The influence of thyroid hormone medication on intra-therapeutic half-life of 131I during radioiodine therapy of solitary toxic thyroid nodules.

Despite a significantly improved dietary iodine supply, solitary toxic thyroid nodules (STN) are still a common clinical problem in former iodine deficient areas. Radioiodine treatment (RIT) is a well-established therapeutic option with few side effects and high success rates. As radioiodine biokinetics are individual for every patient, the necessary activity has to be calculated individually by a pre-therapeutic measurement of the intra-therapeutic effective half-life (EHL) in a radioiodine uptake test (RIUT). A suppressive medication with triiodothyronine (T3) or tetraiodothyronine (T4) is often needed to suppress uptake in normal thyroid tissue. Therefore, the aim of this study was to quantify the possible influence of this medication on intra-therapeutic radioiodine biokinetics. A cohort of 928 patients with STN undergoing RIUT and RIT was analysed. Patients were subdivided into 3 groups. Group T3: medication with T3 (n = 274), group T4: medication with T4 (n = 184) and group NM: no additional medication (n = 470). The T3 and T4 subgroups were further subdivided depending on the dose of thyroid hormone medication. In order to analyse the influence of thyroid hormone medication on individual intra-thyroidal biokinetics, the variance of the determined individual EHL between RIUT and RIT within the single groups and within the subgroups was investigated. EHL was significantly decreased between RIUT and RIT in the T3 and T4 subgroups (EHL: T3: 5.9 ± 1.1 d in RIUT and 3.3 ± 1.4 d in RIT (- 43%) (p < 0.05); T4: 5.9 ± 1.2 d in RIUT and 3.4 ± 1.5 d in RIT (- 42%) (p < 0.05). The decrease of EHL did not differ statistically between T3 or T4. However, both showed a highly significant difference compared to the NM group (p < < 0.05). A further subgroup analysis showed a significant dependence of the decrease in EHL related to the dose of thyroid hormone medication of 35-58% (T3) and 15-67% (T4) (p < 0.05). A significantly reduced EHL compared to RIUT in patients receiving thyroid hormone medication was detected. Moreover, a significant correlation between the dose of thyroid hormone medication (T3 or T4) and the decrease of EHL was found. Therefore, an adaption of the calculated activity should be considered in RIUT to obtain the required radiation dose in RIT of patients suffering from STN.

Clinical Efficacy of Chinese and Western Medicine in the Treatment of Benign Thyroid Nodules: A Meta-Analysis.

Background: Studies have shown that Chinese herbal medicine (CHM) effectively improved the response rate and reduced the maximum nodule diameter of benign thyroid nodules (BTN). This study aimed at systematically reviewing all related studies to assess the clinical efficacy of CHM and Western medicine in the treatment of BTN. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched for randomized controlled trials, published between 2000 and 2021, on CHM for treating BTN. The control group comprised patients treated with Western medicine (oral thyroxine tablets or microwave ablation), while the treatment group was treated with CHM combined with Western medicine. Meta-analysis was performed using the Stata 16.0 software. Results: A total of 264 articles were retrieved, of which 12 were finally selected for analysis after screening. The results showed that combined therapy was associated with a higher response rate (OR = 3.35, 95% CI (2.40, 4.68), P < 0.05). After treatment, the maximum nodule diameter (SMD = -0.76, 95%, CI (-0.98, -0.53), P < 0.05) and thyroid volume (SMD = -1.14, 95%, CI (-1.94, -0.35), P < 0.05) of the treatment group were smaller than those of the control group. Furthermore, the combined treatment was associated with lower levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in the serum of patients and lower traditional Chinese medicine (TCM) syndrome score (SMD = -1.87, 95%, CI (-3.16, -0.58), P < 0.05). Conclusion: CHM combined with thyroid hormone/microwave improved the response rate of BTN. The combined treatment was also associated with reducing the maximum nodule diameter, thyroid volume, levels of FT3, FT4, and TSH, and TCM syndrome score. Therefore, combining CHM with WM could be considered as an alternative and effective treatment for treating BTN, suggesting promising integration of Chinese medicine with Western medicine.

Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Benign thyroid nodules respond to a single administration of 0.3mg recombinant human thyrotropin with highly variable volume increase.

Introduction: The nature of thyroid nodules is heterogenous. Most of them are benign and, in the absence of pressure symptoms of adjunct structures, no treatment is needed. Our objective was to investigate the acute effects of a low dose of recombinant human TSH (rhTSH) on the volume of benign thyroid nodules. Methods: we studied 27 nodules (14 isoechoic and 13 hypoechoic) in 15 (11 women and 4 men; mean age: 51.0 ± 15.9 years) consecutive patients with one to three well-separated asymptomatic benign thyroid nodules. All subjects were euthyroid, with negative thyroid antibodies, and none received levothyroxine. The total thyroid volume and thyroid nodule volume were sonographically determined by two independent examiners (P.B. and M.M.) before, 48 hours and 6 months post intramuscular (IM) administration of 0.3mg rhTSH, and the mean values of the two examiners' measurements were used; thyroid function tests were obtained at the same time points. Results: The mean volume of isoechoic nodules increased by 57.3%, of hypoechoic nodules by 46.6% and of the surrounding thyroid parenchyma by 70.4% 48 hours post-rhTSH; mean volumes had returned to baseline levels 6 months later. A large variance in the volume change responses was observed. The relative change in nodule volume (defined as the percent change in nodule volume divided by the percent change in the surrounding parenchyma) from baseline to 48 hours was significantly higher in isoechoic versus hypoechoic nodules (p<0.05). Conclusions: A single dose of 0.3 mg rhTSH transiently increased the volume of benign thyroid nodules. The increase was more pronounced in isoechoic nodules and had a great variability. Our findings could be useful in the management of benign thyroid nodules, by helping in understanding which nodules would be more responsive to TSH suppression therapy.

Safety and efficacy of Prunella vulgaris preparation in adjuvant treatment of thyroid nodules: A meta-analysis.

BACKGROUND: Prunella vulgaris (PV), a traditional Chinese medical herb, is considered beneficial for some thyroid diseases. However, the effectiveness is not consistent in different studies. This review compiles the evidence from randomized controlled trials (RCTs) and quantifies the effects of PV preparation on thyroid nodules. METHODS: Eight databases were searched up to April 2021 to identify eligible studies. Only RCTs were included. Meta-analysis of homogeneous studies was performed by RevMan5.3 software. Cochrane risk of bias assessment tool version 2.0 was used to assess the risk of bias of each trial. The research screening, data extraction, and risk of bias assessment were employed by 2 reviewers independently, and disagreement will be decided by a third senior reviewer. The risk ratio (RR), mean difference (MD) and corresponding 95% confidence interval (CI) of each study are summarized. RESULTS: Thirteen RCTs with 1468 patients were included in this study. A meta-analysis showed that the RR of the clinical efficacy of PV combined with levothyroxine sodium tablets was 1.22 (95% CI [1.11, 1.33]). The MD of thyroid nodule diameter was -0.43 (95% CI [-0.63, -0.22]). The MD of free triiodothyronine and free tetraiodothyronine levels was -1.99 (95% CI [-3.14, -0.86]) and -3.20 (95% CI [-5.50, -0.89]), respectively. The RR of the adverse reaction rate was 0.67 (95% CI [0.36, 1.22]), and the RR of the clinical efficacy of PV preparation combined with thyroxin tablets was 1.29 (95% CI [1.03, 1.62]). CONCLUSIONS: PV combined with levothyroxine sodium tablets or thyroxin tablets has more benefits for thyroid nodules, further improving the clinical efficiency, reducing the diameter of nodules and reducing the occurrence of adverse reactions. However, the quality of these studies is uncertain, and higher quality and more RCTs are needed to provide comprehensive evidence-based medical evidence in the future.

Modified percutaneous ethanol injection method combined with microwave ablation for the treatment of symptomatic, predominantly cystic, benign thyroid nodules: a retrospective study of 201 cases.

OBJECTIVE: Percutaneous ethanol injection (PEI) and microwave ablation (MWA) are both important methods used in treating benign thyroid nodules. This study aimed to investigate the efficacy and safety of a modified PEI method combined with MWA for the treatment of symptomatic, predominantly cystic and benign thyroid nodules. MATERIALS AND METHODS: This study included 201 patients who underwent treatment in our department between April 2015 and August 2018. Predominantly cystic thyroid nodules were treated by the modified PEI procedure, which included short-term boiling ethanol ablation (STBEA) and was combined with MWA. Complications, the volume reduction ratio (VRR), symptoms and cosmetic scores were recorded at 1, 3, 6 and 12 months after treatment and every 6 months thereafter. RESULTS: No major complications were observed during or after the treatment. Ten patients (4.8%) experienced temporary voice change, which resolved within 3 months. Of 200 (97.6%) out of 205 nodules showed significant volume reduction at the final follow-up. Recurrence occurred for only 5 (2.4%) nodules. The mean thyroid nodule volume decreased from 17.40 ± 3.21 mL at baseline to 1.17 ± 0.37 mL at 12 months. The greatest VRR was observed within the first 3 months after treatment. CONCLUSIONS: The modified PEI method combined with MWA is safe and effective for the treatment of predominantly cystic benign thyroid nodules and provides a shorter operating time and lower recurrence rate than traditional treatments.

Percutaneous injection of ethanol for thyroid nodule treatment: a comparative study

ABSTRACT Objective: Percutaneous ethanol injection (PEI) is an alternative to surgery for the treatment of thyroid nodules (TNs). However, size reductions of treated (TTNs) and untreated TN (UTNs) have not been compared. Volumetric reductions in TTNs with PEI were evaluated by comparing TTNs and UTNs in the same patient, and independent variables predicting good post-PEI outcomes were analyzed. Materials and methods: Overall, 282 patients with multinodular goiters were selected. Two nodules located in different lobes were compared for common disease behaviors. Overall, 150 nodules were selected from 75 patients (6 M: 69 F) with a mean age of 50.1 ± 17.4 years. This prospective nonrandomized intervention study prioritized treating TNs of greater volume or single hyperfunctioning TNs. A single observer experienced in PEI and an ultrasound specialist performed the interventions. Results and discussion: TTNs (mean volume: 14.8 ± 16.2 mL) were reduced by 72.6 ± 27.3% of their initial volume, while UTNs increased by a mean of 365.7 ± 1.403.8% (p < 0.00001). The patients underwent a mean of 4.0 ± 3.1 outpatient PEI sessions without relevant complications. Logistic regression analysis showed that the magnitude of the PEI induced reduction was associated with the number of treatment sessions (p = 0.03, CI [1.1-38.2]) and not with ultrasonographic characteristics of the nodules. Each PEI session increased the rate of TN reduction by a factor of 6.7. Conclusions: PEI is a well-tolerated outpatient procedure that effectively reduces the volume of TNs and is noticeably superior to conservative treatment for all ultrasonographic classifications.

Percutaneous injection of ethanol for thyroid nodule treatment: a comparative study.

OBJECTIVE: Percutaneous ethanol injection (PEI) is an alternative to surgery for the treatment of thyroid nodules (TNs). However, size reductions of treated (TTNs) and untreated TN (UTNs) have not been compared. Volumetric reductions in TTNs with PEI were evaluated by comparing TTNs and UTNs in the same patient, and independent variables predicting good post-PEI outcomes were analyzed. METHODS: Overall, 282 patients with multinodular goiters were selected. Two nodules located in different lobes were compared for common disease behaviors. Overall, 150 nodules were selected from 75 patients (6 M: 69 F) with a mean age of 50.1 ± 17.4 years. This prospective nonrandomized intervention study prioritized treating TNs of greater volume or single hyperfunctioning TNs. A single observer experienced in PEI and an ultrasound specialist performed the interventions. RESULTS: TTNs (mean volume: 14.8 ± 16.2 mL) were reduced by 72.6 ± 27.3% of their initial volume, while UTNs increased by a mean of 365.7 ± 1.403.8% (p < 0.00001). The patients underwent a mean of 4.0 ± 3.1 outpatient PEI sessions without relevant complications. Logistic regression analysis showed that the magnitude of the PEI induced reduction was associated with the number of treatment sessions (p = 0.03, CI [1.1-38.2]) and not with ultrasonographic characteristics of the nodules. Each PEI session increased the rate of TN reduction by a factor of 6.7. CONCLUSION: PEI is a well-tolerated outpatient procedure that effectively reduces the volume of TNs and is noticeably superior to conservative treatment for all ultrasonographic classifications.

Effect of Chinese herbal medicine for patients with benign thyroid nodules in adults: A protocol for systematic review and meta-analysis.

BACKGROUND: Thyroid nodules (TN) are discrete lesions within the thyroid gland and are a common clinical problem detected in 19% to 68% of people. TN are more common as age increases and occur more frequently in women. TN can cause pressure symptoms, cosmetic complaints, and thyroid dysfunction. Treatment for benign thyroid nodules includes thyroid hormone therapy, surgery, radioiodine treatment, percutaneous ethanol injection therapy, and laser or radiofrequency treatment to shrink nodules. In China and many other countries, doctors use Chinese herbal medicines (CHM) to treat TN. However, systematic review and meta-analysis has not been found to assess the effects and safety of CHM in curing TN at present. Hence, the systematic review is conducted to scientifically and methodically evaluate the value of its effectiveness and safety of CHM on TN. METHODS: Literatures related to CHM for TN from the establishment of the database to November 2020 will be retrieved from the following databases: PubMed, Excerpta Medica Database (EMBASE), MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform (ICTRP), Wanfang Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP). There are no language restrictions for retrieving literatures. Case reports, animal studies, editorials, expert opinions, reviews without original data, and studies on pediatric population were excluded. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in TN patients will be put in the study including nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data. RESULT: This study will provide high-quality available evidence for the treatment of TN with CHM based on nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. CONCLUSION: The systematic review will to evaluate the efficacy of CHM in treating benign thyroid nodules in adults and provide evidence for clinicians. INPLASY REGISTRATION NUMBER: INPLASY2020120093.

Long-term follow-up of cystic thyroid nodules treated with percutaneous ethanol injection (PEI) using two different approaches.

BACKGROUND AND AIM: Cystic thyroid nodules (CNs), although generally benign, can cause compressive or aesthetic problems. Percutaneous ethanol injection (PEI) can represent an alternative to surgery. The present retrospective study evaluates: (i) the long-term outcome of CNs after PEI; (ii) the differences between two different PEI protocols; (iii) the CNs response according to the liquid component. MATERIALS AND METHODS: The study comprises 358 nodules post-PEI followed for at least 2 years. PEI was performed according to two different treatment protocols with a single (Foggia) or double (Turin) alcohol injection. CNs were divided according to their composition: cystic (CYS) >90%, mainly cystic (M-CYS) 75-90%, mixed (MIX) 50-75%, solid-mixed (S-MIX) 35-50%. The volume reduction rate (VRR) was defined as nodule volume (mL) after PEI/nodule volume (mL) before PEI x 100. RESULTS: The 1-year VRR was significantly higher than that at 6 months (89.5% vs 72.9%, P = 0.0005), no differences were observed after 1 year. A significant difference between Turin and Foggia was observed only in VRR at early visit (79% vs 86%, respectively, P = 0.002) and recurrence rate (14% vs 24%, respectively, P = 0.001). Minor side-effects were infrequent. In 192 nodules with a 10-year follow-up CYS showed higher VRR than MIX and S-MIX nodules (P < 0.001). CONCLUSION: Our study reported that the long-term outcome of CNs treated with PEI is excellent regardless of the PEI technique utilized; the larger the cystic amount, the higher the VRR. Based on present results, PEI can be considered as the first-line choice for treating thyroid CNs.

A pregnant woman with an autonomously functioning thyroid nodule: a case report.

BACKGROUND: The epidemiology and natural history of autonomously functioning thyroid nodules (AFTNs) have not been elucidated. Here we report the pregnant Japanese woman with an AFTN. CASE PRESENTATION: The patient was a 31-year-old woman who was hospitalized due to the placenta previa associated with threatened abortion at the 16 weeks of her third pregnancy. At her second pregnancy, she was euthyroid but had a single, 2.3 cm nodule on her right thyroid lobe. Her thyroid hormone level was trended increased with her pregnancy progression, and the thyrotoxic state was remained after delivery. Before her third pregnancy, her hyper-vascular nodule enlarged to 3.4 cm at regular monitoring. When she visited our hospital, she was at 16 weeks of pregnancy and had thyrotoxicosis with negative TSH-receptor antibody. She delivered a baby weighing 2615 g without hypothyroidism at 39 weeks of pregnancy by natural delivery. After delivery, a 99mTc scintigram showed a hot spot in her right thyroid lobe. She was diagnosed with AFTN and treated with methimazole while nursing. CONCLUSIONS: This case showed that hCG stimulation during pregnancy caused thyroid nodule enlargement and enhanced thyroid hormone production. The pregnancy could be the pathological stimulus and provides chance to diagnosis for AFTNs.

[Percutaneous ethanol injection efficacy in the treatment of benign thyroid nodules. Ten-year follow-up of 254 patients]. / Jóindulatú pajzsmirigygöbök perkután alkoholinjekciós kezelésének hosszú távú eredményessége. 254 beteg 10 éves követésével szerzett tapasztalatok.

Introduction and aim: Although percutaneous ethanol sclerotherapy for the treatment of benign thyroid nodules (PEI) has been used for more than 30 years, there are only two studies in thyroid cysts (THCY) and 2 in autonomously functioning nodule (AFN) in which the mean follow-up reaches at least five years, while in the event of non-autonomously functioning solid nodules (NAS), there is not any study with at least 5-year mean follow-up. Our study focuses on the long-term efficacy of PEI in benign thyroid nodules. Method: We analyzed the long-term success of PEI in 254 patients treated for more than 10 years. The success was defined as 50% or greater reduction in nodule volume. In addition, the patient had to remain euthyroid without thyrostatic therapy in AFN. Results: The 10-year success rate was 79.4%, 37.1% and 69.4% in THCY, AFN and NAS, respectively. In 23.3% of unsuccessful PEIs, the failure could be revealed only after 5 years of follow-up. The mean nodule volume at 10-year follow-up related to the initial size was 29.8%, 39.6% and 48.9% in THCY, NAS and AFN, respectively. In THCY, PEI proved to be significantly more effective in older patients while other parameters (size of the nodule, amount of the injected alcohol and the ratio of these) did not correlate significantly with the success rate. Conclusions: Our study which presents the longest follow-up in all 3 types of benign thyroid nodules confirms that PEI has a minimal role in AFN, is recommendable in THCY and might have a role in NAS. The success rate decreases over time which emphasizes the importance of the long-term follow-up in the judgement of PEI. Orv Hetil. 2020; 161(6): 224-231.

Treatment for benign thyroid nodules with a combination of natural extracts.

Benign thyroid nodules are among the most common endocrine disorders. Recent advances in diagnostic imaging and pathology have significantly contributed to better risk stratification of thyroid nodules. However, current treatment options, beyond surgical approaches are limited. The following placebo-controlled study presents, to the best of our knowledge, the first results of a non-invasive therapy for benign thyroid nodules. The efficacy and safety of a supplement containing spirulina, curcumin and Boswellia in euthyroid patients with benign thyroid nodules, was assessed by a 3 month, double-blind, placebo-controlled study which was completed by 34 patients. Patients with benign (FNAB documented) single thyroid nodules between 2 and 5 cm were evaluated in a prospective placebo-controlled cross-over trial, across 12 weeks (3 visits with six-week intervals). At each visit, the target thyroid nodule was recorded in two dimensions. In addition, plasma levels of thyroid stimulating hormone, free thyroxine and copper were assessed. The mean initial nodule area at V1 was 4.38±3.14 cm2, at V2 3.87±2.79 cm2, and at V3 3.53±2.84 cm2; P<0.04. Administration of the active substances (n=34) was followed by a mean area decrease of 0.611 cm2±0.933 (SD), while placebo administration (n=29) was followed by a mean decrease of 0.178 cm2±0.515 (SD), (P=0.027). The presented findings suggest that the combination of spirulina-curcumin-Βoswellia is effective in reducing the size of benign thyroid nodules. However, additional studies are needed in order to elucidate the exact mechanisms through which the suggested supplement facilitates a decrease in the size of benign thyroid nodules.

The effect of disease activity on thyroid nodules in patients with acromegaly.

Nodular thyroid disease is a very common disorder in patients with acromegaly. Insulin-like growth factor-1 (IGF-1) is a thyroid growth factor, and there is a correlation between IGF-1 levels and thyroid volume (TV) in patients with acromegaly. There is no study investigating the impact of somatostatin analog (SSA) treatment on thyroid nodule volume in patients with acromegaly. We aimed to assess thyroid nodule volume change with SSA treatment in patients with persistent acromegaly. We retrospectively analyzed data from 108 consecutive patients with acromegaly who were followed up by our clinic after undergoing surgery between 2002 and 2014. Patients who were cured after surgery were excluded. We only selected 43 patients (21 males, 22 females, mean age 52.8 ± 11.9 years) who did not meet the criteria of remission postoperatively, who were treated with SSA for at least six months and had normal thyroid function. Patients were divided into three groups (well-controlled, controlled, and active) according to their IGF-1 and growth hormone (GH) levels. All patients underwent an evaluation of TV and total thyroid nodule volume (TTNV) by ultrasound. TTNV decreased significantly in patients with well-controlled acromegaly (0.44 [0.75] to 0.23 [0.73], p < 0.001). TTNV did not change in controlled patients (0.18 [1.28] to 0.13 [1.54], p = 0.959); however TTNV increased in patients with active acromegaly (0.77 [1.46] to 1.03 [1.88], p = 0.028). Successful medical treatment of patients with active acromegaly decreases thyroid nodule volume. Sustained exposure to IGF-1 may cause an increase in thyroid nodule volume in patients with acromegaly.

Role of Metformin in the Treatment of Patients with Thyroid Nodules and Insulin Resistance: A Systematic Review and Meta-Analysis.

BACKGROUND: Metformin is the most-prescribed oral medication to lower blood glucose worldwide. Some data suggest that metformin may have a role in the treatment of patients with thyroid nodules, but contrasting results are reported in different settings. This study explores and critically reevaluates the knowledge on this topic. METHODS: A literature search identified 250 records. Studies evaluating the size of thyroid nodules before and after metformin treatment were included. Assessed outcomes were the size of thyroid nodules, thyrotropin (TSH) level, thyroid gland volume, and insulin resistance index (HOMA-IR). After screening and full-text assessment, five studies were included in the systematic review. Random-effects meta-analyses of the standardized mean difference (SMD) were performed for the four outcomes of interest. Heterogeneity was estimated using I2, and the quality of evidence was assessed for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation guidelines. RESULTS: A total of 189 patients were included in the final analysis. After metformin treatment, a slight but significant reduction in thyroid nodule size was found in four studies, which included a total of 167 patients (SMD 0.46 [confidence interval (CI) 0.00-0.93]; p = 0.05). Similarly, in four studies reporting on a total of 146 patients, significant reductions in TSH level (SMD 0.30 [CI 0.07-0.53]; p = 0.01) and HOMA-IR level (SMD 0.90 [CI 0.12-1.67]; p = 0.02) were reported after treatment with metformin. In two studies, which included 114 patients, no change in thyroid gland volume was discovered after treatment with metformin (SMD 0.21 [CI -0.05 to 0.47]; p = 0.11). Quality of evidence was generally assessed as low or very low. CONCLUSIONS: Metformin induces reductions in thyroid nodule size and TSH and HOMA-IR levels in patients with thyroid nodules and insulin resistance. In contrast, no change in thyroid gland volumes was found. Whether metformin treatment for thyroid nodules has clinical significance remains to be demonstrated.

High intensity focused ultrasound (HIFU) ablation of benign thyroid nodule is safe and efficacious in patients who continue taking an anti-coagulation or anti-platelet agent in the treatment period.

BACKGROUND: High intensity focused ultrasound (HIFU) ablation is a promising treatment for benign thyroid nodules but because bleeding complications can occur following any intervention to the thyroid gland, the safety and efficacy of HIFU ablation were evaluated in patients who continued taking an anti-coagulation or anti-platelet agent during treatment. METHODS: From 2015 to 2017, 303 patients who underwent a single-session ablation for a benign thyroid nodule were analyzed. The primary study endpoint was thyroid bleeding, intra-lesional or peri-thyroidal hematoma or neck bruising diagnosed within 4 days of the treatment. Other endpoints included treatment-related complications, extent of nodule shrinkage and symptom score. Nodule volume was estimated by ultrasound. Extent of nodule shrinkage (by volume reduction ratio) (VRR)= [Baseline volume - volume at 6-month]/[Baseline volume] × 100. Obstructive symptom score (by 0- 10 visual analog scale, VAS) was evaluated after treatment. RESULTS: Twelve patients continued taking an anti-coagulation or anti-platelet agent while the other 291 patients did not during treatment. No patients in either group suffered active thyroid bleeding, intralesional/pericapsular hematoma or subcutaneous neck bruising in the first 4 days of treatment. Complication rate and the 6-month VRR were comparable between the two groups (0.0% vs. 1.7%, p = 1.000 and 55.96% vs. 61.29%, respectively, p = .073). CONCLUSIONS: HIFU ablation is a feasible treatment in patients who continue to take an anti-coagulation or anti-platelet agent during treatment and might be preferable in patients who continuously require an anti-coagulation or anti-platelet agent for one reason or another during treatment.

Usefulness of core needle biopsy for the diagnosis of thyroid Burkitt's lymphoma: a case report and review of the literature.

BACKGROUND: Thyroid lymphomas are an exceptional finding in patients with thyroid nodules. Burkitt's lymphoma is one of the rarest and most aggressive forms of thyroid lymphomas, and its prognosis depends on the earliness of medical treatment. Given the rarity of this disease, making a prompt diagnosis can be challenging. For instance, fine-needle aspiration (FNA) cytology, which is the first-line diagnostic test that is performed in patients with thyroid nodules, is often not diagnostic in cases of thyroid lymphomas, with subsequent delay of the start of therapy. CASE PRESENTATION: Here we report the case of a 52-year-old woman presenting with a rapidly enlarging thyroid mass. Thyroid ultrasonography demonstrated a solid hypoechoic nodule. FNA cytology was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. It is core needle biopsy (CNB) that helped us to overcome the limitations of routine FNA cytology, showing the presence of thyroid Burkitt's lymphoma. Subsequent staging demonstrated bone marrow involvement. The early start of an intensive multi-agent chemotherapy resulted in complete disease remission. At 60 months after the diagnosis, the patient is alive and has not had any recurrence. CONCLUSIONS: Clinicians should be aware that thyroid Burkitt's lymphoma is an aggressive disease that needs to be treated with multi-agent chemotherapy as soon as possible. To diagnose it promptly, they should consider to order/perform a CNB in any patient with a rapidly enlarging thyroid mass that is suspicious for lymphoma.

Evaluation of thyroid nodule characteristics in subclinical hypothyroid patients under a myo-inositol plus selenium treatment.

OBJECTIVE: The anticancer effect of myo-inositol (MI) is catching researchers' attention worldwide. Thyroid nodules (TNs) have been detected by ultrasound (US) in up to 76% of the general population and, although most of them are benign, thyroid cancer is the most common malignancy of the endocrine system. PATIENTS AND METHODS: A retrospective, observational study was conducted in 642 patients with suspected hypothyroidism undergoing US. The analysis was addressed exclusively to patients with subclinical hypothyroidism (SCH) or thyroid-stimulating hormone (TSH) levels borderline associated to TNs classified as class I and II; 1 group (control, no. 16) no treatment was prescribed; the other group (treated, no. 18) underwent treatment with 1 tablet containing MI plus selenium (Se) every day, for six months. Clinical data were collected to evaluate the nodular size, number, and elasticity, as well as TSH levels. RESULTS: Final data were analyzed from 34 patients: in 76% of mixed TNs was observed a significant reduction of their size and 56% of them significantly regressed nodule stiffness following oral supplementation with MI plus Se. The mean number of mixed nodules for patient shifted from 1.39 ± 0.16 to 1.05 ± 0.15 (p ≤ 0.05). TSH levels dropped from 4.2 ± 0.21 mIU/L at baseline to 2.1 ± 0.20 mIU/L post-treatment (p < 0.001). In the control group, 38% of TNs reduced their diameter but TSH levels significantly increased up to the threshold after six months (from 3.95 ± 0.18 mIU/L to 4.30 ± 0.22 mIU/L, p ≤ 0.05). CONCLUSIONS: In SCH patients undergoing treatment with MI plus Se, a reduction of the size, number and elasticity score of TNs as well as TSH levels was observed. Further studies are required, either in vitro and in vivo, to investigate the use of MI plus Se for the management of TNs.

PERCUTANEOUS ETHANOL INJECTION FOR BENIGN CYSTIC AND MIXED THYROID NODULES.

OBJECTIVE: We aimed to determine the effect of percutaneous ethanol injection (PEI) on volume of cystic and mixed thyroid nodules, thyroid function tests (TFTs), antibody titers, and cytologic changes for 1 year. METHODS: Fifty-five nodules from 53 patients with cystic and mixed properties treated with PEI were included. Nodule volumes, TFTs, and thyroid autoantibodies were analyzed at baseline, 6 months, and 12 months. Fine-needle aspiration biopsy (FNAB) was performed to PEI-treated nodules in the 12th month. Thyroid nodules were classified into three groups by structural properties (purely cystic, predominantly cystic, predominantly solid). RESULTS: PEI caused a volume reduction of 80.7% at 6 months and 82.1% at 12 months, without any serious complications. PEI was repeated 1.4 ± 0.4 times with a mean total ethanol amount of 3.6 ± 3.1 mL. Volume reduction in the purely cystic nodules in the 6th and 12th months after PEI was greater than the volume reductions in predominantly cystic and predominantly solid nodules. We found that smaller nodules had greater volume reductions after PEI in the 12th month. During the study, patients remained euthyroid. Antithyroglobulin levels were decreased at 12 months. None of the FNAB results were compatible with a malignant or suspicious for malignancy cytology at the 12th month. CONCLUSION: PEI is an effective means of treatment for benign cystic and mixed thyroid nodules, without any serious side effects. We can also assume that PEI is not a trigger for autoimmunity and malignancy development over the short term. ABBREVIATIONS: anti-TG = anti-thyroglobulin; anti-TPO = anti-thyroperoxidase; AUS = atypia of unknown significance; CV = coefficient of variation; FNAB = fine-needle aspiration biopsy; fT3 = free triiodothyronine; fT4 = free thyroxine; PEI = percutaneous ethanol injection; TFT = thyroid function test; TSH = thyroid-stimulating hormone; US = ultrasonography.

Galectin-3: The Impact on the Clinical Management of Patients with Thyroid Nodules and Future Perspectives.

Galectins (S-type lectins) are an evolutionarily-conserved family of lectin molecules, which can be expressed intracellularly and in the extracellular matrix, as well. Galectins bind ß-galactose-containing glycoconjugates and are functionally active in converting glycan-related information into cell biological programs. Altered glycosylation notably occurring in cancer cells and expression of specific galectins provide, indeed, a fashionable mechanism of molecular interactions able to regulate several tumor relevant functions, among which are cell adhesion and migration, cell differentiation, gene transcription and RNA splicing, cell cycle and apoptosis. Furthermore, several galectin molecules also play a role in regulating the immune response. These functions are strongly dependent on the cell context, in which specific galectins and related glyco-ligands are expressed. Thyroid cancer likely represents the paradigmatic tumor model in which experimental studies on galectins' glycobiology, in particular on galectin-3 expression and function, contributed greatly to the improvement of cancer diagnosis. The discovery of a restricted expression of galectin-3 in well-differentiated thyroid carcinomas (WDTC), compared to normal and benign thyroid conditions, contributed also to promoting preclinical studies aimed at exploring new strategies for imaging thyroid cancer in vivo based on galectin-3 immuno-targeting. Results derived from these recent experimental studies promise a further improvement of both thyroid cancer diagnosis and therapy in the near future. In this review, the biological role of galectin-3 expression in thyroid cancer, the validation and translation to a clinical setting of a galectin-3 test method for the preoperative characterization of thyroid nodules and a galectin-3-based immuno-positron emission tomography (immuno-PET) imaging of thyroid cancer in vivo are presented and discussed.