A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. METHODS: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). RESULTS: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment. CONCLUSIONS: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

Cushing's syndrome caused by ACTH precursors secreted from a pancreatic yolk sac tumor in an adult-a case report and literature review.

Here, we report the first adult case of pancreatic yolk sac tumor with ectopic adrenocorticotropic hormone (ACTH) syndrome. The patient was a 27-year-old woman presenting with abdominal distension, Cushingoid features, and hyperpigmentation. Endogenous Cushing's syndrome was biochemically confirmed. The ACTH level was in the normal range, which raised the suspicion of ACTH precursor-dependent disease. Elevated ACTH precursors were detected, supporting the diagnosis of ectopic ACTH syndrome. Functional imaging followed by tissue sampling revealed a pancreatic yolk sac tumor. The final diagnosis was Cushing's syndrome due to a yolk sac tumor. The patient received a steroidogenesis inhibitor and subsequent bilateral adrenalectomy for control of hypercortisolism. Her yolk sac tumor was treated with chemotherapy and targeted therapy. Cushing's syndrome secondary to a yolk sac tumor is extremely rare. This case illustrated the utility of ACTH precursor measurement in confirming an ACTH-related pathology and distinguishing an ectopic from a pituitary source for Cushing's syndrome.

Case Report: Insulinoma Co-Existing With Type 2 Diabetes - Advantages and Challenges of Treatment With Endoscopic Ultrasound-Guided Radiofrequency Ablation.

The coexistence of insulinoma and type 2 diabetes is rare and the diagnostic process is often challenging. Continuous glucose monitoring system devices, which are more readily available nowadays, provide a useful tool for the diagnosis and evaluation of treatment response. Curative surgery is often the mainstay of treatment for insulinoma. Here, we report a Chinese patient with insulinoma diagnosed simultaneously with type 2 diabetes. His insulinoma was managed with endoscopic ultrasound guided-radiofrequency ablation (EUS-RFA) and the patient achieved complete resolution of hypoglycaemic episodes. The case illustrates that while EUS-RFA is an emerging non-invasive treatment modality for pancreatic lesions, limitations exist especially when histological confirmation is essential.

Attaining biochemical euthyroidism early after total thyroidectomy in Graves' disease may lower long-term morbidity risk.

BACKGROUND: The relationship between good early control of thyroid hormone levels after thyroidectomy for Graves' disease (GD) and subsequent risks of mortality and morbidities is not well known. The aim of this study was to examine the association between thyroid hormone levels within a short interval after surgery and long-term mortality and morbidity risks from a population-based database. METHODS: Patients with GD who underwent complete/total thyroidectomy between 2006 and 2018 were selected from the Hong Kong Hospital Authority clinical management system. All patients were classified into three groups (euthyroidism, hypothyroidism, and hyperthyroidism) according to their thyroid hormone levels at 6, 12, and 24 months after surgery. Cox proportional hazards models were performed to compare the risks of all-cause mortality, cardiovascular disease (CVD), Graves' ophthalmopathy, and cancer. RESULTS: Over a median follow-up of 68 months with 5709 person-years, 949 patients were included for analysis (euthyroidism, n = 540; hypothyroidism, n = 282; and hyperthyroidism, n = 127). The hypothyroidism group had an increased risk of CVD (HR = 4.20, 95 per cent c.i. 2.37 to 7.44, P < 0.001) and the hyperthyroidism group had an increased risk of cancer (HR = 2.14, 95 per cent c.i. 1.55 to 2.97, P < 0.001) compared with the euthyroidism group. Compared with patients obtaining euthyroidism both at 6 months and 12 months, the risk of cancer increased in patients who achieved euthyroidism at 6 months but had an abnormal thyroid status at 12 months (HR = 2.33, 95 per cent c.i. 1.51 to 3.61, P < 0.001) and in those who had abnormal thyroid status at 6 months but achieved euthyroidism at 12 months (HR = 2.52, 95 per cent c.i. 1.60 to 3.97, P < 0.001). CONCLUSIONS: This study showed a higher risk of CVD in postsurgical hypothyroidism and a higher risk of cancer in hyperthyroidism compared with achieving euthyroidism early after thyroidectomy. Patients who were euthyroid at 6 months and 12 months had better outcomes than those achieving euthyroidism only at 6 months or 12 months. Attaining biochemical euthyroidism early after thyroidectomy should become a priority.

Long-term outcome of patients treated with antithyroid drugs, radioactive iodine or surgery for persistent or relapsed Graves' disease.

BACKGROUND: The aim of this study was to compare long-term mortality, morbidity, and cumulative healthcare costs between antithyroid drugs, radioactive iodine, and surgical treatment for patients with persistent or relapsed Graves' disease. METHODS: Data on patients with persistent or relapsed Graves' disease between 2006 and 2018 were retrieved from the Hong Kong Hospital Authority. Hazard ratios (HRs) estimated by Cox proportional hazards regression models were used to compare the risks of all-cause mortality, cardiovascular disease, atrial fibrillation, psychological disease, Graves' ophthalmopathy, and cancer across treatment groups. The 10-year healthcare cost and change in co-morbidity status were also estimated. RESULTS: Over a median follow-up of 79 months (22 636 person-years), a total of 3443 patients (antithyroid drug 2294, radioactive iodine 755, surgery 394) were analysed. Compared with antithyroid drug treatment, surgery was associated with significantly lower risks of all-cause mortality (HR 0.40, 95 per cent c.i. 0.36 to 0.45), cardiovascular disease (HR 0.54, 0.48 to 0.60), atrial fibrillation (HR 0.11, 0.09 to 0.14), psychological disease (HR 0.85, 0.79 to 0.92), Graves' ophthalmopathy (HR 0.09, 0.08 to 0.10), and cancer (HR 0.56, 0.50 to 0.63). Patients who underwent surgery also had a lower risk of all outcome events than those in the radioactive iodine group. The 10-year direct cumulative healthcare cost was €14 754 for surgery compared with €17 390 for antithyroid drugs, and €17 918 for the radioactive iodine group. CONCLUSION: Patients who underwent surgery for persistent or relapsed Graves' disease had lower risks of all-cause mortality and analysed morbidities. The 10-year cumulative healthcare cost in the surgery group was lowest among the three treatment alternatives.

Prospective association of serum adipocyte fatty acid-binding protein with heart failure hospitalization in diabetes.

AIMS: Adipocyte fatty acid-binding protein (AFABP) is associated with cardiovascular diseases in type 2 diabetes. Whether circulating AFABP levels are associated with the risk of heart failure (HF) in type 2 diabetes remains undefined. We investigated the prospective association of circulating AFABP levels with incident HF hospitalization in type 2 diabetes, and its relationship to the use of sodium glucose co-transporter 2 inhibitors (SGLT2i) which reduce HF risk. METHODS AND RESULTS: Baseline serum AFABP level was measured in 3322 Chinese participants without known history of cardiovascular diseases or hospitalization for HF, recruited from the Hong Kong West Diabetes Registry. Its association with incident HF hospitalization was evaluated using multivariable Cox regression analysis. Use of SGLT2i was included as a time-dependent covariate. Among these 3322 participants (52.9% men; mean age 60.0 ± 12.6), 176 (5.3%) developed HF hospitalization over a median follow-up of 8 years. Seven hundred and thirty-one (22%) were started on SGLT2i during the study period (empagliflozin 55.1%, dapagliflozin 44.2%, canagliflozin 0.4%, and ertugliflozin 0.3%). Serum AFABP levels were significantly higher in participants who developed HF hospitalization than those who did not (men: 14.8 vs. 8.3 ng/mL; women: 21.5 vs. 14.6 ng/mL; all: 18.6 vs. 10.9 ng/mL, P < 0.001). In multivariable Cox regression analysis, baseline serum AFABP level was significantly associated with incident HF hospitalization [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.06-1.80, P = 0.019] independent of the use of SGLT2i, in a model also consisting of age; sex; body mass index; smoking status; duration of diabetes; hypertension, dyslipidaemia; atrial fibrillation; presence of chronic kidney disease and albuminuria; glycated haemoglobin and high-sensitivity C-reactive protein levels; and use of metformin, insulin, aspirin, furosemide, and beta-blockers at baseline. High cumulative defined daily dose (cDDD) of SGLT2i was protective of incident HF hospitalization (HR 0.10, 95% CI 0.01-0.68, P = 0.019). The addition of circulating AFABP level to a clinical model of conventional HF risk factors provided significant improvement in the category-free net reclassification index (11.5%, 95% CI 1.6-22.1, P = 0.02) and integrated discrimination improvement (0.3%, 95% CI 0.1-1.7, P = 0.04). A dose-dependent reduction in cumulative incidence of HF hospitalization in response to SGLT2i, based on cDDD, was more clearly observed in participants with a higher baseline AFABP level above the sex-specific median (P for trend <0.01). CONCLUSIONS: Circulating AFABP level is independently associated with incident HF hospitalization in type 2 diabetes and is potentially helpful in risk stratification for the prevention of HF hospitalization.

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.

Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors.

BACKGROUND: The occurrence of Graves' disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. METHODS: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. RESULTS: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. CONCLUSION: Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Outcomes of Graves' Disease Patients Following Antithyroid Drugs, Radioactive Iodine, or Thyroidectomy as the First-line Treatment.

BACKGROUND: The long-term outcomes of first-line choice among ATD, RAI, and thyroidectomy for GD patients remain unclear. OBJECTIVE: To compare the long-term morbidity, mortality, relapse, and costs of GD patients receiving first-line treatment. METHODS: A population-based retrospective cohort of GD patients initiating first-line treatment with ATD, RAI, or thyroidectomy as a first-line primary treatment between 2006 and 2018 from Hong Kong Hospital Authority was analyzed. Risks of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension were estimated using Cox proportional hazards regression models. The 10-year healthcare costs, change of comorbidities, and risk of relapse were compared across treatments. RESULTS: Over a median follow-up of 90 months with 47,470 person-years, 6385 patients (ATD, 74.93%; RAI, 19.95%; thyroidectomy, 5.12%) who received first-line treatment for GD were analyzed. Compared with ATD group, patients who had undergone surgery had significantly lower risks of all-cause mortality [hazard ratio (HR) = 0.363, 95% confidence interval (CI) = 0.332-0.396], CVD (HR = 0.216, 95% CI = 0.195-0.239), AF (HR = 0.103, 95% CI = 0.085-0.124), psychological disease (HR = 0.279, 95% CI = 0.258-0.301), diabetes (HR = 0.341, 95% CI = 0.305-0.381), and hypertension (HR = 0.673, 95% CI = 0.632-0.718). Meanwhile, RAI group was also associated with decreased risks of all-cause mortality (HR = 0.931, 95% CI = 0.882-0.982), CVD (HR = 0.784, 95% CI = 0.742-0.828), AF (HR = 0.622, 95% CI = 0.578-0.67), and psychological disease (HR = 0.895, 95% CI = 0.855-0.937). The relapse rate was 2.41% in surgery, 75.60% in ATD, and 19.53% in RAI group. The surgery group was observed with a significant lower Charlson Comorbidity Index score than the other 2 groups at the tenth-year follow-up. The mean 10-year cumulative healthcare costs in ATD, RAI, and surgery group was US$23915, US$24260, and US$20202, respectively. CONCLUSIONS: GD patients who received surgery as an initial treatment appeared to have lower chances of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension in the long-term when compared to those treated with ATD or RAI. The surgery group had the lowest relapse and direct healthcare costs among the 3 treatment modalities. This long-term cohort study suggested surgery may have a larger role to play as an initial treatment for GD patients.

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes.

OBJECTIVE: Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4). METHODS: We conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. RESULTS: One hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19-11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17-0.71; P = .004). CONCLUSION: Thyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.

Thyroid Dysfunction in Relation to Immune Profile, Disease Status, and Outcome in 191 Patients with COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2-related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers. METHODS: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission. RESULTS: Among 191 patients with COVID-19 (mean age 53.5 ±â€…17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes. CONCLUSION: Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.

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.

Combining high-intensity focused ultrasound (HIFU) ablation with percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules.

OBJECTIVE: Assessing the 6-month efficacy of combined high-intensity focused ultrasound (HIFU) ablation with percutaneous ethanol injection (PEI) in benign thyroid nodules by comparing it with HIFU ablation alone. METHODS: One hundred and eighty-one (55.2%) patients underwent HIFU alone (group I) while 147 (44.8%) underwent concomitant HIFU and PEI treatment for solid or predominantly solid nodules (group II). Intravenous sedation and analgesia were given before the start of treatment. Extent of nodule shrinkage (by volume reduction ratio (VRR)), pain scores (by 0-10 visual analogue scale) during and after ablation, and rate of vocal cord palsy (VCP), skin burn, and nausea/vomiting were compared between the two groups. RESULTS: The mean amount of ethanol injected in group II was 1.3 ± 0.7 ml. The 3- and 6-month VRR were significantly greater in group II (60.41 ± 20.49% vs. 50.13 ± 21.06%, p = 0.001; and 71.08 ± 21.25% vs. 61.37 ± 22.76%, p = 0.001, respectively), and "on-beam" treatment time was significantly shorter in group II (26.55 min vs. 30.26 min, p = 0.001). Group II patients reported significantly lower pain score during treatment (2.24 ± 3.07 vs. 4.97 ± 3.21, p < 0.001) and 2 h after treatment (2.23 ± 2.50 vs. 2.97 ± 4.39, p = 0.044). Rates of VCP, skin burn, and nausea or vomiting were not significantly different (p > 0.05). CONCLUSIONS: The combined HIFU and PEI approach with improved administration of intravenous sedation and analgesia was associated with a significantly better 6-month efficacy than HIFU alone in benign thyroid nodules without compromising the safety and comfort of patients. KEY POINTS: • Concomitant HIFU and PEI have a better treatment efficacy than HIFU alone. • Concomitant HIFU and PEI have a comparable safety profile as HIFU alone.

Identifying predictive factors for efficacy in high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules - a retrospective analysis.

Objective: Since it is unclear whether clinical parameters can independently predict the subsequent treatment response following high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules, we aimed to examine clinical factors that may independently predict 12-month efficacy after HIFU treatment.Methods: One hundred and forty patients who had single ablation were categorized into two groups, those with 12-month nodule shrinkage above the median (Group I, n = 70) and with shrinkage below or equal to the median (Group II, n = 70). Baseline characteristics, treatment parameters, percentage change in serum TSH, Free thyroxine (FT4) and thyroglobulin (Tg) from baseline to Day 4 and appearance of microbubbles (hyperechoic marks (HEMs)) during treatment were compared between groups. To determine independent factors, a multivariate analysis was done by logistic regression analysis.Results: Baseline characteristics and treatment parameters were comparable between groups. However, on Day-4, group I had significantly lower serum TSH (0.49mIU/L vs. 0.84mIU/L, p = 0.011) and higher FT4 (22.11 pmol/L vs. 18.47 pmol/L, p = 0.008) than group II. The percentage change in TSH, FT4 and Tg were significantly greater in group I (p = 0.002, p = 0.009 and p = 0.001 respectively). The proportion of HEMs observed during treatment was also significantly higher in group I (42.69% vs. 31.72%, p = 0.030). Among the significant factors, the percentage change in FT4 was the only independent factor for 12-month shrinkage (OR = 1.018, 95%CI =1.003-1.032, p = 0.017).Conclusions: Percentage change in serum FT4 on post-treatment Day-4 was an independent blood parameter for the subsequent nodule shrinkage at 12 months. This finding could potentially facilitate the decision for earlier retreatment of treated nodules.

Higher Circulating Adiponectin Concentrations Predict Incident Cancer in Type 2 Diabetes - The Adiponectin Paradox.

INTRODUCTION: Despite the beneficial cardiometabolic effects of adiponectin demonstrated in preclinical studies, paradoxically higher circulating adiponectin concentrations have been found in epidemiological studies to be associated with incident cardiovascular events, renal outcomes, and mortality in patients with diabetes. On the other hand, diabetes is also associated with an increased risk of cancer. Here, we investigated prospectively the association between circulating adiponectin concentrations and incident cancer using a cohort of exclusively individuals with type 2 diabetes. MATERIALS AND METHODS: Baseline serum adiponectin concentrations were measured in 5658 participants recruited from the Hong Kong West Diabetes Registry. The associations of circulating adiponectin concentrations with incident cancer and cancer-related deaths were evaluated using multivariable Cox regression analysis, with hazard ratio (HR) for adiponectin referring to the respective risk per doubling of serum adiponectin concentration. RESULTS: Over a median-follow up of 6.5 years, 7.53% and 3% of participants developed cancer and had cancer-related deaths, respectively. Serum adiponectin concentrations were significantly higher in those who had incident cancer (9.8 µg/mL vs 9.1 µg/mL, P < 0.001) and cancer-related deaths (11.5 µg/mL vs 9.3 µg/mL, P < 0.001) compared with those without. Moreover, in multivariable analyses, serum adiponectin concentration was independently associated with both incident cancer (hazard ratio, 1.19; 95% confidence interval, 1.05-1.35; P = 0.006) and cancer-related deaths (hazard ratio, 1.23; 95% confidence interval, 1.03-1.47; P = 0.024). CONCLUSIONS: Higher serum adiponectin concentration was independently associated with incident cancer and cancer-related deaths in type 2 diabetes, indicating that adiponectin paradox can be observed in another major diabetic complication in addition to cardiovascular and kidney diseases.

Glycogenic hepatopathy as an unusual etiology of deranged liver function in a patient with type 1 diabetes: A case report.

RATIONALE: Deranged liver function is a common finding among patients with diabetes mellitus. We report a case of liver biopsy-proven glycogenic hepatopathy (GH) in a patient with long-standing poorly controlled type 1 diabetes (DM1), presented with recurrent transaminitis. PATIENT CONCERNS: A 28-year-old Chinese woman was noted to have deranged liver function with transaminases elevated to more than 15 times the upper limit of normal. DIAGNOSIS: She had underlying long-standing poorly controlled DM1. Blood tests including hepatitis serology and autoimmune panel were negative. Liver biopsy confirmed the diagnosis of GH, showing an increase in glycogen deposition with intact liver parenchymal architecture, and no inflammation or significant fibrosis. INTERVENTIONS: Her glycemic control was optimized. OUTCOMES: Her transaminase levels normalized upon subsequent follow-up with improved glycemic control. LESSONS: GH is suspected when transaminase flare occurs in patients with poorly controlled DM1, usually with exaggerated hemoglobin A1c levels, especially after drug-induced, viral, autoimmune and metabolic liver diseases are excluded. The gold standard of diagnosis is liver biopsy. When diagnosis of GH is ascertained, the mainstay of treatment is to optimize glycemic control. Typically, the transaminases may become normal within days to months after improvement of glycemic control. Compared to non-alcoholic fatty liver disease, GH is associated with favorable prognosis and runs a benign course, making this differentiation clinically important.

Effect of perithyroidal lignocaine infusion (PLI) to pain experienced during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules.

OBJECTIVE: To assess whether perithyroidal lignocaine infusion (PLI) could provide additional analgesia in high-intensity focused ultrasound (HIFU) treatment of benign thyroid nodules for patients already receiving their usual intravenous doses of Pethidine and Diazemuls. METHODS: Two hundred and five patients who underwent HIFU ablation for a benign thyroid nodule were analyzed. Among them, 104 (50.7%) patients received PLI in addition to their boluses of Pethidine and Diazemuls before treatment (group I), while the rest (n = 101, 49.3%) received intravenous Pethidine and Diazemuls only (group II). After treatment, patients were asked to rate their overall pain experience on a visual analogue scale (VAS) (0-100) (0, no pain; 100, worse possible pain) during treatment. Binary logistic regression was performed to evaluate significant determinants for treatment pain including demographics, doses of medications, and treatment parameters. RESULTS: VAS was significantly lower in group I (51.30 vs. 63.79, p = 0.002). In the multivariate analysis, older age at treatment (OR = 1.036, 95%CI = 1.008-1.065, p = 0.011), lower BMI (OR = 1.202, 95%CI = 1.083-1.334, p = 0.001), higher Diazemuls dose (OR = 1.066, 95%CI = 1.018-1.114, p = 0.006), and use of PLI (OR = 2.096, 95%CI = 1.121-3.922, p = 0.020) were independent determinants of less treatment pain. CONCLUSIONS: PLI can provide additional analgesia in patients already receiving their usual intravenous doses of Pethidine and Diazemuls during HIFU ablation of benign thyroid nodules. Older age, lower body mass index, and greater Diazemuls (i.e., a sedative) dose are significantly associated with less treatment pain. KEY POINTS: • PLI provided an additional analgesic effect in HIFU ablation of thyroid nodules. • Older age and lower BMI were significantly associated with less pain. • Higher doses of Diazemuls lessened pain during HIFU ablation.

Two sequential applications of high-intensity focused ultrasound (HIFU) ablation for large benign thyroid nodules.

OBJECTIVE: High-intensity focused ultrasound (HIFU) ablation is a promising treatment for benign thyroid nodules but single application is less effective in larger-sized nodules. We aimed to assess the efficacy and safety of two sequential applications in larger-sized nodules. METHODS: Fifty patients underwent ablation of a large-sized nodule (baseline volume ≥ 20 mL and diameter ≤ 50 mm). Thirty-one (62.0%) patients underwent single application (group I) while 19 (38.0%) underwent two sequential applications (group II). Nodule shrinkage (by volume reduction ratio or VRR), pain scores during and after ablation, and rate of vocal cord palsy (VCP), skin burn, and nausea/vomiting were compared between the two groups. t test or the Mann-Whitney U test was used for continuous variables while chi-square test was used for categorical variables. To determine factors for VRR, multivariate analysis was done by logistic regression analysis. RESULTS: Total energy delivered and treatment time were significantly more in group II (p < 0.001 and p = 0.001, respectively). Total energy per nodule volume (kJ/mL) was also significantly greater in group II (1.01 kJ/mL vs. 0.57 kJ/mL, p < 0.001). The 6-month VRR was significantly greater in group II (56.74 ± 11.47% vs. 43.49 ± 12.03%, p = 0.004). Pain severity and rates of VCP, skin burn, and nausea/vomiting were comparable between the two groups (p > 0.05). Sequential application was an independent determinant of 6-month VRR (OR = 13.936, 95% CI = 1.738-197.399, p = 0.036). CONCLUSIONS: Sequential application led to better 6-month treatment efficacy than single application in large-sized nodules. Patients undergoing sequential application are not at greater risks of treatment-related side effects afterwards. KEY POINTS: • Sequential application produces better 6-month efficacy over single application for large-sized nodules. • Sequential HIFU application is well-tolerated and safe in patients with large-sized nodules. • Sequential application takes longer and requires larger amount of pethidine and diazepam.

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.