Defining the In Vivo Role of mTORC1 in Thyrocytes by Studying the TSC2 Conditional Knockout Mouse Model.

Background: The thyroid gland is susceptible to abnormal epithelial cell growth, often resulting in thyroid dysfunction. The serine-threonine protein kinase mechanistic target of rapamycin (mTOR) regulates cellular metabolism, proliferation, and growth through two different protein complexes, mTORC1 and mTORC2. The PI3K-Akt-mTORC1 pathway's overactivity is well associated with heightened aggressiveness in thyroid cancer, but recent studies indicate the involvement of mTORC2 as well. Methods: To elucidate mTORC1's role in thyrocytes, we developed a novel mouse model with mTORC1 gain of function in thyrocytes by deleting tuberous sclerosis complex 2 (TSC2), an intracellular inhibitor of mTORC1. Results: The resulting TPO-TSC2KO mice exhibited a 70-80% reduction in TSC2 levels, leading to a sixfold increase in mTORC1 activity. Thyroid glands of both male and female TPO-TSC2KO mice displayed rapid enlargement and continued growth throughout life, with larger follicles and increased colloid and epithelium areas. We observed elevated thyrocyte proliferation as indicated by Ki67 staining and elevated cyclin D3 expression in the TPO-TSC2KO mice. mTORC1 activation resulted in a progressive downregulation of key genes involved in thyroid hormone biosynthesis, including thyroglobulin (Tg), thyroid peroxidase (Tpo), and sodium-iodide symporter (Nis), while Tff1, Pax8, and Mct8 mRNA levels remained unaffected. NIS protein expression was also diminished in TPO-TSC2KO mice. Treatment with the mTORC1 inhibitor rapamycin prevented thyroid mass expansion and restored the gene expression alterations in TPO-TSC2KO mice. Although total thyroxine (T4), total triiodothyronine (T3), and TSH plasma levels were normal at 2 months of age, a slight decrease in T4 and an increase in TSH levels were observed at 6 and 12 months of age while T3 remained similar in TPO-TSC2KO compared with littermate control mice. Conclusions: Our thyrocyte-specific mouse model reveals that mTORC1 activation inhibits thyroid hormone (TH) biosynthesis, suppresses thyrocyte gene expression, and promotes growth and proliferation.

A >50% Intraoperative Parathyroid Hormone Level Decrease Into Normal Reference Range Predicts Complete Excision of Malignancy in Patients With Parathyroid Carcinoma.

INTRODUCTION: The mainstay of successful treatment for parathyroid carcinoma remains complete surgical excision. Although intraoperative parathyroid hormone (ioPTH) monitoring is a useful adjunct during parathyroidectomy for benign primary hyperparathyroidism, its utility for parathyroid carcinoma remains unclear. METHODS: A retrospective review of 796 patients who underwent parathyroidectomy with ioPTH monitoring for primary hyperparathyroidism revealed 13 patients with parathyroid carcinoma on final pathology from two academic institutions. A systematic review yielded 5 additional parathyroid carcinoma patients. Complete excision of malignancy, or operative success (eucalcemia ≥6 mo. after parathyroidectomy); operative failure (persistent hypercalcemia <6 mo. after parathyroidectomy); and perioperative complications were evaluated. Comparison of the >50% ioPTH decrease alone to >50% ioPTH decrease into normal reference range was analyzed using Chi-squared, Kolmogorov-Smirnov, Kruskal-Wallis tests. RESULTS: All 18 parathyroid carcinoma patients achieved a >50% ioPTH decrease, and 14 patients also had a final ioPTH level decrease into normal reference range. 93% of patients who met normal parathyroid hormone reference range had operative success, whereas only two of the four (50%) patients with parathyroid carcinoma with a >50% ioPTH decrease alone demonstrated operative success. CONCLUSIONS: Parathyroidectomy guided by a >50% ioPTH decrease into normal reference range may better predict complete excision of malignant tissue in patients with parathyroid carcinoma compared to >50% ioPTH decrease alone. IoPTH monitoring should be used in conjunction with clinical judgment and complete en bloc resection for optimal treatment and success.

Operative success is achieved regardless of ioPTH criterion used during focused parathyroidectomy for sporadic primary hyperparathyroidism.

BACKGROUND: Focused parathyroidectomy (F-PTX) guided by intraoperative parathormone (ioPTH) monitoring may result in higher operative failure rates from missed multiglandular disease (MGD) in patients with sporadic primary hyperparathyroidism (spHPT) when ioPTH levels do not reach normal range. METHODS: A retrospective review included 690 patients with spHPT who underwent F-PTX and ioPTH monitoring were divided into 2 groups: >50% ioPTH decrease to normal range, and >50% ioPTH decrease to above normal range. Operative success, recurrence, bilateral/unilateral neck exploration (BNE/UNE), MGD were evaluated. RESULTS: 533 patients demonstrated >50% ioPTH decrease to normal range, and 157 patients >50% ioPTH decrease to above normal range. There were no differences in operative success 99% vs. 97%, recurrence 2.5% vs. 5%, BNE 12% vs. 11%, UNE 4% vs. 5%, or MGD 4% vs. 4%, (p > 0.05) with 46 months mean follow-up. CONCLUSIONS: There were no differences in operative success, failure, BNE, UNE or MGD regardless of ioPTH criterion used for F-PTX.

Chronic Lymphocytic Thyroiditis May Limit the Utility of Molecular Testing in AUS/FLUS Thyroid Nodules.

INTRODUCTION: Chronic lymphocytic thyroiditis (CLT) may increase the likelihood of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) results in thyroid nodules by fine needle aspiration (FNA). Gene expression classifier (GEC) and Thyroid Sequencing (ThyroSeq) may better stratify rate of malignancy (ROM) of AUS/FLUS thyroid nodules. This study compares the utility of molecular tests in determining malignancy in surgical patients with concomitant AUS/FLUS thyroid nodules and CLT. METHODS: A retrospective review of 1648 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single institution was performed. Patients with concomitant AUS/FLUS thyroid nodules and CLT were subdivided into three diagnostic groups: FNA only, FNA with GEC, and FNA with ThyroSeq. Patients with AUS/FLUS thyroid nodules without CLT were subdivided into similar groups. Final histopathology of the cohorts was further stratified into benignity and malignancy and analyzed using Chi-squared statistics. RESULTS: Of 463 study patients, 86 had concomitant AUS/FLUS thyroid nodules and CLT with a 52% ROM, and the difference of ROM among FNA only (48%), suspicious GEC (50%), or positive ThyroSeq (69%) was not significant. In 377 patients with AUS/FLUS thyroid nodules without CL, ROM was 59%. ROM among these patients was significantly higher when molecular testing was used (FNA only 51%, suspicious GEC 65%, and positive ThyroSeq 68%; P < 0.05). CONCLUSIONS: Molecular tests may have limited value in predicting malignancy in surgical patients with concomitant AUS/FLUS thyroid nodules and CLT.

Depth of mediastinal extension can predict sternotomy need for substernal thyroid goiters.

BACKGROUND: Surgical excision of substernal thyroid goiters is usually achieved through a conventional transcervical approach, and transthoracic excision is rarely necessary. Currently, there are no clear guidelines for substernal thyroid goiters that may require a transthoracic approach. This study examined what preoperative factors were significantly associated with transthoracic surgical excision for substernal thyroid goiters. METHODS: A retrospective review of prospectively collected data of 109 patients with substernal thyroid goiters from a single institution was performed. The patients were stratified by transcervical and transthoracic approaches for substernal thyroid goiters. The factors possibly predictive of a transthoracic approach, including substernal extension beyond the thoracic inlet, patient-reported symptoms, tracheal deviation, and malignancy, were analyzed. Demographics including age, sex, and race, among others, were also studied. RESULTS: Of 1,080 patients who underwent surgical resection for multinodular goiter, there were 109 (10%) patients with substernal thyroid goiters. Of the substernal thyroid goiter group, 11 (10%) patients underwent partial sternotomy, whereas 6 (5.5%) underwent total sternotomy. On logistic regression, only substernal component of the thyroid goiter extending beyond the sternal notch into the mediastinum was statistically significant in predicting sternotomy (odds ratio 3.43, confidence interval 1.65-6.41, P < .001). Substernal thyroid goiters with mediastinal extension of ≥5 cm beyond the sternal notch showed a sensitivity of 94% and specificity of 86.5% to predict need of sternotomy. CONCLUSION: Patients with substernal thyroid goiters who exhibit progressive enlargement and/or compressive symptoms should undergo surgical excision. Although most are removed through the conventional transcervical approach, substernal thyroid goiters with a depth of mediastinal extension ≥5 cm have a high likelihood of requiring sternotomy.

Intraoperative parathormone monitoring to predict operative success in patients with normohormonal hyperparathyroidism.

BACKGROUND: It is unclear whether parathyroidectomy guided by intraoperative parathormone (PTH) monitoring is predictive of operative success in patients with normohormonal hyperparathyroidism (nhHPT), a variant of primary hyperparathyroidism (pHPT) in which patients develop clinical manifestations similar to those of pHPT. This study examined intraoperative PTH monitoring in patients undergoing parathyroidectomy for nhHPT. METHODS: We performed a retrospective review of prospectively collected data from adult (age > 18 yr) patients who underwent parathyroidectomy for pHPT at 1 of 2 North American medical centres (in Calgary, Alberta, Canada, or Miami, Florida, United States) between 2007 and 2015. In patients with nhHPT, we used the criterion of an intraoperative decrease of more than 50% in PTH after abnormal gland excision. We defined operative success as continuous eucalcemia more than 6 months after parathyroidectomy. RESULTS: Of 333 patients, 38 (11.4%) had nhHPT, with mean preoperative calcium and PTH levels of 2.7 mmol/L and 53 pg/dL, respectively. An intraoperative decrease of more than 50% in PTH level was seen in 27 patients (71.0%) with nhHPT and 265 patients (89.8%) with classic pHPT at 5 minutes (p < 0.001); the corresponding values at 20 minutes were 35 (92.1%) and 286 (96.9%). Although 5 patients (13.2%) with nhHPT did not reach this criterion until 20 minutes, the rate of operative success was still 97.0% at long-term follow-up (mean 13 mo, range 6-67 mo). Of the 38 patients, 3 (7.9%) did not have an intraoperative decrease of more than 50% in PTH level by 20 minutes. Two of the 3 achieved operative success and remained normocalemic, and 1 developed recurrent disease at 12 months. CONCLUSION: Parathyroidectomy guided by intraoperative PTH monitoring accurately predicted operative success in patients with nhHPT. Intraoperative PTH monitoring may also help identify multiglandular disease in patients with nhHPT, using criteria similar to those in classic pHPT, with comparable operative success.

Morbidity Associated With Surgical Removal of Substernal Thyroid Goiters.

INTRODUCTION: Surgical excision of substernal thyroid goiters (STG) can be challenging while minimizing postoperative morbidity. Postoperative complication rates associated with transcervical and transthoracic approaches (i.e., partial or total sternotomy) for STG compared to multinodular goiters (MNG) limited to the neck (i.e., non-substernal) remains unclear. This study examines postoperative morbidity related to surgical approaches in the removal of STG and MNG. METHODS: A retrospective review of prospectively collected data of 988 patients with STG and non-substernal MNG from a single institution between 2010 and 2021 was performed. Patients were stratified by STG and conventional non-substernal MNG limited to the neck excised by transcervical and transthoracic approach. Postoperative complications including neck hematoma requiring return to the operating room, permanent recurrent laryngeal nerve injury and hypocalcemia, and transient or temporary recurrent laryngeal nerve injury and hypocalcemia were identified. Demographics including age, sex, and race, among others, were analyzed. RESULTS: Of the 988 cases, there were 887 (90%) MNG and 101 (10%) STG. Of the STG cohort, 11 (11%) required a partial sternotomy and 4 (4%) required a total sternotomy. Permanent complication rates for non-substernal MNG and STG patients were 1.5% and 0.9%, respectively. Only transient or temporary hypocalcemia rates were statistically different between the STG and MNG cohorts (9.9% versus 3.8%, P < 0.001). CONCLUSIONS: Regardless of transcervical or transthoracic approach, postoperative complications associated with the surgical removal of STG are low in the hands of experienced, high-volume thyroid surgeons.

Transient Hypocalcemia After Total Thyroidectomy: The Obesity Paradox at Work?

INTRODUCTION: With increasing rates of obesity worldwide, a correlation between high body mass index (BMI) and postoperative morbidity after thyroid surgery remains unclear. Postoperative transient hypocalcemia is common after total thyroidectomy due to interruption of parathyroid function. This study examines the relationship between BMI and hypocalcemia after total thyroidectomy. MATERIALS AND METHODS: A retrospective review of prospectively collected data for 1135 patients who underwent total thyroidectomy for cancer, multinodular goiter (MNG), or Graves' disease between June 2009 and November 2020 at a single institution was performed. BMI groups followed the World Health Organization classification. Hypocalcemia was defined as serum calcium ≤8 mg/dL. Calcium levels measured on postoperative day 0 and the following morning were compared between the BMI groups. RESULTS: Of 1135 total thyroidectomy patients, 85% were women. The mean age and standard deviation of patients was 49 (± 13) y, with most of Hispanic origin (64%). Overall, 41.5% of patients had cancer, 45% nontoxic MNG, 5.8% toxic MNG, and 12% Graves' disease. Stratified by BMI, 27% of patients were normal, 34% overweight, and 39% obese. Overall, overweight and obese patients experienced less transient hypocalcemia at both time points compared to normal patients postoperatively (P = 0.01 and P = 0.009). Furthermore, overweight and obese patients with Graves' disease experienced less transient hypocalcemia at both time points (P = 0.04 and P = 0.05). There was no statistical difference in other groups. CONCLUSIONS: A protective role of higher BMI or "obesity paradox" for postoperative hypocalcemia may exist in those obese patients after total thyroidectomy.

Telemedicine During COVID-19 Pandemic: Endocrine Surgery Patient Perspective.

INTRODUCTION: In response to the COVID-19 pandemic, many medical providers have turned to telemedicine as an alternative method to provide ambulatory patient care. Perspectives of endocrine surgery patients regarding this mode of healthcare delivery remains unclear. The purpose of this study is to evaluate the opinions and perspectives of endocrine surgery patients regarding telemedicine. METHODS: The first 100 adult patients who had their initial telemedicine appointment with two endocrine surgeons were contacted at the conclusion of their visit. The survey administered assessed satisfaction with telemedicine, the provider, and whether attire or video background played a role in their perception of the quality of care received using a 5-point Likert scale. Differences in responses between new and returning patients were also evaluated. RESULTS: Telemedicine endocrine surgery patients stated excellent satisfaction with their visit (4.89 out of 5) and their provider (4.96 out of 5). Although there was less consensus that telemedicine was equivalent to in-person or face-to-face clinic visits (4.15 out of 5), patients would recommend a telemedicine visit to others and most agreed that this modality made it easier to obtain healthcare (4.7 out of 5). Attire of the provider and video background did not influence patient opinion in regard to the quality of care they received. Returning patients were more likely to be satisfied with this modality (4.94 versus 4.73, P = 0.02) compared to new patients. CONCLUSIONS: This study shows that telemedicine does not compromise patient satisfaction or healthcare delivery for patients and is a viable clinic option for endocrine surgery.

Sex Differences in Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is three times more common in women than men. However, PTC in men appears to be associated with poorer outcomes than in women. This study compares the clinical presentation and pathologic features of men and women with PTC. MATERIALS AND METHODS: A retrospective review of prospectively collected data for patients with PTC who underwent fine needle aspiration (FNA) of a solitary thyroid nodule and thyroidectomy at a single institution was performed. Factors including age, ultrasound features, FNA results, extent of surgical operation and final histopathology were compared between male and female patients. Descriptive statistics using chi-square and t-test statistics compared outcomes by sex. RESULTS: Of the 851 patients with PTC, 158 (19%) were men and 693 (81%) were women. Mean age and standard deviation (SD) of patients was 48 (± 14) years, and most were of Hispanic origin (69%). Men had a significantly higher rate of radiation exposure relative to women, respectively (8% vs. 2%, P<0.01). There were no ultrasonographic or FNA cytologic differences among sexes. Men had more aggressive pathologic features including lymphovascular invasion (LVI) (47% vs. 34%, P<0.01) and positive lymph nodes (LN) (36% vs. 27%, P<0.05) compared to women. Thyroid lobectomy with isthmusectomy was more commonly performed among men compared to women (24% vs. 13%, P<0.01). CONCLUSION: Men with PTC have higher rates of radiation exposure associated with more aggressive disease with LVI and LN involvement on final histopathology compared to women. Total thyroidectomy with possible central neck dissection should further be considered when counseling men with PTC.

Molecular Testing Has Limited Utility in the Surgical Evaluation of Bethesda III Thyroid Nodules.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology has 6 diagnostic categories, each with an implied cancer risk of malignancy (ROM). Bethesda III, defined as atypia or follicular lesions of undetermined significance (AUS/FLUS) on fine needle aspiration (FNA), has an indeterminate ROM. This study investigates the utility of Afirma Gene Expression Classifier (GEC) and Thyroid Sequencing (ThyroSeq) molecular testing to predict malignancy in AUS/FLUS thyroid nodules. METHODS: A retrospective review of prospectively collected data of 1457 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single academic institution was performed. Use of GEC or ThyroSeq for AUS/FLUS thyroid nodules was examined. GEC testing was reported benign or suspicious for malignancy whereas ThyroSeq testing was reported on a spectrum of low, intermediate or high ROM. Descriptive statistics were utilized to compare the ROM among AUS/FLUS thyroid nodules. RESULTS: Of 1457 patients with FNA thyroid cytology, 359 (25%) corresponded to AUS/FLUS results. There were 132 (37%) patients with GEC testing and 88 (24%) had ThyroSeq testing. ROM without GEC or ThyroSeq testing was 49%, whereas ROM with suspicious GEC was 55%. ROM with positive ThyroSeq was 73%. Among ThyroSeq patients, 43 had intermediate-risk mutations with 60% malignancy, and 23 had high-risk mutations with 96% malignancy (P < 0.01). CONCLUSION: Surgical patients with AUS/FLUS thyroid nodules have a high ROM. High-risk ThyroSeq testing may have some utility in predicting malignancy, but GEC and intermediate-risk TGC results have limited value. Surgeons should carefully consider the utility of molecular tests to determine surgical resection.

Margin Positivity and Survival in Papillary Thyroid Microcarcinoma: A National Cancer Database Analysis.

BACKGROUND: The rising incidence of thyroid cancer has been attributed to increased detection of papillary thyroid microcarcinoma (PTMC). Although some PTMCs are thought to harbor aggressive pathologic features, the clinical significance of these features remains unclear. This study examines factors associated with survival in this patient population. STUDY DESIGN: Adults with PTMC, defined as papillary thyroid carcinoma ≤ 1.0 cm, who underwent thyroidectomy between 2004 and 2016, were identified in the National Cancer Database. Demographic and clinical variables were analyzed. The primary aim was to identify factors associated with survival. The secondary aim was to assess the association of microscopic margins on survival and to identify factors associated with margin positivity. Overall survival was estimated using Kaplan-Meier methods and compared using log rank tests. Cox proportional hazards and binary logistic regression models identified factors associated with survival and margin positivity, respectively. RESULTS: Of 77,817 patients with PTMC, 13,507 met inclusion criteria; 2,649 (20%) of these patients presented with advanced features: extrathyroidal extension (n = 916, 7%), lymphovascular invasion (n = 398, 3%), lymph node involvement (n = 2,003, 15%), and distant metastasis (n = 39, <1%). Microscopic margin positivity was present in 906 patients and associated with increased risk of death (hazard ratio 1.58, 95% CI 1.04-2.41). Academic facilities (odds ratio [OR] 0.75, 95% CI 0.59-0.95) and operative volume (OR 0.98, 95% CI 0.97-0.98) were associated with decreased margin positivity. CONCLUSIONS: Positive margin status was significantly associated with increased risk of death for PTMC. Higher operative volume and treatment at academic centers were associated with lower rates of margin positivity and may help improve survival outcomes in PTMC patients with aggressive features.

Fine needle aspiration and the Bethesda system: Correlation with histopathology in 1,228 surgical patients.

BACKGROUND: Fine-needle aspiration combined with the Bethesda System for Reporting Thyroid Cytopathology is indispensable in the diagnostic evaluation of thyroid nodules. Their increased detection over the last few decades mandates the determination of which thyroid nodules require surgical management for malignancy. This study examines the correlation of fine-needle aspiration to final histopathology of dominant thyroid nodules in a large series of surgical patients undergoing thyroidectomy at a single academic institution. METHODS: A retrospective review of prospectively collected data of 1,228 patients who underwent fine-needle aspiration for a dominant thyroid nodule and thyroidectomy from a single institution between 2010 and 2019 was performed. The cases were stratified into all 6 Bethesda categories. Fine-needle aspiration results were compared to index thyroid nodule malignancy on final histopathology. RESULTS: Of 1,228 patients who underwent thyroidectomy, the overall malignancy rate was 53%. When fine-needle aspiration was stratified by the Bethesda System for Reporting Thyroid Cytopathology, malignancy rate was 29% for nondiagnostic; 11% for benign; 51% for atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); 47% for follicular neoplasm/suspicious for follicular neoplasm (FN/SFN); 84% for suspicious for malignancy (SFM); and 98% for malignant results on final histopathology. There was a false positive rate of 1% and false negative rate ranging from 7 to 11%. CONCLUSION: Fine-needle aspiration of a dominant thyroid nodule in patients who underwent thyroidectomy had an overall malignancy rate of 53%. False negative and false positive rates are within the reported range in surgical patient populations. The majority of patients with AUS/FLUS, FN/SFN and SFM results with underlying malignancy received the appropriate surgical resection.

Margin Positivity and Survival Outcomes: A Review of 14,471 Patients with 1-cm to 4-cm Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) comprises the majority of thyroid malignancy, but it is associated with excellent long-term survival. Highly prevalent, with increasing incidence, the optimal operative management for patients with 1- to 4-cm PTC remains unclear. This study determined factors that affect clinical outcomes, including survival, in this patient population. STUDY DESIGN: Patients with 1- to 4-cm PTC, who underwent thyroidectomy between 2004 and 2016, were identified in the National Cancer Database (NCDB). Factors affecting survival, including margin status, extent of resection, operative volume, and institution type, were studied. Outcomes were estimated by Kaplan-Meier and log rank tests. Cox proportional hazard and binary logistic regression analyses identified factors affecting survival as well as margin positivity. RESULTS: Of 14,471 patients with 1- to 4-cm PTC, 2,269 (15.7%) exhibited lymphovascular invasion, 6,925 (47.9%) had multifocality, 14,235 (98.3%) underwent total thyroidectomy, and 2,212 (15.3%) had microscopic margin positivity, which conferred lower survival (hazard ratio [HR] 1.464, p < 0.05), with 30-day and 90-day mortality of 0.1% and 0.2%, respectively. Operative volume (odds ratio [OR] 0.979, p < 0.01) and thyroid surgery at an academic center (OR 0.623, p < 0.001) were associated with lower odds of margin positivity. CONCLUSIONS: In patients with 1- to 4-cm PTC, margin positivity confers lower survival. Factors associated with lower rate of margin positivity are higher operative volume and referral for treatment at academic center. Because margin positivity is a modifiable risk factor, referral of patients with aggressive features of PTC to high volume academic centers may improve survival.

Long-term outcome success after operative treatment for primary aldosteronism.

BACKGROUND: Primary aldosteronism is a common cause of secondary hypertension. Resolution of hypertension and hypokalemia after adrenalectomy for primary aldosteronism is variable. This study examines preoperative factors for persistent hypertension and long-term outcome after laparoscopic adrenalectomy in patients with primary aldosteronism. METHODS: We reviewed all patients who underwent laparoscopic resection for adrenal tumors from 2010 to 2018. Biochemical success was defined as normalization of hypokalemia and the aldosterone-to-renin ratio. Clinical success was defined as normalization of blood pressure requiring no antihypertensive medications. Descriptive statistics and binary logistic regression analysis were used. RESULTS: Of 202 patients who underwent unilateral laparoscopic adrenalectomy, 37 (18%) had biochemical and clinical confirmation of primary aldosteronism. Postoperatively, biochemical success was attained in all 37 patients with primary aldosteronism. Complete, partial, and absent clinical success was achieved in 41%, 38%, and 21% of patients, respectively. Number of antihypertensives (odds ratio, 2.30 per medication; 95% confidence interval, 1.07-4.93; P < .05), duration of hypertension (odds ratio, 1.11 per year; 95% confidence interval, 1.03-1.25; P < .05), and increased body mass index (odds ratio, 1.13; 95% confidence interval, 1.01-1.29; P < .05) were preoperative factors associated with absent clinical success. CONCLUSION: Biochemical success is more common than clinical resolution of hypertension after adrenalectomy for primary aldosteronism. The number of antihypertensive medications, longstanding hypertension, and high body mass index are preoperative factors associated with absent clinical success.

Impact of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features on Revised Bethesda System Malignancy Rates at a Single Institution.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) standardizes thyroid cytopathology reporting in six tier diagnostic categories. In recent years, noninvasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This study examines the impact of NIFTP on the BSRTC risk of malignancy (ROM). METHODS: This was a retrospective review of prospectively collected data from 565 patients who underwent fine needle aspiration and thyroidectomy at a single institution. ROM for each Bethesda category was analyzed and calculated with NIFTP classified as a malignant and nonmalignant lesion. Absolute and relative differences between ROM were compared. RESULTS: Of 565 patients, 19 were Bethesda I, 159 were Bethesda II, 178 were Bethesda III, 46 were Bethesda IV, 42 were Bethesda V, and 121 were Bethesda VI. ROM differences with NIFTP classified as malignant versus nonmalignant for each class were as follows: Bethesda I, no change; Bethesda II, 18%-14%; Bethesda III, 55%-48%; Bethesda IV, 50%-35%; Bethesda V, 93%-91%; and Bethesda VI, 99%-98%. Absolute ROM differences for each category were as follows: Bethesda I, 0%; Bethesda II, 4%; Bethesda III, 7%; Bethesda IV, 15%; Bethesda V, 2%; and Bethesda VI, 1%. CONCLUSIONS: A decreasing trend in absolute and relative ROM was seen in Bethesda II, III, and IV categories; however, exclusion of NIFTP as a malignant lesion did not significantly alter the ROM of BSRTC categories. Surgeons should assess their respective institution's experiences with NIFTP and the BSRTC.

Case distributions in general surgery residency: Subspecialization occurs before fellowship.

BACKGROUND: In the era of subspecialization and duty-hour restrictions, many General Surgery residents desire additional training in their future subspecialty areas. This study examines the relationship between case distributions performed by General Surgery residents and their chosen future subspecialty. METHODS: A retrospective review of Accreditation Council for Graduate Medical Education case logs of 101 graduated General Surgery residents at a single academic institution (2002-2018) was performed. The total number of operative cases performed during General Surgery residency overall and in Accreditation Council for Graduate Medical Education-defined categories were compared between residents with differing areas of future subspecialization. RESULTS: Residents pursuing surgical fellowships in Endocrine, Cardiothoracic, Vascular, and Trauma/Critical Care Surgery logged respectively more endocrine (63 [11] vs 32 [13]; P < .001), thoracic (61 [15] vs 41 [13]; P < .001), vascular (225 [38] vs 162 [38]; P < .001), and operative trauma (83 [29] vs 71 [25]; P = .045) cases, compared with program average. Residents pursuing General Surgery (no fellowship) performed significantly more endoscopies (131 [47] vs 105 [28]; P = .029) than peers. Residents pursuing Breast, Oncology, Colorectal, and Pediatric Surgery fellowships performed numerically (non-significantly) more breast (94 [16] vs 78 [20]; P = .180), liver/pancreas (39 [3.1] vs 33 [8.0]; P = .173), large intestinal (132 [30] vs 125 [24]; P = .507), and pediatric (173 [27] vs 155 [37]; P = .832) cases, respectively, compared with peers. The majority of these additional cases were performed in postgraduate years 3 to 5. CONCLUSION: In this single-institution study, many General Surgery residents perform more cases than peers in respective areas of future subspecialization. This may reflect residents at the reporting institution, and similar large, university-based programs seeking focused training in preparation for fellowship while still meeting case-volume minimums in all Accreditation Council for Graduate Medical Education-defined categories.

Chronic Lymphocytic Thyroiditis May Lower Accuracy of AUS/FLUS Cytopathology in Surgical Patients.

BACKGROUND: Chronic lymphocytic thyroiditis (CLT) increases cytologic atypia on fine-needle aspiration of thyroid nodules, and its effect on rate of malignancy in atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) thyroid nodules remains unclear. This study evaluates the effect of concomitant CLT on malignancy rates of AUS/FLUS thyroid nodules in surgical patients. METHODS: Retrospective review of 1061 patients who underwent thyroidectomy for a dominant thyroid nodule from a single institution was performed. Fine-needle aspiration was classified according to the Bethesda System for Reporting Thyroid Cytopathology. Patients with AUS/FLUS cytopathology were classified into two cohorts: AUS/FLUS with CLT and AUS/FLUS without CLT. Final pathology was reviewed, and the cohorts were further stratified into benign and malignant subgroups. When applicable, patients with gene expression classifier (GEC) testing were reviewed and the positive predictive value (PPV) was calculated. RESULTS: Of the entire surgical series, 293 (28%) patients had AUS/FLUS cytopathology with a rate of malignancy of 56% (163/293) on final pathology. Seventy-three (25%) patients had AUS/FLUS with CLT, of which 44% (n = 32) were malignant by final pathology. The remaining 75% (n = 220) had AUS/FLUS without CLT, 60% (n = 131) of which were malignant. GEC testing was performed in 36 of the AUS/FLUS with CLT patients, where of the 33 suspicious results, 17 were malignant on final pathology, yielding a PPV of 52%. CONCLUSIONS: The rate of malignancy for AUS/FLUS thyroid nodules is lower with coexisting CLT, and similar to previous studies, the PPV of GEC testing is approximately 50%. Cytologic atypia due to CLT may increase more AUS/FLUS results in thyroid nodules, which may lead to overestimation of malignancy rates in this patient population.

High Rates of Underlying Thyroid Cancer in Patients Undergoing Thyroidectomy for Hyperthyroidism.

BACKGROUND: The rate of thyroid cancer in patients with hyperthyroidism is reported to be rare, and patients with toxic thyroid nodules do not routinely undergo fine-needle aspiration (FNA) to evaluate for malignancy. However, higher rates of malignancy in hyperthyroid patients may exist than previously reported. This study examines the rate of malignancy in patients with hyperthyroidism who have undergone thyroidectomy. METHODS: A retrospective review of prospectively collected data of 138 patients with hyperthyroidism who underwent thyroidectomy at a single institution was performed. Patients were divided into three groups: Graves' disease (n = 80), toxic multinodular goiter (n = 46), and toxic solitary nodule (n = 12). Patients with previous thyroid surgery were excluded from the study. All patients had biochemical confirmation of hyperthyroidism with thyroid-stimulating hormone <0.1 mIU/L and clinical diagnosis by a referring physician. RESULTS: Of 138 patients, 22% (31/138) were found to have malignancy on final pathology. The breakdown of malignancy by hyperthyroid condition was as follows: 16% in Graves' disease, 24% in toxic multinodular goiter patients, and 50% in toxic solitary nodule patients. CONCLUSIONS: There is a clinically significant rate of malignancy seen in patients who undergo thyroidectomy for hyperthyroidism. Patients with distinct thyroid nodules in the presence of hyperthyroidism may have the highest rates of malignancy and should undergo appropriate workup with ultrasound and FNA to exclude underlying malignancy. In cases with suspicious ultrasound features and/or FNA cytopathology, surgical treatment should be considered as initial management.

Increased Incidental Thyroid Cancer in Patients With Subclinical Chronic Lymphocytic Thyroiditis.

BACKGROUND: The autoimmune process and increased TSH associated with chronic lymphocytic thyroiditis (CLT) are factors that may promote development of thyroid cancer. When surgically removed, the cellular changes of CLT are commonly seen surrounding thyroid cancers. This study investigates the malignancy rate in CLT patients when compared with non-CLT patients after thyroidectomy. METHODS: A retrospective review of prospectively collected data for 1268 patients with index thyroid nodules who underwent thyroidectomy at a single institution was performed. Patients were excluded if they had previous thyroid surgery, known thyroid cancer, Graves' disease, family history of thyroid cancer, and history of radiation exposure. Patients were subdivided into CLT and non-CLT groups by final pathology. Final pathology was reviewed and grouped into cancer in the index thyroid nodule and incidental thyroid cancers. Chi-squared analyses were performed using SAS. RESULTS: Of 359 patients that met study criteria, 52 had CLT. Overall, the malignancy rate was 37% in both CLT patients (19/52) and non-CLT patients (114/307) (P = 0.86). However, incidental thyroid cancer was found in 15% (8/52) of CLT patients and 10% (31/307) of non-CLT patients (relative risk = 1.52) who had no index nodule cancer. The breakdown of incidental cancer subtype in CLT patients was classic variant papillary thyroid carcinoma (PTC), n = 3; follicular variant PTC, n = 5. CONCLUSIONS: Patients with CLT have a 1.5-fold increased risk of incidental PTC. CLT should be considered a risk factor for incidental thyroid cancer, and patients with this thyroid condition should be counseled and monitored periodically for underlying thyroid malignancy.