A systematic review, meta-analysis, and trial sequential analysis of the effect of acupuncture and moxibustion cake on thyroid function in patients with Hashimoto thyroiditis

Abstract

Background:

Hashimoto thyroiditis (HT) is a prevalent autoimmune thyroid disorder that currently lacks a specific treatment. While oral levothyroxine sodium tablets have been found to significantly enhance thyroid function, they do not contribute to a decrease in concentrations of thyroid-related antibodies. We aimed to design a systematic review, meta-analysis, and trial sequential analysis of the effect of acupuncture and moxibustion cake on thyroid function in patients with HT.

Methods:

We conducted an unrestricted search up until March 29, 2024, across 7 databases. These included 4 international databases, namely, PubMed, Web of Science, Scopus, and Cochrane Library, as well as 3 Chinese databases such as CNKI, VIP, and Wanfang. We used Review Manager, version 5.3, for meta-analysis and presented the data as mean difference (MD) and 95% confidence interval to evaluate the role of acupuncture or moxibustion on biomarker levels in HT.

Results:

A total of 306 records were identified through databases, and 15 articles were included in the meta-analysis. In the acupuncture group: thyroid peroxidase antibody (TPOAb): the pooled MD is −61.97 (P < .00001), thyroglobulin antibody (TGAb): the pooled MD is −44.78 (P = .001), thyroid-stimulating hormone (TSH): the pooled MD is −2.64 (P < .00001), free triiodothyronine: the pooled MD is 0.47 (P = .09), and free thyroxine: the pooled MD is 1.46 (P = .02). In the moxibustion group: TPOAb: the pooled MD is −11.44 (P = .0002), TGAb: the pooled MD is −8.63 (P = .004), TSH: the pooled MD is −1.00 (P = .27), free triiodothyronine: the pooled MD is 1.12 (P = .14), and free thyroxine: the pooled MD is 1.04 (P = .07).

Conclusion:

The meta-analysis indicates that acupuncture and moxibustion may influence thyroid-related biomarkers (TPOAb, TGAb, and TSH) in patients with HT; however, the evidence is highly limited by methodological weaknesses, heterogeneity, and publication bias. These factors preclude reliable clinical recommendations at this stage. Further well-designed, large-scale randomized controlled trials are essential to determine whether these interventions have true clinical efficacy.

1. Introduction

Hashimoto thyroiditis (HT) is an autoimmune condition that destroys thyroid cells through cell- and antibody-mediated immune responses.^[1,2] It is the leading cause of hypothyroidism in developed nations.^[3] The occurrence of HT differs based on geographical location and socioeconomic status, with a global prevalence of 7.5% in adults^[4] (4.8%–25.8% in women and 0.9%–7.9% in men).^[4–6] Notably, there are variations in the prevalence of HT across regions with different economic levels.^[4]

The diagnosis of HT is based on the detection of specific antibodies in the thyroid gland, namely, thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb).^[3,4] Another characteristic feature of HT is the presence of lymphocytes in thyroid tissue, which can also be detected by ultrasound. Commonly used blood diagnostic markers include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4).^[2–4] Symptoms of HD can vary and may include chronic fatigue, anxiety, mood fluctuations, and issues related to the gastrointestinal or cardiovascular systems.^[4] The treatment protocol typically involves replacing thyroid hormones to manage hypothyroidism associated with HT, with levothyroxine being the primary medication used.^[7]

The combined application of traditional Chinese medicine (TCM) and Western medicine may enhance the clinical effectiveness in treating HT compared with the sole use of Western medicine.^[8] Historical acupuncture texts reveal that the Yangming meridian acupoints have been widely utilized in the treatment of various thyroid conditions.^[9] Acupuncture is beneficial in easing clinical symptoms such as neck pressure, fatigue, and mood swings, and it rarely has side effects. Some research suggests that acupuncture can trigger a series of neurohumoral immune responses in the body, thereby improving the state of an immune disorder.^[10] Moreover, the combination of moxibustion and oral levothyroxine sodium tablet has proven to be an effective and reliable treatment for HT.^[11] Acupuncture stimulates specific meridian points, while moxibustion provides thermal stimulation to enhance circulation and immune function.^[12,13] The integration of both modalities may therefore offer complementary mechanisms that are particularly beneficial for autoimmune conditions. Our goal is to design a systematic review, meta-analysis, and trial sequential analysis (TSA) to evaluate the impact of acupuncture and moxibustion cake on thyroid function in patients with HT.

2. Materials and methods

2.1. Literature search

We conducted a comprehensive search across 7 databases, without restrictions on language or year of publication, covering all records available up to March 29, 2024. These included 4 international databases, namely, PubMed, Web of Science, Scopus, and Cochrane Library, as well as 3 Chinese databases such as CNKI, VIP, and Wanfang. The search keywords included the following: (“Hashimoto’s thyroiditis” OR “chronic lymphocytic thyroiditis” OR “autoimmune thyroiditis” OR “Hashimoto’s disease” OR “Hashimoto thyroiditis” OR “Hashimoto disease”) AND (“prevalence” OR “incidence” OR “occur” OR “frequency”) AND (“moxibustion” OR “moxa” OR “acupuncture”). In addition to the database search, we manually examined articles and their references from eligible studies to find potentially relevant publications. We also used electronic resources like Google Scholar for this purpose. The ethical approval was not necessary for this meta-analysis, as it involved the retrieval and analysis of data from previously published studies. Study selection and data extraction were performed independently by 2 reviewers: 1 reviewer (RH) conducted the initial search and screening, and a second reviewer (LG) independently rechecked all records. Any discrepancies were resolved by a third reviewer (LC) through consensus.

2.2. Study selection

We used the PICOS framework to define the inclusion criteria for this meta-analysis. The Population (P) included patients diagnosed with HT. The Intervention (I) consisted of various TCM modalities, including moxibustion cake, acupuncture, and combinations of these with standard thyroid drug therapy (levothyroxine). The Comparison (C) group in all studies received conventional thyroid hormone therapy alone, typically levothyroxine, serving as the standard treatment control. Thus, the comparisons involved moxibustion cake versus thyroid drugs, acupuncture combined with thyroid drugs versus thyroid drugs alone, and acupuncture or moxibustion in combination with other supportive TCM therapies (e.g., massage) versus thyroid drugs alone. The Outcomes (O) assessed were changes in thyroid-related biomarkers, including TPOAb, TGAb, FT3, FT4, and TSH. The Study design (S) was restricted to randomized clinical trials (RCTs) to ensure the methodological rigor of the analysis.

In studies where the intervention group received acupuncture or moxibustion combined with drug therapy, the drug regimen was consistent across both groups, ensuring comparability. Massage, when present, was used only as an adjunct. Given the limited number of eligible studies, we combined acupuncture-based interventions (acupuncture alone, acupuncture plus massage, and acupuncture plus drug) and likewise grouped moxibustion-related interventions to enable meaningful pooled analyses. This approach aligns with systematic review methodology that permits combining heterogeneous but related interventions when clinically justifiable and necessary for synthesis.

2.3. Eligibility criteria

Inclusion criteria are all clinical trials where the intervention group, or case group, is treated with acupuncture or moxibustion cake, and the control group is treated with thyroid medication. Exclusion criteria include studies involving participants with a history or diagnosis of any systemic diseases that may coincide with HT, cases of HT that are receiving treatments other than thyroid medication or massage, case reports or articles that do not contain statistical data, and articles that do not have a control group. Other documents that are excluded include reviews, meta-analyses, letters to the editors, book chapters, and articles that do not contain any data.^[14]

2.4. Data extraction

Two reviewers (XH and WZ) separately performed a literature review and data extraction to ensure uniformity in the screening of core criteria and the process of data collection. If there were disagreements, they were resolved through further discussions or by involving a third reviewer (RH) in the discussions until a consensus was reached. The analyses were performed independently by 2 authors, and all decisions were made with unanimous agreement.

2.5. Statistical analysis and data synthesis

We used Review Manager, version 5.3 (Cochrane Collaboration, London, UK), for meta-analysis and presented the data as mean difference (MD) and 95% confidence interval (CI) to evaluate the role of acupuncture or moxibustion on biomarker levels in HT.

The heterogeneity of the studies was assessed using the I² statistic and the P value from the Cochran Q test, with a significance level of P < .05. Given the anticipated variability among studies, a random-effects model was applied when heterogeneity was substantial (I² ≥ 50% or P for heterogeneity < .10).^[15–17] Otherwise, a fixed-effect model was used. Publication bias was evaluated using a funnel plot along with Begg and Egger tests, with a significance level of P < .10.^[18,19] Bias and sensitivity analyses were conducted using Comprehensive Meta-Analysis version 2.0 (CMA 2.0; Biostat, Englewood) software.

We used the Cochrane “risk-of-bias tool” for randomized trials to evaluate the methodological quality of the included studies. This tool focuses on 6 domains: sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other potential sources of bias, with each domain assessed individually before an overall judgment is made.^[20] While this approach provides a structured framework, it should be interpreted in the context of contemporary challenges in peer review quality and methodological standardization, as highlighted by recent literature.^[21]

A TSA was performed using TSA software (version 0.9.5.10 beta; Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark). The required information size (RIS) for blood cytokine levels was determined with an alpha risk of 5% and a beta risk of 20%.^[22,23] The MD was derived from empirical assumptions. If the Z-curve intersected the RIS, it indicated that the studies had a sufficient number of cases, and the conclusion could be considered reliable.

3. Results

3.1. Search selection

A total of 306 records were identified through databases (Fig. 1). After removing duplicates, 134 records were screened. Seventy records were excluded after screening. Sixty-four full-text articles were assessed for eligibility. Forty-nine full-text articles were excluded with reasons. Finally, 15 articles^[11,24–37] were included in the systematic review and meta-analysis.

Figure 1.

Flowchart of the study selection.

3.2. Characteristics of the articles

Table 1 lists the characteristics of articles included in a meta-analysis. The studies were conducted between 1992 and 2023. The participants in these studies had HT, with some also having hypothyroidism. The interventions used in these studies include moxibustion cake and acupuncture. Some studies used a combination of these interventions with massage and thyroid drugs. The number of individuals in the intervention and control groups varied across studies, ranging from 29 to 49. The treatment duration in these studies ranged from 1 to 6 months. The mean age of participants varied across studies and groups. The Jadad score, which assesses the quality of a clinical trial’s methodology, ranged from 3 to 6. The outcomes measured in these studies include TPOAb, TGAb, FT3, FT4, and TSH.

Table 1.

Characteristics of the articles included in the meta-analysis.

First author, publication yr	Participants	Intervention		Number of individuals (intervention/control)	Treatment duration, mo	Mean age (case/control)	Jadadscore	Outcomes
		Case group	Control group
Xia, 2012a[33]	HT	Moxibustion cake	Thyroid drug	40/40	1	47.15/46.45	5	FT3, FT4
Wang, 2003[31]	HT & hypothyroidism	Moxibustion cake	Thyroid drug	34/32	6	26–53/26–51	4	TPOAb, TGAb, TSH
Cui, 2020[24]	HT	Moxibustion cake + drug	Thyroid drug	31/31	3	46/47	4	FT3, FT4, TSH
Hu, 1992[26]	HT	Moxibustion cake	Thyroid drug	35/32	2	19–66/19–66	3	TPOAb, TGAb
Hong, 2020 [25]	HT & hypothyroidism	Acupuncture + thyroid drug	Thyroid drug	37/38	3	43.11/41.53	4	TPOAb, TGAb, FT3, FT4, TSH
Wu, 2021[32]	HT & hypothyroidism	Acupuncture + thyroid drug	Thyroid drug	39/39	3	42.86/42.33	4	TPOAb, TGAb, FT3, FT4, TSH
Lin, 2017[27]	HT & hypothyroidism	Acupuncture + thyroid drug	Thyroid drug	33/32	3	35.27/34.87	6	TPOAb, TGAb, FT4, TSH
Zheng, 2019[35]	HT	Acupuncture + thyroid drug	Thyroid drug	45/54	3	44.61/42.78	6	TPOAb, TGAb, FT3, FT4, TSH
Wang, 2021[29]	HT	Moxibustion cake	Thyroid drug	29/29	4	48.55/42.52	6	TPOAb, TGAb, FT3, FT4, TSH
Zhou, 2013[36]	HT	Acupuncture + thyroid drug	Thyroid drug	40/40	1	18–70/18–70	3	FT3, FT4, TSH
Chen, 2019[23]	HT	Acupuncture + massage	Thyroid drug	33/33	1	37.65/38.46	5	TPOAb, TGAb, FT3, FT4, TSH
Ren, 2022[28]	HT	Acupuncture + massage	Thyroid drug	49/49	3	43.27/18–69	4	TPOAb, TGAb, FT3, FT4, TSH
Wang, 2023[30]	HT	Acupuncture + thyroid drug	Thyroid drug	30/30	4	36.1/35.7	5	TPOAb, TGAb, TSH
Xia, 2012b[11]	HT	Moxibustion cake + thyroid drug	Thyroid drug	42/43	1	47.1/46.6	4	FT3, FT4, TSH
Xu, 2013[34]	HT	Moxibustion cake + thyroid drug	Thyroid drug	30/29	1	45.3/43.5	5	FT3, FT4, TSH

Drug = thyroid tablets, FT3 = free triiodothyronine, FT4 = free thyroxine, TGAb = thyroglobulin antibody, TPOAb = thyroid peroxidase antibody, TSH = thyroid-stimulating hormone.

3.3. Pooled analyses

Figure 2 shows the forest plot analyses for biomarker levels in the acupuncture group compared with the control group. TPOAb showed a pooled MD of −61.97, with a 95% CI of [−82.20, −35.73], indicating a substantial and precise reduction. TGAb decreased with a pooled MD of −44.78 (95% CI = [−72.41, −17.15]), reflecting a significant but more variable effect. TSH levels also decreased (MD = −2.64, 95% CI = [−3.75, −1.53]), while FT4 increased (MD = 1.46, 95% CI = [0.27, 2.66]). FT3 showed no significant change (MD = 0.47, 95% CI = [−0.08, 1.03]). These results demonstrate that acupuncture is associated with robust reductions in TPOAb, TGAb, and TSH and a modest increase in FT4, with effect sizes and precision indicated by the CIs. Analyses were performed following standardized protocols for comparative biomarker studies.^[38]

Figure 2.

Forest plot analyses for biomarker levels in the acupuncture group compared with the control group. (A) TPOAb: thyroid peroxidase antibody, (B) TGAb: thyroglobulin antibody, (C) TSH: thyroid-stimulating hormone, (D) FT3: free triiodothyronine, (E) FT4: free thyroxine. CI = confidence interval, SD = standard deviation.

Figure 3 shows the forest plot analyses for biomarker levels in the moxibustion group compared with the control group. TPOAb decreased with a pooled MD of −11.44 (95% CI = [−17.40, −5.48]), indicating a significant and reasonably precise reduction. TGAb also decreased (MD = −8.63, 95% CI = [−14.53, −2.73]), showing a smaller but statistically significant effect. TSH levels showed a nonsignificant decrease (MD = −1.00, 95% CI = [−2.79, 0.78]), while FT3 (MD = 1.12, 95% CI = [−0.37, 2.60]) and FT4 (MD = 1.04, 95% CI = [−0.08, 2.17]) showed nonsignificant increases. These results indicate that moxibustion is associated with modest but significant reductions in TPOAb and TGAb, whereas changes in TSH, FT3, and FT4 were not statistically significant. Analyses were conducted following standardized comparative biomarker protocols,^[38] allowing the magnitude and precision of effects to be clearly interpreted.

Figure 3.

Forest plot analyses for biomarker levels in the moxibustion group compared with the control group. (A) TPOAb: thyroid peroxidase antibody, (B) TGAb: thyroglobulin antibody, (C) TSH: thyroid-stimulating hormone, (D) FT3: free triiodothyronine, (E) FT4: free thyroxine. CI = confidence interval, SD = standard deviation.

3.4. Sensitivity analysis

Both “one-study-removed” and “cumulative” sensitivity analyses were conducted to assess the robustness of the pooled MDs for outcomes with at least 3 studies. In the one-study-removed analysis, each study was sequentially excluded, and the pooled MDs remained consistent in magnitude and direction, indicating no single study disproportionately influenced the results. In the cumulative analysis, studies were added sequentially by publication year, showing a stable trend in effect estimates over time. These findings collectively suggest that the pooled results are robust and not driven by outlier studies.

3.5. Risk of bias

Risk of bias assessment revealed significant concerns across multiple domains. Specifically, 2 studies did not report methods for random sequence generation, and 12 studies lacked information on allocation concealment. Thirteen studies failed to report blinding of outcome assessors, which is particularly concerning given that several outcomes (e.g., symptom scores or quality-of-life measures) were subjective and therefore susceptible to detection bias. Furthermore, none of the included studies provided sufficient information on attrition bias, selective reporting, or other potential sources of bias. Four studies were judged to have a high risk of selection bias. These limitations, illustrated in Figure 4, suggest that the overall evidence quality may be compromised. The lack of blinding and incomplete methodological reporting raises the possibility that treatment effects could be overestimated. This risk of bias was evaluated using the Cochrane Risk of Bias tool (RoB 1; Cochrane Collaboration, London, UK), and although sensitivity analyses were conducted, the consistent reporting gaps highlight the need for cautious interpretation of the findings.

Figure 4.

Bias risk assessment. (A) Risk of bias summary and (B) risk of bias graph. Green circles with plus marks represent low risk of bias, yellow circles with question marks indicate unclear risk, and red circles with minus marks denote high risk.

3.6. Subgroup analysis

Table 2 presents a subgroup analysis based on Jadad score grade and treatment duration for different biomarkers in acupuncture and moxibustion groups. The results showed that Jadad score grade could affect TPOAb, TGAb, and FT3 levels, and treatment duration on FT3 level for the acupuncture group. Treatment duration could affect TSH, FT3, and FT4 levels for the moxibustion group.

Table 2.

Subgroup analysis based on Jadad score grade and treatment duration.

	Variable	Subgroup, N	MD	95% CI		Z value	P value	I 2
				Min.	Max.
Acupuncture	TPOAb	Jadad score grade
		1–4 (3)	−52.08	−56.12	−49.47	31.10	<.00001	6%
		5–7 (4)	−77.71	−154.95	−0.47	1.97	.05	96%
		Treatment duration
		1 mo (1)	−142.47	−166.27	−118.67	11.73	<.00001	–
		>1 mo (6)	−44.66	−62.84	−26.49	4.82	<.00001	80%
	TGAb	Jadad score grade
		1–4 (3)	−42.59	−46.37	−38.81	22.06	<.00001	1%
		5–7 (4)	−55.86	−128.22	16.50	1.51	.13	90%
		Treatment duration
		1 mo (1)	−105.95	−124.33	−87.57	11.30	<.00001	–
		>1 mo (6)	−42.09	−45.84	−38.33	21.97	<.00001	42%
	TSH	Jadad score grade
		1–4 (4)	−2.76	−4.44	−1.09	3.23	.001	98%
		5–7 (4)	−2.54	−4.50	−0.58	2.54	.01	99%
		Treatment duration
		1 mo (2)	−4.39	−9.97	1.18	1.54	.12	99%
		>1 mo (6)	−2.09	−3.34	−0.84	3.29	.001	99%
	FT3	Jadad score grade
		1–4 (4)	0.67	0.08	1.26	2.22	.03	94%
		5–7 (2)	0.14	−0.03	0.31	1.60	.11	69%
		Treatment duration
		1 mo (2)	0.21	0.13	0.28	5.58	<.00001	0%
		>1 mo (4)	0.64	−0.11	1.38	1.68	.09	98%
	FT4	Jadad score grade
		1–4 (4)	1.92	−0.35	4.19	1.66	.10	99%
		5–7 (3)	0.87	−0.00	1.75	1.95	.05	81%
		Treatment duration
		1 mo (2)	0.71	−0.20	1.61	1.53	.13	98%
		>1 mo (5)	1.80	0.02	3.58	1.98	.05	96%
Moxibustion	TSH	Jadad score grade
		1–4 (3)	−1.35	−3.96	1.26	1.01	.31	88%
		5–7 (2)	0.03	−0.17	0.23	0.28	.78	0%
		Treatment duration
		1 mo (2)	−3.42	−4.54	−2.31	6.02	<.00001	0%
		>1 mo (3)	0.03	−0.17	0.23	0.28	.78	0%
	FT3	Jadad score grade
		1–4 (2)	0.15	−0.08	0.37	1.25	.21	12%
		5–7 (3)	1.71	−0.07	3.48	1.88	.06	97%
		Treatment duration
		1 mo (3)	0.74	0.12	1.36	2.34	.02	62%
		>1 mo (2)	1.66	−1.42	4.75	1.06	.29	1000%
	FT4	Jadad score grade
		1–4 (2)	0.94	−1.57	3.45	0.74	.46	89%
		5–7 (3)	1.22	−0.58	3.02	1.33	.18	81%
		Treatment duration
		1 mo (3)	2.18	1.27	3.10	4.67	<.00001	0%
		>1 mo (2)	0.05	−0.06	0.15	0.86	.39	0%

The boldfaced values are statistically significant (P < .05).

CI = confidence interval, FT3 = free triiodothyronine, FT4 = free thyroxine, MD = mean difference, TGAb = thyroglobulin antibody, TPOAb = thyroid peroxidase antibody, TSH = thyroid-stimulating hormone.

3.7. Trial sequential analysis

Supplementary 1, Figures S1 to S8, Supplemental Digital Content, https://links.lww.com/MD/R699, shows the plots for TSA for the analyses with a minimum of 3 studies. The results showed that the Z-curve crossed the RIS line for TPOAb, TGAb, and TSH levels for the acupuncture group, not FT3 and FT4 for the acupuncture group and TSH, FT3, and FT4 levels for the moxibustion group.

3.8. Publication bias

Supplementary 2, Figures S1 to S8, Supplemental Digital Content, https://links.lww.com/MD/R700, shows the funnel plots for publication bias. Both Begg and Egger tests revealed a publication bias for TPOAb (P value = .0242 and .0003), TSH (P value = .0259 and .0001), and FT3 (P value = .0388 and .0011) levels in acupuncture group, and Egger test alone revealed a publication bias for FT4 level (P value = .0006) in acupuncture group and FT3 level (P value = .0532) in moxibustion group. The presence of such bias substantially reduces confidence in the observed positive effects and should be carefully considered when interpreting the results. Overall, the findings underscore the need for more high-quality, prospectively registered trials with transparent reporting to provide a more reliable assessment of acupuncture and moxibustion efficacy in HT.

4. Discussion

The present meta-analysis suggests that acupuncture may lead to significant reductions in TPOAb, TGAb, and TSH levels, along with an increase in FT4 levels, compared with control interventions. Moxibustion also demonstrated a significant decrease in TPOAb and TGAb levels. However, these findings must be interpreted with caution. Subgroup analyses revealed that the observed effects were more pronounced in studies of lower methodological quality and shorter treatment duration, raising concerns about the clinical meaningfulness of the pooled estimates. Moreover, significant publication biases were detected for several outcomes, including TPOAb, TSH, FT3, and FT4 levels in the acupuncture group, and FT3 levels in the moxibustion group. These limitations suggest that the apparent efficacy of acupuncture and moxibustion may be overstated. To establish their true therapeutic value in managing HT, future trials should prioritize rigorous study designs and standardized intervention protocols.

While acupuncture and moxibustion were analyzed separately in this meta-analysis, we recognize that each therapy – and combinations thereof – may have unique mechanisms of action and clinical effects. The inclusion of varied combination therapies (e.g., acupuncture + drugs, moxibustion + massage) introduces clinical heterogeneity that may influence outcomes. Although subgroup and sensitivity analyses were performed, the diversity of interventions remains a limitation and may partially explain the observed heterogeneity. These findings underscore the need for future trials that isolate specific interventions using standardized treatment protocols.

HT, identified by the presence of thyroid-specific autoantibodies, is among the most prevalent autoimmune disorders.^[7] The precise cause remains unclear,^[7,39] but it is known that HT arises from a complex interplay of genetic components, environmental influences, and epigenetic factors.^[39,40] Both cellular and humoral immunity are crucial in HT’s development, leading to frequent inflammatory infiltration by T and B cells.^[41,42] The diagnosis of HT is clinical, relying on specific characteristics, the presence of serum antibodies against thyroid antigens (such as thyroid peroxidase and thyroglobulin), and the detection of lymphocytic infiltration through cytological examination.^[7,43,44] Patients with HT may experience a range of symptoms, including slowed speech, excessive sleepiness, headaches, sensitivity to cold, fatigue, weight gain, a pale complexion, constipation, swollen eyes, rough and dry skin, brittle hair, facial and leg swelling, stiff joints, light or absent menstrual periods, and mental disorientation.^[45,46]

TCM offers distinct benefits in the realms of healthcare, prevention, and wellness, and is increasingly recognized and embraced by both domestic and international researchers.^[47] The early inflammatory stage of HT aligns with the TCM principle of “excess circulation is fire.”^[48] At present, there is no definitive treatment for HT. Existing methods, including oral medication, selenium, L-T4 tablets, surgery, and low-intensity laser techniques, either lack clear evidence of efficacy or have unpredictable long-term toxicity and side effects.^[47,49]

A review highlighted that acupuncture, either as a standalone treatment or in conjunction with other therapies, led to symptom reduction and biomarker improvement in patients with thyroid disorders. It also underscored the potential of acupuncture as an alternative, complementary, or adjunctive therapy for both healing and rehabilitation.^[50] A case study demonstrated significant improvement in a hypothyroid patient’s condition following acupuncture treatment.^[51] Acupuncture has been found to positively impact thyroid disorders by regulating energy flow and restoring internal body balance.^[52]

Preliminary experimental studies suggest that herb-partitioned moxibustion may influence the expression of miRNA-346 and miRNA-331-5p, which in turn could regulate immune and inflammatory pathways in animal models of autoimmune thyroiditis.^[53] Similarly, combinations of mild moxibustion and pharmacological agents have been reported to modulate cytokine levels and enhance sodium–iodide symporter expression in hypothyroid rat models.^[54] While these findings offer intriguing insights into potential mechanisms, they are largely derived from small-scale, preclinical studies with limited methodological transparency. The generalizability of these results to human populations remains uncertain, and the absence of robust clinical trials evaluating these mechanistic pathways limits their interpretive value. Therefore, while TCM-based interventions may hold promise, the proposed biological mechanisms should be viewed as exploratory and require further validation through rigorously designed human studies.

Aconite cake-separated moxibustion applied at Guanyuan (CV 4) and Mingmen (GV 4), along with the oral intake of Euthyrox, can enhance clinical symptoms and thyroid function in HT patients. This combination therapy is more effective than just taking Euthyrox orally.^[26] The combination of moxibustion and oral levothyroxine sodium tablet has been proven to be a reliable treatment for HT.^[11] However, the research on treating HT with acupuncture-moxibustion therapies is somewhat limited in terms of quantity and content. In the future, there is a need for more standardized research, deeper investigation into specific moxibustion, and a focus on the action mechanism of moxibustion.^[55]

This study has several critical limitations that substantially affect the reliability of its conclusions. Most notably, significant publication bias was detected for key outcomes in the acupuncture group (TPOAb, TSH, FT3, and FT4) and for FT3 in the moxibustion group. This raises serious concerns about selective reporting and small-study effects, suggesting that the observed benefits may be inflated. Furthermore, high levels of heterogeneity (I² ranging from 62% to 99%) across most analyses indicate considerable inconsistency among studies in terms of patient populations, intervention protocols, treatment durations, and outcome measurements. While random-effects models were used to account for variability, the magnitude of heterogeneity fundamentally challenges the appropriateness of pooling these data. Such extreme heterogeneity reduces confidence in the aggregated effect sizes and suggests that the results may not be generalizable across clinical settings. Therefore, findings should be interpreted with caution, and future research should aim to reduce heterogeneity through more standardized study designs and clearly defined intervention protocols.

In addition, the methodological quality of the included studies was often suboptimal. Many trials had unclear or high risk of bias in domains such as random sequence generation, allocation concealment, and blinding – especially problematic for subjective or biochemical outcomes susceptible to measurement bias. These quality concerns go beyond the mere limitation of sample size and raise fundamental doubts about the internal validity of the evidence base. To improve future research, trials should adhere to contemporary standards for RCT design, such as those exemplified by Cherni et al,^[56] which emphasize transparent randomization procedures, allocation concealment, and standardized intervention protocols. Taken together, these limitations significantly weaken confidence in the observed treatment effects. Therefore, the findings should be interpreted cautiously, and there remains an urgent need for well-designed, transparent, and rigorously conducted randomized controlled trials to more reliably assess the efficacy and safety of acupuncture and moxibustion in HT.

5. Conclusions

The meta-analysis indicates that both acupuncture and moxibustion treatments can have significant effects on patients with HT. Specifically, these treatments led to a significant decrease in TPOAb, TGAb, and TSH levels. Furthermore, a significant increase in FT4 levels was observed in the acupuncture group compared with the control group. However, the results also revealed some publication bias for TPOAb, TSH, and FT3 levels in the acupuncture group and FT3 levels in the moxibustion group.

Future studies should aim to improve the methodological quality of clinical trials, as indicated by the Jadad scores and the lack of reporting on random sequence generation, allocation concealment, blinding of outcome data, attrition, assessment, and other biases in some studies. In addition, more research is needed to understand the effects of treatment duration and JADA grade on different biomarkers in acupuncture and moxibustion groups.

The findings of this meta-analysis suggest that acupuncture and moxibustion could be considered potential therapeutic interventions for patients with HT. These treatments not only improve thyroid function by regulating the levels of TPOAb, TGAb, TSH, and FT4 but also have the potential to enhance the quality of life for these patients. However, clinicians should be aware of the potential publication bias and the need for high-quality RCTs to confirm these findings.

Author contributions

Conceptualization: Ren Haitao, Li Gaokai.

Formal analysis: Ren Haitao, Li Gaokai, Wang Zongjiao.

Funding acquisition: Ren Haitao, Li Gaokai.

Supervision: Ren Haitao, Li Gaokai.

Project administration: Li Gaokai.

Visualization: Li Gaokai, Wang Zongjiao.

Data curation: Liao Chunxia, Xia Hongchen.

Investigation: Liao Chunxia, Xia Hongchen.

Methodology: Liao Chunxia, Wang Zongjiao.

Resources: Liao Chunxia, Xia Hongchen.

Validation: Liao Chunxia, Xia Hongchen.

Software: Wang Zongjiao.

Writing – original draft: Wang Zongjiao.

Writing – review & editing: Ren Haitao, Li Gaokai, Liao Chunxia, Xia Hongchen, Wang Zongjiao.

Supplementary Material

medi-105-e48352-s001.pdf ^{(723.8KB, pdf)}

medi-105-e48352-s002.pdf ^{(248.1KB, pdf)}