiency, effectiveness, and patient centeredness of care. Conclusion A panel of Canadian and United States experts achieved consensus on workflows and quality metric statements to help reduce unwarranted variation in care, improving overall quality of care for patients diagnosed with thyroid nodules.

CONTEXT Modern pheochromocytomas (PHEOs) are often discovered by incidental finding on cross-sectional imaging or mutation-based genetic case detection testing. Little is known about how these PHEOs behave. OBJECTIVE To describe the characteristics and behavior of PHEOs discovered incidentally on imaging or through mutation-based genetic case detection testing. DESIGN Retrospective study. SETTING Referral center. PATIENTS Consecutive patients with pathology-confirmed PHEOs, treated from 2005 to 2016. MAIN OUTCOME MEASURE(S) Tumor size, plasma/urine fractionated metanephrines and catecholamines, and preoperative management. RESULTS Two hundred seventy-one patients (52% women, median age 52.0 years) presented with 296 PHEOs. Discovery method was most often incidental finding on cross-section imaging (61%) rather than PHEO-related symptoms (27%) or mutation-based case detection testing (12%). Patients with incidentally discovered PHEOs were older than symptomatic and mutation-based case detection testing patients (median age 56.6 vs 43 vs 35 years, P < 0.0001). Mutation-based case detection PHEOs were smaller than those discovered due to symptoms (median size 29.0 vs 50.5 mm, P = 0.0027). Patients with PHEOs discovered due to symptoms had the highest median concentration of 24-hour urinary metanephrines and total plasma metanephrines (P < 0.0001). These patients required a higher cumulative phenoxybenzamine dose than patients with incidental or case detection PHEO (median 450 vs 375 vs 270 mg, P = 0.029). CONCLUSIONS PHEOs are primarily discovered due to incidental finding on cross-sectional imaging rather than PHEO-related symptoms. PHEOs discovered through mutation-based genetic case detection testing were smaller and required less α-adrenergic blockade preoperatively compared with PHEOs found due to symptoms, which supports routine case detection testing for patients genetically predisposed for PHEOs.

Context Amiodarone-induced thyrotoxicosis (AIT) is a difficult diagnostic and management challenge, especially during severe thyrotoxicosis accompanied by cardiovascular compromise. Objective To evaluate thyroidectomy for the management of AIT. Design Retrospective cohort study of adults with noncongenital heart disease with AIT after >3 months of amiodarone who underwent thyroidectomy from 1 November 2002 to 31 December 2016. Setting Referral center. Patients The group was comprised of 17 patients. Main outcome measures Thyroid function, left ventricular ejection fraction (LVEF), and surgical complications were the main outcome measures. Results Patients had median age of 60 years, 82.4% were male, and 47% had systolic heart failure. At diagnosis, median TSH was 0.005 mIU/L, median free T4 was 3.25 ng/dL, and total T3 was 198.5 ng/dL. We classified five patients as type 1 and type 2 and two patients as mixed; five patients remained undefined. The most common surgical indications were medically refractory disease, worsening cardiac status, and severe thyrotoxicosis requiring prompt resolution. Within 1 week post-thyroidectomy, median TSH was 0.565 mIU/L, and free T4 was 1.8 ng/dL. Median LVEF improved by 8% in patients with systolic heart failure. Seven patients had a complication within 30 days postsurgery (rehospitalization, n = 4; cervical hematoma, n = 2; recurrent arrhythmia, n = 2; symptomatic hypocalcemia, n = 1; death, n = 1). A larger thyroid gland was a risk factor for complications. Conclusions Thyroidectomy resulted in rapid resolution of thyrotoxicosis. Its complication rate was higher than for non-AIT indications but lower than previously reported in a similar population of high-risk surgical patients.

Introduction: Cowden syndrome patients are at an increased risk of developing differentiated thyroid carcinoma (DTC). There are limited studies of thyroid cancer biology within this population. We aimed to describe the frequency and progression of DTC in this population. Method: We reviewed all patients with clinically or genetically confirmed Cowden syndrome treated at our institution between 1979 and 2017. Presentation, operative details, pathology, and adjuvant treatment for all thyroid diseases were analyzed. Results: Forty-seven patients were identified. Thirty-seven received a clinical diagnosis while 10 tested positive on genetic testing for the PTEN gene. Average follow-up time was 10 years. Twenty-three patients underwent a total thyroidectomy. Nine patients were diagnosed with thyroid cancer, with a mean age of 28.5 years, 4 cases of the follicular variant of papillary thyroid cancer (PTC), 4 of PTC, and 1 of cystic PTC. One patient required an interval lateral neck dissection but no patients developed distant metastasis. Fourteen patients underwent thyroidectomy, 12 due to follicular adenoma, Hürthle cell adenoma, or multinodular goiter, 1 due to Graves’ disease, and 1 who elected to undergo a prophylactic thyroidectomy. No mortality was associated with thyroid cancer in these patients. Conclusion: Patients with Cowden syndrome are at a significantly increased risk of developing DTC and have a younger age of onset. In this study, 20% of the patients with Cowden syndrome were diagnosed with DTC, but distant metastasis and overall mortality were absent. Clinical features were similar to those of sporadic DTC, proving that, apart from screening, Cowden syndrome-related DTC can be treated in similar fashion.

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).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.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.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.

This study assessed the influence of extrathyroid extension (EE) on cause-specific mortality (CSM) and tumor recurrence (TR) in patients treated for papillary thyroid carcinoma (PTC).We studied outcome in 3,524 patients with PTC without distant metastases at diagnosis. CSM and TR were investigated in 422 patients with gross EE (GEE) or microscopic EE (MEE).The 30-year CSM rate for GEE of 25% was 12-fold greater (P.001) than 2% seen with surgically intra-thyroid tumors (SIT); no patient who underwent MEE died of PTC. No difference (P = .36) existed in CSM rates between 127 MEE and 3,102 microscopically intra-thyroid tumors (MITs). The 20-year TR rate for GEE was 43% versus 12% with SIT (P.001). Analyzing only 2,067 pN0 tumors, we found that GEE patients had greater TR rates (all sites), compared with SIT or MEE (P.001). When 44 MEE were compared with 1,941 MIT cases, TR (all sites) rates were not different (P = .74). In patients aged45 with tumors41 mm, 20-year TR rates for MIT (stages I/II) and MEE (stage III) were not different at 4.7% and 3.8% (P = .71).MEE without concomitant GEE did not increase rates of either CSM or TR in PTC. Accordingly, these results raise concerns regarding current AJCC staging recommendations.

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed.A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force.These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided.In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

The most common feature of multiple endocrine neoplasia type 1 (MEN1) is primary hyperparathyroidism (PHP), which occurs in approximately 95% of MEN1 patients. Approximately 40-60% of patients with MEN1 develop recurrent hypercalcemia within 10-12 years after their initial parathyroid surgery and the successful management of recurrent PHP is challenging.This study sought to evaluate the safety and efficacy of percutaneous ethanol ablation (PEA) for the treatment of recurrent PHP in patients with MEN1. DESIGN, SETTING, PATIENTS, INTERVENTION, OUTCOME MEASURED: We performed an electronic search to identify patients with a billing code for MEN1 who were seen at Mayo Clinic between 1977 and 2013. Patients with recurrent PHP who underwent PEA were identified and their clinical information was collected. We performed t test analyses to compare mean values.Thirty-seven patients underwent 80 PEA treatments that included 123 sessions of ethanol administration. Twenty-one patients were women (56.8%) and the mean age at diagnosis of PHP was 33.8 years. The mean preprocedure calcium level was 10.7 mg/dl ± 0.57 (SD) and the mean postprocedure calcium level was 9.6 mg/dl ± 0.76 (P.01). In 14 treatments (18.9%) the postprocedure calcium was greater than 10.1 mg/dl. Postprocedure hypocalcemia occurred in six treatments (8.1%). Normocalcemia was achieved in 54 of the treatment episodes (73%) and the mean duration of normocalcemia was 24.8 months. PEA was safe with transient hoarseness occurring in four of the treatments (5%).The treatment of recurrent PHP in patients with MEN1 represents a challenge that is associated with increased morbidity. PEA is an effective treatment option for achieving normocalcemia in the majority of the patients with MEN1. PEA is associated with low rates of hypocalcemia and no permanent complications.

BACKGROUND Revision parathyroid is challenging due to possible diagnostic uncertainty as well as the technical challenges it can present. METHODS A multidisciplinary panel of distinguished experts from the American Head and Neck Society (AHNS) Endocrine Section, the British Association of Endocrine and Thyroid Surgeons (BAETS), and other invited experts have reviewed this topic with the purpose of making recommendations based on current best evidence. The literature was also reviewed on May 12, 2017. PubMed (1946-2017), Cochrane SR (2005-2017), CT databases (1997-2017), and Web of Science (1945-2017) were searched with the following strategy: revision and reoperative parathyroidectomy to ensure completeness. RESULTS Guideline recommendations were made in 3 domains: preoperative evaluation, surgical management, and alternatives to surgery. Eleven guideline recommendations are proposed. CONCLUSION Reoperative parathyroid surgery is best avoided if possible. Our literature search and subsequent recommendations found that these cases are best managed by experienced surgeons using precision preoperative localization, intraoperative parathyroid hormone (PTH), and the team approach.

The accurate distinction between unilateral and bilateral adrenal disease in patients with primary aldosteronism (PA) guides surgical management. Adrenal venous sampling (AVS), the criterion standard localization procedure, is not readily available at many centers throughout the world.The objective of the study was to determine factors most consistent with surgically curable PA.This was a retrospective observational study.The study was conducted at the Mayo Clinic (Rochester, Minnesota), a tertiary referral center.All patients who underwent unilateral adrenalectomy for treatment of PA between January 1993 and December 2011 participated in the study.The intervention in the study was unilateral adrenalectomy.Variables associated with the prediction of unilateral disease were measured.Over 19 years, 263 patients underwent unilateral adrenalectomy for the treatment of PA. Long-term postoperative follow-up was obtained in 143 patients (54.4%). The overall effective cure rate of PA was 95.5% in those patients sent for adrenalectomy for presumptive unilateral disease. In patients with cured PA, defined as the resolution of autonomous aldosterone secretion, hypertension was cured in 53 (41.7%) and improved in 59 (46.5%) patients. PA was not cured with unilateral adrenalectomy in six patients (4.2%). Adrenal imaging and AVS were concordant to the surgically documented side in 58.6% and 97.1% of the patients, respectively. Although there was no statistically significant difference in mean age between the inaccurate vs the accurate adrenal imaging group, we found that the minimum age in the former was 35.1 years.Using adrenal imaging and AVS, the effective surgical cure rate for PA was 95.5%. Although the overall accuracy of computed tomography and magnetic resonance imaging in detecting unilateral adrenal disease was poor at 58.6%, adrenal imaging performed well in those patients younger than 35 years of age.

We describe a woman with a rare extra-adrenal pheochromocytoma who presented with a chronic hypertension and a hypertensive crisis initiated by an invasive cardiac catheterization procedure. We present a case report, review the relevant literature, and discuss management strategies. A 49-year-old woman with a 4-year history of hypertension experienced a hypertensive crisis following a catheterization procedure. Evaluation of the episode led to identification of a catecholaminesecreting pelvic paraganglioma as confirmed by 24-hour urine fractioned metanephrines and catecholamines as well as magnetic resonance imaging. The patient was carefully pharmacologically prepared for surgical resection. Paragangliomas may exhibit 30% inheritability, and the patient was counseled on genetic testing for early diagnosis of tumor in family members. Catecholamine-secreting paragangliomas are rare tumors that may present as hypertensive emergencies. Diagnosis relies on biochemical testing followed by imaging to avoid crisis induced by invasive procedures. Surgical excision is the treatment of choice, and pharmacological preparation for surgery begins at least 1 week prior to the procedure to ensure adequate adrenergic blockade. Following treatment for a paraganglioma, genetic testing should be recommended for early identification of affected family members. How to cite this article Cai Y, Kundel A, Young W, Thompson G. Paravesicular Paraganglioma manifesting as Chronic Hypertension and Hypertensive Crisis. World J Endoc Surg 2014; 6(2):85-88.

We describe a young woman with multiple endocrine neoplasia-1 (MEN-1) who presented with severe nausea as a result of hyperparathyroidism (HPT). We present a case report, review the relevant literature in regards to physiology, and offer a target source for symptom control. A 19-year female with MEN-1 initially presented with neuroglycopenia and hyperinsulinism. She had concomitant HPT. She underwent a distal pancreatectomy with enucleation of neuroendocrine tumors from the pancreatic head. Postoperatively, she developed severe nausea and was found to have worsening HPT. She was placed on a calcimimetic and had immediate resolution of symptoms. She ultimately underwent a subtotal parathyroidectomy and has been symptom-free since that time. Severe nausea can occur in up to 25% of patients with HPT. Two theories exist regarding the mechanism behind this symptomatology. The first involves destruction of gastric mucosa leading to peptic ulcer disease. The second suggests that the etiology is gastrointestinal atony due to high calcium levels or parathyroid hormone (PTH). Based on the available data, therapies to treat nausea in HPT should focus on decreasing high levels of calcium. How to cite this article Pandian TK, Thompson G, Benzon Dy. Extreme Nausea due to Hyperparathyroidism in Multiple Endocrine Neoplasia-1. World J Endoc Surg 2015;7(3):69-71.

Background In patients with multiple endocrine neoplasia type 1 (MEN-1), pancreaticoduodenal (PD) neuroendocrine tumors (NETs) are associated with early mortality, yet, the best treatment strategy, remains uncertain. Aim To assess patient important outcomes (mortality and metastasis) of PD NETs and predictors of outcomes in patients with MEN-1. Methods Retrospective cohort of patients with MEN-1 who attended the Mayo Clinic, Rochester, MN from 1997-2014. Results We identified 287 patients with MEN-1; 199 (69%) patients had 217 PD NETs. Among those with a PD NETs, 129 (65%) had surgery of which 90 (70%) had their primary surgery performed at Mayo Clinic. The median postoperative follow-up was 8 years during which, 13 (14%) patients died. The mean (± standard deviation) age of death was 51(±9) years. Tumor size, metastasis at surgery, or tumor type were not predictive of mortality, but for every year older at surgery the odds of metastasis increased by 6%. Surgery was not performed in 70 (35%) patients. Among those who were observed/medically managed without known metastatic disease, mean tumor growth was 0.02 cm/yr (range, - 0.13 - 0.4 cm/yr). Four patients (7%) died at a median age of 77 (range, 51-89) years. Conclusion PD NETs are common in patients with MEN-1 and are associated with early mortality even after surgical intervention. Active surveillance is a viable option in nonaggressive PD NETs, although definitive factors identifying such patients are lacking. Therefore, counselling regarding risks and benefits of current treatment options remains integral to the care of patients with MEN-1. This article is protected by copyright. All rights reserved.

Praise for the previous edition: "At once a textbook, a surgical atlas, and a source of current practice guidelines...This is a high-quality, thorough and insightful resource that provides accessible and essential information...recommend[ed]." -- Doody's Review Thyroid and Parathyroid Diseases, Second Edition, has been revised and updated to reflect recent advances in the medical and surgical management of thyroid and parathyroid diseases. This new edition serves as both a comprehensive guide to patient evaluation as well as an atlas of advanced surgical techniques for managing patients needing operative intervention. Separate chapters are devoted to minimally invasive techniques and remote access/robotic thyroidectomy techniques, both of which have enjoyed increased application throughout the world. New in the second edition: * A section on state-of-the-art, evidence-based management of challenging parathyroid conditions such as multiple endocrine neoplasia and renal hyperparathyroidism * A more detailed discussion of thyroid cancer evaluation and staging * A new chapter dedicated to parathyroid cancer * Nearly 200 additional full-color illustrations This new edition is a valuable resource for all surgeons, endocrinologists, and residents seeking to expand their knowledge of thyroid and parathyroid diseases, as well as seasoned clinicians who want to improve patient care and incorporate the latest surgical advancements into their practice.

Pheochromocytoma in pregnancy is a rare condition with an estimated incidence of one in 54,000 pregnancies. Pheochromocytoma in the setting of multiple endocrine neoplasia (MEN) type 2A develops in approximately 40% of the patients with this germline mutation. MEN 2A patients with pheochromocytoma are often asymptomatic compared to those with nonsyndromic pheochromocytoma. We present a 28-year-old pregnant woman with a known MEN 2A mutation who was incidentally found to have a pheochromocytoma. She underwent an uncomplicated laparoscopic right adrenalectomy after proper α- and α-adrenergic blockade. Her serum fractionated metanephrines normalized prior to discharge from the hospital. The remainder of her pregnancy was uneventful and she delivered a health baby at term. Pheochromocytoma in pregnancy requires careful management to assure the well being of both the mother and the fetus. In pregnancy, laparoscopic surgical removal of the pheochromocytoma is feasible with excellent results when performed in the second trimester. In late pregnancy, medical management with close monitoring of the mother and fetus is recommended until fetal maturity is achieved. In the third trimester, cesarean section followed by open adrenalectomy is the preferred operation. An integrated and multidisciplinary approach with close communication among the endocrinologist, surgeon and perinatal services is paramount to achieve excellent outcomes for both patients. Women with MEN 2 should be advised to refrain from pregnancy until updated biochemical and imaging studies have ruled out pheochromocytoma. How to cite this article Dy BM, Podgaetz E, Young WF, Thompson GB. Pheochromocytomas, MEN 2A and Pregnancy: A Case Report with Review of the Literature. World J Endocr Surg 2012;4(1):29-32.

Noninsulinoma pancreatogenous hypoglycemia (NIPH) is a rare cause of hypoglycemia, especially affecting postbariatric surgery patients, related to excessive insulin secretion. Partial pancreatectomy controls hypoglycemia in the early postoperative period; however, multiple patients have experienced symptomatic relapse. The study goal was to assess frequency and severity of recurrent symptoms in operated patients.All patients who underwent pancreatic resection for NIPH at Mayo Clinic from January 1996 through December 2008 were reviewed for demographics, preoperative testing, operative and postoperative details. Data from patient records, mail survey, European Quality of Life Survey (EQ-5D), and Fear of Hypoglycemia Scale (FOHS) were used to assess outcome.Seventy-five patients underwent pancreatic resection for NIPH (5 dead, 1 incarcerated). 48 patients (70%) completed the survey; mean follow-up, 53 months. Median time to recurrent symptoms was 16 months in 41 patients (87%). Despite symptom recurrence, 36 patients (75%) reported overall improvement in symptoms and quality of life (QOL); median EQ-5D health scores increased from 40 to 75 out of 100 (P.001). Moreover, they reported marked reduction in psychologic stress and hypoglycemic symptoms with greater than 50% decrease in FOHS overall, worry, and behavioral median scores (P.001). Overall, half of the patients were classified as highly/moderately surgically successful, whereas the other half was minimally successful or surgical failures.Although nearly 90% of NIPH patients reported recurrent symptoms suggestive of hypoglycemia, a majority reported improvements in QOL and marked reduction in other symptoms after pancreatic resection. Nevertheless, 25% of patients experienced no benefit from partial pancreatectomy.

Pheochromocytomas are rare, but potentially fatal, neoplasms. The diagnosis and localization of pheochromocytoma can be challenging, and recently there has been some debate regarding the role for adrenal venous sampling (AVS). The utility of AVS in this setting is hampered by a lack of normative value data for adrenal vein catecholamine concentrations and the reliability of lateralization ratios. We sought to address these concerns by analyzing AVS catecholamine concentrations from patients who did not have pheochromocytoma.Eighteen patients underwent successful AVS for evaluation of cortisol-producing adrenal masses. All had normal 24-h urinary excretion of fractionated catecholamines and metanephrines.There was a wide range of catecholamine concentrations in both the right (epinephrine 389-118326 pg/ml; norepinephrine 156-11193 pg/ml) and left (epinephrine 113-9327 pg/ml; norepinephrine 229-2216 pg/ml) adrenal veins. The right adrenal vein-to-left adrenal vein epinephrine gradient was as high as 83:1 (median 2.1:1; P0.02). Although less striking, similar findings were also seen for norepinephrine.This report provides a reference range for adrenal vein catecholamine concentrations in nonpheochromocytoma patients and illustrates the wide variation in epinephrine and norepinephrine concentrations. Epinephrine and norepinephrine concentrations are statistically significantly higher in the right vs. the left adrenal vein; in the case of epinephrine, up to an 83-fold difference was found between the right and left adrenal veins. These data highlight why AVS should not be used in the investigation of adrenal pheochromocytoma.

Background: The primary goals of this interdisciplinary consensus statement are to review the relevant anatomy of the central neck compartment, to identify the nodal subgroups within the central compartment commonly involved in thyroid cancer, and to define a consistent terminology relevant to the central compartment neck dissection. Summary: The most commonly involved central lymph nodes in thyroid carcinoma are the prelaryngeal (Delphian), pretracheal, and the right and left paratracheal nodal basins. A central neck dissection includes comprehensive, compartment-oriented removal of the prelaryngeal and pretracheal nodes and at least one paratracheal lymph node basin. A designation should be made as to whether a unilateral or bilateral dissection is performed and on which side (left or right) in unilateral cases. Lymph node “plucking” or “berry picking” implies removal only of the clinically involved nodes rather than a complete nodal group within the compartment and is not recommended. A therapeutic cen...

Diacylglycerol acyltransferase (DGAT) could be a rate limiting step in triglyceride (TG) synthesis as it is the final step in this pathway. As such, between depot differences in DGAT activity could influence regional fat storage. DGAT activity and in vitro rates of direct free fatty acid (FFA) storage were measured in abdominal subcutaneous and omental adipose tissue samples from 12 non-obese (BMI < 30kg/m2) and 23 obese men and women (BMI > 30kg/m2) undergoing elective surgery. DGAT activity was greater in omental than in abdominal subcutaneous adipose tissue from non-obese patients (2.0 ± 0.9 vs. 0.9 ± 0.3 pmol/min/mg lipid, respectively, P = 0.003), but not from obese patients (1.4 ± 0.6 vs. 1.7 ± 0.7 pmol/min/mg lipid, respectively, P = 0.10). DGAT activity per unit adipose weight was negatively correlated with adipocyte size (p

The basis of hepatocellular injury and progressive fibrosis in a subset of patients with nonalcoholic fatty liver disease (NAFLD) is poorly understood. We sought to identify hepatic proteins that are differentially abundant across the histologic spectrum of NAFLD. Hepatic protein abundance was measured in liver samples from four groups (n = 10 each) of obese (body mass index >30 kg/m2) patients: (1) obese normal group (normal liver histology), (2) simple steatosis (SS), (3) nonalcoholic steatohepatitis (NASH)-mild (steatohepatitis with fibrosis stage 0-1), and (4) NASH-progressive (steatohepatitis with fibrosis stage 2-4). Hepatic peptides were analyzed on an API Qstar XL quadrupole time-of-flight mass spectrometer using Analyst QS software. Linear trends tests were performed and used to screen for differential abundance. Nine known proteins were expressed with differential abundance between study groups. For seven proteins differential abundance is likely to have been on the basis increased hepatic lipid content and/or inflammation. Lumican, a 40-kDa keratin sulfate proteoglycan that regulates collagen fibril assembly and activates transforming growth factor-beta and smooth muscle actin, was expressed similarly in obese normal and SS but was overexpressed in a progressive manner in NASH-mild versus SS (124%, P < 0.001), NASH-progressive versus NASH-mild (156%, P < 0.001) and NASH-progressive versus obese normal (178%, P < 0.001). Fatty acid binding protein-1 (FABP-1), which is protective against the detergent effects of excess free fatty acids, facilitates intracellular free fatty acid transport and is an important ligand for peroxisome proliferator-activated receptor–mediated transcription, was overexpressed in SS when compared to the obese normal group (128%, P < 0.001), but was paradoxically underexpressed in NASH-mild versus SS (73%, P < 0.001), NASH-progressive versus NASH-mild (81%, P < 0.001), and NASH-progressive versus obese normal (59%, P < 0.001). Conclusion: Histologically progressive NAFLD is associated with overexpression of lumican, an important mediator of fibrosis in nonhepatic tissues, whereas FABP-1 is paradoxically underexpressed in NASH, suggesting a new potential mechanism of lipotoxicity in NAFLD. Further studies are needed to determine the biologic basis of lumican and/or FABP-1 dysregulation in NAFLD. (HEPATOLOGY 2009;49:1375–1384.)

Hypoglycemia secondary to nesidioblastosis is rare in adults, and the pathogenesis of this condition is unknown. To determine factors leading to nesidioblastosis in adults, we analyzed 36 cases of nesidioblastosis including 27 cases of postgastric bypass nesidioblastosis and 9 cases of idiopathic nesidioblastosis in adults by immunohistochemistry using antibodies to insulin-like growth factor 1, insulin-like growth factor 2 (IGF2), insulin-like growth factor one receptor-alpha epidermal growth factor receptor, transforming growth factor-beta1 and 2, and transforming growth factor-beta receptor type 3. Fifty-two surgically excised pancreatic specimens from patients with benign exocrine tumors and no evidence of hypoglycemia were used as controls. There was increased IGF2, insulin-like growth factor receptor 1 receptor-alpha and transforming growth factor-beta receptor 3 expression in islets from nesidioblastosis patients compared to controls. Peliosis-type vascular ectasia was more common in nesidioblastosis patients compared to controls. These findings suggest that increased production of growth factors and growth factor receptors may contribute to the development of nesidioblastosis in adults.

In adult patients with endogenous hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging, insulinoma and non-insulinoma pancreatogenous hypoglycemic syndrome (NIPHS) resulting from diffuse nesidioblastosis must be considered in the differential diagnosis. It is not known whether the biochemical results of selective arterial calcium stimulation (SACST) with hepatic venous sampling can differentiate insulinoma from diffuse nesidioblastosis.To determine the specificity of SACST with hepatic venous sampling in differentiating insulinoma from diffuse nesidioblastosis.Retrospective review (January 1996 to March 2014).Tertiary referral center.A total of 116 patients with biochemical evidence of endogenous hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging who were subsequently shown at surgery to have insulinoma (n = 42) or nesidioblastosis (n = 74) after undergoing SACST with hepatic venous sampling.SACST with hepatic venous sampling before pancreatic exploration.Receiver operating characteristic curves were generated from the biochemical results of SACST to determine the specificity of the maximum hepatic venous insulin concentration (mHVI) and the relative-fold increase in hepatic venous insulin concentration (rHVI) over baseline after calcium injection from the dominant artery in differentiating insulinoma from nesidioblastosis.The mHVI (21.5-fold; P.001) and rHVI (3.9-fold; P.001) were significantly higher in the insulinoma group compared to the nesidioblastosis group. The areas under the receiver operating characteristic curve for mHVI and rHVI were excellent (0.94; P.0001) and good (0.83; P.0001), respectively, for differentiating insulinoma from nesidioblastosis. mHVI cutoffs of91.5 and263.5 μIU/mL were 95 and 100% specific for insulinoma, respectively. A 19-fold increase in rHVI over baseline was 99% specific for insulinoma.These data suggest that the mHVI and rHVI at SACST may be useful in differentiating insulinoma from nesidioblastosis with high specificity in patients with hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging.

The clinical features of thymic carcinoid (TC) and bronchial carcinoid (BC) tumors as part of multiple endocrine neoplasia type 1 (MEN1) have been rarely described and their importance in clinical practice is debated. The objective of this study was to describe the clinical presentation and outcome of this uncommon manifestation of MEN1 in a tertiary care center setting. We present the clinical features of patients with MEN1 and either TC or BC evaluated at the Mayo Clinic from 1977 to 2013. A total of 348 patients with MEN1 were evaluated and the prevalence of TC was 2.0% (n = 7) and of BC 4.9% (n = 17). The majority of the patients with BC were men (61%) diagnosed on routine screening (77%) and BC was not the confirmed cause of death in any patient. In contrast, TC patients were all men and during follow-up 43% died due to TC complications. We conclude that TC and BC tumors are uncommon, but important components of MEN1. BC were most commonly diagnosed during routine screening and associated with an indolent course. TC were predominantly seen in men and associated with a more aggressive behavior.

Abnormalities in gas exchange that occur during anesthesia are mostly caused by atelectasis, and these alterations are more pronounced in morbidly obese than in normal weight subjects. Sustained lung insufflation is capable of recruiting the collapsed areas and improving oxygenation in healthy patients of normal weight. We tested the effect of this ventilatory strategy on arterial oxygenation (Pao2) in patients undergoing laparoscopic bariatric surgery. After pneumoperitoneum was accomplished, the recruitment group received up to 4 sustained lung inflations with peak inspiratory pressures up to 50 cm H2O, which was followed by ventilation with 12 cm H2O positive end-expiratory pressure (PEEP). The patient's lungs in the control group were ventilated in a standard fashion with PEEP of 4 cm H2O. Variables related to gas exchange, respiratory mechanics, and hemodynamics were compared between recruitment and control groups. We found that alveolar recruitment effectively increased intraoperative Pao2 and temporarily increased respiratory system dynamic compliance (both P < 0.01). The effects of alveolar recruitment on oxygenation lasted as long as the trachea was intubated, and lungs were ventilated with high PEEP, but soon after tracheal extubation, all the beneficial effects on oxygenation disappeared. The mean number of vasopressor treatments given during surgery was larger in the recruitment group compared with the control group (3.0 versus 0.8; P = 0.04). In conclusion, our data suggest that the use of alveolar recruitment may be an effective mode of improving intraoperative oxygenation in morbidly obese patients. Our results showed the effect to be short lived and associated with more frequent intraoperative use of vasopressors.

To determine the safety and results of laparoscopic resection of benign pheochromocytomas.We retrospectively reviewed the medical charts of all patients who underwent laparoscopic adrenalectomy for benign pheochromocytomas at all 3 Mayo Clinic sites between January 1, 1992, and December 31, 2001. Demographics, comorbidities, clinical presentation, imaging studies, biochemical findings, operative intervention, and outcome were examined. Long-term follow-up was obtained via chart review and/or by direct telephone contact with the patient or a relative.Twenty-four women and 23 men with a mean age of 53.1 years (range, 16-81 years) underwent attempted laparoscopic resection of pheochromocytomas. In 5 patients, the procedure was converted to open laparotomy because of bleeding (2), inadequate exposure (2), and adhesions (1). The mean tumor size was 4.3 cm. The mean operative time (181.8 vs 1405 minutes; P = .03), mean hospital stay (6.00 vs 2.64 days; P.001), and mean blood loss (340 mL vs 80 mL; P.001) were greater in patients who underwent open laparotomy vs those who underwent laparoscopic resection. All specimens were classified as benign. The mean follow-up was 41 months (range, 10-89 months). No patients experienced a recurrence or developed metastatic disease.In light of surgical and anesthesia expertise, laparoscopic resection of benign pheochromocytomas is safe and effective with resultant short hospital stays. A low threshold to convert to an open procedure reduces operative times and decreases potentially serious complications. Although there have been no recurrences to date, long-term follow-up is required for all patients, especially those with hereditary forms of pheochromocytomas.

BACKGROUND The authors proposed to determine risk factors associated with postoperative progression of parathyroid carcinoma within the neck (locoregional) and to assess the efficacy of postoperative adjuvant radiation therapy in preventing disease progression within the neck. METHODS A retrospective review of patients with pathologically confirmed parathyroid carcinoma who underwent surgical resection was performed. Risk factors identified on univariate analysis were applied in a proportional hazards analysis to identify significant independent predictors of locoregional disease progression and cause-specific survival after surgical resection. Fifty-seven patients were treated with surgery alone (no adjuvant radiation therapy [RT]) and were determined to have sufficient follow-up and pathologically confirmed features to be included in the current analysis. Four patients were treated with surgery and adjuvant RT. Four patients received RT to the neck and mediastinum for unresectable locoregional disease progression. Patients were followed for a median of 75.6 months (range, 8.4–358 months). RESULTS Twenty-five patients (44%) developed locoregional disease progression at a median of 27.1 months after surgery (range, 6.2–138.3 months). The univariate analysis revealed that surgical margin status and the institution at which the initial surgery was performed were predictive of locoregional progression-free survival. The institution at which the initial surgery was performed was found to be an independent predictor of cause-specific survival. Of the four patients treated with surgery and adjuvant RT, all were alive and without disease at the time of last follow-up. All four patients who received RT for locoregional disease progression after initial surgery achieved locoregional disease control. CONCLUSIONS Patients with parathyroid carcinoma are reported to have a significant risk of locoregional disease progression after surgery alone. The results of the current study demonstrated that the risk of postoperative disease progression can be predicted by surgical margin status and the institution at which the initial surgery is performed. Patients treated with surgery and postoperative RT may have a lower risk of locoregional disease progression and improved cause-specific survival. RT can be used to provide locoregional control of recurrent disease. Cancer 2003. © 2003 American Cancer Society.

Hypercalcemia is frequently encountered in healthy outpatients. Reliable measurements of the mediators of hypercalcemia have improved diagnostic certainty about the etiology in most patients. Hyperparathyroidism is overwhelmingly the most common cause. Medical evaluation of the patient with hyperparathyroidism requires an understanding of the complications of the disorder and the associated syndromes. At present decreased bone mineral density and nephrolithiasis are the major sequelae of hyperparathyroidism. Most cases of primary hyperparathyroidism are sporadic; however, hereditary forms can occur in patients with the multiple endocrine neoplasia syndromes. Surgery is the only curative therapy. Results are excellent when an experienced endocrine surgeon performs parathyroid surgery.

Background To determine the impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation (SACST) with hepatic venous sampling for preoperative localization of occult insulinoma. Methods An institutional review board–approved retrospective review was undertaken of 42 patients with surgically confirmed, occult insulinoma who underwent SACST from January 1996 to March 2014. Location of the insulinoma was predicted initially based on the biochemical results of SACST alone according to Doppman's criteria. Pancreatic arteriograms were reviewed blinded to the biochemical results and the regional perfusion of each artery assessed. The anatomic and perfusion data were combined with the biochemical results to make a second prediction and compared with the surgical findings. Results The biochemical results were positive in 1, 2, and 3 arterial distributions in 73.8%, 21.4%, and 4.8% of patients, respectively. The celiac trunk and superior mesenteric artery (SMA) anatomy were aberrant in 38.1% and 35.7% of patients, respectively. Clinically significant variations included dorsal pancreatic artery replaced to SMA (21.4%) and celiac stenosis (4.8%). Significant variation and overlap in regional pancreatic perfusion was observed, particularly for the SMA. Sensitivity for insulinoma localization was 54.8% (diagnostic arteriography), 73.8% (biochemical data), 88.1% (biochemical, anatomic, perfusion data), and 92.8% (arteriographic, biochemical, anatomic, perfusion data). Conclusion Careful review of the pancreatic arterial anatomy and regional perfusion is critical for correct interpretation of the biochemical results of SACST and improves the sensitivity of localization for occult insulinoma, particularly in the presence of pancreatic arterial variants or overlap in regional perfusion.

Context: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. Objective: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. Design: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. Results: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III–IV (females, 74%; males, 91%) compared with patients with TNM stage I–II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. Conclusion: Widely invasive HCC with TNM stage III–IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.

Surgically managed endocrinopathies are rare in children. Most surgeons have limited experience in this field. Herein we report our operative experience with pediatric patients, performed over two decades by high-volume endocrine surgeons.The study was conducted at the Mayo Clinic (a tertiary referral center).Patients were19 years old and underwent an endocrine operation (1993-2012).Demographics, surgical procedure, diagnoses, morbidity, and mortality were retrospectively reviewed.A total of 241 primary cases included 177 thyroid procedures, 13 neck dissections, 24 parathyroidectomies, 14 adrenalectomies, 7 paragangliomas, and 6 pancreatic procedures. Average age of patients was 14.2 years. There were 133 total thyroidectomies and 40 hemithyroidectomies. Fifty-three cases underwent a central or lateral neck dissection. Six-month follow-up was available for 98 total thyroidectomy patients. There were four cases of permanent hypoparathyroidism (4%) and no permanent recurrent laryngeal nerve (RLN) paralyses. Sequelae of neck dissections included temporary RLN neurapraxia and Horner's syndrome. Parathyroidectomy was performed on 24 patients: 20 with primary hyperparathyroidism (HPT), three with tertiary HPT, and one with familial hypocalciuric hypocalcemia. Three patients (16%) had recurrent HPT, all with multiglandular disease. One patient had temporary RLN neurapraxia. We performed seven bilateral and seven unilateral adrenalectomies; eight were laparoscopic. Indications included pheochromocytoma, Cushing's syndrome, adrenocortical carcinoma, congenital adrenal hyperplasia, and ganglioneuroma. One death was due to adrenocortical carcinoma. Five paraganglioma patients had succinate dehydrogenase subunit B mutations, and one recurred. Six patients with insulinoma underwent enucleation (n = 5) or distal pancreatectomy (n = 1). A single postoperative abscess was managed nonoperatively.Pediatric endocrine procedures are uncommon but can be safely performed with complication rates comparable to those of the adult population. It is imperative that these operations be performed by high-volume surgeons.

Paragangliomas are rare tumors that arise from extraadrenal chromaffin cells. We examined the clinical characteristics, location, treatment, and outcome of 236 patients (141 females, 60%) with 297 benign paragangliomas evaluated at the Mayo Clinic during 1978-1998. The mean age (+/-SD) at diagnosis was 47 +/- 16 yr. Of the 297 paragangliomas, 205 were in the head and neck region, and 92 were below the neck. Paragangliomas were discovered and diagnosed incidentally on imaging studies in 9% of patients. Biochemical screening was performed in 128 patients; 40 patients (17% of the total and 31% of those screened) had hyperfunctional tumors. Of the 40 patients with tumoral catecholamine excess, 38 had documented hypertension. In patients identified with catecholamine-secreting paragangliomas, the sensitivities achieved by measurements in the 24-h urine collection were 74% for total metanephrines, 84% for norepinephrine, 18% for dopamine, and 14% for epinephrine. Multiple imaging modalities were used for tumor localization. The false negative rates were 0% for magnetic resonance imaging, 5.8% for computed tomography, 3.4% for angiography, 10.7% for ultrasonography, and 39% for radioactive iodine-labeled metaiodobenzylguanidine scintigraphy. Of 192 patients (81.4%) with follow-up data (mean, 43.9 months; range, 0.5-240), operative cure was achieved in 133 (69%). Of the 59 patients without cure, 23 had persistent disease, 5 had recurrent disease, 16 had multiple persistent synchronous tumors, and 15 subsequently developed metachronous tumors. In conclusion, most paragangliomas are nonhypersecretory and located in the head and neck region. Magnetic resonance imaging was associated with the lowest false negative rate, and metaiodobenzylguanidine was the least sensitive imaging study. A significant proportion of patients (31%) has persistent or recurrent disease, and long-term follow-up is important.

Pheochromocytoma is a rare tumor. To our knowledge only 15 cases have been reported in patients with end-stage renal disease (ESRD). We describe a 46-year-old woman with ESRD and a history of paroxysmal and difficult-to-control hypertension. During anesthesia for a surgical procedure, the patient experienced blood pressure lability with systolic blood pressures ranging from 76 to 360 mm Hg. Serum catecholamine concentrations were 2,698 pg/ mL (reference value,750 pg/mL) for norepinephrine, 33 pg/mL (110 pg/mL) for epinephrine, and 55 pg/mL (30 pg/mL) for dopamine. The concentrations of plasma metanephrines were 6.84 nmol/L (0.50 nmol/L) for metanephrine and 14.64 nmol/L (0.90 nmol/L) for normetanephrine. Abdominal computed tomography showed a right-sided, 4-cm mass posterior to the infrahepatic inferior vena cava. Following blood pressure control with alpha- and beta-adrenergic blockade, the mass was removed. Pathologic examination demonstrated the mass was a pheochromocytoma. The maximum postoperative systolic blood pressure was 160 mm Hg. Postoperative plasma normetanephrine concentration was 2.80 nmol/L, and metanephrine was obscured by interfering substances. This case report and literature review emphasizes the difficulty in diagnosing pheochromocytomas in patients with ESRD despite the myriad of available diagnostic tests.

Objective To determine prospectively the results of Roux-en-Y gastric bypass (RYGB) used as the primary weight-reducing operation in patients with medically complicated ("morbid") obesity. The RYGB procedure combines the advantages of a restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high-energy liquids without requiring an externally reinforced (banded) stoma. Patients and Methods Between April 1987 and December 1998, a total of 191 consecutive patients with morbid obesity (median weight, 138 kg [range, 91–240 kg]; median body mass index, 49 kg/m 2 [range, 36–74 kg/m 2 ]), all of whom had directly weight-related morbidity, underwent RYGB and prospective follow-up. Results Hospital mortality was 0.5% (1/191), and hospital morbidity occurred in 10.5% (20/191). Good longterm weight loss was achieved, and patients adapted well to the required new eating habits. The mean ± SD weight loss at 1 year after operation (113 patients) was 52±1 kg or 68% ±2% of initial excess body weight. By 3 years postoperatively (74 patients), weight loss was still 66% ±2% of excess body weight. Overall, 53 (72%) of 74 patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight 3 years after the operation. In addition, only 1 (1%) of 98 patients had persistent postoperative vomiting 1 or more times per week. Conclusion We believe that RYGB is a safe, effective procedure for most patients with morbid obesity and thus may be the current procedure of choice in patients requiring bariatric surgery for morbid obesity.

Making a histologic distinction between Hurthle cell adenomas and carcinomas sometimes may be difficult. We analyzed a series of Hurthle cell lesions to determine whether specific histologic features and expression of Ki67 and cyclin D1 could be useful in distinguishing Hurthle cell adenomas from carcinomas. Formalin-fixed, paraffin-embedded tissues from 128 Hurthle cell neoplasms, including 59 adenomas; 55 carcinomas; and 14 tumors classified as neoplasms of uncertain malignant behavior (UMB), which had equivocal capsular invasion but no vascular invasion, were analyzed for expression of Ki67 and cyclin D1 by immunostaining. The distribution of immunoreactivity for Ki67 with antibody MIB-1 was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index. None of the patients with adenomas or UMB tumors developed recurrent or metastatic disease after a mean follow-up of 7.8 and 7.9 years, respectively. Of the 55 patients with Hurthle cell carcinoma, 19 were associated with metastatic disease, 13 of whom died with disease. No patient with a Hurthle cell carcinoma without vascular invasion developed metastatic disease. The mean tumor size for Hurthle cell carcinomas (4.8 cm) was significantly larger than that of Hurthle cell adenomas (3.1 cm) or UMB tumors (3.7 cm). No patient with a Hurthle cell tumor smaller than 3.5 cm developed metastatic disease, even when vascular invasion was present. The Ki67 labeling index in Hurthle cell carcinomas (10.0 +/- 1.2) was 3-fold higher than in Hurthle cell adenomas (3.2 +/- 0.3). The Ki67 labeling index in the UMB group was 5.0 +/- 0.7. Cyclin D1 showed diffuse nuclear staining in 1 of the 59 (1.7%) Hurthle cell adenomas, in 10 of the 55 (18%) Hurthle cell carcinomas, and in none of the UMB tumors. In summary, analyses of the cell cycle proteins Ki67 and cyclin D1 in Hurthle cell thyroid neoplasms indicate that these markers may assist in distinguishing some Hurthle cell carcinomas from adenomas. Among the Hurthle cell carcinomas, large tumor size and vascular invasion are associated with clinically aggressive tumors. Our study also suggests that Hurthle cell neoplasms with only equivocal capsular invasion and no vascular invasion should behave in a benign manner.