Abstract
Objective
Hashimoto’s thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis.
Methods
Forty patients with Hashimoto’s thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months.
Results
After 6 months of a low-carbohydrate diet, patients with Hashimoto’s thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63–614.62) vs 89.45 (15.9–215.67); TgAb: 17.05 (1.47–81.64) vs 4.1 (0.51–19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto’s thyroiditis following a normal diet after 6 months (P < 0.05).
Conclusion
Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto’s thyroiditis.
Background
Hashimoto’s thyroiditis (HT), also known as autoimmune thyroiditis or chronic lymphocytic thyroiditis, is the most common type of thyroiditis and autoimmune endocrine disease, representing the primary non-iatrogenic cause of hypothyroidism (1). In the majority of cases, the onset of HT is insidious, and thyroid hormone levels typically remain within the normal range until inflammation progresses to hypothyroidism, revealing initial symptoms (2). Fundamentally, HT is an inflammatory disorder characterized by chronic low-grade inflammation and excessive production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Experimental and clinical evidence suggests that chronic inflammation can lead to an increase in extracellular fluid levels and water retention (3). This effect is also observed in patients with Hashimoto’s disease, where thyroid inflammation results in an increase in thyroid tissue water content (4). Research indicates that a low-carbohydrate diet may have potential anti-inflammatory effects, contributing to the improvement of biochemical markers and clinical symptoms in patients with HT (5, 6, 7). However, there is currently a lack of relevant imaging data to confirm these findings.
Dixon-T2-weighted imaging (WI) is a fat-suppression technique based on chemical shift analysis, differentiating fat and water directly (8). Compared to flip-angle-based fat-saturation (FS) sequences, Dixon-T2WI has lower sensitivity to magnetization transfer effects. Its advantages include a short acquisition time due to the high-field strength-related short chemical shift (9). Given these benefits, Dixon-T2WI is particularly suitable for imaging of the head and neck (10, 11). As it can directly differentiate between fat and water, Dixon-T2WI has been proven to assist in the quantitative assessment of tissue fat and water content (12, 13). It is an imaging technique capable of evaluating tissue inflammation and edema, where an increase in water content is associated with the severity of tissue inflammation. Previous studies have demonstrated the effectiveness of Dixon-T2WI in assessing tissue inflammation (14). Therefore, the aim of this study is to utilize Dixon-T2WI for the quantitative assessment of the impact of a low-carbohydrate diet on the inflammation level of patients with Hashimoto’s thyroiditis.
Methods
Study design and participants
From January to October 2022, a total of 40 patients with HT were recruited for a prospective study at the Second Affiliated Hospital of Zhejiang Chinese Medical University. All participants underwent testing for thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and thyroid ultrasound. Using standardized questionnaires to collect information about the health status of each patient (including diabetes, autoimmune diseases, etc.) and medication treatment. Venous blood samples were obtained after overnight fasting. All participants’ plasma samples were stored at −80°C. Using the Abbott Architect i2000, serum concentrations of TgAb and TPOAb are detected using chemiluminescent immunoassay. Inclusion criteria for the diagnosis of HT were elevated levels of TPOAb and/or TgAb (>60.00 IU/mL, reference range: 0.00–60.00 IU/mL) and typical heterogeneous hypoechoic patterns on thyroid ultrasound (15). Exclusion criteria included subjects with systemic inflammatory diseases, cancer, metal implants, or claustrophobia and individuals who were pregnant, possibly pregnant, or taking medications known to affect thyroid function. All patients with HT were randomly assigned to two groups. The control group received a standard diet, while the low-carbohydrate diet group followed a low-carbohydrate diet (carbohydrates 12–15%, protein 50–60%, and lipids 25–30%). Weekly dietary recommendations and sample meal plans will be provided, prescribed by a nutritionist. The implementation of the low-carbohydrate diet was jointly supervised by a physician through phone inquiries and reminders, along with the involvement of the patient’s family. Both groups underwent thyroid MRI and thyroid hormone biochemical tests before the experiment and were re-evaluated 6 months later. In the low-carbohydrate diet group, two cases had hypothyroidism, while the remaining cases had normal thyroid function. In the standard diet group, one case had hypothyroidism, while the remaining cases had normal thyroid function. There was no statistically significant difference in thyroid function status between the two groups of patients. Written informed consent was obtained from all participants. The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University.
Thyroid MRI examination and image analysis measurements
MRI scans were conducted using the SIEMENS MAGNETON Avanto 1.5T magnetic resonance imaging system. Patients were positioned in a supine position with the head first. The thyroid coil was selected for imaging. Axial parameters included: (i) T1WI: TR 400 ms, TE 11 ms; T2WI: TR 3000 ms, TE 100 ms; slice thickness 4 mm; gap 0.4 mm; FOV 300 mm × 300 mm; (ii) Dixon-T2WI: TR 3000 ms; TE 90 ms; slice thickness 4 mm; gap 0.4 mm; flip angle 150°; FOV 300 mm × 300 mm. The SIEMENS syngo MRI post-processing workstation was employed for image observation and analysis. After post-processing to obtain water content images, two experienced radiologists measured the water content of the thyroid’s left and right lobes. The measurements were performed three times, and the average value was calculated. The final thyroid water content represented the average water content of the left and right lobes.
Statistical analysis
Data analysis was performed using SPSS 26.0 statistical software. Normally distributed variables were expressed as mean ± s.d., while variables with a skewed distribution including TPOAb and TgAb were given as the median and upper and lower quartiles. Differences between the two groups were analyzed using the independent samples t-test or Mann–Whitney U test. The results were considered statistically significant with two-tailed analyses (P < 0.05).
Results
Baseline data for control group and low-carbohydrate diet group
There were no significant differences in baseline characteristics between the control group and the low-carbohydrate diet group in terms of age, gender, body mass index (BMI), TPOAb, TgAb, and thyroid water content values (Table 1).
Baseline data for two groups.
| Parameter | Control group | Low-carbohydrate diet group | P |
|---|---|---|---|
| Gender, males/females | 1/19 | 1/19 | |
| Age | 33.33 ± 9.11 | 34.10 ± 10.01 | 0.800 |
| BMI | 22.06 ± 3.57 | 21.48 ± 2.69 | 0.567 |
| TPOAb | 29.21 (2.59–488.13) | 211.30 (92.63–614.62) | 0.133 |
| TgAb | 3.86 (0.60–409.79) | 17.05 (1.47–81.64) | 0.695 |
| Mean thyroid water content (left lobe) | 94.79 ± 2.51% | 95.10 ± 1.81% | 0.672 |
| Mean thyroid water content (right lobe) | 94.80 ± 2.93% | 94.59 ± 1.64% | 0.798 |
| Mean thyroid water content (both lobes) | 94.83 ± 2.62% | 94.85 ± 1.57% | 0.982 |
Impact of low-carbohydrate diet on clinical parameters and thyroid water content values
After 6 months, there were no significant statistical differences in TPOAb (29.21 (2.59–488.13) vs 34.12 (1.61–34.12)), TgAb (3.86 (0.60–409.79) vs 5.80 (1.24–362.93)), and mean thyroid water content values (94.83 ± 2.62% vs 94.38 ± 2.39%) within the control group (P > 0.05). In the low-carbohydrate diet group, after 6 months of a low-carbohydrate diet, there was a significant decrease in TPOAb, TgAb, and mean thyroid water content values with statistical significance (P < 0.05) (Table 2, Figs. 1, 2, and 3).
Comparison of thyroid antibodies (TPOAb and TgAb) in the low-carbohydrate diet group before and after 6 months revealed statistically significant differences in both TPOAb and TgAb levels (P < 0.05).
Citation: Endocrine Connections 13, 5; 10.1530/EC-23-0477
Comparison of thyroid water content in the low-carbohydrate diet group before and after 6 months of low-carbohydrate diet, with a statistically significant difference in thyroid water content (P < 0.05).
Citation: Endocrine Connections 13, 5; 10.1530/EC-23-0477
Water fraction imagings (B and D) were obtained through Dixon-T2WI processing. T2WI-FS (A) and water fraction imaging (B) represent the images before the low-carbohydrate diet. T2WI-FS (C) and water fraction imaging (D) represent the images after 6 months of the low-carbohydrate diet, demonstrating a significant reduction in thyroid water content and a decrease in the degree of inflammation in patients with Hashimoto’s thyroiditis after 6 months of a low-carbohydrate diet.
Citation: Endocrine Connections 13, 5; 10.1530/EC-23-0477
Impact of low-carbohydrate diet on clinical parameters and thyroid water content in patients with Hashimoto’s thyroiditis.
| Parameter | Baseline | After 6 months (low-carbohydrate diet group) | P |
|---|---|---|---|
| TPOAb | 211.30 (92.63–614.62) | 89.45 (15.9–215.67) | 0.040 |
| TgAb | 17.05 (1.47–81.64) | 4.1 (0.51–19.42) | 0.049 |
| Mean thyroid water content (left lobe) | 95.10 ± 1.81% | 93.24 ± 2.31% | 0.014 |
| Mean thyroid water content (right lobe) | 94.59 ± 1.64% | 92.91 ± 1.94% | 0.011 |
| Mean thyroid water content (both lobes) | 94.84 ± 1.57% | 93.07 ± 2.05% | 0.008 |
Discussion
In this study, no significant change was observed in TPOAb, TgAb, and thyroid water content after 6 months in the control group of patients with HT. In contrast, the experimental group, after intervention with a low-carbohydrate diet, showed a significant reduction in thyroid water content, accompanied by a noticeable decrease in TPOAb and TgAb levels.
Previous research has indicated that Dixon-T2WI can assist in confirming inflammation, even in cases of subtle inflammation challenging to detect clinically. This sequence can effectively reveal inflammation within tissues and better reflect the extent of edema compared to traditional T2-weighted imaging (14). HT is characterized by inflammatory changes involving diffuse lymphocytic infiltration, destruction of follicular epithelial cells, and subsequent fibrosis, ultimately leading to hypothyroidism (16). As inflammation intensifies in HT, increased lymphocytic infiltration results in aggravated interstitial edema and a higher presence of free water in thyroid tissues (17). Our study demonstrates that, after 6 months of a low-carbohydrate diet intervention, patients with HT exhibited a significant reduction in thyroid water content, accompanied by a noticeable decrease in TPOAb and TgAb levels. Considering that MRI Dixon-T2WI water fraction imagings reflect tissue inflammation and edema, these results suggest that a low-carbohydrate diet intervention can alleviate the inflammation of the thyroid in patients with HT.
HT is a complex disease primarily mediated by autoimmune reactions at the cellular level, with apparent concurrent humoral autoimmune responses (18). CD8+ cytotoxic T cells directly damage thyroid cells, leading to thyroid swelling through the induction of cell necrosis or apoptosis (19, 20). Activated CD4+ T lymphocytes, by producing cytokines that damage thyroid cells, such as TNF-α and interleukin 1 (IL-1), further induce increased lymphocytic infiltration (21, 22), exacerbating inflammation and swelling in the thyroid. Research has reported that the ChREBP protein is necessary for inducing gene transcription involved in both fat synthesis and the glucose-dependent genes L-PK and ACC (23, 24). Excess adipose tissue produces various cytokines and inflammatory markers, such as IL-1, IL-6, TNF-α, and leptin. These substances mediate immune and inflammatory responses (25), with leptin considered to mediate immune responses by shifting helper T cell balance toward a helper T cell 1 (Th1) phenotype and inhibiting regulatory T (Treg) cell function (promoting the production of TPOAb) (26, 27). Dysfunction of Treg cells impairs the body’s ability to clear autoantibodies, leading to the preferential differentiation of lymphocytes into pro-inflammatory cell subtypes, such as Th1 and Th17 cells, and further increasing the production of inflammatory cytokines and the state of inflammation (21, 28).
Studies have shown that a low-carbohydrate diet can reduce the expression of ChREBP protein, decreasing the production of inflammatory cytokines and alleviating overall inflammation in patients (6). Our study results are consistent with previous research, indicating that a low-carbohydrate diet intervention can alleviate thyroid inflammation. The reduction in thyroid inflammation, manifested by decreased lymphocytic infiltration and reduced interstitial edema in the thyroid, results in decreased thyroid water content. TPOAb and TgAb are primarily produced by B lymphocytes infiltrating the thyroid (29, 30). Therefore, after the alleviation of thyroid inflammation, the levels of these autoantibodies also decrease.
For patients with HT, ultrasound examination is the most commonly used imaging technique, but it has certain limitations in assessing thyroid function changes. In recent years, thyroid MRI has been increasingly used for the diagnosis of thyroid diseases, and the Dixon-T2WI sequence has been gradually applied to small organs in the neck, which is believed to have potential benefits for evaluating HT. Compared to traditional ultrasound examinations, the Dixon-T2WI sequence can not only evaluate changes in the size and morphology of the thyroid but also accurately quantify the degree of inflammation in patients with HT. Therefore, the Dixon-T2WI sequence may become an important tool for assessing the inflammation of the thyroid in patients with HT, helping to better guide clinical treatment and follow-up management.
The limitations of this study include: first, it is a single-center study with a relatively small sample size, warranting the expansion of the sample size to further validate our results. Secondly, due to the limited sample size, the thyroid functional status of patients with HT was not specifically differentiated. Therefore, expanding the sample size to analyze the response of patients with both normal and reduced thyroid function to a low-carbohydrate diet intervention is necessary.
In conclusion, the MRI Dixon-T2WI sequence can quantitatively assess the degree of inflammation in patients with HT. After a low-carbohydrate diet intervention, a significant reduction in thyroid water content and a decrease in TPOAb and TgAb levels were observed, suggesting that a low-carbohydrate diet may help alleviate inflammation in patients with HT.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding
This study was supported by grants from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project (No. 2024ZR018).
Author contribution statement
FSF and HXS conceptualized and designed the study, while also planning, organizing, and supervising its execution. XJX, XJY, and ZXZ conducted data collection. HXS and DN wrote the early and final draft of manuscript. KTY, MLY, and SQH were responsible for statistical analysis and result interpretation. All authors thoroughly reviewed and approved the manuscript.
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