Thyroid Research最新文献

Background and aim: Papillary thyroid carcinoma (PTC) is the most common form of thyroid malignancy, and activating mutations in the RAS gene family have been implicated in its pathogenesis and clinical behavior. This study aimed to evaluate the role of RAS mutations in clinical outcomes of patients with PTC.

Methods: We conducted a comprehensive literature search of PubMed, Scopus, and WOS. Eligible studies included data on RAS mutation prevalence and at least one of the predefined endpoints. Hazard ratios (HR) for recurrence-free survival (RFS), odds ratios (OR) for mortality, distant metastasis, and tumor recurrence, and mean differences (MD) for tumor size were used as effect sizes.

Results: A total of 22 studies, involving 4727 patients, were included in this analysis. The pooled prevalence of RAS mutations was 20% (95% CI: 14%-28%). Presence of RAS mutation was associated with significantly higher odds of distant metastasis (OR = 3.12, 95% CI: 1.48-6.59, p < 0.01), while no significant associations were found with RFS (HR = 1.05, 95% CI: 0.52-2.13, p = 0.88), overall mortality (OR = 2.01, 95% CI: 0.60-6.70, p = 0.21), tumor recurrence (OR = 0.35; 95% CI: 0.08-1.61, p = 0.13). Moreover, our findings revealed no significant differences in tumor size between RAS-positive and RAS-negative cases (MD = 0.01, 95% CI: -0.73-0.72, p = 0.96).

Conclusions: RAS mutations are present in 20% of PTC cases and are associated with increased risk of distant metastasis. However, these mutations were not significantly associated with other clinical outcomes. These findings support the integration of RAS mutation testing into postoperative risk stratification to identify patients who may benefit from more intensive surveillance and personalized therapeutic strategies.

Objectives: A role of mTOR (mammalian target of rapamycin) in the pathogenesis of Graves' Orbitopathy (GO) has been proposed and rapamycin, better known as sirolimus, an mTOR inhibitor, was recently used in patients with GO. Here we review the available studies evaluating the role of mTOR in GO pathogenesis and the effects of sirolimus on GO.

Design: A comprehensive search of PubMed was conducted using the following keywords: "Graves' orbitopathy", or "thyroid eye disease", or "Graves' ophthalmopathy", or "thyroid-associated ophthalmopathy"; and: "mTOR", or "sirolimus", or "rapamycin".

Inclusion criteria: 1) original articles (preclinical and clinical studies); 2) English language. The articles that did not adequately explore the role of mTOR in GO pathogenesis and those in which the effects of sirolimus on GO were not investigated were excluded. At the end of the screening process, nine studies were included in this systematic review.

Results: mTOR signaling pathway was found to be upregulated in patients with GO. In addition, studies in a mouse model of GO, in orbital fibroblasts and peripheral blood mononuclear cells (PBMCs) derived from GO patients showed a significant reduction in inflammatory mediators, adipogenesis and fibrosis after treatment with sirolimus. In 2007 and 2019 two cases of patients with GO unresponsive to glucocorticoids and successfully treated with sirolimus were described. Consistently with these results, two retrospective investigations showed that treatment with sirolimus, used at low dosage for 12 weeks, was followed by a greater overall response of GO compared with methylprednisolone at 24 weeks. In addition, a good response in diplopia and ocular motility restriction after treatment with sirolimus was reported by two case series. All of these studies reported a good tolerability of sirolimus. Finally, GO response to treatment was shown to correlate with the serum levels of sirolimus at the end of treatment.

Conclusions: Sirolimus may represent a cheap, effective, and safe alternative treatment for GO. In addition, serum levels of sirolimus may be used to predict the response to treatment. Randomized clinical trials are needed to confirm the efficacy of sirolimus on GO and establish the best possible treatment protocol.

Background: This study aims to investigate the effects of iodinated contrast media (ICM) exposure on thyroid function in patients with subclinical hyperthyroidism.

Methods: The study included 46 patients with subclinical hyperthyroidism who presented to the cardiology outpatient clinic and underwent angiographic imaging procedures. Thyroid function tests (TSH, fT3, fT4) of the patients before and after the procedure were analyzed retrospectively. Patients were divided into two groups as low volume (< 200 ml) and high volume (≥ 200 ml) according to the volume of contrast medium received. Pre- and post-procedure comparisons as well as analyses according to low and high-volume exposure were performed.

Results: After the procedure, 50% of the patients became euthyroid and 41.3% remained in the same group (subclinical hyperthyroidism). 2 patients (4.3%) developed clinical hyperthyroidism, and another 2 patients (4.3%) developed clinical hypothyroidism. TSH values increased significantly after the procedure (p < 0.01), but no significant change was observed in fT3 and fT4 values.

Conclusions: In patients with subclinical hyperthyroidism, thyroid function mostly remained stable or became euthyroid after ICM exposure. However, a group of patients developed clinical hypothyroidism or hyperthyroidism. These results suggest that patients with subclinical hyperthyroidism should be closely monitored when using ICM. Long-term follow-up will contribute to a better understanding of the possible risks in this patient group.