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Autonomously functioning thyroid nodules present intermediate malignancy risk according to European Thyroid Imaging Reporting and Data System (EU-TIRADS) and yield indeterminate cytology results. 根据欧洲甲状腺成像和报告数据系统(EU-TIRADS),自主功能甲状腺结节呈现中等恶性风险,细胞学结果不确定。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-12-20 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0135
Aglaia Kyrilli, Nunzia Tacelli, Lucia Russo, Laetitia Lebrun, Isabelle Salmon, Gilles Russ, Rodrigo Moreno-Reyes, Bernard Corvilain

Objectives: The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients.

Methods: A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 - scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis.

Results: More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03-0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1-35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12).

Conclusions: Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

目的:评价连续患者自主功能甲状腺结节(AFTN)的临床、超声和病理组织学特征。方法:我们从2018年3月至2021年9月进行了一项前瞻性单中心研究,纳入了901例连续转诊进行甲状腺工作的患者,共评估了67例AFTN。所有入组患者均接受99mTcO4-闪烁成像,仅在血清TSH正常的情况下附加123I闪烁成像,甲状腺功能评估,使用欧洲甲状腺成像和报告数据系统(EU-TIRADS)进行美国检查,并在必要时进行美国引导的细针穿刺(FNA)细胞学检查。所有不确定的FNA样本进行DNA测序分析。结果:半数以上的AFTN患者甲状腺功能正常;血清TSH中位数为0.41 (IQR: 0.03 ~ 0.97) mU/L。US测定的AFTN中位大小为27.0 (IQR: 21.1-35.0) mm。28.4%的AFTN被划分为EU-TIRADS评分3分,71.6%的AFTN被划分为EU-TIRADS评分4分,根据US,大多数AFTN具有中等恶性风险。在接受细胞学评估的47个AFTN中,24个(51%)产生不确定的FNA结果。DNA测序显示60%的病例发生致病性TSHR和GNAS突变。手术切除的AFTN (N=12)最终组织学未检出恶性肿瘤。结论:在本研究评估的67例AFTN中,50%血清TSH正常,70%超声特征提示中度恶性肿瘤风险,50%提交细胞学检查的AFTN结果不确定。未检出恶性AFTN。
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引用次数: 0
Effects of iodine status on thyroid volume and goiter in children living in an iodine-replete area. 碘水平对生活在缺碘地区儿童甲状腺体积和甲状腺肿的影响。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-12-18 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0219
Yun Jeong Lee, Young Hun Choi, Youn-Hee Lim, Bung-Nyun Kim, Johanna Inhyang Kim, Yun-Chul Hong, Young Joo Park, Choong Ho Shin, Sun Wook Cho, Young Ah Lee

Objective: Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea.

Methods: Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 μg/L), adequate (100-299 μg/L), mild excess (300-499 μg/L), moderate excess (500-999 μg/L), and severe excess (≥1000 μg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol greater than 97th percentile value by age- and body surface area (BSA)-specific international references.

Results: The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (P for trend <0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (adjusted odds ratio (aOR) = 3.1 (95% CI: 1.1-9.2) and aOR = 3.1 (95% CI: 1.2-8.3), respectively; age-specific criteria) than the iodine-adequate group.

Conclusions: Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.

目的:充足的碘摄入对成长中的儿童至关重要,甲状腺体积(Tvol)被认为是碘状态的一个指标。我们对228名生活在韩国的6岁儿童进行了Tvol和甲状腺肿超声检查,并研究了它们与碘含量的关系。方法:使用尿碘浓度(UIC)评估碘状态,并根据年龄和体表面积(BSA)特异性国际参考文献将其分类为缺碘(第97百分位值)。结果:Tvol中位数为2.4 mL,高于国际参考值1.6 mL。年龄特异性和bsa特异性甲状腺肿率分别为25.9% (n = 59)和34.6% (n = 79)。碘过量患病率为73.7% (n = 168)。随着碘含量从充足增加到严重过量,甲状腺肿率显著增加(p < 0.05)。中度和重度碘过量组甲状腺肿- us的风险较高(aOR分别为3.1 [95% CI, 1.1-9.2]和aOR为3.1 [95% CI, 1.2-8.3]);年龄特异性标准)比碘充足组高。结论:韩国儿童碘含量普遍偏高,Tvol高于国际参考值。甲状腺肿率与碘过量有关,在中度和重度碘过量组显著增加。需要进一步的研究来确定儿童的最佳碘摄入量。
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引用次数: 0
Real-World Practice Patterns and Outcomes for RAI-Refractory Differentiated Thyroid Cancer RAI 难治性分化型甲状腺癌的实际应用模式和结果
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-12-01 DOI: 10.1530/etj-23-0039
Andrew G Gianoukakis, Jennifer H. Choe, Daniel W. Bowles, Marcia S. Brose, Lori Wirth, Taofeek Owonikoko, Svetlana Babajanyan, Francis P. Worden

Background: The optimal timing for initiating multi-kinase inhibitors (MKIs) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC) remains unclear. Thus, we evaluated the real-world practice patterns and outcomes in asymptomatic patients with progressive RAI-R DTC (≥1 lesion ≥1 cm in diameter) in the United States (US) and outside the US (non-US).

Methods: In this prospective, non-interventional, open-label study, eligible patients were chosen by treating physicians to receive MKI therapy (Cohort 1) or undergo active surveillance (Cohort 2) at study entry. Cohort 2 patients were allowed to transition to MKI therapy later. The primary endpoint was time to symptomatic progression (TTSP) from study entry. Data were compared descriptively. When endpoints were inestimable, 36-month rates were calculated.

Results: Among 647 patients, 478 underwent active surveillance (Cohort 2) and 169 received MKI treatment (Cohort 1). Patients underwent surveillance at a higher rate in the US (92.6%) versus the non-US (66.9%). Half of US and non-US patients who qualified for MKI treatment had initial American Thyroid Association (ATA) low-to-intermediate-risk disease. Among Cohort 2, the 36-month TTSP rates from study entry were 65.6% and 66.5% in the US and non-US, respectively. Cohort 2 patients treated later demonstrated 36-month TTSP rates of 30.8% and 55.8% in the US and non-US, respectively.

Conclusions: Active surveillance is a viable option for asymptomatic patients with progressive RAI-R DTC. However, early intervention with MKI therapy may be more suitable for others. Further research is needed to identify patients who are optimal for active surveillance.

Registration: NCT02303444

背景:放射性碘难治性(RAI-R)分化型甲状腺癌(DTC)患者开始使用多激酶抑制剂(MKIs)的最佳时机仍不明确。因此,我们评估了美国(US)和美国以外地区(非US)无症状进展期 RAI-R DTC(≥1 个直径≥1 厘米的病灶)患者的实际治疗模式和疗效。方法:在这项前瞻性、非介入、开放标签的研究中,符合条件的患者由主治医生在研究开始时选择接受 MKI 治疗(队列 1)或接受主动监测(队列 2)。队列 2 患者可在之后过渡到 MKI 治疗。研究的主要终点是研究开始后出现症状进展的时间(TTSP)。对数据进行描述性比较。如果终点无法估计,则计算36个月的比率:在 647 名患者中,478 人接受了主动监测(队列 2),169 人接受了 MKI 治疗(队列 1)。美国患者接受监测的比例(92.6%)高于非美国患者(66.9%)。有资格接受 MKI 治疗的美国和非美国患者中,有一半最初患有美国甲状腺协会(ATA)低至中危疾病。在队列 2 中,美国和非美国患者自研究开始后 36 个月的 TTSP 率分别为 65.6% 和 66.5%。随后接受治疗的队列2患者在美国和非美国的36个月TTSP率分别为30.8%和55.8%:结论:对于无症状的进行性 RAI-R DTC 患者来说,积极监测是一个可行的选择。然而,对其他患者来说,使用 MKI 治疗进行早期干预可能更合适。需要进一步研究来确定哪些患者最适合接受主动监测。注册:NCT02303444
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引用次数: 0
Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease. 甲状腺过氧化物酶和甲状腺球蛋白抗体在药物治疗Graves病中的意义。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-30 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0193
Stefan Matei Constantinescu, Julien Hospel, Chantal Daumerie, Orsalia Alexopoulou, Dominique Maiter, Maria-Cristina Burlacu

Background: Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial.

Methods: We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse.

Results: At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034).

Conclusion: In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.

目的甲状腺过氧化物酶(TPOAb)和甲状腺球蛋白(TgAb)抗体在Graves病(GD)中高度流行,但其意义尚存在争议。方法我们回顾性分析了2000年至2022年间136名新诊断的GD患者的TPOAb和TgAb水平和演变,这些患者在阻断和替代(B+R)方案中接受了抗甲状腺药物(ATD)治疗至少12个月,并在ATD停用后或疾病复发前随访至少一年。结果在诊断时,98/136(72%)的患者TPOAb阳性,73/136(54%)的患者TgAb阳性。诊断时TPOAb或TgAb抗体的存在通常与GD表现无关,也不影响复发风险(分别为p=0.304和p=0.348)。在诊断时,TgAb阳性患者的TED(甲状腺眼病)少于Tg Ab阴性患者(11/73(15.1%)对21/63(33.3%),p=0.012)。相反,诊断时TPOAb的存在与TED无关(p=0.354),在多变量逻辑回归中与TED相关。治疗期间和停药后的TPOAb和TgAb水平不能预测复发,除了复发患者在18个月时TgAb滴度较低(p=0.034)。结论在接受B+R方案第一个疗程ATD治疗的GD患者中,我们观察到复发患者在治疗结束时Tg阿布滴度较低,并且在诊断时Tg阿布阳性的患者中对TED有显著的保护作用,而与TPOAb无关。
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引用次数: 0
Decreased hepatic thyroid hormone signaling in systemic and liver-specific but not brain-specific accelerated aging due to DNA repair deficiency in mice. 由于小鼠DNA修复缺陷,全身性和肝特异性但非脑特异性的肝甲状腺激素信号减少加速了衰老。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-23 Print Date: 2023-12-01 DOI: 10.1530/ETJ-22-0231
Sander Barnhoorn, Marcel E Meima, Robin P Peeters, Veerle M Darras, Selmar Leeuwenburgh, Jan H J Hoeijmakers, Wilbert P Vermeij, W Edward Visser

Background: Thyroid hormone signaling is essential for development, metabolism, and response to stress but declines during aging, the cause of which is unknown. DNA damage accumulating with time is a main cause of aging, driving many age-related diseases. Previous studies in normal and premature aging mice, due to defective DNA repair, indicated reduced hepatic thyroid hormone signaling accompanied by decreased type 1 deiodinase (DIO1) and increased DIO3 activities. We investigated whether aging-related changes in deiodinase activity are driven by systemic signals or represent cell- or organ-autonomous changes.

Methods: We quantified liver and plasma thyroid hormone concentrations, deiodinase activities and expression of T3-responsive genes in mice with a global, liver-specific and for comparison brain-specific inactivation of Xpg, one of the endonucleases critically involved in multiple DNA repair pathways.

Results: Both in global and liver-specific Xpg knockout mice, hepatic DIO1 activity was decreased. Interestingly, hepatic DIO3 activity was increased in global, but not in liver-specific Xpg mutants. Selective Xpg deficiency and premature aging in the brain did not affect liver or systemic thyroid signaling. Concomitant with DIO1 inhibition, Xpg -/- and Alb-Xpg mice displayed reduced thyroid hormone-related gene expression changes, correlating with markers of liver damage and cellular senescence.

Conclusions: Our findings suggest that DIO1 activity during aging is predominantly modified in a tissue-autonomous manner driven by organ/cell-intrinsic accumulating DNA damage. The increase in hepatic DIO3 activity during aging largely depends on systemic signals, possibly reflecting the presence of circulating cells rather than activity in hepatocytes.

背景甲状腺激素信号传导对发育、代谢和对压力的反应至关重要,但在衰老过程中会下降,其原因尚不清楚。DNA损伤随着时间的推移而积累是衰老的主要原因,导致许多与年龄相关的疾病。先前对正常和早衰小鼠的研究表明,由于DNA修复缺陷,肝脏甲状腺激素信号传导减少,同时1型脱碘酶(DIO1)减少,DIO3活性增加。我们研究了脱碘酶活性的衰老相关变化是否由系统信号驱动,或代表细胞或器官自主变化。方法我们对小鼠的肝脏和血浆甲状腺激素浓度、脱碘酶活性和T3反应基因的表达进行了量化,Xpg是一种关键参与多种DNA修复途径的核酸内切酶,具有全局性、肝脏特异性和脑特异性失活。结果在全肝和肝特异性Xpg敲除小鼠中,肝脏DIO1活性均降低。有趣的是,肝脏DIO3活性在全局中增加,但在肝脏特异性Xpg突变体中没有增加。选择性Xpg缺乏和大脑过早衰老不会影响肝脏或全身甲状腺信号传导。伴随DIO1抑制,Xpg-/-和Alb-Xpg小鼠表现出TH相关基因表达变化减少,与肝损伤和细胞衰老的标志物相关。结论我们的研究结果表明,衰老过程中DIO1的活性主要是由器官/细胞内在积累的DNA损伤以组织自主的方式改变的。衰老过程中肝脏DIO3活性的增加在很大程度上取决于系统信号,可能反映了循环细胞的存在,而不是肝细胞的活性。
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引用次数: 0
A 20-year study of autoimmune polyendocrine syndrome type II and III in Taiwan. 台湾地区II型和III型自身免疫多内分泌综合征的二十年研究。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-23 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0162
Hsu-Hua Tseng, Yen-Bo Lin, Kuan-Yu Lin, Chia-Hung Lin, Hung-Yuan Li, Chia-Hsuin Chang, Yi-Ching Tung, Pei-Lung Chen, Chih-Yuan Wang, Wei-Shiung Yang, Shyang-Rong Shih

Purpose: Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan.

Methods: Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed.

Results: Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001).

Conclusion: This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.

目的:自身免疫性多内分泌综合征(APS)是一种罕见的免疫内分泌疾病,其特征是至少两个内分泌器官衰竭。临床特征主要描述在西方人群中。本研究综合分析台湾地区APS-II和APS-III的人口学和临床表现。方法:纳入2001年至2021年间在10家医院诊断为APS-II或APS-III的年龄≥20岁的患者。对患者的临床和血清学特征进行回顾性分析。结果:在187名入选患者中(45名男性和142名女性);只有7人(3.7%)患有APS-II,而其他人患有APS-III。55名患者出现甲状腺功能亢进,44名患者出现甲减。男性被诊断为APS的年龄比女性小(16.8岁对27.8岁,p=0.007)。大多数患者最初被诊断为1型糖尿病。诊断时的年龄与发生甲状腺功能障碍的可能性呈正相关。老年患者每诊断一年患有APS-III,患甲状腺功能亢进的风险就会增加3.6%(p=0.002),并且发展为甲状腺功能减退症的风险增加了3.7%(p=0.035)。抗顶细胞抗体(APCA)阳性与APS-III患者贫血的风险较高相关(p<0.001)。结论:本研究提供了亚洲最全面的APS-II和APS-III分析。APS-II患者的比例明显低于西方人群。第二种自身免疫性内分泌病可能在第一种后几年发生。APCA检查在评估APS患者贫血时很有价值。
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引用次数: 0
European thyroid journal: passing on the baton. 欧洲甲状腺杂志:传递接力棒。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-08 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0216
S H S Pearce, L Persani
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引用次数: 0
Mortality among papillary thyroid cancer patients by detection route: a hospital-based retrospective cohort study. 癌症甲状腺乳头状癌患者检测途径的死亡率:一项基于医院的回顾性队列研究。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-06 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0127
Lan Wu, Salvatore Vaccarella, Chen-Yang Feng, Luigino Dal Maso, Yu Chen, Wei-Wei Liu, Miao-Bian Liang, Zike Zhang, Jun Yang, Su-Mei Cao, Mengmeng Li

Background: Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients.

Methods: We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were then utilized to explore the association between detection routes and PTC-specific and competing mortality.

Results: Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04-0.46; P = 0.01) and 0.47 (95% CI: 0.20-1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively.

Conclusions: Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.

背景:癌症(PTC)的发病率迅速上升,其中偶然发现的癌症占很大比例。我们旨在探讨偶然检测对PTC患者甲状腺癌特异性和竞争性死亡率的影响。方法:我们在广州癌症中心对PTC患者进行了回顾性队列研究。2010-2018年间收集了检测途径和其他协变量的基线信息,并对每位患者的死亡结果进行了随访。累计发病率函数用于估计甲状腺癌症的死亡率风险和竞争风险。然后利用病因特异性危险模型来探索检测途径与PTC特异性和竞争性死亡率之间的关系。结果:在纳入的2874名患者中,2011名(70.0%)是偶然发现的,这一比例从2011年的36.9%上升到2018年的82.3%。在5.6年的中位随访中,发生了42例死亡,其中60%是由于相互竞争的原因。非偶然组和偶然组在5年时竞争性死亡率的概率分别为1.4%和0.4%,非偶然组的PTC特异性死亡率为1.0%和0.1%。校正协变量后,PTC特异性和竞争性死亡率中偶然检测的HR分别为0.13(95%CI:0.04-0.46;P=0.01)和0.47(95%CI:0.20-1.10;P=0.010)。结论:偶然检测与PTC特异性和竞争性死亡率的风险较低有关。在过度诊断日益严重的背景下,将检测途径纳入临床决策可能有助于确定哪些患者可能受益于更广泛或更保守的治疗策略。
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引用次数: 0
Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model. 在基于机器的学习模型中加入氨基酸和酰基肉毒碱,优化荷兰新生儿先天性甲状腺功能减退症筛查。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-03 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0141
Heleen I Jansen, Marije van Haeringen, Marelle J Bouva, Wendy P J den Elzen, Eveline Bruinstroop, Catharina P B van der Ploeg, A S Paul van Trotsenburg, Nitash Zwaveling-Soonawala, Annemieke C Heijboer, Annet M Bosch, Robert de Jonge, Mark Hoogendoorn, Anita Boelen

Objective: Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007-2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model.

Methods: Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed.

Results: The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model's performance.

Conclusions: The PPV improved significantly (26-48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

目的先天性甲状腺功能减退(CH)是一种先天性甲状腺激素(TH)缺乏症,主要由甲状腺(原发性CH)或下丘脑/垂体(中枢性CH)紊乱引起。大多数CH新生儿筛查(NBS)项目都是以促甲状腺激素(TSH)为基础的,因此只检测原发性CH。荷兰NBS基于测量干血点的总甲状腺素(T4),旨在以更多假阳性转诊(FPR)为代价检测原发和中心CH(2007-2017年阳性预测值(PPV)为21%)。当在下面描述的基于荷兰CH NBS的调整数据集(方法)上使用基于机器的学习模型时,产生了26%的人工PPV。最近,氨基酸(AAs)和酰基肉毒碱(ACs)被证明与TH浓度有关。因此,我们旨在通过使用修订的基于机器的学习模型,研究在NBS期间测量的AAs和AC是否有助于荷兰CH筛查的更好性能。方法使用荷兰国家统计局2007-2017年的数据(CH筛查结果、AAs和ACs),来自1079名FPR、515名原发性和中心性CH新生儿(431名)和1842名健康对照。开发了一个包含这些数据的随机森林模型。结果人工灵敏度为100%的随机森林模型的PPV为48%,AUROC为0.99。除T4和TSH外,酪氨酸和琥珀酰丙酮是影响模型性能的主要参数。结论通过在我们的基于机器的学习模型中添加几个AA和AC,PPV显著提高(26%至48%),这表明添加这些参数有利于当前的算法。
{"title":"Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model.","authors":"Heleen I Jansen, Marije van Haeringen, Marelle J Bouva, Wendy P J den Elzen, Eveline Bruinstroop, Catharina P B van der Ploeg, A S Paul van Trotsenburg, Nitash Zwaveling-Soonawala, Annemieke C Heijboer, Annet M Bosch, Robert de Jonge, Mark Hoogendoorn, Anita Boelen","doi":"10.1530/ETJ-23-0141","DOIUrl":"10.1530/ETJ-23-0141","url":null,"abstract":"<p><strong>Objective: </strong>Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007-2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model.</p><p><strong>Methods: </strong>Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed.</p><p><strong>Results: </strong>The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model's performance.</p><p><strong>Conclusions: </strong>The PPV improved significantly (26-48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of metabolic syndrome and lifestyle factors on thyroid nodules in Chinese adult men: a cross-sectional study. 代谢综合征和生活方式因素对中国成年男性甲状腺结节的影响:一项横断面研究。
IF 4.7 2区 医学 Q2 Medicine Pub Date : 2023-11-03 Print Date: 2023-12-01 DOI: 10.1530/ETJ-23-0168
Ziyu Wan, Ying Li, Xiaoqian Dong, Yue Kang, Juan Luo, Jiangang Wang, Pingting Yang, Yaqin Wang, Yinglong Duan, Jianfei Xie, Andy S K Cheng

Introduction: Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China.

Methods: This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables.

Results: The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules.

Conclusion: The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.

引言:鉴于甲状腺结节的高患病率和恶性肿瘤的可能性,必须了解导致其发展的各种因素。本研究旨在探讨中国南方成年男性代谢综合征、生活方式和甲状腺结节之间的关系。方法:本研究于2015年1月1日至2020年12月31日在中国南方一家综合医院的体检中心招募了183990名受试者。采用多变量逻辑回归分析来评估代谢综合征、生活方式因素与甲状腺结节之间的关系。此外,结构方程建模(SEM)阐明了这些变量之间的复杂关系。结果:中国成年男性甲状腺结节的患病率为14.9%,年龄大、吃饭时间不规律、吸烟或戒烟、戒酒、体力劳动重、高血压、糖尿病、血脂异常和向心性肥胖等因素被确定为甲状腺结节的危险因素。而且,少数民族和饮酒被发现是预防甲状腺结节的保护因素。结构方程模型强调了代谢综合征在生活方式对甲状腺结节影响中的中介作用。结论:中国成年男性甲状腺结节的患病率为中低度。本研究中确定的因素可以帮助临床医生识别高危患者,并制定有针对性的筛查策略,及时检测甲状腺结节。然而,需要进一步的机制研究和纵向研究来探索根本原因并建立因果关系。
{"title":"Influence of metabolic syndrome and lifestyle factors on thyroid nodules in Chinese adult men: a cross-sectional study.","authors":"Ziyu Wan, Ying Li, Xiaoqian Dong, Yue Kang, Juan Luo, Jiangang Wang, Pingting Yang, Yaqin Wang, Yinglong Duan, Jianfei Xie, Andy S K Cheng","doi":"10.1530/ETJ-23-0168","DOIUrl":"10.1530/ETJ-23-0168","url":null,"abstract":"<p><strong>Introduction: </strong>Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China.</p><p><strong>Methods: </strong>This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables.</p><p><strong>Results: </strong>The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules.</p><p><strong>Conclusion: </strong>The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41178336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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European Thyroid Journal
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