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.

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.

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.

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.

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.

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.

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.

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.

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.