Thyroid最新文献

Background: Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. Methods: This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). Results: Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; p value = 0.006; mean working memory scores: 6.8 vs 6.4; p value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. Conclusions: We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms.

Background: Iodinated contrast is commonly used for radiological procedures, with one dose delivering several hundred-fold the daily requirements needed for normal thyroid hormone production. Risks of excess iodine include incident thyroid dysfunction, which is associated with adverse cardiac outcomes, yet there are no prospective studies investigating the changes in cardiac physiology following iodine contrast administration. This study was conducted to investigate the longitudinal relationships between the amount of iodinated contrast administration and changes in cardiac electrophysiology and structure. Methods: A longitudinal cohort study was conducted with prospectively enrolled participants who received iodine contrast for elective computed tomography or coronary angiography. Serum thyroid function tests, electrocardiograms (EKG), and transthoracic echocardiograms were obtained serially until 36 months. Trends of electrical and structural cardiac changes following iodine contrast administration were assessed using mixed effect models. Results: The cohort was composed of 129 patients (median age, 70 [interquartile range: 63, 75] years; 98% male). Larger amounts of iodine exposure were associated with increases in QRS and QTc durations and decreased ejection fraction (EF), and these associations were still observed for follow-up EF after additionally adjusting for baseline values (the high-iodine contrast group vs. the low-iodine contrast group, -4.23% [confidence interval, -7.66% to -0.79%]). Dose-response analyses also showed lower EF with larger amounts of iodine received; these trends were not significant for the EKG parameters studied. Conclusions: Over a period of up to 36 months, a larger amount of administered iodine contrast was associated with lower EF among participants. Further investigation is needed to elucidate the long-term trends of electrical and structural cardiac function after iodine contrast administration.

Background: Obesity and hypothyroidism are common medical conditions that are associated with each other. Bariatric surgery (BS) is a common approach used to achieve substantial weight loss in obese patients. However, there is limited evidence regarding the need for postsurgery levothyroxine (LT4) dose adjustment in patients with hypothyroidism undergoing BS. Methods: This was a three-year prospective cohort study assessing postsurgery LT4 requirements with attention to body composition changes. The current study included 1030 patients with hypothyroidism, who underwent sleeve gastrectomy (SG) (n = 707, 88.3% women) or one anastomosis gastric bypass (OAGB) (n = 323, 92% women). Patients were followed for 36 months after surgery. A bioelectrical impedance analyzer was used for body composition assessment. LT4 requirements were assessed by generalized estimating equation (GEE) methods adjusted for weight as a time-varying covariate. Results: During the follow-up, TSH (mIU/L) and T4 (ng/dL) measurements did not significantly change in the OAGB group over time. However, in the SG group, TSH measurement decreased over time (p_trend = <0.001). In the third year of the follow-up, 56.1% and 33.3% of patients in the SG and OAGB groups experienced LT4 (μg/day) dose reduction, while 24.4% and 9.1% of the participants experienced LT4 dose increments, respectively. GEE analysis showed a significant increase in the LT4/fat mass (FM) (μg/kg) ratio after 36 months of follow-up compared with the baseline in both the SG [1.8 (1.5-2.2) to 2.7 (2.0-3.5), p_trend = 0.039)] and OAGB [1.7 (1.4-2.2) to 3.2 (2.7-4.8), p_trend = <0.001)] groups. Moreover, patients who underwent OAGB experienced greater LT4/FM (μg/kg) dose adjustments compared to those undergoing SG (p_between = 0.060). In both groups, after the first year, the increase in LT4/FM (μg/kg) plateaued (p_interaction = 0.009). Conclusion: Most hypothyroid patients experienced either a reduction or no change in LT4 (μg/day) dosage after 36 months in both surgical groups. The LT4/FM (μg/kg) was significantly increased in patients undergoing either SG or OAGB with greater alterations in the latter. Further studies on larger populations and with longer duration of follow-up are needed to confirm our results.

Background: We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. Methods: We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with confidence intervals (CIs). The I² statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. Results: The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of PEI was 32% ([CI 25-40%], I² 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of "Minor" complications of PEI was 32% ([CI 25-40%], I² 92.7%, 952 of 3195 TNs). The prevalence of "Major" complications of PEI was 2% ([CI 1-2%], I² 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results. The pooled prevalence rate of local pain was 21% (CI [16-27] I² 90.3). Local pain was typically transient and mild, sometimes moderate, and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1-2], I² 0). Dysphonia was transient and could last from several hours to 12 months after PEI. Conclusions: Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique.

Background: Diagnostic classification of thyroid malignancy is primarily accomplished through examination of histomorphological features and may be substantiated and clarified by molecular data. Individual molecular drivers show relatively robust and specific associations with histological subtypes of thyroid malignancy, including BRAF sequence variants and kinase gene fusions in papillary thyroid carcinoma, predominantly RAS variants in follicular-patterned neoplasia, and additional "late" mutations affecting TERT promoter, TP53, and the PI3K/AKT/PTEN pathway in high-grade malignancies. Given the oncogenic role of FGFR, particularly FGFR1-3, the goal of this study was to explore the role of FGFR in thyroid carcinoma biology. Methods: We completed a multicenter retrospective observational study for thyroid carcinomas with pathogenic alterations in the FGFR gene family. We performed this study by querying the molecular data accumulated for thyroid carcinomas from each center. Results: Overall, 5030 sequenced thyroid malignancies were reviewed, yielding 17 tumors with FGFR alterations, including 11 where FGFR was the primary molecular driver and 6 where FGFR was a secondary pathogenic alteration, with a subset for which there was available clinical follow-up data. Of the 11 carcinomas with an FGFR driver, 9 were gene fusions involving FGFR2:VCL (4 tumors), TG::FGFR1 (3 tumors), FGFR2::CIT, and FGFR2::SHTN1, and the remaining 2 were driven by FGFR1 amplification. In the 6 tumors where a canonical driver of thyroid neoplasia was present (5 cases) or no clear primary driver was detected (1 case), sequencing detected secondary FGFR2 p.W290C, p.Y375C, and p.N549K, as well as FGFR1 p.N546K in the respective tyrosine kinase domains, some at subclonal variant allele frequencies. Conclusions: This study presents the first description of a collection of thyroid carcinomas grouped by primary driver alterations in FGFR, as well as a cohort of thyroid tumors with secondary alterations that potentially lead to tumor progression or resistance to targeted therapy. Given the availability of small molecular inhibitors targeting oncogenic FGFR, this study emphasizes the significant implications for patients from identification of FGFR alterations as they are currently under-recognized in the literature and, most importantly, have potential novel treatment options.

Background: Active surveillance (AS) of papillary thyroid microcarcinomas (PTMC) is emerging as an alternative to immediate surgery. While thermal ablation has also shown promise for low-risk PTMC, it has not been prospectively studied in patients appropriate for AS. This study aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for tumor control and quality of life (QoL) management in patients with PTMC who favored AS over immediate surgery. Methods: This prospective clinical trial was conducted at a single tertiary referral hospital from 2018 to 2021. Of 227 adult patients aged ≤60 years with low-risk unifocal PTMC favoring AS over immediate surgery, 100 patients underwent RFA for their management. The primary endpoint was the disease progression rate, and secondary endpoints were technical success, volume reduction rate (VRR), complication rates, and QoL. Results: The median age of the study population was 42 years (range, 27-59 years), and 83% (83/100, [CI: 66.1-100]) were female. The median follow-up was 30 months (range, 12-56 months). All 100 patients underwent RFA with technical success. Most of the ablation zones showed continuous volume reduction, and 95.9% (94/98, [CI: 77.5-100.0]) showed complete disappearance at the last follow-up. The median VRR was 100.0% at 1-year follow-up and persisted throughout the last follow-up. The cumulative disease progression rate among 98 patients who underwent at least 1-year follow-up was 3.1% (3/98, [CI: 0.6-9.0]); one patient had lymph node metastasis (treated with surgery), and two patients had new PTMC (1 treated with RFA, 1 ongoing AS). Major complications were not observed. Psychological (baseline vs. last follow-up, 7.3 vs. 8.0, p = 0.002) and social (8.0 vs. 8.7, p = 0.005) QoL scores significantly improved during follow-up without compromising physical QoL (8.6 vs. 8.5, p = 0.99). Conclusions: RFA can be a reasonable strategy for effectively and safely controlling tumors and improving QoL in non-elderly patients with low-risk PTMC appropriate for AS. Clinical Trial registration: This trial is registered with ClinicalTrials.gov: NCT03432299.

Background: Exposure to particles with an aerodynamic diameter of ≤2.5 μm (PM_2.5) is associated with the occurrence of thyroid dysfunction among pregnant women and neonates, but it is not known if this association occurs in the general population. We aimed to determine the association of prolonged exposure to PM_2.5 with the prevalence of thyroid disorders among adults in China. Methods: A nationally representative cross-sectional study of thyroid disorders, iodine status, and diabetes status was carried out in all 31 provinces across China from 2015 to 2017. In total, 73,900 adults aged 18 years and older were included. Serum concentrations of thyroid hormones, thyrotropin, and thyroid antibodies and the urine iodine concentration were measured. The environmental concentration of PM_2.5 for each participant's residential address at a spatial resolution of 1 × 1 km was estimated. Results: The average long-term exposure to PM_2.5 at residential addresses was 66.41 μg/m³, ranging from 17.58 μg/m³ to 120.40 μg/m³. Compared with that of individuals with lower exposure levels, the prevalence of thyroid diseases such as autoimmune thyroiditis and subclinical hypothyroidism was greater in those with PM_2.5 concentrations within the third quartile range (60.18 to 73.78 μg/m³). Compared with those in the first quartile (17.58 to 46.38 μg/m³), participants in the highest PM_2.5 quartile (73.78 to 120.40 μg/m³) presented an increased risk of overt hypothyroidism (OR 1.23 [CI 0.94-1.61]), subclinical hypothyroidism (1.10 [1.01-1.21]), autoimmune thyroiditis (1.09 [1.00-1.18]), and thyroglobulin antibody positivity (1.17 [1.07-1.29]). However, there was no association between PM_2.5 exposure and overt hyperthyroidism, subclinical hyperthyroidism, Graves' disease, or thyroid peroxidase antibody positivity (p > 0.05). Each 10 μg/m³ increase in the PM_2.5 concentration was associated with an increased risk of overt hypothyroidism (OR 1.05 [1.00-1.11]), subclinical hypothyroidism (1.02 [1.00-1.03]), and thyroglobulin antibody positivity (1.02 [1.00-1.04]). Furthermore, a nearly linear exposure-response relationship was observed between long-term PM_2.5 exposure and thyroglobulin antibody positivity. Conclusions: PM_2.5 exposure was associated with thyroid disorders among Chinese adults. A dose-response relationship between PM_2.5 exposure and autoimmune thyroiditis, as well as thyroglobulin antibody positivity, was also observed.