Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

US Predictors of Papillary Thyroid Microcarcinoma Progression at Active Surveillance.

Background Active surveillance (AS) is an accepted strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). While previous studies have evaluated the prognostic value of US features, results have been inconsistent. Purpose To determine if US features can help predict tumor progression in patients with low-risk PTMC undergoing AS. Materials and Methods This prospective study enrolled 1177 participants with PTMC from three hospitals between June 2016 and January 2021. Participants were self-assigned to either immediate surgery or AS, and those with two or more US examinations in the absence of surgery were included in the analysis. A χ2 test was used to compare estimated tumor progression rate at 4 years between participants stratified according to US features. Multivariable Cox regression analysis was used to assess the association of clinical and US features with overall tumor progression and specific progression criteria. Results Among 699 participants included in the analysis, 68 (mean age, 49 years ± 12 [SD]; 40 female participants) showed tumor progression (median follow-up, 41.4 months ± 16 [SD]). Tumor progression was associated with the US features of diffuse thyroid disease (DTD) (hazard ratio [HR], 2.3 [95% CI: 1.4, 3.7]; P = .001) and intratumoral vascularity (HR, 1.7 [95% CI: 1.0, 3.0]; P = .04) and the participant characteristics of male sex (HR, 2.8 [95% CI: 1.7, 4.6]; P < .001), age less than 30 years (HR, 2.9 [95% CI: 1.2, 6.8]; P = .01), and thyroid-stimulating hormone level of 7 µU/mL or higher (HR, 6.9 [95% CI: 2.7, 17.4]; P < .001). The risk of tumor progression was higher for participants with DTD (14%, P = .001) or intratumoral vascularity (14%, P = .02) than for participants without these features (6%). DTD and intratumoral vascularity were associated with tumor enlargement (HR, 2.7 [95% CI: 1.4, 5.1]; P = .002) and new lymph node metastasis (HR, 5.0 [95% CI: 1.3, 19.4]; P = .02), respectively. Conclusion DTD and intratumoral vascularity were associated with an increased risk of tumor progression in participants with PTMC undergoing AS. Clinical trial registration no. NCT02938702 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Reuter and the review "International Expert Consensus on US Lexicon for Thyroid Nodules" by Durante et al in this issue.

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review.

BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.

Clinicopathological indicators for TERT promoter mutation in papillary thyroid carcinoma.

OBJECTIVE: Mutations in the telomerase reverse transcriptase (TERT) promoter have been reported as a convincing prognostic factor in papillary thyroid carcinomas (PTCs). We aimed to investigate the frequency of TERT promoter mutations in patients with thyroid cancer and identify the clinicopathological factors associated with them in PTCs. DESIGN: A total of 1086 consecutive cases of thyroid cancer composed of mostly PTCs were included in this study. TERT promoter and BRAF mutations were detected by pyrosequencing and their associations with clinicopathological features of tumour were analyzed. RESULTS: TERT promoter mutations were observed in 1.9% of PTCs, 6.7% of follicular thyroid carcinomas, 8.3% of Hurthle cell carcinomas and 25.0% of poorly differentiated thyroid carcinomas and in a single case of anaplastic thyroid carcinoma. In PTCs, aggressive clinicopathological features, higher stage and BRAF V600E mutation were all found to be associated with TERT promoter mutations. Distant metastasis and disease recurrence were more frequent in TERT promoter-mutated PTCs. In multivariate analysis, age ≥55 years, tall cell variant, mitoses ≥3/10 high-power fields, tumour necrosis, and gross extrathyroidal extension (ETE) were identified as independent factors associated with TERT promoter mutations in PTCs. CONCLUSIONS: This study revealed a relatively low frequency of TERT promoter mutations in Korean patients with PTC. Certain clinicopathological features including old age, tall cell variant, increased mitoses, tumour necrosis and gross ETE were found to be indicative of TERT promoter mutations in PTCs, suggesting that mutational analysis in a particular group of PTCs can be effective in regions with low mutation rates.

Effect of increased levothyroxine dose on depressive mood in older adults undergoing thyroid hormone replacement therapy.

OBJECTIVE: Depressive mood consequent to hypothyroidism can be reversed with levothyroxine (LT4) replacement therapy. However, it is unclear whether increasing LT4 dose confers additional mood benefits. DESIGN AND PATIENTS: A single-blinded before-and-after study of 24 patients with hypothyroidism who were aged 65 years or older and undergoing LT4 replacement therapy with stable doses. MEASUREMENTS: Geriatric Depression Scale (GDS-K) and Hyperthyroid Symptom Scale (HSS-K) were assessed at baseline, 3 months after increasing LT4 dose by an additional 12.5 µg/d, and finally 3 months after returning to the baseline dose. RESULTS: Serum thyroid-stimulating hormone (TSH) concentrations decreased at the higher LT4 dose (1.95 ± 2.16 vs 0.47 ± 1.09 mIU/L, P < .001) and recovered after returning to the baseline dose. Serum-free thyroxine levels and HSS-K scores were unchanged during the study period. GDS-K scores improved on the increased dose (9.5 ± 6.6 vs 7.5 ± 4.7, P = .029), and this improvement was maintained after returning to the baseline dose (9.5 ± 6.6 vs 7.4 ± 5.4, P = .010). Higher serum TSH was independently associated with both higher GDS-K and depression risk among those with depressive mood (GDS-K > 10) at baseline. CONCLUSIONS: Depressive mood improves with increased LT4 dose, without significant hyperthyroid symptoms or signs, in older adults undergoing thyroid hormone replacement. These findings suggest the potential for varying the treatment target for hypothyroidism based on mood status and that low-dose LT4 treatment might be an ancillary treatment for depression.

Effect of cilostazol, a phosphodiesterase-3 inhibitor, on coronary artery stenosis and plaque characteristics in patients with type 2 diabetes: ESCAPE study.

AIM: To perform a prospective study to evaluate the effect of cilostazol (CTZ) compared with aspirin (acetylsalicylic acid; ASA) in Korean people with diabetes and subclinical coronary atherosclerosis. MATERIALS AND METHODS: A total of 100 people with diabetes who had mild to moderate coronary atherosclerosis, assessed by coronary computed tomographic angiography (CCTA), were randomly assigned to either 200 mg/d CTZ or 100 mg/d ASA (n = 50 each group). The primary outcome was change in coronary artery stenosis assessed by CCTA after 12 months of treatment. Secondary outcomes included changes in plaque composition, coronary artery calcium score and cardiac markers. RESULTS: The mean age, body mass index and glycated haemoglobin concentration were 61.5 years, 25.0 kg/m2 and 56.8 mmol/mol, respectively, and were well matched between the two groups. Coronary artery stenosis decreased in the CTZ group (from 44.0 ± 2.1% to 40.4 ± 2.5%) but remained unchanged in the ASA group (from 38.9 ± 2.1% to 40.6 ± 2.1%). In the CTZ group, the non-calcified portion of plaques decreased significantly (from 20.6 ± 3.0 to 17.3 ± 3.0 mm3 ), whereas it did not change significantly in the ASA group (15.2 ± 2.8 vs 16.6 ± 2.9 mm3 ). Increases in HDL cholesterol, decreases in triglycerides, liver enzyme and high-sensitivity C-reactive protein levels, and reductions in abdominal visceral fat area and insulin resistance were observed only in the CTZ group. CONCLUSION: CTZ treatment for 12 months decreased coronary artery stenosis and the non-calcified plaque component. These results suggest that CTZ treatment may be an option for preventing the progression of coronary atherosclerosis in people with diabetes.

Suppression of Nrf2 attenuates adipogenesis and decreases FGF21 expression through PPAR gamma in 3T3-L1 cells.

Adipogenesis is the process of differentiation from preadipocytes to adipocytes and is orchestrated by various transcription factors, such as the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). Oxidative stress is also a crucial factor in adipogenesis, and adipocyte differentiation is affected by the cellular redox status. The nuclear factor E2-related factor 2 (Nrf2), which is a basic leucine zipper (bZIP) transcription factor, acts as a regulator of cellular oxidative stress. Although several previous studies examined the function of Nrf2 in adipogenesis, their results were controversial. In this study, we investigated whether the suppression of Nrf2 in 3T3-L1 cells affected adipogenesis. We found that adipogenesis master regulator genes, such as PPARγ and C/EBPα, were downregulated during the differentiation stage in Nrf2-knockdown 3T3-L1 cells. Moreover, the fibroblast growth factor 21 (FGF21) and manganese superoxide dismutase (MnSOD) were markedly downregulated in Nrf2-knockdown 3T3-L1 cells. Taken together, the results of the present study suggest that the suppression of Nrf2 attenuates adipogenesis and decreases FGF21 expression through PPARγ in 3T3-L1 cells.

Case-Control Study of Papillary Thyroid Carcinoma on Urinary and Dietary Iodine Status in South Korea.

BACKGROUND: The association between iodine levels and the risk of papillary thyroid cancer (PTC) has been suggested, but not definitively established. This study is to compare the iodine status of a group of patients with PTC (with and without BRAF V600E) with that of a healthy population cohort. METHODS: A cohort of patients scheduled for thyroidectomy was enrolled, along with a community-based health-screening cohort with no known history of thyroid disease. Median urinary iodine (UI) levels, creatinine-adjusted median UI levels, and food frequency questionnaire (FFQ) scores (mean ± SD) were compared. In a subgroup analysis, these values were compared between BRAF V600E-positive and BRAF V600E-negative patients in the PTC group. RESULTS: The PTC group consisted of 210 patients, and the control group consisted of 90 healthy individuals. Among the 191 PTC patients whose BRAF V600E mutational status was reported, 169 (88.5%) were revealed positive for the mutation. The median UI levels were significantly higher in the PTC group (786.0 µg/l) than the control group (112.0 µg/l; p < 0.001), as was the case with creatinine-adjusted median UI levels (884.6 µg/g creatinine versus 182.0 µg/g creatinine; p < 0.001) and FFQ scores (66.2 ± 17.5, range 13-114 versus 54.6 ± 21.5, range 16-134; p < 0.001). No significant differences were seen in the subgroup analysis between BRAF V600E-positive and BRAF V600E-negative patients. CONCLUSIONS: Our results indicate that iodine status differs significantly between patients with PTC and healthy controls, suggesting that iodine may be involved in the occurrence of PTC, although the association between iodine levels and BRAF mutational status did not reach statistical significance.

One-hour postload plasma glucose concentration in people with normal glucose homeostasis predicts future diabetes mellitus: a 12-year community-based cohort study.

OBJECTIVE: In Caucasians, plasma glucose concentration at 1 h during an oral glucose tolerance test (OGTT) may be a better predictor of future diabetes mellitus than the fasting or 2-h postload glucose concentration. We investigated whether the 1-h glucose concentration could be used to predict future diabetes mellitus in Asian ethnicity. MEASUREMENTS: A total of 5703 Koreans with normal glucose tolerance were enrolled from the Korean Genome and Epidemiology Study. Indices of insulin sensitivity and ß-cell function estimated from standard 75-g OGTTs performed every 2 years for 12 years were used to identify whether the 1-h glucose concentration could predict future diabetes mellitus. RESULTS: The mean age and body mass index at baseline were 51·3 ± 8·7 years and 24·2 ± 3·0 kg/m2 , respectively. During the 12-year follow-up, 593 subjects (10·3%) developed diabetes mellitus. The area under the receiver-operating characteristic curve for incident diabetes mellitus was higher for the 1-h postload glucose concentration than for the fasting or postload 2-h glucose concentration (0·74 vs 0·61 or 0·63). The cut-off value of ≥8·0 mmol/l identified incident diabetes mellitus with 70% sensitivity and 68% specificity. After adjusting for typical risk factors, subjects with a 1-h postload glucose concentration ≥8·0 mmol/l had lower ß-cell function and a 2·84-fold increased risk of incident diabetes mellitus compared with their counterparts. CONCLUSIONS: In this community-based 12-year prospective cohort study, 1-h postload plasma glucose concentration was an independent predictor of future diabetes mellitus and 8·0 mmol/l was suggested as a cut-off value.

Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus.

CONTEXT: A previous genome-wide association study showed that a genetic variant of sortilin was associated with the risk of coronary artery disease (CAD). However, the role of circulating sortilin is still unknown. We investigated the potential role of plasma sortilin as a biomarker for CAD and diabetes mellitus. METHODS: We enrolled statin-naïve subjects with CAD (n = 31) who underwent coronary artery bypass surgery and control subjects (n = 116) who were free from CAD as evaluated by coronary CT angiography. The presence of diabetes mellitus was evaluated and plasma sortilin levels were measured with a commercial ELISA kit. RESULTS: Plasma sortilin levels were higher in subjects with CAD and subjects with diabetes mellitus than in those without CAD or diabetes mellitus. Subjects in the highest sortilin tertile group were older and had higher glucose and HbA1c levels, but lipid profiles in the three tertile groups were comparable. Multivariable logistic regression analysis revealed that sortilin levels were independently associated with CAD. In addition, the receiver operating characteristic curve analysis showed that plasma sortilin levels could identify the presence of CAD or diabetes mellitus. CONCLUSIONS: Elevated circulating sortilin levels are associated with CAD and diabetes mellitus and can be used as a biomarker of both diseases in statin-naïve subjects.

Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients.

BACKGROUND: Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes. METHODS: In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years). RESULTS: TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after additional adjustments for pathologic characteristics. Furthermore, TERT promoter mutations significantly increased the risk of both recurrence and mortality in the ATA high-risk (HR for recurrence, 5.79; 95% CI, 2.07-16.18; HR for mortality, 16.16; 95% CI, 2.10-124.15) and TNM stage III/IV groups (HR for recurrence, 3.60; 95% CI, 1.19-10.85; HR for mortality, 9.06; 95% CI, 2.09-39.26). CONCLUSIONS: The coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high-risk patients with DTC. Cancer 2016;122:1370-1379. © 2016 American Cancer Society.

Recombinant human thyrotropin-stimulated thyroglobulin level at the time of radioactive iodine ablation is an independent prognostic marker of differentiated thyroid carcinoma in the setting of prophylactic central neck dissection.

OBJECTIVE: We investigated the value of the stimulated thyroglobulin (Tg) level at the time of recombinant human thyrotropin (rhTSH)-aided remnant ablation for predicting disease status 1 year later in patients with DTC who underwent total thyroidectomy with central neck dissection (CND). DESIGN, SETTING, AND PARTICIPANT: This was a prospective observational study of 253 consecutive patients with DTC who underwent rhTSH-aided RAI ablation after total thyroidectomy and prophylactic CND. Patients with evidence of initial distant metastasis or positive Tg antibodies were excluded. MAJOR OUTCOME MEASURE: We compared rhTSH-stimulated Tg level at RAI ablation according to the disease status at 1 year and evaluated optimal cut-off value of rhTSH-stimulated Tg. Binary logistic regression analysis was performed to investigate the independent predictive factors for disease status 1 year after ablation. RESULTS: Among study participants, 228 (90·1%) were considered disease free at 1 year after remnant ablation. Patients with persistent or recurrent disease were more likely to be aged ≥45 years, and to have N1b stage, TNM stage III or IV, and higher rhTSH-stimulated Tg level at RAI ablation. The optimal cut-off of rhTSH-stimulated Tg for predicting persistent or recurrent disease was 1·79 ng/ml, with a negative predictive value of 99·5%. A serum rhTSH-stimulated Tg level ≥1·79 at the time of ablation was independently associated with persistent or recurrent disease 1 year later. N1b stage tended to be associated with persistent or recurrent disease. CONCLUSION: A low stimulated serum Tg level at rhTSH-aided RAI ablation may be a favourable prognostic marker in the setting of prophylactic CND.

Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults.

BACKGROUND AND PURPOSE: We investigated the association between cardiovascular risk factors, including carotid intima-media thickness (CIMT), and future risk of mild cognitive impairment (MCI) and dementia in elderly subjects. METHODS: We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Our study included 348 participants who were nondemented at the baseline (mean age, 71.7±6.3 years) and underwent cognitive evaluation at the 5-year follow-up. Baseline cardiovascular risk factors were compared according to the development of MCI or dementia during the study period. RESULTS: At the baseline evaluation, 278 subjects were cognitively normal and 70 subjects had MCI. Diagnoses of cognitive function either remained unchanged or improved during the study period in 292 subjects (nonprogression group), whereas 56 subjects showed progression of cognitive impairment to MCI or dementia (progression group). The progression group exhibited a higher prevalence of hypertension and greater CIMT compared with the nonprogression group. Other baseline cardiovascular risk factors, including sex, body mass index, diabetes mellitus, insulin resistance, total cholesterol, waist-to-hip ratio, visceral fat, pulse wave velocity, and ankle-brachial index, were not significantly different between 2 groups. The association between greater baseline CIMT and the progression of cognitive impairment was maintained after adjustment for conventional baseline risk factors of cognitive impairment. Greater baseline CIMT was also independently associated with the development of MCI in the subjects whose baseline cognitive function was normal. CONCLUSIONS: Greater baseline CIMT was independently associated with the risk of cognitive impairment, such as MCI and dementia in elderly subjects.

The amount of C1q-adiponectin complex is higher in the serum and the complex localizes to perivascular areas of fat tissues and the intimal-medial layer of blood vessels of coronary artery disease patients.

BACKGROUND: The complement component C1q triggers activation of the classical immune pathway and can bind to adiponectin (APN). Recently, some studies have been reported that serum C1q-APN/total APN ratio correlates with atherosclerosis and coronary artery disease (CAD). We assessed the relationships between C1q related variables and the severity of CAD, and investigated the localization of the C1q-APN complex. METHODS: The sample included 153 subjects comprising healthy controls and patients with subclinical or overt CAD. We measured the serum concentrations of C1q, total APN, and high-molecular weight (HMW)-APN, and the amount of C1q-APN complex. We identified the sites of C1q-APN complex deposition in various adipose tissues and blood vessels. RESULTS: Serum concentrations of C1q and HMW-APN and the C1q/HMW-APN ratio were independently associated with the severity of coronary stenosis. The amount of C1q-APN complex was significantly higher in patients with CAD compared with controls. C1q and APN co-localized in perivascular areas of subcutaneous, visceral, and pericardial fat tissues, and the internal mammary artery of patients with severe CAD. CONCLUSIONS: Serum C1q concentration and the C1q/HMW-APN ratio were independent markers of coronary artery stenosis. The amount of C1q-APN complex was significantly greater in serum from CAD patients. C1q and APN co-localized to perivascular areas in adipose tissue and blood vessels. The association between the increased amount of the C1q-APN complex and CAD should be investigated further.

The role of ultrasound findings in the management of thyroid nodules with atypia or follicular lesions of undetermined significance.

BACKGROUND: Atypia or follicular lesions of undetermined significance (AUS/FLUS) is a broad cytological category in the Bethesda system for classifying thyroid cytology. This study investigated the diagnostic accuracy of ultrasound (US) analysis of thyroid nodules with AUS/FLUS. PATIENTS AND METHODS: Of 5062 subjects with nodules subjected to fine-needle aspiration cytology (FNACs) at our institution from January 2010 through May 2012, 383 met the Bethesda criteria for AUS/FLUS. After excluding subjects who had a history of thyroid cancer, who only underwent repeat FNA or who underwent no further examinations, we selected 249 subjects who had subsequently undergone a core-needle biopsy and/or surgery. Of these, 100 were found to have malignant nodules (40·2%), 122 had benign nodules (49%), and 27 had nodules with indeterminate status (10·8%). We compared specific US parameters, including size, location, content, shape, margin, echogenicity, echotexture and calcification across these subject groups. RESULTS: Multivariate analysis revealed that malignancy was associated with taller-than-wide shape (TDW) (OR = 8·43, P = 0·002), ill-defined margin (OR = 3·23, P = 0·002) and marked hypoechogenicity. (OR = 3·61, P = 0·001). The specificity and positive predictive values of TDW were 98% and 90·6%,respectively. The specificity and positive predictive values of 'TDW and marked hypoechogenicity' were both 100%. CONCLUSION: US findings play a complementary role in the diagnosis of thyroid nodules with AUS/FLUS. In case of highly suspicious US findings such as 'TDW and marked hypoechogenicity', could be very helpful in the diagnosis of malignancy.

Cost-Effectiveness Analysis Comparing Conventional and Digital Software Supported Management for Hypothyroidism.

BACKGROUND: Wearable devices can now leverage the established correlation between thyroid function and heart rate to monitor thyroid function alongside exercise levels and heart rate. The objective was to assess the cost-effectiveness of introducing a wearable/mobile-based thyroid function digital monitoring solution for the management of hypothyroidism compared to the conventional management approach. METHODS: A decision-analytic Markov state-transition simulation model employed for utilizing a simulated cohort of 10,000 40-year-old patients with hypothyroidism to estimate costs and health outcomes. Cost-effectiveness from the healthcare sector perspective was evaluated using a 4.5% annual discount rate and the costs adjusted to 2022 levels, and lifetime outcomes were presented through incremental cost-effectiveness 49 ratios (ICERs). Deterministic and probabilistic sensitivity analyses evaluated the robustness of the results. RESULTS: The digital monitoring solution supported group yielded an additional 0.65 QALYs with an incremental cost of $11700.87, resulting in an ICER value of $17988.97 per QALY gained. Digital-powered software could be an optimal strategy in 99% of iterations against willingness-to-pay thresholds of $32,255/QALY gained. The ICER was most sensitive to the annual cost of a digital monitoring solution for hypothyroidism. CONCLUSION: The incorporation of the digital monitoring solution has demonstrated positive cost-effectiveness in hypothyroidism management when compared to the standard care. The cost of the digital monitoring solution and its sensitivity are key factors in determining cost-effectiveness. Striking a balance among the cost of digital monitoring support, the precision of hormonal level monitoring, and its effectiveness for the specific group of hypothyroid patients in real-world clinical practice is essential.

Artificial intelligence-based CT-free quantitative thyroid SPECT for thyrotoxicosis: study protocol of a multicentre, prospective, non-inferiority study.

INTRODUCTION: Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves' disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT. METHODS AND ANALYSIS: The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves' disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy-SPECT/CT accuracy) for Graves' disease is greater than -0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

A Preliminary Evaluation of the Diagnostic Performance of a Smartphone-Based Machine Learning-Assisted System for Evaluation of Clinical Activity Score in Digital Images of Thyroid-Associated Orbitopathy.

Background: We previously developed a machine learning (ML)-assisted system for predicting the clinical activity score (CAS) in thyroid-associated orbitopathy (TAO) using digital facial images taken by a digital single-lens reflex camera in a studio setting. In this study, we aimed to apply this system to smartphones and detect active TAO (CAS ≥3) using facial images captured by smartphone cameras. We evaluated the performance of our system on various smartphone models and compared it with the performance of ophthalmologists with varying clinical experience. Methods: We applied the preexisting ML architecture to classify photos taken with smartphones (Galaxy S21 Ultra, iPhone 12 pro, iPhone 11, iPhone SE 2020, Galaxy M20, and Galaxy A21S). The performance was evaluated with smartphone-captured images from 100 patients with TAO. Three ophthalmology residents, three general ophthalmologists with <5 years of clinical experience, and three oculoplastic specialists independently interpreted the same set of images taken under a studio environment and compared their results with those generated by the smartphone-based ML-assisted system. Reference CAS was determined by a consensus of three oculoplastic specialists. Results: Active TAO (CAS ≥3) was identified in 28 patients. Smartphone model used in capturing facial images influenced active TAO detection performance (F1 score 0.59-0.72). The smartphone-based system showed 74.5% sensitivity, 84.8% specificity, and F1 score 0.70 on top three smartphones. On images from all six smartphones, average sensitivity, specificity, and F1 score were 71.4%, 81.6%, and 0.66, respectively. Ophthalmology residents' values were 69.1%, 55.1%, and 0.46. General ophthalmologists' values were 61.9%, 79.6%, and 0.55. Oculoplastic specialists' values were 73.8%, 90.7%, and 0.75. This smartphone-based ML-assisted system predicted CAS within 1 point of reference CAS in 90.7% using facial images from smartphones. Conclusions: Our smartphone-based ML-assisted system shows reasonable accuracy in detecting active TAO, comparable with oculoplastic specialists and outperforming residents and general ophthalmologists. It may enable reliable self-monitoring for disease activity, but confirmatory research is needed for clinical application.

Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines.

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Comparison of Patient-Reported Outcomes Between Active Surveillance and Immediate Lobectomy in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Initial Findings from the KoMPASS Cohort.

Background: Patients diagnosed with low-risk papillary thyroid microcarcinoma (PTMC) face the decision between thyroid lobectomy and active surveillance (AS). This study aimed to investigate the factors influencing treatment decisions in low-risk PTMC and to compare the quality of life (QoL) according to the treatment plan. Methods: The multicenter prospective cohort study comparing AS and thyroid lobectomy was conducted. Clinical characteristics were compared between the AS and Lobectomy groups. QoL questionnaires were administered every 6 months in the initial year and annually thereafter. Results: A total of 927 patients (453 in the AS group and 474 in the Lobectomy group) with low-risk PTMC were included in this study. The mean age was 47.4 ± 12.2 years, and 72.2% of the patients were women. Older age (odd ratio [OR] 1.04, confidence interval [CI] 1.02-1.05, p < 0.001), smaller tumor size (OR 0.78, CI 0.69-0.87, p < 0.001), family history of thyroid cancer (OR 1.48, CI 1.03-2.12, p = 0.035), prior awareness of AS (OR 1.53, CI 1.16-2.02, p = 0.003), and higher income (OR 1.79, CI 1.13-2.83, p = 0.013) were significantly associated with a higher likelihood of choosing AS. The median follow-up was 27.3 months (23.9-43.9) in the AS group and 28.7 months (20.4-44.5) in the Lobectomy group. During the follow-up period, the AS group showed significantly better QoL scores compared with the Lobectomy group (ß 0.17, CI 0.02-0.33, p = 0.029). Although baseline QoL scores favored the AS group significantly (7.1 ± 1.2 vs. 6.7 ± 1.2, p < 0.001), no significant difference was observed after 12 months (7.2 ± 1.2 vs. 7.1 ± 1.2, p = 0.592). Conclusions: This study demonstrated that age, tumor size, family history of thyroid cancer, awareness of AS, and income were associated with patients' treatment choices. Although the overall QoL scores were significantly higher in the AS group, the QoL became similar between the two groups after 12 months. Clinical Trial Registration: KCT0004935.