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.

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.

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.

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.

Intraoperative Parathyroid Hormone Monitoring in the Surgical Management of Sporadic Primary Hyperparathyroidism.

Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or ">50% intraoperative PTH drop" criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.

Additional 20-Minute Intraoperative Parathormone Measurement Can Minimize Unnecessary Bilateral Neck Exploration.

BACKGROUND: Parathyroidectomy guided by intraoperative parathormone (ioPTH) monitoring for primary hyperparathyroidism (pHPT) confirms removal of all hyperfunctioning parathyroid glands. This study evaluates the utility of an additional 20-min ioPTH measurement in patients who fail to meet the >50% ioPTH drop criterion. METHODS: A retrospective review of prospectively collected data of 706 patients with pHPT who underwent parathyroidectomy guided by ioPTH monitoring was performed. When a >50% ioPTH decrease from the highest either preincision or preexcision level was achieved after 10 min, parathyroidectomy was completed. If this criterion was not met, further exploration was performed or an additional 20-min ioPTH measurement was obtained. RESULTS: Of 706 patients, 72 (10%) patients did not meet the >50% ioPTH drop criterion at 10 min. Of these patients, 67% (48/72) underwent immediate bilateral neck exploration (BNE). For the other 33% of patients (24/72), a 20-min parathormone (PTH) measurement was drawn. Of patients with an additional 20-min PTH measurement, 46% (11/24) had a >50% ioPTH decrease at 20 min where BNE was avoided and parathyroidectomy completed, whereas 54% (13/24) did not. Compared to patients with insufficient ioPTH drop at 10 min and subsequent BNE, there was a statistically significant 46% reduction of BNE in patients with a 20-min PTH level (P < 0.01). CONCLUSIONS: A 20-min ioPTH measurement is useful in preventing unnecessary BNE in some patients who undergo focused parathyroidectomy with a delayed >50% ioPTH drop.

Stricter ioPTH criterion for successful parathyroidectomy in stage III CKD patients with primary hyperparathyroidism.

BACKGROUND: The effects of underlying renal insufficiency on intraoperative parathormone monitoring during parathyroidectomy (PTX) for primary hyperparathyroidism remain unclear. This study evaluates operative outcomes in patients undergoing parathyroidectomy using classic or stricter >50% intraoperative parathormone decrease criterion for primary hyperparathyroidism with mild or moderate renal insufficiency. METHODS: A retrospective review of prospectively collected data in 577 patients undergoing parathyroidectomy guided by intraoperative parathormone monitoring for primary hyperparathyroidism was performed. Patients were stratified by stages I to III of chronic kidney disease; those with overt secondary hyperparathyroidism (chronic kidney disease stages IV and V) were excluded. Patients were further subdivided into subgroups based on the classic criterion of a >50% intraoperative parathormone decrease and a stricter criterion of a >50% intraoperative parathormone decrease e to a normal range (<65 pg/mL). Long-term operative outcomes were compared across the 3 chronic kidney disease groups. RESULTS: Of 577 patients, 38% (221) had normal renal function or stage I chronic kidney disease, 44% (251) had stage II chronic kidney disease, and 18% (105) had stage III chronic kidney disease. In stages I and II chronic kidney disease patients, there were no differences in operative success, failure, recurrence, bilateral neck exploration, and multiglandular disease between classic and stricter criterion groups. In contrast, in stage III chronic kidney disease patients, operative success was greater using the stricter intraoperative parathormone criterion than the classic intraoperative parathormone criterion (100% vs 92%, respectively, P < .05). No other outcome differences were identified between classic and stricter intraoperative parathormone criterion subgroups in stage III chronic kidney disease patients. CONCLUSION: In patients with primary hyperparathyroidism and concurrent stage III chronic kidney disease, a stricter criterion of a >50% intraoperative parathormone decrease to a normal range should be used for successful parathyroidectomy.

Intraoperative parathormone spikes during parathyroidectomy may be associated with multiglandular disease.

BACKGROUND: The importance of intraoperative parathormone "spikes" during parathyroidectomy remains unclear. This study compared patients with and without intraoperative parathormone spikes during parathyroidectomy using the criterion of a > 50% parathormone and determined the effect of intraoperative parathormone spikes on operative outcome. METHODS: We performed a retrospective review of prospectively collected data on 683 patients who underwent parathyroidectomy guided by intraoperative parathormone monitoring. An intraoperative parathormone "spike value" was calculated by subtracting the preincision intraoperative parathormone value from the pre-excision intraoperative parathormone value (SV = PE - PI). An intraoperative parathormone spike was defined as having a positive spike value ≥9 pg/mL (≥10th percentile of all spike values). RESULTS: Of 683 patients, 224 (33%) had intraoperative parathormone spikes and a greater rate of multiglandular disease (8% vs. 3%, P < 0.05) and bilateral neck exploration (10% vs. 5%, P < 0.05) compared with patients without intraoperative parathormone spikes. Overall, there were no differences between parathyroidectomy patients with and without intraoperative parathormone spikes in terms of operative success (98.2% vs. 98.0%), failure (1.8% vs. 2.0%), or recurrence rates (0.4% vs. 1.3%). CONCLUSIONS: Although the presence of intraoperative parathormone spikes may increase suspicion for multiglandular disease, the ability of intraoperative parathormone monitoring to predict operative success after parathyroidectomy is not affected by spikes.

High perioperative morbidity and mortality in patients with malignant nonfunctional adrenal tumors.

BACKGROUND: Both functional (hormone hypersecreting) and nonfunctional (nonhypersecreting) adrenal tumors can have benign or malignant pathology. This study compares perioperative in-hospital outcomes after adrenalectomy in patients with benign versus malignant nonfunctional primary adrenal tumors. METHODS: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database (2006-2011) to identify patients who underwent unilateral open or laparoscopic adrenalectomy for nonfunctional primary adrenal tumors. Patients were subdivided by benign and malignant final pathology. Demographics, comorbidities, and perioperative complications were compared between groups using bivariate and multivariate logistic regression. RESULTS: Of 23,297 patients, 89.7% (n = 20,897) had benign tumors, whereas 10.3% (n = 2400) had malignant tumors. Those with malignant tumors had higher Charlson Comorbidity Index scores and were more likely to undergo adrenalectomy at high volume centers. For both laparoscopic and open approach, patients with malignant nonfunctional tumors had higher rates of intraoperative complications including vascular and splenic injury (P < 0.01), as well as postoperative complications including hematoma, shock, acute kidney injury, venous thromboembolism, and pneumothorax (P < 0.01). In addition, the malignant group had higher rates of blood transfusions, longer hospital stay, and higher in-hospital mortality (P < 0.05) than benign counterparts. On risk-adjusted multivariate analysis, malignant nonfunctional primary adrenal tumors were independently associated with increased risk of complications following adrenalectomy. CONCLUSIONS: Patients with malignant nonfunctional primary adrenal tumors have higher perioperative morbidity and mortality compared to patients with benign nonfunctional adrenal tumors. Such patients should be medically optimized before adrenalectomy, and surgeons must remain vigilant in preventing perioperative complications.

Location of abnormal parathyroid glands: lessons from 810 parathyroidectomies.

BACKGROUND: Primary hyperparathyroidism (pHPT) is commonly treated with targeted parathyroidectomy (PTX) guided by preoperative imaging and intraoperative parathormone monitoring. Despite advanced imaging techniques, failure of parathyroid localization still occurs. This study determines the anatomical distribution of single abnormal parathyroid glands, which may help direct the surgeon in PTX when preoperative localization is unsuccessful. METHODS: A retrospective review of prospectively collected data of 810 patients with pHPT who underwent initial PTX at a tertiary medical center was performed. All patients had biochemically confirmed pHPT and single-gland disease. Abnormal parathyroid gland localization was determined at time of operation, correlated with operative and pathology reports, and confirmed by operative success defined as eucalcemia for ≥6 mo after PTX. Patients with multiple endocrine neoplasia, secondary, tertiary, or familial hyperparathyroidism, multiglandular disease, parathyroid cancer, and ectopic glands were excluded. Data were analyzed by chi-square and Z-test analyses. RESULTS: Among 810 patients who underwent PTX for pHPT, single abnormal parathyroid glands were unequally distributed among the four eutopic locations (left superior, 15.7%; left inferior, 31.3%; right superior, 15.8%; right inferior, 37.2%; P < 0.01). Abnormal inferior parathyroid glands (68.5%) were significantly more common than abnormal superior glands (31.5%), respectively (P < 0.01). In men, the most common location for single abnormal parathyroid glands was the right inferior position (43.4%, P < 0.01). Overall, there was no significant difference in laterality. CONCLUSIONS: This large series of patients suggests that single eutopic abnormal parathyroid glands are more likely to be inferior. In men, moreover, if an abnormal parathyroid gland is not localized preoperatively, the right inferior location should be explored first. Nevertheless, successful PTX remains predicated on knowledge of parathyroid anatomy, experience, and judgment of the surgeon.

GLP-1 plays a limited role in improved glycemia shortly after Roux-en-Y gastric bypass: a comparison with intensive lifestyle modification.

Rapid glycemic improvements following Roux-en-Y gastric bypass (RYGB) are frequently attributed to the enhanced GLP-1 response, but causality remains unclear. To determine the role of GLP-1 in improved glucose tolerance after surgery, we compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification (ILM) (n = 10 per group) before and after equivalent short-term weight reduction. The GLP-1 receptor antagonist exendin(9-39)-amide (Ex-9) was administered, in random order and in double-blinded fashion, with saline during two separate visits after equivalent weight loss. Despite the markedly exaggerated GLP-1 response after RYGB, changes in postprandial glucose and insulin responses did not significantly differ between groups, and glucagon secretion was paradoxically augmented after RYGB. Hepatic insulin sensitivity also increased significantly after RYGB. With Ex-9, glucose tolerance deteriorated similarly from the saline condition in both groups, but postprandial insulin release was markedly attenuated after RYGB compared with ILM. GLP-1 exerts important insulinotropic effects after RYGB and ILM, but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery. Instead, enhanced hepatic metabolism, independent of GLP-1 receptor activation, may be more important for early postsurgical glycemic improvements.