European Thyroid Journal最新文献

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.

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.

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.

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.

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.

Objective: Some studies suggest that hypothyroidism is associated with increased oxidative stress. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders.

Methods: In 45 Danish women with newly diagnosed hypothyroidism, we compared 8-oxoGuo and 8-oxodG before or shortly after initiating levothyroxine with the excretion rates at euthyroidism. We also compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with 18 healthy control subjects.

Results: Compared with baseline, none of the biomarkers changed significantly in the patients after becoming euthyroid. The geometric mean of 8-oxoGuo was 1.63 (95% CI: 1.49-1.78) nmol/mmol creatinine at baseline and 1.67 nmol/mmol at euthyroidism (95% CI: 1.53-1.83) (P = 0.39), while that of 8-oxodG was 1.28 nmol/mmol creatinine at baseline (95% CI: 1.14-1.44) and 1.32 nmol/mmol at euthyroidism (95% CI: 1.18-1.48), respectively (P = 0.47). The relative mean differences were 0.97 (95% CI: 0.91-1.04) for 8-oxoGuo and 0.97 (95% CI: 0.88-1.06) for 8-oxodG. At baseline, multiple linear regression revealed a positive association between free thyroxine and both biomarkers (8-oxoGuo, P < 0.001; 8-oxodG, P = 0.04). Furthermore, 8-oxoGuo was positively associated with age (P = 0.04) and negatively associated with thyrotropin (P = 0.02). In the control group, the geometric mean of 8-oxoGuo was 1.23 nmol/mmol creatinine (95% CI: 1.07-1.42), while that of 8-oxodG was 1.04 nmol/mmol creatinine (95% CI: 0.88-1.23). Thus, compared with control subjects, euthyroid patients showed a significantly higher level of both 8-oxoGuo (P < 0.001) and 8-oxodG (P = 0.03).

Conclusion: In hypothyroid women, no significant effect of levothyroxine treatment on the oxidative stress biomarkers 8-oxoGuo and 8-oxodG could be demonstrated. However, the excretion of these biomarkers was significantly higher than in healthy controls.

Background: Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment.

Objective: The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR).

Patients and methods: One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated.

Results: After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment.

Conclusions: Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

Purpose: The purpose of this study was to evaluate the feasibility of radiofrequency ablation (RFA) for thyroid nodules with cytological atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III).

Materials and methods: A total of 28 adults presenting with 30 initial Bethesda III nodules underwent thyroid RFA at a single medical center. Thyroid nodules with Bethesda IV or V according to the second aspiration were excluded. All RFA procedures were performed using the free-hand, 'moving-shot' technique under local anesthesia. Clinical features and demographics, RFA details, nodule volume reduction rate (VRR), and complications were analyzed.

Results: The mean age of patients was 47.6 years, 82.1% of whom were females. Mean nodule volumes at pre-RFA, and at 6 months and 12 months post-RFA were 7.92, 2.42, and 1.25 mL, respectively, with a VRR of 77.9% at 6 months, and 87.4% at 12 months. Post-RFA complications were noted in two patients, one with transient vocal cord palsy and another with isthmus minor rupture.

Conclusion: RFA may be another safe alternative except for active surveillance or surgical excision for AUS/FLUS nodules with low-suspicion Thyroid Imaging Reporting and Data System features for patients who are unsuitable or strongly refuse surgery. Long-term results remain uncertain, thus further follow-up study is necessary.

Purpose: The purpose of this study was to evaluate the feasibility of radiofrequency ablation (RFA) for thyroid nodules with cytological atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III).

Materials and methods: A total of 28 adults presenting with 30 initial Bethesda III nodules underwent thyroid RFA at a single medical center. Thyroid nodules with Bethesda IV or V according to the second aspiration were excluded. All RFA procedures were performed using the free-hand, 'moving-shot' technique under local anesthesia. Clinical features and demographics, RFA details, nodule volume reduction rate (VRR), and complications were analyzed.

Results: The mean age of patients was 47.6 years, 82.1% of whom were females. Mean nodule volumes at pre-RFA, and at 6 months and 12 months post-RFA were 7.92, 2.42, and 1.25 mL, respectively, with a VRR of 77.9% at 6 months, and 87.4% at 12 months. Post-RFA complications were noted in two patients, one with transient vocal cord palsy and another with isthmus minor rupture.

Conclusion: RFA may be another safe alternative except for active surveillance or surgical excision for AUS/FLUS nodules with low-suspicion Thyroid Imaging Reporting and Data System features for patients who are unsuitable or strongly refuse surgery. Long-term results remain uncertain, thus further follow-up study is necessary.