Thyroid最新文献

Background: Multimodal treatment, including both conventional and myeloablative chemotherapy (MAT), radiotherapy, surgery, immunotherapy, and differentiating therapy, has increased survival for children affected by high-risk neuroblastoma (HRNB) at the potential cost of long-term endocrine morbidities. In this retrospective single-center study we investigate the long-term thyroid toxicity in neuroblastoma survivors.

Methods: This is a retrospective, single-center cohort study. HRNB survivors were followed in outpatient clinic with a scheduled long-term follow-up program; for this report, we considered patients alive on June 1, 2023 at least 5 years from diagnosis treated during 1996-2018 period. Data were obtained from a chart review and were evaluated as risk factors for long-term toxicity occurrence.

Results: Forty-five patients with a median follow-up from diagnosis of 10.6 years (range 5-25.8 years) were evaluated. Long-term thyroid toxicities were reported in 24/45 (53%) patients at a median time of 7.5 years (range 1.2-18.2; interquartile range 3-12) from diagnosis; hypothyroidism was the most common toxicity (12/24, 50% of patients). The probability of being free from thyroid toxicity at 10 years was 62% (CI: 44-75%). Analyzing children's exposure to different treatments, the probability was 0% in patients who have undergone molecular radiotherapy and 72% (CI: 53-85%) in those who did not (p < 0.001); 30% (CI: 6-59%) in those who received immunotherapy and 78% (CI: 65-90%) in those who did not (p = 0.008); 37% (CI: 12-64%) in patients treated with tandem MAT and 71% (CI: 49-85%) in children who underwent single MAT (p = 0.016); and 86% in patients who did not receive Busulfan (CI: 39-98%) and 55% (CI: 35-71%) in those who did receive Busulfan (p = 0.002). Patients undergoing immunotherapy, ¹³¹I-meta-iodobenzylguanidine therapy or Busulfan experienced thyroid toxicity significantly earlier than those who did not (p = 0.047).

Conclusions: The high cumulative treatment burden in this population results in a substantial risk of thyroid toxicity, even many years after therapy. Therefore, long-term endocrine follow-up should be considered also during adulthood.

Background: Thyrotropin levels increase with age, but standard reference intervals do not account for this, potentially leading to overdiagnosis of subclinical hypothyroidism (SCH) and overuse of levothyroxine in older adults.

Methods: Using data from The Health Improvement Network, this observational emulated target trial study assessed 10-year outcomes in adults over 50 years with SCH (thyrotropin 4.1-10.0mU/L, free thyroxine 10.0-24.0 pmol/L) who were prescribed levothyroxine versus those who were not. Subgroup analyses were limited to patients with age-specific thyrotropin levels. The primary outcome was cardiovascular events (angina, myocardial infarction, peripheral vascular disease, stent procedures, or stroke). Secondary outcomes included bone events (fragility fractures or osteoporosis) and all-cause mortality. Hazard ratios, adjusted through inverse probability of treatment weighting (IPTW) for age, sex assigned at birth, body mass index, Charlson comorbidity index, total cholesterol, hypertension, thyrotropin, hormonal medications, and smoking, were estimated.

Findings: Between January 1, 2006, and January 1, 2022, 22,621 patients (median age [interquartile range]: 66 [59-75] years, 76.7% female) were identified; 62% received levothyroxine and 38% did not. Levothyroxine was associated with reduced cardiovascular (IPTW-adjusted hazard ratio [aHR]: 0.82; CI: 0.74-0.91; p < 0.0001) and all-cause mortality (aHR: 0.71; CI: 0.67-0.75; p < 0.0001), with no adverse effects on bone (aHR: 1.04; CI: 0.93-1.17; p = 0.45). Cardiovascular benefits were limited to patients with thyrotropin levels above the age-specific range and after at least five years of treatment.

Interpretation: Long-term levothyroxine use in older adults with SCH was associated with lower long-term cardiovascular and all-cause mortality risks, with no significant harm to bone health. Age-specific thyrotropin levels should guide treatment decisions.

Background: Over 90% of all thyroid cancers are differentiated thyroid cancer (DTC) with an excellent overall survival rate after thyroidectomy with or without radioactive iodine (RAI) therapy. There is a large variation in the use of RAI therapy in DTC. This population-based study was performed to study the survival advantage offered by RAI therapy in DTC.

Methods: In this population-based retrospective cohort study, we reviewed the medical records of 3330 patients with DTC operated on between 1970 and 2020 and recorded patient and disease characteristics and the oncological status to January 1, 2025. Disease-specific survival (DSS) and disease-free survival (DFS) were estimated by the Kaplan-Meier product limit method, and the association of the individual prognostic factors on DSS and DFS was assessed by the log-rank test. Multivariable analyses were performed with Cox proportional hazards models. Inverse probability of treatment weighting was used to adjust for the difference between the prognostic factors in RAI and non-RAI groups using propensity scores. Secondary analyses were performed using competing risk models to account for the competing influence of non-DTC-related causes of death.

Results: Our cohort included 783 males and 2547 females with a mean age of 48 years. RAI therapy was administered to 34.9% of all cases (24.2% of low, 31.1% of intermediate, and 68.4% of high-risk cases, respectively). 10-year DSS was 97.2% after a median follow-up of 14.1 years. DSS was adversely influenced by the presence of distant metastasis, incomplete resection, advanced age, male sex, non-papillary histology, and advanced T stage. RAI therapy was not significantly associated with DSS overall, but it was associated with over 80% risk reduction in metastatic DTC in the Cox proportional hazards model (hazard ratio 0.192; [CI: 0.088-0.417]; p < 0.001) and competing risk analysis (sub-hazard ratio 0.162; [CI: 0.072-0.368]; p < 0.001).

Conclusions: Excellent DSS can be achieved in DTC with selective use of adjuvant RAI, with the greatest benefit of RAI seen in those with metastatic DTC.

Background: Iodine deficiency disorders (IDDs) remain a public health concern, especially in pregnancy, despite universal salt iodization (USI) programs. Iran has sustained iodine sufficiency since the 1990s through national USI, but recent evidence suggests recurrent iodine insufficiency among pregnant women. This study reports findings from the sixth National Monitoring Survey (2022-2023) to reassess iodine status in schoolchildren and pregnant women in Iran.

Methods: This cross-sectional survey included 11,221 schoolchildren aged 8-10 years and 2929 pregnant women from all 31 provinces. Multistage cluster sampling ensured national representativeness for children. At the same time, pregnant women were recruited from health centers by equal provincial quotas (60 per province, not population-weighted), and their individual intake of iodide along with folic acid supplements was documented. Urinary iodine concentration (UIC) was measured using the Sandell-Kolthoff method, and salt iodine content was assessed by iodometric titration at production and household levels. Data were analyzed with descriptive and nonparametric statistical methods.

Results: The median UIC in schoolchildren was 133 µg/L (interquartile range [IQR]: 88-183), within the World Health Organization (WHO)-recommended range, with 67.7% having UIC ≥100 µg/L. However, 22.8% had a UIC of 50-100 µg/L and 9.5% <50 µg/L. In pregnant women, the median UIC was 128 µg/L (IQR: 84-187), below the WHO threshold of 150 µg/L, with 61.2% having UIC <150 µg/L and 34.4% <100 µg/L. 73.7% of pregnant women used iodide + folic acid supplement, with wide provincial variation of 38-84%. Household salt median iodine content was 32 ppm, but 30.6% of samples were <20 ppm, and only 54% were stored properly. Production-level salt had a median iodine content of 33.8 ppm.

Conclusions: Although Iran has maintained iodine sufficiency in the general population during the last three decades, mild iodine deficiency has reappeared among pregnant women due to incomplete usage of iodide folic acid supplementation. Strengthened monitoring, stricter quality assurance in salt production, improved adherence to iodine supplementation in pregnant women, and targeted provincial interventions are needed to sustain IDD elimination.

Background: Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may be exposed to periods of excess and/or inadequate circulating thyroid hormone levels, which may increase the risk of cardiovascular disease (CVD). We hypothesized that the risk of CVD events in women treated with LT4 may be higher than in women without thyroid disease in the period from midlife to early old age.

Methods: The Study of Women's Health Across the Nation is a multisite longitudinal study of a diverse cohort of midlife women from seven geographic sites across the United States. Women were screened for a history of thyroid disease and the use of LT4. Each participant completed up to 17 follow-up visits during which the occurrence of CVD events was ascertained. The composite CVD outcome was defined as any of the following fatal or nonfatal events myocardial infarction, stroke, heart failure, percutaneous coronary intervention, and coronary artery bypass graft surgery. A multivariable Cox proportional hazards model with time-varying exposure was used to determine the relationship of LT4 treatment to the incidence of the first CVD event. A sensitivity analysis was conducted, stratifying the group with LT4 treatment by thyrotropin (TSH) level.

Results: Of the 2647 women who were included in the study, 421 (15.9%) received LT4 treatment during the study period. A total of 33 (7.8%) CVD events occurred in the group with LT4 treatment compared with 191 (8.6%) in the group without thyroid disease (p = 0.616). In the adjusted Cox proportional hazards model, there was no statistically significant relation of LT4 treatment to risk of CVD events (hazard ratio 0.85, confidence interval [0.55-1.31]; p = 0.463). No significant relation was identified after stratification by TSH level at baseline in the LT4 group.

Conclusions: In a diverse sample of women with long-term follow-up through the menopause transition, we observed no difference in the risk of CVD events between women receiving LT4 treatment for hypothyroidism compared with women without thyroid disease.

Background: Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy, disproportionately affecting women. Despite excellent survival outcomes, DTC treatment, particularly long-term thyrotropin (TSH) suppression therapy, has been associated with differences in psychological well-being and sexual function. Although the association between thyroid dysfunction and female sexual dysfunction (FSD) is well-established, limited data exist regarding FSD in premenopausal women with DTC.

Objective: To investigate the presence and severity of depressive symptoms and FSD in premenopausal women with DTC and examine their association with thyroid hormone levels and thyroid autoimmunity.

Methods: This cross-sectional study included 110 premenopausal women with DTC on stable TSH suppression therapy, stratified into three groups by TSH level (<0.1, 0.1-0.5, and 0.5-2.5 mIU/mL), and 40 healthy controls. Sexual function and depressive symptoms were assessed using the Female Sexual Function Index (FSFI) and Beck Depression Inventory-II (BDI-II), respectively. Thyroid function tests, thyroid antibodies, and sex hormones were evaluated. Correlation and logistic regression analyses were performed.

Results: Women with DTC showed higher rates of sexual dysfunction and depressive symptoms than controls (FSD 53.6% vs. 10%; depressive symptoms 65.5% vs. 15%), with the greatest impairment under stronger TSH suppression. Increased BDI-II scores were inversely correlated with FSFI total and subdomain scores (desire, satisfaction, pain). TSH levels were positively associated with FSFI scores, while free thyroxine and free triiodothyronine showed inverse correlations with satisfaction and lubrication. Elevated thyroglobulin antibody levels were associated with higher depression scores. Multivariable models were adjusted for age. Covariates included body mass index, risk of recurrence, disease duration, TSH, free thyroxine, free triiodothyronine, thyroglobulin antibody, total testosterone, prolactin, and BDI-II. Logistic regression analysis showed that suppressed TSH and higher BDI-II scores were independently associated with higher odds of FSD.

Conclusions: Sexual dysfunction and depressive symptoms were more frequent in women with DTC than in healthy controls; moreover, among women with DTC, the greatest deterioration was seen in those receiving stronger TSH suppression. These findings highlighted the need for comprehensive care that includes psychological and sexual health assessment in the long-term management of women with DTC.

Background: Defects in thyroid hormone synthesis at birth lead to congenital hypothyroidism (CH). Recently, pathogenic variants in the SLC26A7 gene have been linked to dyshormonogenetic goitrous CH. This anion transporter is highly expressed in the thyroid and is involved in thyroid hormone synthesis; however, its exact function and cellular localization remain unclear. In this study, we investigated SLC26A7 variants in Finnish patients with CH, characterized the phenotypes, and analyzed thyroid-specific gene expression.

Methods: SLC26A7 variants were identified from a clinical CH cohort (n = 139) using exome sequencing, and the FinnGen database (R12 release) was screened for disease associations. Thyroid histology and thyroid-specific gene expression were analyzed in six human samples (including two homozygous SLC26A7 pathogenic variant carriers, patients with goitrous and hyperactive thyroids, and normal controls) and in thyroids from different mouse models (including hypo- and hyperthyroid mice, thyroid-specific G-protein deficient, and Slc26a7-knockout mice).

Results: Four CH patients from four novel families carried the homozygous SLC26A7 (c.1893delT, p.F631Lfs*8) pathogenic variant. Two had large trachea-compressing goiters, requiring thyroidectomy already at birth. In addition, one homozygous participant with normal CH screening results developed hypothyroidism at age 16, and one patient with heterozygous SLC26A7 pathogenic variant had permanent CH at birth. Dentofacial abnormalities were frequently noted, including enamel hypoplasia (in four carriers), pro- or retrognathia, and malocclusion requiring orthodontic treatment (in 8/24 carriers). Thyrocyte hypertrophy with large colloid aggregates was a hallmark of homozygous patients. FinnGen screening revealed a 75-fold enrichment of the variant in the Finnish population, identifying a few other homozygous and seven heterozygous cases with early-onset hypothyroidism and dentofacial abnormalities. In human thyrocytes, SLC26A7 was localized to the basolateral membrane, with intense staining in hyperthyroid samples, while in mouse thyroid models, its expression pattern depended on dietary iodide levels, thyrotropin signaling, and GNAS activity.

Conclusions: We describe variable phenotypes associated with the SLC26A7 pathogenic variant, ranging from severe CH with large congenital goiters to delayed onset hypothyroidism and dentofacial abnormalities. SLC26A7 shows thyrotropin-, GNAS-, and dietary iodine-dependent basolateral localization, suggesting their role in phenotypic variations.

Background: One of the challenges in tumor molecular profiling for therapeutic decisions is the unavailability of tumor tissue or its inadequacy to provide high-quality nucleic acids. Although tissue biopsy remains the "gold-standard," analysis of circulating tumor DNA (ctDNA) may offer an alternative to characterize mutations necessary to initiate systemic therapy with selective inhibitors in eligible patients. This study aimed to identify cases of sporadic medullary thyroid carcinoma (sMTC) in which plasma ctDNA analysis may be useful for RET gene testing when tumor tissue is unavailable.

Methods: We conducted a retrospective cohort study analyzing plasma from 36 patients affected by RET-mutated sMTC. Patients were divided into three cohorts (1) 18 patients with progressive sMTC; (2) nine patients with stable disease under treatment with a multikinase inhibitor; and (3) nine patients with metastatic but stable disease without treatment. For patients in cohort 1, we studied plasma collected at the time of progression just before the initiation of systemic therapy, while in cohorts 2 and 3, we studied last plasma available at follow-up. The RET driver mutation was analyzed in ctDNA using specific digital droplet PCR assays.

Results: The RET driver mutation was detected in 16/36 (44.4%, CI 27.9-61.9) ctDNA samples, with a statistically significant difference among the three cohorts 16/18 (88.9%, CI 65.3-98.6) in cohort 1 and 0/9 (0%, CI 0-33.6) in cohorts 2 and 3 (p < 0.001) with a mean variant allele frequency of 5.4%. The presence of detectable RET-mutated ctDNA was associated with disease progression (p < 0.001), higher percentage of metastatic sites with > five lesions (i.e., tumor burden; p = 0.001), and higher levels of serum calcitonin (Ct) (p = 0.009), and carcinoembryonic antigen (p = 0.038).

Conclusions: Our study demonstrates that ctDNA analysis may be a valid approach to genotype sMTC patients. Thus, liquid biopsy-based RET mutation profiling may be beneficial in advanced and progressive sMTC cases when primary tumor tissue is unavailable or inadequate for high-quality nucleic acid extraction, enabling RET-inhibitor therapy, if needed, according to specific indications. However, to obtain reliable results, ctDNA molecular profiling should be performed when tumor burden is high and the disease is progressing.

Background: Active surveillance (AS) has been proposed as a management option for recurrence of thyroid cancer. However, the current evidence for AS remains limited because of retrospective study designs, small sample sizes, and follow-up loss. We therefore performed a systematic review and meta-analysis to provide a more reliable estimate of disease progression during AS for recurrent thyroid cancers.

Methods: This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched MEDLINE, EMBASE, and COCHRANE databases through July 2025. Eligible studies included patients with recurrent thyroid cancer (thyroid bed nodules or lymph node metastases) managed with AS after complete resection of the primary tumor. Pooled progression rates were calculated using a random-effects model, with subgroup, sensitivity, and meta-regression analyses also being performed. Progression rates were also adjusted using modeling for follow-up loss.

Results: Ten retrospective studies (n = 841) were included. All included lesions were locoregional metastases from differentiated thyroid cancer (DTC). The pooled mean follow-up duration was 51.6 months (95% confidence interval [CI], 36.0-67.2). Across 10 studies, the overall pooled progression rate was 23% [95% CI, 12-34%] and was higher in biopsy-confirmed cases (32%; 95% CI, 15-55%). Progression was higher in studies with <40 months of mean follow-up than in studies with ≥40 months of mean follow-up (36% vs. 17%, p < 0.05). Log-transformed baseline serum thyroglobulin levels were significantly higher in the progression group compared with the stable group (1.02 vs. -0.07, p < 0.05). Subgroup analyses revealed higher progression rates in studies with <75% Stage I patients (30% vs. 11%, p < 0.05) and with ≥5% Stage IV patients (28% vs. 14%, p < 0.05). Adjustment for follow-up loss increased the estimated pooled progression rate up to 35-70%.

Conclusions: Reported progression rates of AS for locoregional recurrent DTC may be underestimated due to heterogeneity and follow-up loss. Consequently, AS should be considered with caution. Higher progression rates were observed in patients with elevated baseline serum thyroglobulin levels and advanced tumor stage, suggesting that these factors may help identify patients who require closer monitoring or earlier intervention.