Introduction

Traditionally, free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) concentrations have been used in the clinic to evaluate whether thyroid function is normal. However, these indices may not be sufficient to reflect complex interactions in thyroid status1. Previous studies have indicated the use of comprehensive interpretations of thyroid hormone homeostasis or status based on indices of sensitivity to thyroid hormone, such as the thyrotroph–thyroxine resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), thyroid feedback quantile-based index (TFQI) or parametric thyroid feedback quantile-based index (PTFQI)2. The TT4RI, TSHI, and TFQI are indicators of pituitary thyroid thyrotropic function, whereas the FT3-to-FT4 ratio (FT3/FT4) indirectly reflects peripheral sensitivity to thyroid hormones3. For individuals with primary hyperthyroidism or hypothyroidism, the TFQI is a more reliable marker than the TT4RI or the TSHI, even when thyroid gland responsiveness to TSH is abnormal4. Researchers have recently focused on the impaired thyroid hormone sensitivity index as a predictor of cardiovascular disorders, obesity, papillary thyroid cancer risk, and cervical lymph node metastasis5,6,7. Notably, it has been proven that there is a relationship between sensitivity to thyroid hormone and several body composition indices, including fat mass and muscle mass8.

Thyroid dysfunction, as a proven risk factor, has been shown to be associated with musculoskeletal dysfunction9. In other words, skeletal muscle weakness often occurs in patients with hyperthyroidism or hypothyroidism. Thyrotoxicosis accompanied by several associated typical muscle symptoms, such as skeletal muscle weakness, paralysis, and pain, is primarily referred to as thyrotoxic myopathy10. Chronic thyrotoxic myopathy (CTM), characterized by symmetrical proximal muscles, progressive weakness, atrophy and wasting, is a muscle disease associated with hyperthyroidism11. Moreover, scapular and girdle muscle weakness, rather than bulbar paralysis, are frequently observed in CTM12. Although the characteristics of CTM are well known, there is little specific research on skeletal muscle-related function, such as that indicated by muscle power tests, in patients with CTM. In a study comparing skeletal strength between hyperthyroidism patients and controls, it was shown that both knee flexor and extensor muscle strength were reduced in patients with overt hyperthyroidism13. Skeletal muscle is one of the primary targets of thyroid hormones, which impact body composition and physical performance via the thyroid hormone receptor found in mitochondria14. One of the critical functions of thyroid hormones is to convert slow-twitch skeletal fibres (type 1) to fast-twitch fibres (type 2) by modulating the transcriptional activity of MYH genes15,16. According to histological microscopy, there is a significant increase in white type 2 fibres at the expense of mitochondrial type 1 fibres in patients with chronic hyperthyroid myopathy17. At least one muscle group associated with the free thyroxine concentration causes clinical muscle weakness in 62% of hyperthyroidism patients11. Electromyography and muscle biopsy are difficult to apply clinically due to their high invasiveness and low repetition rate18. Therefore, it is necessary to find alternative means to observe skeletal muscle function.

The aim of this study was to investigate the clinical features of skeletal muscle among patients with CTM, with a focus on strength and physical performance. Another objective was to explore a feasible tool based on strength and physical tests to screen potential CTMs. We also explored the association between TH sensitivity and the risk of CTM.

Methods

Subjects

In this study, we originally enrolled a total of 466 participants with Graves’ disease who visited the Department of Endocrinology, First Affiliated Hospital of Guangxi Medical University, between September 2020 and October 2023. The authors excluded participants who had missing physical examination data (n = 170); who had a history of other endocrine, autoimmune, rheumatic, neuromuscular, or articular diseases; who had severe chronic or acute illnesses (n = 39); who were pregnant (n = 2); or who had a history of potential treatment (n = 34). Finally, 221 subjects were eligible for the final analysis. The author conducted a survey and grouped the participants based on sex and whether they suffered from CTM. Then, participants were randomly selected from each group using a random number generator software. The number of participants gradually increased while satisfying the basic sample size requirements. This study complied with the Declaration of Helsinki and was approved by the First Affiliated Hospital Ethics Committee of Guangxi Medical University (No.2024-E378-01). The study confirm that all experiments were performed in accordance with relevant guidelines and regulations. The authors ensured that all participants were given the necessary information and signed informed consent forms before proceeding with the study. A diagnosis of CTM undeniably satisfies the diagnostic criteria for Graves’ disease19. In addition to the general symptoms of hyperthyroidism, there are unmistakable symptoms of progressive muscle weakness, emaciation, or atrophy present in the absence of other neuromuscular disease causes20. In cases where the symptoms of skeletal muscle atrophy in CTM are not prominent, the diagnosis of CTM can be aided by detecting myogenic damage through electromyography21. In this study, we excluded the following individuals: (1) those with endocrine diseases or disorders; (2) those with severe chronic or acute illnesses; (3) those with other autoimmune, rheumatic, neuromuscular, or articular diseases; (4) those who abused drugs or alcohol or were on long-term glucocorticoid regimens; (5) those who underwent thyroidectomy; and (6) those who were pregnant during the study period.

Anthropometric measurements and physical examinations

All participants underwent physical examination. Height, weight, weight loss, body mass index (BMI), blood pressure (BP), lean weight, arm muscle area (AMA), and thigh muscle area (TMA) were included. BMI was calculated as weight in kilograms divided by the squared height in metres22. BP was measured on the patient’s right arm in a quiet state, and the average of three readings was recorded as the BP8. Lean weight was calculated according to the “Brozek” improved formula using measurements obtained with skinfold callipers (TIXING, Jiangsu, China), as previously described23. The AMA and TMA were calculated using the method proposed by Heymsfield S B24. For grip strength measurement, participants stood in a stable position and gripped the hand dynamometer (CAMRY, SENSSUN, Guangdong, China), and after a 5-second stabilization period, the data were recorded25. The measurements were rounded to the nearest 0.01 kg, and the maximum value of the three tests was taken as the grip force. The upper-limb fatigue test (ULFT) process was performed as follows26: Participants stood on level ground with their feet apart and their arms raised until their hands were parallel to the floor. Upper-limb fatigue was induced and recorded for the left and right sides separately. The experiment ended if the limbs sagged or the angle between the upper arm and torso was less than 90° or if the posture was maintained for more than 120 s, and the end-time was recorded. The lower-limb FT (LLFT) test was performed as follows26: Participants lay supine on the exam bed, with their legs raised at 90 degrees each for hip and knee flexion. The time to induce limb fatigue was recorded separately for each side. If the limbs bent or sagged beyond 90 degrees or the posture was maintained for 120 s, the experiment was stopped, and the end-time was recorded. The squat-up test (SUT) process was performed as follows27. The participants stood with their feet shoulder-width apart, raised their arms forwards to shoulder level, squatted, and stood up again; the exercise was repeated 10 times while keeping their arms raised straight ahead. The experiment ended if the subject had to stand for more than 5 s between squat repetitions. The amount of time taken to perform 10 repetitions was recorded. A 10-metre walking test was used for practice to measure walking speed28.

Thyroid function measurements and indices of thyroid hormone sensitivity

Approximately 5 ml of venous blood was obtained after an overnight fast. Serum levels of thyroid hormone were determined via chemiluminescent immunoassay using a TEGEN, TESMI i-200 (Shanghai, China). The reference ranges for the FT3, FT4, TSH and TRAb concentrations are 3.6–6.0 pmol/L, 7.86–14.41 pmol/L, 0.34–5.65 mIU/L, and 0–1.5 IU/L, respectively29. To indicate peripheral thyroid hormone activity, the FT3/FT4 index was calculated by dividing the FT3 concentration by the FT4 concentration3. The TSHI was computed by taking the natural logarithm of the TSH concentration, adding 0.1345, and then multiplying that by the FT4 concentration3. The TT4RI was obtained by multiplying the FT4 concentration by the TSH concentration3. The TFQI was calculated using the cumulative distribution function (CDF) as follows: CDFFT4-(1 − CDFTSH)3. The PTFQIFT4 was calculated using an Excel spreadsheet formula reported in a previous study3, where µ FT4 = 45.99, σFT4 = 21.51, µ ln TSH=-4.53, and σ ln TSH = 0.32 for our study. The TT3RI and PTFQIFT3 were also calculated using formulas similar to those used for the TT4RI and PTFQIFT4, and the values for µ FT3 = 21.38 and σFT3 = 11.71 were obtained and used in the formulas.

Statistical analysis

The sample size was calculated by the Power Analysis and Sample Size (PASS) 15.0 (NCSS, LLC. Kaysville, Utah, United States) to determine the primary outcome of the study with 90% power at a significance level of 0.05; Group allocation: equal; AUC0 = 0.50, AUC1 = 0.80; Lower false positive rate limits = 0.00, Upper FPR = 1.00. With a CTM prevalence ranging from 67-79.6%11,30, the total sample size was at least 1731. The number of participants gradually increased while satisfying the basic sample size requirements. Continuous variables are presented as the mean ± standard deviation (SD) or median (interquartile range) depending on their distribution. Categorical variables are presented as numbers and percentages. To compare differences between groups, the chi-square test or Fisher’s exact test was used for categorical variables, while a two-sample t test, analysis of variance, or nonparametric test was used for continuous variables depending on their distribution. Pearson or Spearman correlation coefficients were calculated to assess the relationships between indices of sensitivity to thyroid hormone and anthropometric measurements or physical examinations. Multivariate logistic regression analysis was used to examine the associations of thyroid hormone indices with skeletal muscle function. Model 1 was not adjusted for any parameters, while Model 2 was adjusted for age, ethnic and sex. Model 3 was further adjusted for BMI, duration of Graves’ disease, SBP, Loss Weight, and TRAb. Given that some basic characteristics were significantly different in subjects with participants, the weight method of inverse probability of treatment weighting (IPTW) was calculated, and IPTW multivariate logistic regression models were established to further control confounders. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of skeletal muscle function indices to distinguish CTM patients from non-CTM patients. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) 22.0 (IBM Corp., Armonk, New York, United States), R 4.4.1(R Foundation for Statistical Computing, Vienna, Austria) and GraphPad Prism 9 (Dotmatics, Boston, Massachusetts, United States) with default parameters. Bivariate and multivariate analysis have been performed considering two-tailed and a significance level of 0.05 to indicate statistical significance in the study. Multiple comparisons were two-tailed with a p-value of 0.0083 or smaller as significant by Bonferroni adjustments.

Results

Characteristics of the study population

The results of the experiment showed the clinical baseline characteristics of the Graves’ disease patients (Tables 1 and 2). Compared to participants without CTM, participants with CTM had greater weight loss, disease duration, SBP, SUT, FT3, FT4, TRAb, TT3RI, TT4RI, TSHI, TFQIFT3, PTFQIFT3, TFQIFT4, and PTFQIFT4 (all P < 0.05). Weight, BMI, AMA, TMA, grip, grip/height, ULFT, LLFT and walking pace were significantly lower (all P < 0.05) in the CTM group than in the non-CTM group; however, there was no between-group difference in the FT3/FT4 ratio (Tables 1 and 2).

Table 1 Comparison of Basic demographic characteristics of CTM and Non-CTM Population.
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Table 2 Comparison of thyroid parameters of CTM and Non-CTM population.
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In the context of sex, the author shows the basic characterization of Graves’ disease patients in women and men. The disease duration, weight loss, SUT, FT3, FT4, TRAb, TT3RI, TT4RI, TSHI, TFQIFT3, PTFQIFT3, TFQIFT4, and PTFQIFT4 were significantly greater in thyrotoxic women with CTM than in those without CTM (all P < 0.05), while the FT3/FT4 ratio (P = 0.567) did not differ. Although thyrotoxic women with CTM had a significantly lower AMA, TMA, grip strength, grip/height ratio (all P < 0.05), ULFT, LLFT and walking pace than women in the non-CTM group (all P < 0.05), there were no significant differences in lean weight (P = 0.538) or BMI (P = 0.088) were found between the study groups. We observed that patients with CTM in the male group had a longer Graves’ disease duration and greater SUT, FT3, FT4, TRAb, and TSHI (all P < 0.05). Grip strength, grip strength/height, ULFT, LLFT and walking pace significantly differed between the CTM and control groups in males (all P < 0.05). The analysis of participants’ features revealed that CTM was associated with weaker physical performance and greater hormone levels and TH sensitivity (see Supplementary Table S1-S4 online).

Relationships between thyroid hormone concentrations or indices and skeletal muscle function

Relationships between thyroid function levels and skeletal muscle function were assessed using Pearson or Spearman correlation coefficients. In the male subgroup, TFQIFT4 and PTFQIFT4 were negative with ULFT (r=-0.360, P = 0.005; r= -0.355, P = 0.005), other TH sensitivity index was not found relation with muscle performance or power. The relationships of TFQIFT3, PTFQIFT3, TFQIFT4, and PTFQIFT4 between grip, grip/height, ULFT and LLFT were negative and with SUT was positive (all P < 0.05) in the female subgroup. Correlation analysis revealed a connection between weaker skeletal muscle function and greater TH levels in Graves’ disease (see Supplementary Table S5 online).

Levels of skeletal muscle function in different quantile-based groups of indices of sensitivity to TH

Trend test for the association between indices of sensitivity to TH and changes in skeletal muscle function. Examinees were classified into four groups (Q1-Q4) based on their sensitivity to thyroid hormones. Because the TFQI is more reliable than the TTRI and TSHI in patients with hyperthyroidism or hypothyroidism4, the TFQI and PTFQI were included. Figure 1 displays the changes in skeletal muscle function among the quartile groups based on TFQIFT3, PTFQIFT3, TFQIFT4 and PTFQIFT4. Overall, the grip, grip/height, ULFT and LLFT decreased from the lowest to the highest quartiles of TFQIFT3, PTFQIFT3, TFQIFT4 and PTFQIFT4, whereas SUT increased from the lowest to the highest quartiles of TH sensitivity index (all adjust P for Trend < 0.0083).

The authors also observed a trend of skeletal muscle function in different quantile-based groups of TFQIFT3, PTFQIFT3, TFQIFT4 and PTFQIFT4 in the context of sex. In the female subgroup, the grip, grip/height, and LLFT decreased linearly from the lowest to the highest of TFQIFT3, PTFQIFT3, TFQIFT4, and PTFQIFT4 (all adjust P for trend < 0.001), but the SUT increased linearly from the lowest to the highest of TFQIFT4 (14.79, 14.90, 16.23, 22.00s, P for trend = 0.002)and PTFQIFT4 (14.79, 14.90, 16.17, 21.00s, adjust P for Trend = 0.002). Among the male subgroup, only the ULFT levels decreased linearly from the lowest to the highest values for TFQIFT4 (120.00, 120.00, 89.62, 94.81, adjust P for trend = 0.0082) (see Supplementary Table S6-S11 online). Changes in skeletal muscle function with changes in the TH sensitivity index in patients with Graves’ disease.

Fig. 1
figure 1

Skeletal muscle strength and function in different quantiles of indices of sensitivity to thyroid hormone. Performance on the grip strength test (a), grip/height assessment (b), ULFT (c), LLFT (d), SUT (e), and walking pace (f) assessment in patients with Graves’ disease in different quantiles of indices of sensitivity to thyroid hormone.

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Multivariate regression analyses of the associations between the TH sensitivity indices and the risk of developing CTM

Multivariate regression analyses were performed to assess the associations between TH sensitivity indices and the risk of developing CTM. The TFQI and PTFQI were included in multivariate regression analyses due to their superior reliability compared to the TTRI and TSHI in patients with hyperthyroidism or hypothyroidism4. According to the multivariable regression analysis in Tables 3 and 4, PTFQIFT4 were strongly associated with the incidence of CTM in Models 1–3. As continuous variables, the odds ratio (OR) for comparing individuals with and without CTM was not significant in TFQIFT3, PTFQIFT3, TFQIFT4, and PTFQIFT4 in Model 3. The sensitivity indices of thyroid hormones were classified into quartiles, revealing significant positive correlations between TFQIFT4 and PTFQIFT4 and the risk of developing CTM. In Model 3, the ORs for the risk of developing CTM associated with the highest quartiles of TFQIFT4 and PTFQIFT4 were 6.85 (95% CI 1.97–23.85) and 8.96 (95% CI 2.53–31.84), respectively.

Table 3 Association between TFQIFT3 and PTFQIFT3 with CTM risk.
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Table 4 Association of TFQIFT4 and PTFQIFT4 with CTM risk.
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Association of TH sensitivity indices and the risk of developing CTM using IPTW multivariate logistic regression

As shown in Tables 5 and 6, population characteristics differed significantly between patients with and without CTM across all covariates. Using the inverse probability weight, IPTW was employed to further control confounding effects, followed by IPTW-weight multivariate logistic regression analysis. TFQIFT3, PTFQIFT3, TFQIFT4, PTFQIFT4 were positively associated with CTM risk in model1, model2, and model3. Compared to the lowest TH sensitivity quartile, the highest TH sensitivity quartile was positive associated with CTM in model 3 (TFQIFT3: OR: 5.39, 95%CI: 1.94–15.74; PTFQIFT3: OR: 4.87, 95%CI: 1.74–14.30; TFQIFT4: OR: 5.05, 95CI%1.80-15.17; PTFQIFT4: OR: 3.78, 95%CI: 1.31-11.50). The results from the IPTW-weighted regression unequivocally demonstrate a significant positive association between TH sensitivity and CTM in all three models. This conclusively suggests that the conflicting results from the unweighted regression were indeed due to confounding. With a per-SD increase in TFQIFT3 (OR:1.67, 95%CI: 1.17–2.48), PTFQIFT3 (OR:1.64, 95%CI:1.51–2.93), TFQIFT4 (OR:1.60, 95%CI: 1.12–2.32), and PTFQIFT4 (OR:1.58, 95%CI: 1.11–2.30). After adjustment for multiple confounders, TFQIFT3, PTFQIFT3, TFQIFT4, PTFQIFT4 were positively associated with the risk of CTM.

Table 5 Association of TFQIFT3 and PTFQIFT3 and CTM risk using IPTW-weighted regression.
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Table 6 Association of TFQIFT4 and PTFQIFT4 and CTM risk using IPTW-weighted regression.
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ROC curves for the optimal cut-off points for CTM according to skeletal muscle parameters

ROC curves are utilized to determine the optimal cut-off points for skeletal muscle parameters based on skeletal muscle function parameters. Figure 2 and Supplementary Table S11 online shows that the areas under the curve (AUCs) for grip strength, grip/height, ULFT, LLFT, SUT, and walking pace were 0.82, 0.80, 0.80, 0.84, 0.84, 0.85, 0.76, respectively, in the female group. The results indicated the AUCs of the SUT were greater than those of grip strength, grip/height, the ULFT, the LLFT, and walking pace on ROC analyses for female CTM prediction. The optimal cut-off point of the SUT for CTM prediction was 95.60%, and the sensitivity and specificity of this cut-off point were 82.69% and 92.31%, respectively.

Fig. 2
figure 2

ROC curves for the optimal cut-off points for skeletal muscle function and CTM function. (a) ROC curve for CTM from skeletal muscle and function in the male subgroup; (b) ROC curve for CTM from skeletal muscle and function in the female subgroup.

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Figure 2 and Supplementary Table S11 online also shows that the areas under the curve (AUCs) for grip strength, grip/height, ULFT, LLFT, SUT, and walking pace were 0.78, 0.78, 0.75, 0.89, 0.84 and 0.85, respectively, in the male group. The results revealed that the AUCs of the LLFT were greater than those of grip strength, grip/height, the SUT, the ULFT, and walking pace on ROC analyses for male CTM prediction. The optimal cut-off point of the LLFT for CTM prediction was 91.60%, and the sensitivity and specificity of this cut-off point were 90.00% and 83.33%, respectively. The SUT and LLFT are feasible methods for diagnosing potential CTM in hyperthyroidism patients in females and males, respectively.

Discussion

In this study, we investigated the relationship between sensitivity to TH and the prevalence of CTM in Graves’ disease and investigated a novel assessment for potential screening of CTM. This study demonstrated that CTM, which has a weaker effect on skeletal muscle function, including grip strength, ULFT, LLFT, and SUT, was positively associated with FT3 and FT4. The novelty of the present study is that TFQIFT4 and PTFQIFT4 were positively associated with the risk of CTM, and the LLFT and SUT were used as novel predictors of CTM in males and females.

The first important finding of our study was that CTM patients are characterized by higher serum FT3, FT4 and TRAb levels, longer disease duration, lower BMI, and weaker skeletal muscle power and function than Graves’ disease patients without CTM. The serum thyroid hormone concentration was negatively correlated with grip and muscle function, as were the ULFT and LLFT. These results further suggest that impaired skeletal muscle behaviour is associated with increased thyroid function and disease duration in patients with Graves’ disease, but these results are not entirely consistent with previous research. Kung et al. showed that the extent of skeletal muscle behaviour was related to the duration of hyperthyroidism but not to the severity of TH18. The specific mechanism of thyroid function and muscle function is unclear. It is possible that abnormal thyroid hormone and TSH levels can impair muscle protein synthesis, resulting in skeletal muscle mass reduction32. An increase in muscle protein breakdown was observed in patients with hyperthyroidism due to increased amino acid release33. In addition, the level of TRAb in the CTM group was greater than that in the non-CTM group in our study. Proinflammatory factors released by effector T cells in Graves’ disease can lead to muscle mass and strength loss in patients34. In short, the relationships among thyroid function, antibody levels and skeletal muscle performance are unclear, and more human and animal research is needed to elucidate the pathogenesis of CTM.

Considering that skeletal muscle performance is affected by sex, a sex-stratified subgroup analysis was performed to assess muscle status and conditions according to sex. According to the sex-stratified subgroup analysis, even though muscle grip strength and muscle function in the CTM group were weaker than those in the non-CTM group, as shown in Table S1-S4, the significant variables were different in both the female subgroup and the male subgroup. In addition, fewer variables were correlated with thyroid hormones and the index of thyroid hormone sensitivity according to simple correlation analysis of the male subgroup. Differences in sex steroid levels and composition may explain the inconsistent outcomes between the sexes. Testosterone is a synthetic metabolic factor that can effectively promote muscle protein synthesis and regeneration, while oestrogen protects skeletal muscles by reducing inflammation35. The maintenance of skeletal muscle homeostasis by oestrogen in skeletal muscle is not better than that by testosterone35.

Considering the weaker skeletal muscle performance in CTM, the current study aimed to screen potential CTM in hyperthyroidism patients with muscle function tests. The second important finding of our study was that according to the ROC curve analysis, for both males and females, we found that the AUC of the lower-limb-associated functional test was greatest among the subgroups. Fatigue and weakness in the pelvic girdle muscle are common complaints in patients with thyrotoxic myopathy36. These findings indicate that the CTM is more affected by the pelvic girdle or other lower-limb muscles than by the upper-limb muscles. Nevertheless, other studies have shown that the scapular girdle muscle is more involved than the pelvic girdle muscle21. This is contrary to our results. In the future, the above contradiction may be solved by molecular receptor position and differences in receptor distribution in the upper and lower muscle groups affected. Overall, our study proposes a workable method to screen potential CTMs in the clinic.

At present, studies on the relationships between TH sensitivity and the risk of CTM are very limited or have not been published. Notably, the third important finding of our study was that a positive association was still significant between TFQIFT3, PTFQIFT, TFQIFT4 and PTFQIFT4, and the incidence of CTM in patients with hyperthyroidism after adjusting for multiple covariates according to IPTW multivariate logistic regression. The FT3/FT4 ratio was not significantly correlated with clinical baseline characteristics in our study. FT3/FT4 is considered to have deiodinase activity, especially D1 and D237. In skeletal muscle, D2 converts T4 to T3 to provide intracellular T3, whose level is essential for skeletal muscle differentiation and regeneration38. Increased FT3/FT4 conversion in skeletal muscle promotes its growth and regeneration. Previous studies confirmed that a higher FT3/FT4 ratio was positively linked to muscle strength, muscle mass, and physical performance in individuals with obesity and type 2 diabetes mellitus39,40. In patients with Graves’ disease, there is a disproportionate increase in the serum T3 concentration compared to the serum T4 concentration41. This has led to the hypothesis that the increase in the TT3/TT4 or FT3/FT4 ratio in Graves’ disease patients could reflect an increase in peripheral deiodinase activity41. Our study revealed no significant difference in the FT3/FT4 ratio between the CTM and non-CTM groups, even though the FT3/FT4 ratio in the CTM group was lower than that in the non-CTM group, indicating that it is still unclear whether peripheral deiodinase activity is involved in the pathogenesis of CTM, and more research is needed to confirm these findings. In brief, our results suggested that TFQIFT3, PTFQIFT, TFQIFT4 and PTFQIFT4, and other comprehensive indicators could be used to investigate the relationship between TH sensitivity and CTM.

CTM involves a complex interplay of factors. Elevated thyroid hormone levels are known to increase the basal metabolic rate and correlated with muscle pathology, leading to heightened protein turnover and potential muscle degradation42,43. In chronic cases, persistently high thyroid hormone levels can exacerbate muscle symptoms43. The TH Sensitivity Index is a critical parameter for gauging an individual’s sensitivity to thyroid hormones, which reflects the body’s responsiveness to circulating thyroid hormones, offering valuable insights into the relationship between thyroid hormone levels and muscle function8. Patients with CTM may exhibit varying degrees of muscle dysfunction, influenced by their sensitivity to thyroid hormones. A higher TH sensitivity index indicates more thyroid hormones were produced spontaneously in thyrotoxicosis status from our results, suggesting that even slightly elevated levels could lead to significant muscle symptoms. Interestingly, even normal levels TH could lead to muscle atrophy44. A Chinese study showed that higher FT3 concentrations within a normal range are correlated to muscle mass and muscle function44. No studies have indicated an association between thyroid hormone sensitivity and muscle implications in patients with thyrotoxic so far, a study from China revealed that TFQI and PTFQI were negatively correlated with skeletal muscle area and skeletal muscle indexes in the euthyroid population8. These indicated the potential relation between the TH sensitivity index and skeletal muscle. Therefore, understanding the TH sensitivity index in these patients is essential for tailoring precise treatment strategies. This individualized approach optimizes thyroid hormone levels to alleviate muscle-related symptoms while managing the underlying thyroid condition. It is imperative for clinical practitioners to remain vigilant regarding potential complications associated with elevated TH sensitivity indices in patients with hyperthyroidism. Monitoring of TH sensitivity index in CTM patients allows clinicians to comprehend individual variations in thyroid hormone sensitivity. This personalized approach can enhance disease management and patient outcomes by addressing specific needs based on hormonal sensitivity.

There are several limitations in our research. First, a potential selection bias may be generated because the participants were from a single hospital. Second, comprehensive results need to be acquired with a larger sample size. Some patients reported improved muscle weakness symptoms within one month or less after follow-up. Therefore, a future analysis of improvements in the subjective feelings of muscle fatigue would be interesting.

Conclusion

In summary, our study indicated that elevated TFQIFT3 and PTFQIFT, TFQIFT4 and PTFQIFT4, levels were significantly associated with the risk of developing CTM in patients with Graves’ disease. Doctors can evaluate the effect of skeletal muscles on hyperthyroidism with the aid of grip strength and functional tests. Muscle function tests, especially the SUT and LLFT, could assist clinicians in assessing CTM status in patients with hyperthyroidism. Based on these results, the prevention and treatment of CTM by ameliorating sensitivity to thyroid hormones may be a new approach in clinical practice. Our study provided evidence for the significance of TH and its sensitivity indices in interactions with the occurrence risk of CTM and skeletal muscle performance, and the exploration of the underlying mechanism is crucial for gaining a comprehensive understanding.