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.

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.

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.

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.

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.

Chinese herbal medicines for benign thyroid nodules in adults.

BACKGROUND: A thyroid nodule is a discrete lesion within the thyroid gland that might be palpable and is ultrasonographically distinct from the surrounding thyroid parenchyma. Thyroid nodules are more common as age increases and occur more frequently in women. Benign thyroid nodules often cause pressure symptoms and cosmetic complaints. In China and many other countries, doctors use Chinese herbal medicines (CHM) to treat thyroid nodules. OBJECTIVES: To assess the effects of Chinese herbal medicines in the treatment of benign thyroid nodules in adults. SEARCH METHODS: Review authors searched the following electronic databases: The Cochrane Library, MEDLINE, EMBASE, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), VIP information (a Chinese database), WANFANG Data (a Chinese database), the Chinese Conference Papers Database and the Chinese Dissertation Database (all searched up to April 2013). SELECTION CRITERIA: Randomised controlled trials comparing CHM or CHM plus levothyroxine versus levothyroxine, placebo or no treatment in adults with benign thyroid nodules. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed studies for risk of bias and evaluated overall study quality according to GRADE (Grading of Recommendations Assessment, Development and Evaluation), with differences resolved by consensus. MAIN RESULTS: We included one randomised trial involving 152 participants with a randomisation ratio of 2:1 (CHM vs no treatment). The trial applied adequate sequence generation; however, allocation concealment was unclear. Duration of treatment was three months, and follow-up six months. Our a priori defined outcomes of interest (i.e. nodule volume reduction ≥ 50%; pressure symptoms, cosmetic complaints or both; health-related quality of life; all-cause mortality; cancer occurrence; changes in number and size of thyroid nodules; changes in thyroid volume; and socioeconomic effects) were not investigated in the included study. Thyrotropin (TSH), thyroxine (T4) and tri-iodothyronine (T3) serum levels were normal in both groups before and after the trial was conducted. No adverse events were reported (low quality evidence). AUTHORS' CONCLUSIONS: Firm evidence cannot be found to support or refute the use of Chinese herbal medicines for benign thyroid nodules in adults.

A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations.

The purpose of this work is to evaluate if the coffee-associated malabsorption of tablet levothyroxine (L-T4) is reduced by soft gel capsule. We recruited 8 patients with coffee-associated L-T4 malabsorption including one hypothyroid patient. For 6 months, the patients were switched to the capsule maintaining the L-T4 daily dose. Patients took the capsule with water, having coffee 1 h later (proper habit, PH) on days 1-90, or with coffee ≤ 5 min later (improper habit, IH) on days 91-180. After 6 months, 2 patients volunteered for an acute loading test of 600 µg L-T4 (capsule) ingested with water (PH) or with coffee (IH). In the single hypothyroid patient, the post-switch TSH ranged 0.06-0.16 mU/L (PH) versus 5.8-22.4 mU/L pre-switch (PH) and 0.025-0.29 mU/L (IH) versus 26-34 mU/L pre-switch (IH). In the other 7 patients, post-switch TSH was 0.41 ± 0.46 (PH) versus 0.28 ± 0.20 pre-switch (PH) (P = 0.61) and 0.34 ± 0.30 (IH) versus 1.23 ± 1.47 pre-switch (IH) (P < 0.001). Importantly, TSH levels in PH versus IH habit did not differ post-switch (P = 0.90), but they did pre-switch (P < 0.0001). The proportions of post-switch TSH levels <0.10 mU/L with PH (33.3 %) or with IH (33.3 %) were borderline significantly greater than the corresponding pre-switch levels with PH (10.3 %) (P = 0.088) or with IH (0 %) (P = 0.0096). In the two volunteers, the L-T4 loading test showed that coffee influenced L-T4 pharmacokinetics minimally. Soft gel capsules can be used in patients who are unable/unwilling to change their IH of taking L-T4.

[The use of phytotherapy for treatment of thyroid diseases].

The main tasks during treatment of hyperplastic thyroid diseases--to stop the growth of thyroid nodules; compensation of hypothyrosis; normalization of thyroid size. One of the perspective methods in combine therapy of diffuse and mix goiter is a phytotherapy. The most often for thyroid diseases we have used the plant drug Polentilla alba, which on Ukrainian market was registered as "Alba". Investigation has shown, that phytodrug of Polentilla alba could be recommended for monotherapy and for combine conservative therapy of diffuse and mix benign euthyroid goiter, and also for complex treatment of toxic and hypothyroid goiters.

Exploring new applications for Rhodiola rosea: can we improve the quality of life of patients with short-term hypothyroidism induced by hormone withdrawal?

Patients treated for differentiated thyroid cancer (DTC) are subjected to periodic surveillance that includes serum thyroglobulin measurements followed by radioiodine administrations for diagnostic and therapeutic purposes if necessary. Both procedures require adequately elevated blood levels of thyroid-stimulating hormone (TSH), which can be achieved by two approaches: parenteral administration of recombinant human TSH (rhTSH) or stopping thyroid hormone replacement until optimal levels of endogenous TSH are achieved. Although rhTSH administration does not require hormone withdrawal, it is not inexpensive and carries the risk of secondary effects. The latter option is simpler but induces a profound state of hypothyroidism, which results in physical and mental complaints that may interfere severely with the patient's activities of daily living. Rhodiola rosea is a popular plant in traditional medical systems in Eastern Europe and Asia with a reputation for stimulating the nervous system, decreasing depression, enhancing work performance, and eliminating fatigue, all features of clinical hypothyroidism. Investigators have also suggested additional benefits such as cardioprotection or even tumor growth inhibition. Here, we propose R. rosea as a viable alternative treatment for the symptoms of short-term hypothyroidism in patients with DTC who require hormone withdrawal.

[The effect of levothyroxine suppression therapy for benign thyroid nodules on bone metabolism in premenopausal women]. / Menopoz öncesinde selim tiroid nodülleri için uygulanan levotiroksin supresyon tedavisinin kemik metabolizmasina etkisi.

OBJECTIVES: This prospective study was designed to investigate the effect of levothyroxine suppression therapy for benign thyroid nodules on markers of bone turnover in premenopausal women. PATIENTS AND METHODS: The study included 28 premenopausal women who received levothyroxine suppression therapy for benign thyroid nodules for one year. The size of the thyroid gland and nodules, biochemical markers of bone turnover and urinary calcium excretion were measured before and after levothyroxine suppression therapy. RESULTS: No significant adverse effects were seen during levothyroxine treatment. Decreases in total thyroid volume and the size of the nodules were not significant at the end of treatment. Although levothyroxine suppression therapy did not result in changes in serum levels of calcium and phosphor, and urinary calcium excretion, bone turnover markers, namely serum osteocalcin and urinary deoxypyridinoline levels, increased significantly. Serum intact parathyroid hormone levels showed a minimal decrease, which was not statistically significant. CONCLUSION: Data from our study suggest that levothyroxine suppression therapy is associated with increased osteoblastic and osteoclastic activity in premenopausal women with benign thyroid nodules.

[Percutaneous ethanol injections in the treatment of nodular thyroid disease--fourteen years of experience]. / Przezskórne wstrzykniecia etanolu w leczeniu guzkowej choroby tarczycy, 14 lat doswiadczen.

Surgery, radioactive iodine, and suppressive doses of Lthyroxine are commonly used in the treatment of benign nodular thyroid disease, with the best results achieved with surgery. However, recent advances in cytological diagnostic methods enable patients to choose alternative therapies if there are some contraindications or there is no agreement for surgery. Over past 14 years percutaneous ethanol injections (PEI), used in the past as a therapy for liver, kidney, parathyroid and adrenal cortical tumors, have been developed as an alternative method in the management of thyroid nodules. This paper reviews the investigations of a number aspects of PEI in the treatment of thyroid nodules reported in the literature. The evidence demonstrate that PEI is effective in the case of both solid non-toxic and autonomously functioning toxic nodules as well as cystic nodules. In majority of cases restore normal serum fT4, fT3 and TSH concentrations and shrink the tumor volume. The method seems to be safe and generally well tolerated by the patients. However, the current research base on the efficacy and PEI-associated risks is still inadequate to determine definitively its role as a standard treatment of benign nodular thyroid disease. For example, there is no detailed data comparing the results of treatment with PEI to standard treatment with radioactive iodine and L-thyroxine. Despite it, we conclude that PEI is a valuable method that earned recognition among other methods of the thyroid nodules treatment.

[Use of autohemoozonotherapy in the treatment of nodular thyroid in adolescents]. / Ispol'zovanie autogemoozonoterapii pri lechenii uzlovykh obrazovanii shchitovidnoi zhelezy u podrostkov.

Two groups of adolescents with nodular lesions of the thyroid were treated: 17 patients of group 1 received efferent therapy (autohemoozonotherapy by V.I. Afanasyev) and routine pharmacological treatment; 41 controls received drugs only (levothyroxine or potassium iodide). The results were evaluated 6 and 12 months after treatment. The study group patients demonstrated marked improvement of blood flow, structure of thyroid tissue. Growth stabilization and reduction of the thyroid lesion occurred more frequently, complications or side effects were not observed.

Percutaneous ethanol injection plus radioiodine versus radioiodine alone in the treatment of large toxic thyroid nodules.

UNLABELLED: Therapeutic options for toxic thyroid nodules (TTNs) are surgery, radioiodine (RAI), and percutaneous ethanol injection (PEI). Surgery is generally considered for TTNs larger than 4 cm. However, some patients may be at high surgical risk. The purpose of the study was to evaluate the efficacy of 2 nonsurgical modalities for these TTNs. METHODS: Twenty-two patients with TTNs larger than 4 cm were randomly assigned to 2 different treatments: to 11 (subgroup A), RAI was administered at a dose of 12,580 kBq/mL of nodular volume (NV) and was corrected for 100% 24-h (131)I uptake (RAIU); to 11 (subgroup B), 2-4 PEI sessions (ethanol injected = 30% NV) preceded 2 mo of 24-h RAIU and RAI dosing. Inclusion criteria were clinical and biochemical hyperthyroidism; a single palpable, hot nodule at (99m)Tc scintigraphy; and high surgical risk or refusal to have surgery. Patients gave informed consent. Local symptoms were evaluated by a previously validated score (symptom score, or SYS). RESULTS: Both treatments were well tolerated. Subgroup B showed a significant reduction of NV 2 mo after PEI: 33.6 +/- 18.5 versus 60.8 +/- 29.5 mL. Their 24-h RAIU was similar to that of subgroup A: 53.9 +/- 13.9 versus 61.8% +/- 11.0%. Consequently, the administered RAI dose was significantly lower for subgroup B (730 +/- 245 MBq) than for subgroup A (1,048 +/- 392 MBq). Twelve months after RAI, subgroup B had a higher NV reduction and a lower SYS than did subgroup A. In subgroup A, 1 patient was subclinically hyperthyroid, 2 showed a slight increase of thyroid-stimulating hormone, and 1 was clinically hypothyroid. In subgroup B, 1 patient had a slight increase of thyroid-stimulating hormone. CONCLUSION: We demonstrated that RAI, alone or with PEI, can be considered a valid alternative for TTNs larger than 4 cm when surgery is either refused or contraindicated. PEI plus RAI can be considered when marked shrinkage of a nodule is required or when reduction of the RAI dose can prevent hospitalization.

[The echo-guided percutaneous injection of ethanol: a therapeutic alternative in the "autonomous thyroid nodule". Our experience]. / Iniezione percutanea ecoguidata di etanolo: alternativa terapeutica del "nodulo tiroideo autonomo". Nostra esperienza.

The authors report their experience on the therapeutic value, in terms of efficacy and tolerance, of percutaneous ethanol injection (PEI) in the treatment of autonomous thyroid nodules (ATN). A group of 15 patients, 13 in clinical pretoxicity and 2 in initial thyrotoxicosis, were submitted to fine-needle ethanol injection (95%) performed under US guidance. The amount of injected alcohol was measured on the basis of the volume and diffusion of alcohol itself within the nodule, in the whole of 79 injections given. Follow-up lasted 3-15 months. Thyroid scanning demonstrated a complete or partial recovery of extranodular parenchymal function in 80% and 20% of cases, respectively. In all cases a volume reduction greater than 50% was obtained, with an initial sharp fall, already after the first month, thanks to early alcohol cytotoxicity. In the 2 patients with toxic ATN serum, normal values of free hormones have been observed ever since the third weekly injection. Good tolerance to treatment was observed, and no permanent complications. In agreement with other authors, we believe our experience to show that PEI represents a new therapeutic approach in patients with ATN. PEI will certainly play a preferential role, relative to other conventional therapies, in the management of clinical pretoxic ATN, regarding which no uniform treatment protocol exists yet.