The two-year results of using radiofrequency ablation as a novel treatment for persistent or relapsed Graves' disease, a prospective study.

Objectives Graves' disease(GD) is the most common cause of hyperthyroidism. Antithyroid drug(ATD) is the first-line treatment but when discontinued, >50% of patients suffer relapses. Conventional definitive treatment options include surgery and radioiodine therapy(RAI), each with its own disadvantages. Radiofrequency ablation (RFA) achieved promising short-term remission rates in a previous pilot study. The current study reports our experience of using RFA to treat relapsed GD from the largest cohort of patients with longer period of follow-up. Methods This single-arm prospective study recruited consecutive patients aged ≥18 with persistent / relapsed GD requiring ATD from two tertiary endocrine surgery centers. Those with compressive goiter, suspected thyroid malignancy, moderate to severe Graves' ophthalmopathy, preferred surgery/RAI or pregnant were excluded. Eligible patients received ultrasound-guided RFA to the entire bulk of the thyroid gland. ATDs were discontinued afterwards and thyroid function tests were monitored bi-monthly. The primary outcome was disease remission rate at 24-months follow-up after single-session RFA, defined as being biochemically euthyroid or hypothyroid without ATD. Secondary outcomes were complication rates. Results Of the 100 patients considered, 30 (30.0%) patients were eligible and received RFA. Most were female patients (93.3%). The median total thyroid volume was 23mL (15.9 - 34.5). All completed 24-months follow-up. After single-session RFA, disease remission rates were 60.0% at 12-months and 56.7% at 24-months. Amongst the 13 patients with relapse after RFA, 9 (69%) required lower ATD dose than before RFA; 2 received surgery without complications. Total thyroid volume was the only significant factor associated with relapse after RFA (OR 1.054, 95% CI 1.012 - 1.099, p=0.012). At 24-months, RFA led to disease remission in 100% of the 9 patients with total thyroid volume <20ml, and 35% of patients with total thyroid volume ≥20ml (p=0.007). There was no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. Conclusions In a highly selected group of patients with relapsed GD and predominantly small thyroid glands, single-session RFA may achieve disease remission. Smaller total thyroid volume may be a favorable factor associated with disease remission after RFA. The results of this study need to be confirmed with a long-term clinical trial.

General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement.

Background: The primary goal of this interdisciplinary consensus statement is to provide a framework for the safe adoption and implementation of ablation technologies for benign thyroid nodules. Summary: This consensus statement is organized around three key themes: (1) safety of ablation techniques and their implementation, (2) optimal skillset criteria for proceduralists performing ablative procedures, and (3) defining expectations of success for this treatment option given its unique risks and benefits. Ablation safety considerations in pre-procedural, peri-procedural, and post-procedural settings are discussed, including clinical factors related to patient selection and counseling, anesthetic and technical considerations to optimize patient safety, peri-procedural risk mitigation strategies, post-procedural complication management, and safe follow-up practices. Prior training, knowledge, and steps that should be considered by any physician who desires to incorporate thyroid nodule ablation into their practice are defined and discussed. Examples of successful clinical practice implementation models of this emerging technology are provided. Conclusions: Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. Careful patient and nodule selection are critical to the success of these procedures as is extensive pre-procedural patient counseling. Although these emerging technologies hold great promise, they are not without risk and require the development of a unique skillset and environment for optimal, safe performance and consistent outcomes.

A Prospective Study Evaluating the Feasibility and Accuracy of Post-operative Laryngeal Ultrasonography (LUSG) in Assessment of Vocal Cord Function After Esophagectomy.

BACKGROUND: Vocal cord paresis (VCP) is a serious complication after esophagectomy. Conventional diagnosis of VCP relies on flexible laryngoscopy (FL), which is invasive. Laryngeal ultrasonography (LUSG) is non-invasive and convenient. It has provided accurate VC evaluation after thyroidectomy but it is unclear if it is just as accurate following esophagectomy. This prospective study evaluated the feasibility and accuracy of LUSG in VC assessment on day-1 after esophagectomy. METHODS: Consecutive patients from a tertiary teaching hospital who underwent elective esophagectomy were prospectively recruited. All received pre-operative FL, and post-operative LUSG and FL on Day-1, each performed by a blinded, independent assessor. The primary outcomes were feasibility and accuracy of LUSG in the diagnosis of VCP on Day-1 post-esophagectomy. The accuracy of voice assessment (VA) was analyzed. RESULTS: Twenty-six patients were eligible for analysis. The median age was 70 years (66-73). Majority were male (84.6%). Twenty-five (96.2%) received three-phase esophagectomy. Twenty-four (96%) had same-stage anastomosis at the neck. Three (11.5%) developed temporary and one (3.8%) developed permanent unilateral VCP. Overall VC visualization rate by LUSG was 100%; sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of LUSG were 75.0%, 100%, 100%, 98.0%, 98.1% respectively, and superior to VA. Combining LUSG with VA findings could pick up all VCPs i.e. improved sensitivity and NPV to 100%. CONCLUSION: LUSG is a highly feasible, accurate and non-invasive method to evaluate VC function early after esophagectomy. Post-operative FL may be avoided in patients with both normal LUSG and voice.

Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.

BACKGROUND: In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). METHODS: Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. RESULTS: Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). CONCLUSION: In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.

Efficacy of single-session radiofrequency ablation (RFA) in rendering euthyroidism for persistent/relapsed Graves' disease, a pilot study.

OBJECTIVES: Graves' disease (GD) is the most common cause of hyperthyroidism. Antithyroid drug (ATD) is often the first-line treatment but > 50% patients suffer a relapse when ATD is discontinued. Surgery or radioiodine remains the current options of definitive treatment in these patients. This pilot study examined the short-term efficacy of single-session thyroid radiofrequency ablation (RFA) as a novel definitive treatment for persistent/relapsed GD. METHODS: Consecutive patients with persistent/relapsed GD requiring ATD were considered. Those with a clear surgical indication, either thyroid lobe volume ≥ 20 mL; those who were pregnant or lactating; and those who had any severe medical conditions that would pose extra treatment risks were excluded. Eligible patients received ultrasound-guided RFA of the entire bulk of thyroid gland. Thyroid function tests were monitored bi-monthly. The primary outcome was disease remission rate, defined as a state of biochemical euthyroidism or hypothyroidism without ATD. Secondary outcomes were complication rates. RESULTS: Of the 68 patients considered, 15 (22.1%) patients were eligible. Most were females (93.3%). The median age was 37 (IQR 31-48) years old. The disease remission rates were 79.0% at 6 months and 73.3% at 12 months. Among the 4 patients who relapsed after RFA, three required less ATD dose than before RFA. RFA was well-tolerated in the ambulatory setting. There were no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. CONCLUSIONS: In well-selected patients, single-session RFA of the thyroid gland may be a potential treatment for patients with persistent/relapsed GD. It is a safe and well-tolerated ambulatory procedure. KEY POINTS: • Radiofrequency ablation of the thyroid gland is an efficacious treatment for persistent/relapsed Graves' disease in well-selected patients. • Radiofrequency ablation of the thyroid gland for the treatment of persistent/relapsed Graves' disease is a safe and well-tolerated ambulatory procedure. • Radiofrequency ablation of the thyroid gland may be a potential alternative treatment for well-selected patients with persistent/relapsed GD who do not wish to undergo either thyroidectomy or radioactive iodine or continue antithyroid drugs.

Parathyroidectomy versus oral cinacalcet on cardiovascular parameters in peritoneal dialysis patients with advanced secondary hyperparathyroidism (PROCEED): a randomized trial.

BACKGROUND: This trial aimed to evaluate oral cinacalcet versus total parathyroidectomy (PTx) with forearm autografting on cardiovascular surrogate outcomes and health-related quality of life (HRQOL) measures in dialysis patients with advanced secondary hyperparathyroidism (SHPT). DESIGN: In this pilot prospective randomized trial conducted in two university-affiliated hospitals, 65 adult peritoneal dialysis patients with advanced SHPT were randomized to receive either oral cinacalcet or PTx. Primary endpoints were changes in left ventricular (LV) mass index by cardiac magnetic resonance imaging and coronary artery calcium scores (CACS) over 12 months. Secondary endpoints included changes in heart valves calcium scores, aortic stiffness, biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and HRQOL measures over 12 months. RESULTS: Changes in LV mass index, CACS, heart valves calcium score, aortic pulse wave velocity and HRQOL did not differ between groups or within groups, despite significant reductions in plasma calcium, phosphorus and intact parathyroid hormone in both groups. Cinacalcet-treated patients experienced more cardiovascular-related hospitalizations than those who underwent PTx (P = .008) but the difference became insignificant after adjusting for baseline difference in heart failure (P = .43). With the same monitoring frequency, cinacalcet-treated patients had fewer hospitalizations due to hypercalcemia (1.8%) than patients who underwent PTx (16.7%) (P = .005). No significant changes were observed in HRQOL measures in either group. CONCLUSIONS: Both cinacalcet and PTx effectively improved various biochemical abnormalities of CKD-MBD and stabilized but did not reduce LV mass, coronary artery and heart valves calcification, or arterial stiffness, or improve patient-centered HRQOL measures in PD patients with advanced SHPT. Cinacalcet may be used in place of PTx for treating advanced SHPT. Long-term and powered studies are required to evaluate PTx versus cinacalcet on hard cardiovascular outcomes in dialysis patients. Trial registration: ClinicalTrials.gov identifier: NCT01447368.

A Population-Based Study of SGLT2 Inhibitor-Associated Postoperative Diabetic Ketoacidosis in Patients with Type 2 Diabetes.

INTRODUCTION AND OBJECTIVES: Operations are a major precipitating factor for sodium-glucose co-transporter 2 inhibitor (SGLT2i)-associated diabetic ketoacidosis (DKA). This study aimed to investigate the risks of SGLT2i-associated postoperative DKA. METHODS: We analysed a population-based cohort of patients with type 2 diabetes who underwent operations during 2015-2020. Patients with SGLT2i prescriptions within 6 months before operations were assigned to the SGLT2i group, while others were assigned to the control group. Inverse probability treatment weighting with propensity scores was used to balance the baseline covariates. Postoperative DKA was defined as DKA within 30 days postoperatively. RESULTS: Overall, 147,115 subjects were included (3,419 SGLT2i users; 143,696 controls). Preoperative SGLT2i exposure was associated with increased risks of postoperative DKA (incidence = 6.40/1,000 person-years; incidence rate ratio [IRR] 6.33, 95% confidence interval [CI] 5.57-7.18; p < 0.001). Risk factors of SGLT2i-associated postoperative DKA included emergency operation (IRR 24.56, 95% CI 7.42-81.24; p < 0.001), preoperative HbA1c ≥8% (IRR 3.10, 95% CI 1.31-7.33; p = 0.010) and insulin use (IRR 2.88, 95% CI 1.27-6.51; p = 0.011). SGLT2i users who developed postoperative DKA had worse outcomes (invasive mechanical ventilation, dialysis, infections/sepsis, intensive care, and length of hospitalization; p < 0.05) than those who did not, although SGLT2i users who developed postoperative DKA had better outcomes than non-SGLT2i users who developed postoperative DKA (p < 0.05). The risk of postoperative DKA decreased following the implementation of an automatic electronic health record pop-up alert on perioperative precaution regarding SGLT2i (from IRR 4.06 [95% CI 3.41-4.83] to 2.97 [95% CI 2.41-3.65]; p for interaction = 0.020). CONCLUSIONS: Preoperative SGLT2i use was associated with increased risks of postoperative DKA in patients with type 2 diabetes. Clinicians could optimize patients' outcomes by appropriate prescription of SGLT2i, while watching out for high-risk features. Implementing automatic electronic health record pop-up alerts may reduce the risk of SGLT2i-associated postoperative DKA.

Using Intra-Operative Laryngeal Ultrasonography as a Real-Time Tool in Assessing Vocal Cord Function During Radiofrequency Ablation of the Thyroid Gland.

BACKGROUND: Inadvertent injury of the recurrent laryngeal nerve can occur during radiofrequency ablation (RFA) of thyroid nodules. Methods to avoid permanent injury have not been described. Laryngeal ultrasonography (LUSG) can assess the function of vocal cords (VCs) in real time. The present study aimed to evaluate the feasibility and accuracy of LUSG in assessing real-time VC function during RFA of benign thyroid nodules. METHODS: Consecutive patients undergoing RFA for benign thyroid nodules under local anesthesia were included. Spontaneous VC movements were checked with intra-operative LUSG (iLUSG) following each transverse ablation plane. In case of reduced VC movement, the ablation was stopped immediately. Post-ablation VC function was rechecked by LUSG on day-0 and flexible laryngoscopy (FL) on day-7. A concordance with day-0 LUSG or day-7 FL was a "true positive" or "true negative" depending on the presence or absence of VC palsy (VCP). Accuracy was calculated as the sum of all true positives and negatives divided by total nerves-at-risk. RESULTS: Of 65 eligible patients, 56 (86.2%) were females. Twelve (18.5%) patients had bilateral lobe RFA, while 53 (81.5%) had unilateral RFA. The total number of nerves-at-risk was 77. Three unilateral VCPs (3.9%) were initially detected on iLUSG and confirmed by day-0 LUSG. All recovered fully within one week. The overall accuracy of iLUSG was 100%. CONCLUSION: iLUSG is a highly accurate method that permits real-time feedback on the function of the VCs during RFA procedure. Real-time detection of VCP may prevent permanent injury. Methodological routine use of iLUSG is recommended during thyroid RFA.

Safety and Efficacy of Single-Session Radiofrequency Ablation Treatment for Benign Non-toxic Multinodular Goiter.

BACKGROUND: Radiofrequency ablation (RFA) is an effective treatment for benign thyroid nodules. However, it remains unclear if ablating multiple nodules in single-session offers comparable safety and efficacy to ablating single nodule. Our study compared early complication rate and 6-month nodule shrinkage between multiple-nodules ablation and single-nodule ablation by RFA. METHODS: Among the 174 eligible patients undergoing RFA of one or more benign thyroid nodules, 85 (48.8%) had single-nodule ablation (group I) while 89 (51.1%) had two or three nodules ablation (group II). The 6-month nodule shrinkage of each nodule (by volume reduction ratio) (VRR) was calculated by (Baseline volume - volume at 6-month)/(Baseline volume)*100 and compared between two groups. To determine independent predictors for VRR, a multivariate analysis was done by logistic regression analysis. RESULTS: Patients in group II reported significantly higher pain scores during and 2-h after treatment than group I (42.31 vs. 29.66, p = 0.029 and 38.21 vs. 26.18, p = 0.037, respectively). Two vocal cord paresis occurred in each group. 3- and 6-month VRR of the largest nodule were comparable between two groups (67.39% vs. 63.89%, p = 0.248 and 77.29% vs. 73.38%, p = 0.182). Similar 3- and 6-month VRR were observed for 2 and 3 largest nodules in group II. In multivariate analysis, total energy given per nodule volume (OR = 1.007, 95% CI = 1.001-1.012, p = 0.036) was the only independent predictor for 6-month VRR. CONCLUSION: In the presence of multinodular goiter, ablating two or more nodules by RFA within one session appears to offer a comparable level of safety and efficacy to ablating single nodule.

Intraoperative trans-laryngeal ultrasound (LUSG) of the vocal cord is a novel method of confirming the recurrent laryngeal nerve (RLN) integrity during thyroid and neck surgery.

BACKGROUND: Eliciting a normal electromyography signal has been the usual method to confirm the functional integrity of the recurrent laryngeal nerve during intraoperative nerve monitoring. Given that oscillations of the vocal cord can be detected with trans-laryngeal ultrasound when the ipsilateral recurrent laryngeal nerve is stimulated with the endotracheal tube in situ, we aimed to compare the accuracy and cost of this novel method with the conventional electromyography method. METHODS: Consecutive patients who underwent elective thyroid, parathyroid or neck dissection procedures were included. The NIM-Neuro 3.0 system was used. Endotracheal tube-based surface electrodes were utilized for electromyography signal recording. Standard anesthetic technique was adopted. Recurrent laryngeal nerve integrity was verified by both detection methods (laryngeal ultrasound and electromyography) independently. Vocal cord function was validated by flexible direct laryngoscopy postoperatively. For each method, concurrence with flexible direct laryngoscopy was defined as "true-positive" or "true-negative," based on the presence or absence of vocal cord paresis. Accuracy was calculated as the sum of all true positives and negatives divided by the total of nerves-at-risk. The cost of each method was calculated. RESULTS: One hundred and four patients were eligible. Total number of nerves-at-risk was 155. Based on flexible direct laryngoscopy findings, the test sensitivity, specificity, positive predictive value, and negative predictive value of intraoperative laryngeal ultrasound were 75.0%, 99.3%, 85.7%, and 98.6%, respectively, while those of electromyography were 87.5%, 98.0%, 70.0%, and 99.3%, respectively. The prognostic accuracy in laryngeal ultrasound versus electromyography was comparable (98.1% vs 97.4%). The cost of the laryngeal ultrasound per operation was less than electromyography ($82 vs $454). CONCLUSION: Laryngeal ultrasound has a similar detection accuracy to electromyography during intraoperative nerve monitoring. Apart from being a cheaper alternative, laryngeal ultrasound may be useful when there is unexplained loss of electromyography signals during surgery and may play a role in the intraoperative nerve monitoring troubleshooting algorithm.

A prospective study comparing the midline and lateral trans-laryngeal ultrasonography approaches in vocal cord assessment before and after thyroid and neck surgeries.

INTRODUCTION: It is unclear if placing an ultrasound probe along each thyroid cartilage lamina (i.e. the lateral approach) can improve vocal cord (VC) visualization over in the midline (i.e. the midline approach) in trans-larygeal ultrasonography (TLUSG). This study compared VC visualization rates and diagnostic accuracy between the two approaches. METHODS: Consecutive patients undergoing surgery had their VCs assessed by the two TLUSG approaches and flexible laryngoscopy within the same session. VC visualization rates and diagnostic accuracy of each approach were calculated and compared. RESULTS: Ninety patients (or 180 VCs) were analyzed. The lateral approach had significantly better overall VC visualization rate than the midline approach (93.3% vs. 82.2%, p=<0.001), especially for males (75.0% vs. 33.3%, p = 0.002). Both approaches had comparable accuracy (100% vs. 99.4%). CONCLUSIONS: The lateral approach should be preferred because of the significantly better VC visualization rate and comparable accuracy to the midline approach.

Higher SARS-CoV-2 viral loads correlated with smaller thyroid volumes on ultrasound among male COVID-19 survivors.

PURPOSE: Thyroid dysfunction, including thyroiditis, is well recognized in COVID-19 patients. We evaluated thyroid ultrasonographic features among COVID-19 survivors, which are less well known. METHODS: Adult COVID-19 survivors without known thyroid disorders who attended dedicated COVID-19 clinic underwent thyroid ultrasonography and assessment of thyroid function and autoimmunity. Adults admitted for acute non-thyroidal surgical problems and negative for COVID-19 were recruited as control. SARS-CoV-2 viral load (VL) was presented as the inverse of cycle threshold values from the real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission. RESULTS: In total, 79 COVID-19 patients and 44 non-COVID-19 controls were included. All abnormal thyroid function tests during acute COVID-19 recovered upon follow-up. Thyroid ultrasonography was performed at a median of 67 days after acute COVID-19. The median thyroid volume was 9.73 mL (IQR: 7.87-13.70). In multivariable linear regression, SARS-CoV-2 VL on presentation (standardized beta -0.206, p = 0.042) inversely correlated with thyroid volume, in addition to body mass index at the time of ultrasonography (p < 0.001). Sex-specific analysis revealed similar results among men but not women. Eleven COVID-19 patients (13.9%) had ultrasonographic changes suggestive of thyroiditis, comparable to non-COVID-19 patients (p = 0.375). None of these 11 patients had isolated low thyroid-stimulating hormone levels suggestive of thyroiditis at initial admission or the time of ultrasonography. CONCLUSIONS: Higher SARS-CoV-2 VL on presentation were associated with smaller thyroid volumes, especially in men. Further research is suggested to investigate this possible direct viral effect of SARS-CoV-2 on the thyroid gland. There was no increased rate of ultrasonographic features suggestive of thyroiditis in COVID-19 survivors.

A territory-wide assessment of the incidence of persistent hypoparathyroidism after elective thyroid surgery and its impact on new fracture risk over time.

BACKGROUND: Although persistent (≥6 months) postoperative hypoparathyroidism is often believed to be rare after elective total thyroidectomy, we hypothesized a higher incidence in the community and that patients with persistent postoperative hypoparathyroidism may have a higher fracture risk. A population-based analysis was performed using an electronic health database to address these issues. METHODS: All elective total thyroidectomies performed in 14 major hospitals across the territory over 20 years were analyzed. Persistent postoperative hypoparathyroidism was defined by the requirement of oral calcium and vitamin D shortly postoperatively and continued for ≥6 months. Those with albumin-corrected calcium <1.90 mmol/L on ≥1 occasion beyond 1 year postoperation were considered suboptimally controlled. Patients were followed until an index fracture, death, or the time of analysis, whichever was earlier. Multivariable Cox regression analysis was used to identify clinical predictors for fractures. RESULTS: Among 4,123 eligible patients, 460 patients (11.2%) had persistent postoperative hypoparathyroidism. Over a median of 10.3 years, 126 patients suffered from a new fracture (2.77 per 1,000 person-years). There was no difference in fracture events between patients with and without persistent postoperative hypoparathyroidism (P = .761). Subgroup analyses according to the adequacy of persistent postoperative hypoparathyroidism control did not reveal significant differences in fracture events. Age, female, history of fall, and diabetes independently predicted post-thyroidectomy fractures. CONCLUSION: Persistent postoperative hypoparathyroidism appeared to be a more common complication in the community after elective total thyroidectomy than previously thought. We did not observe a significant difference in fracture risk between patients with and without persistent postoperative hypoparathyroidism. The impact of persistent postoperative hypoparathyroidism control on fracture risk remained to be determined.

A prospective study evaluating the feasibility and accuracy of very early postoperative translaryngeal ultrasonography in the assessment of vocal cord function after neck surgery.

BACKGROUND: Early recognition of postoperative vocal cord palsy enhances postoperative care. Translaryngeal ultrasonography can assess vocal cord function accurately and noninvasively, but it is unclear whether it is feasible or accurate when done immediately after extubation in the recovery room owing to possible interference from laryngeal swelling. This study assessed the feasibility and accuracy of translaryngeal ultrasonography in this setting. METHODS: Consecutive patients undergoing neck operations were subjected to translaryngeal ultrasonography and flexible direct laryngoscopy 1 day before and day 7 after thyroidectomy and parathyroidectomy. Translaryngeal ultrasonography was performed early in the recovery room immediately after extubation in the operating room. A standardized assessment protocol was used. Patient parameters were compared between those with assessable and unassessable vocal cords. RESULTS: Sixty-five patients (91 recurrent laryngeal nerves-at-risk) were analyzed after excluding 2 male patients who failed preoperative translaryngeal ultrasonography. Fifty-six patients underwent thyroidectomy and 9 parathyroidectomy. The median age (range) was 57 (46-69); 44 (68%) were women. Sixty-one patients (94%) had assessable bilateral vocal cords on translaryngeal ultrasonography in the recovery room. Translaryngeal ultrasonography in the recovery room findings corresponded completely with day-7 findings on direct laryngoscopy. Long operative time was associated with nonassessable vocal cords on translaryngeal ultrasonography in the recovery room (P = .026). CONCLUSION: Very early postoperative translaryngeal ultrasonography in the recovery room after neck surgery is highly feasible and accurate. Long operative time may hinder the use of translaryngeal ultrasonography in the recovery room.

Intraoperative parathyroid hormone (IOPTH) assay might be better than the second-generation assay in parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: It is unclear whether the third-generation intraoperative parathyroid hormone assay can improve surgical outcomes over second-generation assay in primary hyperparathyroidism. We aimed to compare the rate of decrease and diagnostic accuracy between the two assays after parathyroid adenoma excision. METHODS: Consecutive patients undergoing parathyroidectomy with intraoperative parathyroid hormone were analyzed. Blood was drawn before and 10 minutes and 20 minutes after excision of the adenoma. The same blood sample was run simultaneously in the second-generation assays (Elecsys PTH STAT) and third-generation assays (Elecsys 1-84 PTH). Biochemical cure meant >50% intraoperative parathyroid hormone decrease at 10 minutes. Cure meant normocalcemia 6 months after operation. RESULTS: Relative to the second-generation assay, the value of the intraoperative parathyroid hormone level was less in the third-generation assay before excision (P < .001), at 10 minutes (P < .001), and at 20 minutes (P < .001). The intraoperative parathyroid hormone rate of decrease and the proportion of normalized post-excision intraoperative parathyroid hormone were greater in the third-generation assay (P < .001), but the prediction accuracy appeared similar between the 2 (91.5% vs 91.0%). Patients with worse renal function (estimated glomerular filtration rate <80mL/min/1.73m2) had a slower intraoperative parathyroid hormone decrease in the second-generation but not in the third-generation assay. CONCLUSION: Despite comparable accuracy between the two generations of assay, the third-generation assay might be better than the second-generation assay because of the more rapid decrease in the intraoperative parathyroid hormone and a greater percentage of normalized intraoperative parathyroid hormone, regardless of baseline renal function.

The Potential Role of Preoperative Trabecular Bone Score in Predicting Changes in Bone Mineral Density After Parathyroidectomy.

BACKGROUND: The skeletal indication for parathyroidectomy for primary hyperparathyroidism (PHPT) is based on bone mineral density (BMD) T-score < - 2.5. Whether trabecular bone score (TBS) additionally identifies patients who benefit from parathyroidectomy in terms of bone health is unknown. We aimed to study changes in BMD and TBS among Chinese who underwent curative parathyroidectomy for PHPT, in relation to their preoperative parameters, especially in those with worst site BMD T-score ≥ - 2.5 (non-osteoporotic range). METHODS: We included consecutive Chinese individuals who underwent curative parathyroidectomy during 2002-2015 for PHPT and completed preoperative and postoperative BMD and TBS measurements in Queen Mary Hospital. Correlations between preoperative parameters and changes in densitometric parameters were studied. RESULTS: 45 Chinese individuals (13 men, 32 women) were included (mean age 62.0 ± 10.0 years and BMI 24.6 ± 4.7 kg/m2). After parathyroidectomy, BMD at lumbar spine (LS) improved by 6.7% (p < 0.001) while TBS did not change. Among women, peak preoperative parathyroid hormone and calcium levels independently predicted LS BMD gain. Among women with BMD in non-osteoporotic range, LS BMD also improved after parathyroidectomy, where preoperative TBS was the only significant variable inversely correlating with percentage change in LS BMD (ρ - 0.775, p = 0.005). Particularly, those with preoperative TBS ≤ 1.25 gained 7.1% LS BMD post-parathyroidectomy (p = 0.003). CONCLUSIONS: LS BMD, but not TBS, improved after parathyroidectomy. Among non-osteoporotic PHPT women, preoperative TBS inversely correlated with postoperative BMD improvement. Hence, low preoperative TBS may be an additional indication for surgical benefit with parathyroidectomy in non-osteoporotic PHPT women, as those with worse preoperative TBS tend to benefit more from surgery.

Thyroid Carcinoma Showing Thymus-Like Differentiation (CASTLE) with Tracheal Invasion: A Case Report.

BACKGROUND Thyroid carcinoma showing thymus-like differentiation (CASTLE) is a rare disease entity. It arises from ectopic thymic tissue in the thyroid gland. Patients usually present with enlarging neck mass and hoarseness. CASE REPORT A 49-year-old man presented to our clinic with hoarseness and a right thyroid mass. Ultrasound showed a 6-cm right thyroid tumor and computer tomography confirmed invasion into the trachea. He received total thyroidectomy together with excision of one-third of the tracheal wall. No gross tumor was left behind. The tracheal defect was repaired using a pedicled right sternocleidomastoid muscle flap. He had a good recovery and was discharged 2 days after surgery. Histology revealed carcinoma showing thymus-like differentiation (CASTLE). The patient had regular follow-up and showed no clinical evidence of recurrence 18 months after surgery. CONCLUSIONS Thyroid carcinoma showing thymus-like differentiation (CASTLE) is a rare yet potentially extensive disease with favorable prognosis. Imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), is helpful in aiding diagnosis and operative planning. Surgical resection is currently the treatment of choice, with generally favorable outcomes. The role of adjuvant therapies such as radiotherapy and chemotherapy require further studies.

Two-year outcomes of single-session high-intensity focused ultrasound (HIFU) treatment in persistent or relapsed Graves' disease.

OBJECTIVE: To evaluate the longer-term disease relapse of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) ablation as a treatment for persistent/relapsed Graves' disease (GD). METHODS: After ethics approval, consecutive patients with persistent or relapsed GD who underwent bilateral US-guided HIFU ablation from 2016 to 2017 were retrospectively analyzed. Altogether, 75 patients received HIFU ablation of the central portion of the right and left thyroid lobes with areas near the trachea-esophageal groove and common carotid artery un-ablated. They were followed for 24 months or longer. Baseline thyrotropin (TSH), free T4, anti-thyroid autoantibodies, and TSH receptor (TSHR) antibody were checked. Primary outcome was the 24-month relapse rate. Relapse referred to hyperthyroidism (free T4 (FT4) > 23 pmol/L) afterwards. Variables associated with relapse were analyzed by binary logistic regression. RESULTS: The cohort comprised mostly females (84.0%) with a mean age of 42.05 ± 10.74 years. The 24-month relapse rate was 41.3% with 31 patients suffering a relapse. No patient suffered from hypothyroidism. Three patients (4.0%) suffered from temporary vocal cord palsy but these injuries recovered spontaneously after 2 months. In univariate analysis, higher daily dose of carbimazole (OR = 1.125, 95% CI = 1.023-1.237, p = 0.015) and higher baseline TSHR level (OR = 1.085, 95% CI = 1.022-1.152, p = 0.007) were significant factors for disease relapse. In the multivariate analysis, higher baseline TSHR level was a significant independent factor for disease relapse within 24 months (OR = 1.079, 95% CI = 1.014-1.148, p = 0.016). CONCLUSIONS: US-guided HIFU of the thyroid gland was a safe and relatively efficacious treatment in the longer term for patients with persistent or relapsed GD. KEY POINTS: • US-guided HIFU ablation is relatively efficacious in the longer term. • US-guided HIFU ablation of the thyroid is safe. • Higher TSHR level may lead to higher disease relapse after treatment.

Vocal Cord Palsies Missed by Transcutaneous Laryngeal Ultrasound (TLUSG): Do They Experience Worse Outcomes?

INTRODUCTION: Transcutaneous laryngeal ultrasound (TLUSG) is an innovative, non-invasive tool in detecting post-thyroidectomy vocal cord palsy (VCP). However, TLUSG failed to detect about 6-15% laryngoscopic examination (LE)-confirmed VCP. It is unclear whether the outcome of patients with VCP missed by TLUSG [false negative (FN)] is different from those with VCP diagnosed by TLUSG [true positive (TP)]. Therefore, this study aimed to compare the clinical outcome and prognosis between patients with FN results and TP results. METHODS: Over 46 months, all consecutive patients undergoing thyroidectomy or endocrine-related neck procedure were recruited. They underwent pre-operative and post-operative voice assessments on symptoms, voice-specific questionnaire [voice handicap index questionnaire (VHI-30)], TLUSG and LE. For patients with post-operative vocal cord palsy, reassessment LE would be arranged at second, fourth, sixth and twelfth months post-operatively until VCP recovered. RESULTS: In total, 1196 patients, including 74 post-thyroidectomy VCP, were recruited. For those with assessable vocal cords (VC), 58 VCP were correctly diagnosed by TLUSG (TP) and 10 VCP were missed by TLUSG (FN). Sensitivity and specificity of detecting a VCP by TLUSG were 85.3% and 94.7%, respectively. VHI-30 score was significantly increased after operation in TP group [31 (range - 6-105), p < 0.001] but not in FN group [20 (14-99), p = 0.089]. Comparing to TP group, VCP recovered earlier (69 vs. 125 days, p < 0.001) and less patients suffered from permanent VCP in patients with FN results. (34.5% vs. 0.0%, p = 0.027). CONCLUSION: The VCP missed by TLUSG had a milder course of disease. Early recovery of VC function and non-permanent palsy were expected.

Role of second high-intensity focused ultrasound (HIFU) treatment for unsatisfactory benign thyroid nodules after first treatment.

BACKGROUND: We aimed to assess the efficacy and safety of second high-intensity focused ultrasound (HIFU) ablation treatment in benign thyroid nodules that had failed to shrink by > 50% 6 months after the first treatment. METHODS: Twenty-eight patients who did not achieve 50% volume reduction at 6 months after the first HIFU treatment underwent a second HIFU treatment. Nodule volume was measured on ultrasound at baseline, 3 months and 6 months. Extent of nodule shrinkage (by volume reduction ratio) (VRR) = [Baseline volume - volume at 6 months]/[Baseline volume] * 100. Treatment success was defined as VRR > 50%. Obstructive symptom score (by 0-10 visual analogue scale, VAS) was evaluated for 6 months after treatment. RESULTS: No complications occurred after the second treatment. The mean 6-month VRR was 21.78 ± 16.87% with a median (range) of 16.16 (1.63-54.07)%. At 6 months, only two (7.1%) patients achieved treatment success, while nine (32.1%) patients had VRR < 10%. However, relative to baseline (3.96 ± 1.04), the mean VAS significantly improved at 3 and 6 months (2.96 ± 1.43, p<0.001 and 2.58 ± 1.39, p<0.001, respectively). There was a significant correlation between VRR and improvement in VAS score at 6 months (ρ=0.438, p=0.025). Greater nodule volume before the second treatment (OR=1.169, 95% CI=1.004-1.361, p=0.045) was a significant factor for greater VRR after the second treatment. CONCLUSIONS: Although subjective obstructive symptoms continued to improve after the second treatment, the actual extent of nodule shrinkage was small. Larger-volume nodules tended to shrink more significantly than smaller-volume nodules in the second treatment. KEY POINTS: • Second treatment resulted in small shrinkage in unsatisfactory nodules after first treatment. • Obstructive symptoms tended to continue to improve after second treatment. • Larger-size nodules tended to respond better in the second treatment.