Thyroid Research最新文献

Background: Age is an independent risk factor for central lymph node metastasis (CLNM) in clinically negative lymph node (cN0) papillary thyroid microcarcinoma (PTMC) patients. The objective of this study was to investigate the impact of age on CLNM in clinically low-risk PTMC patients.

Methods: A retrospective analysis was performed on patients with clinically low-risk PTMC who underwent surgery between January 2016 and December 2018. Logistic regression analysis was used to examine the impact of age on the risk of CLNM. The associations between age and pN1a and the lymph node ratio (LNR) were examined by a restricted cubic spline (RCS) curve with logistic regression models.

Results: A total of 1352 patients (mean [range] age, 43[18-76] years; 325 males [24.0%]) were enrolled in this study. Logistic regression analysis revealed that age was a significant factor influencing the risk of CLNM (OR 0.95, 95% CI 0.94-0.96; p < 0.001). The RCS curve revealed a significant nonlinear association between age and pN1a status and the LNR. For patients under the age of 55, the risk of CLNM (OR 0.59, 95% CI 0.55-0.65, p < 0.001) and the LNR (beta - 0.23, 95% CI -0.27, -0.19, p < 0.001) significantly decreased as age increased. For patients aged ≥ 55 years, the risk of LNM (OR 1.03, 95% CI 0.81-1.32; p = 0.79) and the LNR (Beta - 0.03, 95% CI -0.07,0.13, p = 0.54) did not change with age.

Conclusions: This study confirmed that age was a significant factor influencing the risk and severity of CLNM in patients with low-risk PTMC. The risk and severity of LNM were lowest in patients aged ≥ 55 years.

Background: Celastrol, a naturally occurring bioactive compound, has demonstrated potential in treating inflammation, obesity, and tumors, particularly in colorectal, gastric, and breast cancers. However, its therapeutic effects on thyroid cancer (TC), which have poor clinical outcomes, remain unclear. This study aimed to investigate Celastrol's potential in treating thyroid cancer using cell lines.

Methods: The viability and proliferation of thyroid cancer cells treated with or without Celastrol were analyzed by CCK-8 and colony formation assay. The state of thyroid cancer cells treated with or without Celastrol were observed by microscopy. Further evidence from flow cytometry and TUNEL staining demonstrated the induction of apoptotic processes in thyroid cancer cells. The expression of PARP1, Caspase-3, Bax, BCL2 in thyroid cancer cells after indicated treatment was analyzed by Western blot and Caspase-3 expression in thyroid cancer cells after 12 and 24 h of Celastrol treatment was detected by immunofuorescence assay. Anaplastic thyroid cancer growth-limiting of Celastrol was evaluated in nude mice.

Results: Celastrol induction promoted apoptotic in TC cells, increased the expression of PARP1, Bax and Caspase-3 and reduces expression of BCL2 by Western Blot. The expression of Caspase-3 was increased by immunofluorescence, which indicating that Celastrol may serve as an adjuvant therapeutic agent for thyroid cancer treatment by inducing apoptosis through the caspase-3 pathway. Celastrol treatment of mice implanted with anaplastic thyroid cancer cells also inhibited tumor growth, associated with reduced Ki-67 and increased Caspase-3.

Conclusions: Celastrol promotes apoptotic cell death in thyroid carcinoma cells by the Caspase-3 pathway.

Thyroid dysfunction can adversely affect pregnancy outcomes. Apart from gestational thyrotoxicosis, thyroid dysfunction during pregnancy shares similar etiologies with the non-gravid state. Graves' disease is the most common cause of spontaneous hyperthyroidism in pregnancy, followed by thyroid autonomy. Although subacute thyroiditis is a less common cause of thyrotoxicosis in pregnancy, its associated pain, systemic symptoms, and thyroid dysfunction can present diagnostic and therapeutic challenges. In its painful form, subacute thyroiditis may lead to severe disability, with systemic glucocorticoids being the best effective treatment option. When painless, the condition often comes to medical attention due to thyroid dysfunction. During the thyrotoxic phase, subacute thyroiditis should be differentiated from gestational thyrotoxicosis, Graves' disease, and thyroid autonomy. Additionally, the transient hypothyroid phase may be misdiagnosed as permanent hypothyroidism, such as in Hashimoto's thyroiditis. Once properly diagnosed, management is symptomatic and focused on correcting the predominant abnormality. In this review, we summarize the current reported cases of subacute thyroiditis in pregnancy and discuss the challenges in diagnosis and management. Clinical trial number Not applicable.

Background: The antiangiogenic multi-kinase inhibitors (MKIs) apatinib, donafenib, and anlotinib have demonstrated satisfactory efficacy in radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) in their phase II/III trials. However, the potential impact factors on the efficacy of these MKIs remain unclear.

Methods: RAIR-DTC patients enrolled in clinical trials of apatinib, donafenib, and anlotinib in our center were retrospectively reviewed. The Kaplan-Meier method was used to examine the relationship between clinicopathological variables and progression-free survival (PFS) and overall survival (OS), followed by a multivariate Cox analysis on PFS.

Results: A total of 71 progressive RAIR-DTC patients were reviewed, of which 26.7% were treated by anlotinib, 45.1% by apatinib, and 28.2% by donafenib. The median follow-up time was 44.1 months, the median PFS was 21.1 months, and the estimated median OS was 47.7 months. PFS and OS showed no significant differences in patients treated with apatinib, donafenib, or anlotinib. In the univariate analyses, patients with BRAF^V600E mutation showed longer PFS (HR 0.345, 95% CI 0.187-0.636, p < 0.001) and OS (HR 0.382, 95% CI 0.166-0.878, p = 0.019) compared with patients with wild-type BRAF. Patients with follicular thyroid cancer and bone metastases had shorter PFS, and patients with worse Eastern Cooperative Oncology Group performance status, bone metastases, and a larger tumor burden had shorter OS. In the multivariate Cox analysis, BRAF^V600E mutation was the only independent predictor of longer PFS (HR 0.296, 95% CI 0.138-0.638, p = 0.002). The overall response rate and disease control rate didn't differ between BRAF^V600E mutation status. Subgroup analysis of PFS in papillary thyroid cancer patients stratified by BRAF^V600E mutation status showed that BRAF^V600E mutation was associated with longer PFS in all clinicopathological subgroups (hazard ratio < 1).

Conclusion: RAIR-DTC patients with BRAF^V600E mutation treated with apatinib, donafenib, or anlotinib achieved better prognoses compared with patients with wild-type BRAF, indicating that the genetic background may play a role in predicting the efficacy of MKIs therapies.

Trial registration: This retrospective cohort included patients in our center from clinical trials of apatinib (NCT02731352, NCT03048877), donafenib (NCT02870569, NCT03602495), and anlotinib (NCT05007093).

Background: There has been an increasing comprehension and recognition of endocrine dysfunction among both pediatric and adult patients with sickle cell disease (SCD). Thyroid disorders can have significant clinical consequences, including growth retardation and impaired cognitive function. However, there is a disparity in the available data concerning the magnitude and spectrum of thyroid abnormalities in this population. This review aimed to provide a systematic summary and analyses on the status of thyroid function abnormalities in individuals with SCD.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across Medline/PubMed, Google Scholar, World Health Organization Virtual Health Library Regional Portal, and ScienceDirect. Pooled prevalence and standardized mean difference (SMD) estimates with 95% confidence intervals (CIs) were calculated using Comprehensive Meta-Analysis Software version 3.3.

Results: Nineteen studies met the inclusion criteria and were incorporated into the analyses. Serum thyroid-stimulating hormone (TSH) levels were significantly higher in SCD patients compared to controls (SMD = 1.184; 95% CI, 0.269-2.099; p = 0.011). While non-significant, there was a trend towards lower levels of triiodothyronine (T3), thyroxin (T4), free T3, and free T4 in the SCD group (T3: SMD = -1.746; 95% CI, -3.561-0.070; p = 0.059; T4: SMD = -1.365; 95% CI, -3.030-0.300; p = 0.108; free T3: SMD = -0.384; 95% CI, -1.128-0.356; p = 0.311; free T4: SMD = -1.205; 95% CI, -2.522-0.111; p = 0.073). The pooled prevalence of hypothyroidism and subclinical hypothyroidism among SCD patients was found to be 4.9% and 8.7%, respectively.

Conclusion: Individuals with SCD exhibit a tendency towards elevated TSH levels compared to the general population, with a subset potentially developing thyroid abnormalities, particularly subclinical hypothyroidism. Although not highly prevalent in the SCD population, monitoring thyroid function remains essential due to the potential for progression to overt hypothyroidism and its associated adverse health outcomes.

This is an invitation letter for the principal investigators and cohort studies to join the Consortium on Thyroid and Pregnancy. The inclusion criteria are population-based cohorts with data on maternal thyroid function during pregnancy and any measurement of known groups of endocrine disrupting chemicals.

Background: This study aimed to evaluate the efficacy and safety of thermal ablation in the treatment of patients with Bethesda IV thyroid nodules (follicular neoplasms) by analyzing large-scale data on various outcomes.

Materials and methods: Literature searches were conducted in PUBMED, EMBASE, Web of Science, and the Cochrane Library for studies on the use of thermal ablation in patients with Bethesda IV thyroid nodules published from March 1, 2014, to March 1, 2024. Data on volume change at 12 months; the volume reduction rate (VRR) at 1, 3, 6, and 12 months; the complete disappearance rate (CDR); and the complication rate were evaluated. All the data were analyzed with STATA 15.

Results: Five eligible studies were included. The findings indicate that thermal ablation is both effective and safe. The mean change in tumor volume at 12 months postthermal ablation was characterized by a standardized mean difference (SMD) of -1.13 (95% CI: -1.36 - -0.90, p = 0.000). Specifically, the mean changes in tumor volume at 12 months after radiofrequency ablation (RFA) and microwave ablation (MWA) were - 1.19 (95% CI: -1.75 - -0.64) and - 1.26 (95% CI: -1.71 - -0.81), respectively. The VRRs at 1, 3, 6, and 12 months postthermal ablation were 43% (95% CI: 33 - 53%), 47% (95% CI: 20 - 74%), 69% (95% CI: 62 - 76%), and 85% (95% CI: 79 - 90%), respectively. The VRRs at 12 months after RFA and MWA were 84% (95% CI: 76 - 91%) and 85% (95% CI: 75 - 95%), respectively. The VRR at 12 months, stratified by initial nodule size, was 84% (95% CI: 77 - 91%) and 86% (95% CI: 78 - 94%). The CDR at the final follow-up was 88% (95% CI: 80 - 95%). The complication rate was 4.0% (95% CI: 0.0 - 8.0%), with pain and hoarseness being the most frequently reported complications; no life-threatening complications were documented.

Conclusions: Thermal ablation is a reliable treatment for Bethesda IV thyroid nodules, and RFA and MWA are advantageous treatment strategies. However, more prospective, multicenter, and large-sample studies are needed in the future.

Introduction: Thyroid disease (TD), particularly hypothyroidism, is an important etiology of hyperprolactinemia (HPRL). We conducted a systematic review of the clinical characteristics, management, and outcomes of adults (> 18 years) with this clinical association.

Materials and methods: We searched PUBMED, SCOPUS, and EMBASE to find eligible articles published in English from any date till 15th December 2022.

Results: The final systematic review included 804 patients from 47 articles, of which the majority (85.9%) were females. Menstrual irregularity was the most prominent symptom of HPRL (74.3%). Subclinical hypothyroidism (57.1%) was the most reported TD. Individual patient data were available for 62 patients from 35 studies. The median age was 32 (25-42) years, TSH was 110.25 (50-345.4) mU/L, and PRL level was 60 (37.6-91) ng/ml. On treating TD, 38 (70.4%) patients had complete resolution and 10 (18.5%) had an improvement in HPRL. Of 38 patients with pituitary imaging, 26 (68.4%) showed pituitary enlargement, and 13 (34.2%) showed a suprasellar extension. 13 (76.5%) patients had complete resolution and 3 (17.6%) had an improvement in pituitary enlargement on TD treatment. A positive correlation was observed between higher serum TSH levels and higher serum prolactin levels. Patients with pituitary enlargement on imaging had a higher TSH level compared to those without any pituitary enlargement (Median of 263 (61-602) vs. 50 (24.3-128) mU/L; p-value = 0.01).

Conclusion: Thyroid hormone replacement can lead to resolution of HPRL and pituitary enlargement in the majority of patients with HPRL due to overt or subclinical hypothyroidism without the need for dopamine agonist treatment.

The occurrence of post-radioactive iodine thyroid storm among patients with hyperthyroidism is relatively rare and only a few cases have been reported. We conducted a literature review of cases reported from 1951 to 2023 and determined the risk factors and clinical characteristics of patients who developed thyroid storm. A total of 19 cases were documented and reviewed. The mean age was 51.2 ± 20.1 years (range 7.5 to 75). Approximately two-thirds were females. Major etiologies were diffuse toxic goiter (57.9%) and nodular disease (36.8%). Mean dose was 11.3 ± 7.7 mCi (range 3.3 to 35), with 52.6% receiving less than 10 mCi. Mean interval time from administration to development of thyroid storm was 6.6 ± 5.5 days (range 0.5 to 20). The most common preexisting conditions were weight loss, heart failure, atrial fibrillation, hypertension and coronary artery disease. Thyroxine levels were not routinely measured prior to and during storm. Among those with available data, only 26.3% had hormone levels prior to and during storm. Thyroxine levels during storm (range 19.8 to 65 µg/dL) were higher than levels prior to storm (range 9.6 to 45 µg/dL). Pretreatment regimens varied consisting of no intervention, beta blockers, steroids, reserpine, phenobarbital and anti-thyroid drugs. Treatment regimens are more uniform and consistent with American Thyroid Association recommendations. The mortality rate remains high at ~ 26.3%. Statistical analyses did not show any significant differences. Even though the frequency of this condition is quite rare, it is an important and potentially prognostic condition underscoring the value of this review. The inclusion of this severe adverse effect should be part of patient discussion with emphasis on the need to seek early consultation when severe symptoms appear.

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, representing the majority of thyroid cancer cases. Most patients with PTC have an excellent prognosis following treatment, yet approximately 10% face mortality within ten years, primarily due to lymph node metastasis (LNM) or local recurrence. The SIX1 gene, a member of the SIX gene superfamily, encodes a transcription factor integral to the development of certain tissues during embryogenesis. The impact of SIX1 in different subtypes of PTC has not been studied previously.

Objective: The purpose of this study was to investigate the expression of SIX1 protein in PTC and to explore its relationship with clinical behavior in two subtypes of PTC: classic PTC (C-PTC) and follicular variant PTC (FV-PTC).

Materials and methods: Using immunohistochemistry, the study analyzed 125 primary PTC cases, including 85 cases of C-PTC and 40 cases of FV-PTC.

Results: The study found significant positive associations between high SIX1 expression and several adverse clinical features across the PTC samples. High SIX1 expression was linked with increased tumor size, multifocal tumors, LNM, high-grade tumor features, advanced tumor stage, lymphovascular invasion, perineural invasion, and extrathyroidal extension (ETE). Within the classic PTC subgroup, high SIX1 expression showed significant positive correlations with Tumor size (P = 0.04), Multifocality (P = 0.02) and High-grade features (P = 0.03). In the follicular variant subgroup, high SIX1 expression was significantly associated with Lymph node metastasis (LNM) (P = 0.001), Lymphovascular invasion (P = 0.03), ETE (P = 0.003) and tumor stage (P = 0.007).

Conclusions: The findings of this study indicate that SIX1 expression is a marker of poor prognosis in PTC, suggesting that its high expression is linked with more aggressive tumor characteristics and advanced disease stages. Importantly, the impact of SIX1 expression varies between C-PTC and FV-PTC, predicting distinct prognostic factors in each subtype. This suggests that SIX1 could be utilized not only as a prognostic biomarker but also in developing subtype-specific therapeutic strategies for PTC patients.