Abstract
Objectives
The objective of this study was to evaluate the Systemic Inflammation Index (SII), Platelet to Lymphocyte Ratio (PLR), and Neutrophil to Lymphocyte Ratio (NLR) in HT and NIH, as well as their diagnostic value to predict the presence of inflammation.
Subjects and Methods
The study included 505 patients, including 190 healthy controls, 166 euthyroid Hashimoto's thyroiditis (HT), 91 hypothyroid HT, and 58 non- immunogenic hypothyroidism (NIH) patients. The records of the patients in each group were reviewed retrospectively
Results
In terms of SII, there was a significant difference between the control and patient groups (p<0.001). PLR and NLR values were also found to be significantly higher in the patient group (p<0.001 and p=0.007, respectively). When euthyroid HT, hypothyroid HT, and NIH subgroups were compared to the control group, there was a significant difference in SII, PLR (for all p<0.001), but not in NLR (p=0.059). SII, PLR, and NLR were not different between the subgroups (p=0.595, p=0.861, and p=0.777, respectively).
Conclusions
It was found that the PLR, NLR, and SII indices were higher in Hashimoto’s thyroiditis and non-immunogenic hypothyroidism. Of these indices, SII was the most powerful marker to predict the presence of inflammation.
Keywords: systemic inflammation index, hashimoto thyroiditis, autoimmune thyroiditis, PLR, NLR, non-immunogenic hypothyroidism
INTRODUCTION
In clinical practice, hypothyroidism is a very common health problem, and early diagnosis is important because it may lead to a wide range of complications, such as congenital anomalies, encephalopathy, dementia, hypo-hyperkinetic neurological diseases, and cardiovascular diseases like dyslipidemia, hypertension, and myocardial dysfunction (1-4). Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is the most common form of autoimmune thyroid disease. In its etiopathogenesis, in addition to many genetic factors including polymorphisms in HLA class 1-2, CTLA4, PD1, and similar immunoregulatory genes, environmental factors such as excessive iodine intake, congenital rubella and hepatitis C infections, lithium treatment, and radiotherapy are considered to be effective (5-7). While patients can be asymptomatic at the time of administration, they could present with a variety of problems such as neck pain, voice alterations, throat discomfort, difficulty in swallowing, and shortness of breath. According to thyroid hormone profiles, clinical signs of hypothyroidism and hyperthyroidism can also be seen (7,8). Thyroid function tests, depending on the balance between the amount of produced and reserved hormone, and the released hormone from destroyed thyroid cells as a result of lymphocyte infiltration and the autoantibody response to thyroid peroxidase, it can range from euthyroidism to overt hypothyroidism and, in rare cases, hyperthyroidism. Anti-thyroid peroxidase (anti-Tpo) and anti-thyroglobulin (anti-Tg) antibody positivity is significant in the identification of the disease. Ultrasonography is useful in determining the severity of inflammation caused by lymphocyte infiltration into the thyroid gland, and the possible presence of nodules (7).
Non-immunogenic hypothyroidism (NIH) can be caused by a variety of factors, including diet- induced, iatrogenic (surgery, radiotherapy, or medicine), or viral. The prevalence of patients diagnosed with NIH is lower than that of patients with autoimmune hypothyroidism. Because of this, researchers do not pay much attention to NIH (9,10).
Systemic inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to- lymphocyte ratio (NLR) are markers that can be calculated using platelet (PLT), neutrophil, and lymphocyte parameters obtained from a complete blood count, which is the most commonly requested, least expensive, and most easily applicable test in clinical practice. In recent years, many studies investigating the relationship between SII and the diagnosis, severity, and prognosis of various clinical conditions, especially chronic inflammatory, cardiovascular, and malignant diseases, have been conducted (11-15).
Because of its chronic inflammatory nature, Hashimoto's thyroiditis has been linked in numerous studies to a variety of inflammatory metabolic and biochemical markers (16,17).
The objective of our study was to examine the levels of the novel inflammation indices SII, PLR, and NLR in patients diagnosed with Hashimoto's thyroiditis, who were either in a euthyroid or hypothyroid state, and those with NIH. We also aimed to evaluate the diagnostic potential of these hemogram-derived inflammation indices for identifying inflammation in these patients.
MATERIAL AND METHODS
Study design and ethics committee approval
The data of the patients who applied to the Taksim Training and Research Hospital Internal Medicine outpatient clinic were evaluated retrospectively from the medical records of our hospital. Pregnant women, those with autoimmune diseases other than Hashimoto's thyroiditis, and HT patients with hyperthyroid status and having hepatic, renal, cardiac, hematological, or oncological diseases, or use of steroids, anticoagulants, antiproliferative drugs, etc. that may affect hematological parameters, and those with acute or chronic infectious diseases were excluded from the study. Participants were divided into four groups: healthy controls, HT in euthyroid state, HT in hypothyroid state, and NIH. The hospital software system was utilized to obtain and record the participants' demographic and laboratory data.
Individuals in the control group were those who applied for routine control and did not have any disease or medication, whose thyroid function tests were normal, and thyroid autoantibodies were both negative. The determination of euthyroid and hypothyroid HT groups with Anti-Tpo and/or Anti-Tg positivity was made according to TSH, fT4 and fT3 levels. Patients with high TSH, low fT4 and fT3 values, and autoantibody negativity were included in the NIH group. Approval of the study was obtained from the Ethics Committee of Gaziosmanpasa Training and Research Hospital (decision number 50, dated 2023).
Laboratory data
Laboratory results for all participants were retrospectively obtained from patients` records. Routine biochemistry tests and CRP levels were analyzed by a clinical chemistry autoanalyzer (Roche Diagnostics, Germany). Thyroid function tests were measured by the immunoassay method on the Roche Cobas 601 autoanalyzer (Roche Diagnostics, Germany). The whole blood count was measured on the Mindray BC-800. NLR and PLR indices were calculated as simple ratios by dividing neutrophil count to lymphocyte count, and similarly, platelet count to lymphocyte count, respectively. The SII formula was as follows: (platelet count x neutrophil count) / (lymphocyte count).
Statistical analysis
The all statistical analysis was performed by SPSS software version 23.0 (Armonk, USA). The distributions of variables were determined by the Kolmogorov-Smirnov test. The variables that were not normally distributed were expressed as the median (interquartile range). Also, categorical parameters were indicated as percentages. The Kruskal-Wallis test was used to determine differences between study groups. Also, the directional relationships between hemogram-derived indices and thyroid function tests were determined by the Pearson and Spearman correlation tests. Lastly, we evaluated the diagnostic power of inflammation indices to indicate the presence of inflammation by using receiver operating characteristic (ROC) analysis. The cut-off value was determined based on the optimal point for sensitivity and specificity in ROC analysis. The statistical significance cut-off value was accepted as p < 0.05.
RESULTS
Demographic and laboratory data of the healthy control and all patients group who consisted of HT in the euthyroid state, HT in the hypothyroid state, and NIH, are shown in Table 1. The gender distribution was statistically different between the two groups (p<0.001). Additionally, CRP and ESR values were higher in the all patient groups than the control subjects without clinical importance (p=0.004 and p<0.001, respectively). In terms of SII values, a statistically significant difference was observed between the control and the patient group (p<0.001). PLR and NLR values were also found to be significantly higher in the patient groups compared to the control group (p<0.001 and p=0.007, respectively). There was no difference in lymphocyte counts between the control group and the whole patient group or between individual subgroups (p=0.516).
Table 1.
Demographic and laboratory data of healthy control and patient groups
| Healthy control n=190 |
All patients n=315 |
p | |
|---|---|---|---|
| Age | 43 (32-55.2) | 46 (38-56) | 0.31 |
| Gender | |||
| Female n (%) | 121 (63.7) | 257 (81.6) | <0.001 |
| Male n (%) | 69 (36.3) | 58 (18.4) | |
| Creatinine (mg/dL) | 0.74 (0.64-0.88) | 0.70 (0.62-0.81) | 0.014 |
| AST (U/L) | 17.0 (15.0-20.0) | 18.0 (15.0-21.1) | 0.098 |
| ALT (U/L) | 16.0 (11.0-23.0) | 15.1 (11.0-22.0) | 0.84 |
| fT3 (ng/L) | 3.20 (2.91-3.43) | 2.91 (2.61-3.27) | <0.001 |
| fT4 (pmol/L) | 12.0 (10.9-13.1) | 11.4 (10.1-13.0) | <0.001 |
| TSH (mU/L) | 1.64 (1.08-2.42) | 3.82 (2.17-5.82) | <0.001 |
| TpoAb (kU/L) | 9.0 (9.0-9.68) | 88.0 (13.4-207) | <0.001 |
| TgAb (kU/L) | 12.2 (10.4-15.3) | 98.2 (18.7-350) | <0.001 |
| CRP (mg/L) | 1.25 (0.60-2.49) | 1.62 (0.70-4.14) | 0.004 |
| ESR (mm/h) | 3.0 (2.0-7.0) | 6.0 (2.0-13.0) | <0.001 |
| Leukocytes (103/mm3) | 6.85 (5.52-8.18) | 7.01 (5.84-8.24) | 0.587 |
| Neutrophil (103/mm3) | 3.43 (2.71-4.80) | 3.88 (3.06-4.85) | 0.037 |
| Lymphocyte (103/mm3) | 2.32 (1.93-2.80) | 2.28 (1.84-2.80) | 0.516 |
| Platelet (103/mm3) | 235 (200-284) | 265 (225-308) | <0.001 |
| PLR | 98.5 (79.2-130) | 115 (92.4-142) | <0.001 |
| NLR | 1.37 (1.12-2.46) | 1.69 (1.30-2.10) | 0.007 |
| SII | 297 (249-742) | 433 (331-567) | <0.001 |
AST: aspartate aminotransferase, ALT: alanine aminotransferase, TSH: thyroid stimulating hormone, TpoAb: thyroid peroxidase antibody, TgAb: thyroglobulin antibody, CRP: C reactive protein, ESR: erythrocyte sedimentation rate, PLR: platelet/lymphocyte ratio, NLR: neutrophil/lymphocyte ratio, SII: systemic inflammation index.
Table 2 summarized all participants into divided subgroups such as healthy controls (n=190), HT in the euthyroid state (n=166), HT in the hypothyroid state (n=91), and NIH (n=58). There was a statistically significant difference in SII, thrombocytes, and thus PLR (for all p<0.001), but no difference in neutrophils and thus NLR (p=0.132 and p=0.059, respectively). SII, PLR, and NLR values did not differ between the subgroups of immunogenic and NIH (p=0.595, p=0.861, and p=0.777, respectively). The lymphocyte levels were not different between control and all subgroups (p=0.902).
Table 2.
Demographic and laboratory data of the control group and patient subgroups
| Healthy control n=190 |
Euthyroid HT n=166 | Hypothyroid HT n=91 | NIH n=58 |
p | |
|---|---|---|---|---|---|
| Age | 43 (32-55) | 46 (38-54) | 45 (34-56) | 48 (35-58) | 0.173 |
| Gender | |||||
| Female (%) | 121 (63.7) | 142 (85.5) | 72 (79.1)142 (85.5) | (74.1) | <0.001 |
| Male n (%) | 69 (36.3) | 24 (14.5) | 19 (20.9) | 15 (25.9) | |
| Creatinine (mg/dL) | 0.74 (0.64-0.88) | 0.70 (0.62-0.78) | 0.71 (0.61-0.84) | 0.70 (0.61-0.84) | 0.088 |
| AST (U/L) | 17.0 (15.0-20.0) | 17.7 (15.0-21.0) | 18.0 (15.0-21.0) | 19.0 (15.0-25.0) | 0.111 |
| ALT (U/L) | 16.0 (11.0-23) | 15.0 (11.0-21.1) | 15.0 (11.0-20.0) | 18.0 (12.0-26.0) | 0.393 |
| fT3 (ng/L) | 3.20 (2.91-3.43) | 2.92 (2.64-3.25) | 2.84 (2.50-3.28) | 2.93 (2.59-3.29) | <0.001 |
| fT4 (pmol/L) | 12.0 (10.9-13.1) | 11.9 (10.8-13.7) | 10.3 (8.91-12.5) | 10.9 (9.78-12.6) | <0.001 |
| TSH (mU/L) | 1.64 (1.08-2.42) | 2.21 (1.36-3.07) | 6.22 (5.16-10.5) | 5.63 (5.06-6.85) | <0.001 |
| TpoAb (kU/L) | 9 (9-9.68) | 126 (48.6-216) | 147 (66.7-314) | 9.0 (9.0-12.2) | <0.001 |
| TgAb (kU/L) | 12.2 (10.4-15.3) | 179 (31.5-395) | 198 (39.5-423) | 13.3 (11.3-24.5) | <0.001 |
| CRP (mg/L) | 1.25 (0.60-0.49) | 1.23 (0.62-2.85) | 1.99 (0.67-5.60) | 2.14 (1.14-5.02) | <0.001 |
| ESR (mm/h) | 3.00 (2.00-7.00) | 5.0 (2.0-11.2) | 8.0 (2.0-15.0) | 8.0 (2.50-13.0) | <0.001 |
| Leukocytes (103/mm3) | 6.85 (5.52-8.18) | 6.87 (5.74-8.15) | 6.99 (5.66-8.49) | 7.33 (6.06-8.09) | 0.683 |
| Neutrophil (103/mm3) | 3.43 (2.71-4.80) | 3.67 (3.05-4.79) | 3.96 (3.0-5.0) | 4.27 (3.13-4.77) | 0.132 |
| Lymphocyte (103/mm3) | 2.32 (1.93-2.80) | 2.34 (1.85-2.76) | 2.26 (1.86-2.78) | 2.26 (1.79-2.97) | 0.902 |
| Platelet (103/mm3) | 235 (200-284) | 262 (225-299) | 258 (221-317) | 282 (229-309) | <0.001 |
| PLR* | 98.5 (79.2-130) | 114 (92.2-139) | 116 (94.7-136) | 115 (92.1-146) | 0.002 |
| NLR** | 1.37 (1.12-2.46) | 1.63 (1.35-2.03) | 1.66 (1.28-2.20) | 1.88 (1.25-2.15) | 0.059 |
| SII*** | 297 (249-742) | 434 (344-530) | 425 (323-609) | 462 (341-633) | <0.001 |
Compared to control group p=0.002 (euthyroid HT); p=0.002 (hypothyroid HT) and p=0.011 (NIH), respectively). **Compared to control group (p=0.13 (euthyroid HT); p=0.073 (hypothyroid HT) and p=0.114, (NIH), respectively). ***Compared to control group p<0.001 (for all). HT: Hashimoto’s thyroiditis, NIH: non-immunogenic hypothyroidism, AST: aspartate aminotransferase, ALT: alanine aminotransferase, TSH: thyroid stimulating hormone, TpoAb: thyroid peroxidase antibody, TgAb: thyroglobulin antibody, CRP: C reactive protein, ESR: erythrocyte sedimentation rate, PLR: platelet to lymphocyte ratio, NLR: neutrophil to lymphocyte ratio, SII: systemic inflammation index.
A correlation analysis between thyroid function tests and hemogram-derived inflammatory indices is shown in Table 3. TpoAb levels were positively correlated with SII (r=0.290; p<0.001), PLR (r=0.182; p<0.001), and NLR (r=0.163; p=0.001). Also, TgAb levels correlated with SII and NLR (r=0.170; p=0.026 and r=0.169; p<0.001, respectively). Diagnostic power of hemogram-derived inflammatory indices was assessed by ROC analysis. The results were summarized in Figure 1 and Table 4.
Table 3.
Correlation analysis between thyroid function tests and inflammatory indices derived from hemogram
| TSH | TgAb | TpoAb | fT3 | fT4 | |
|---|---|---|---|---|---|
| SII | r=0.083 | r=0.170 | r=0.290 | r=- 0.107 | r=-0.074 |
| p=0.080 | p=0.026 | p<0.001 | p=0.026 | p=0.122 | |
| PLR | r=0.047 | r=0.087 | r=0.182 | r=- 0.103 | r=-0.051 |
| p=0.320 | p=0.066 | p<0.001 | p=0.031 | p=0.285 | |
| NLR | r=0.074 | r=0.169 | r=0.163 | r=- 0.105 | r=- 0.069 |
| p=0.118 | p<0.001 | p=0.001 | p=0.028 | p=0.148 | |
| CRP | r=0.007 | r=0.076 | r=0.013 | r=- 0.117 | r=- 0.005 |
| p=0.877 | p=0.089 | p=0.766 | p=0.009 | p=0.909 |
TSH: thyroid stimulating hormone, TpoAb: thyroid peroxidase antibody, TgAb: thyroglobulin antibody, CRP: C reactive protein, PLR: platelet to lymphocyte ratio, NLR: neutrophil to lymphocyte ratio, SII: systemic inflammation index.
Figure 1.
ROC curve of hemogram-derived inflammatory indices to indicate presence of inflammation in patients with autoimmune and non-immunogenic hypothyroidism.
Table 4.
ROC analysis for hemogram-derived inflammatory indices in the diagnosis of autoimmune tiroid diseases
| AUC±SD | Cut-off | %95 CI | Sensitivity | Specificity | p | |
|---|---|---|---|---|---|---|
| SII | 0.707±0.033 | 434 | 0.644-0.771 | 59.2 | 69.8 | <0.001 |
| PLR | 0.576±0.038 | 107 | 0.502-0.650 | 54.9 | 55.3 | 0.042 |
| NLR | 0.650±0.037 | 1.60 | 0.577-0.723 | 59.2 | 63.1 | <0.001 |
| PLT | 0.660±0.035 | 266 | 0.592-0.727 | 57.7 | 65.8 | <0.001 |
| NEU | 0.721±0.032 | 3.89 | 0.658-0.784 | 66.2 | 66.8 | <0.001 |
| LYM | 0.533±0.040 | 2.36 | 0.455-0.612 | 52.1 | 52.3 | 0.374 |
| ESR | 0.821±0.028 | 8.5 | 0.767-0.875 | 74.6 | 77.1 | <0.001 |
SII: systemic inflammation index, PLR: platelet to lymphocyte ratio, NLR: neutrophil to lymphocyte ratio, PLT: platelet, Neu: neutrophil, Lym: lymphocyte, ESR: erythrocyte sedimentation rate, CI: confidence interval, AUC: area under curve.
DISCUSSION
In our study, it was concluded that PLR, NLR, and SII values in hypothyroid patients were statistically significant greater than in the control group. There was no difference in these indices between the euthyroid, hypothyroid HT, and NIH subgroups. SII was found to be the most powerful hemogram- based index in detecting the presence of inflammation with the highest specificity. In addition, a positive correlation was found between SII and NLR values and TgAb levels, which is a marker of autoimmunity.
Thyroid diseases, especially hypothyroidism, constitute the most common endocrine disease group in current medical practice. HT stands out as the most prevalent clinical entity in this patient group. In recent years, novel inflammatory markers derived from complete blood count parameters have been the subject of studies with increasing interest. In the meta-analysis and review of 19 articles published by Cao et al., similar to our study, the PLT value was found to be statistically significantly higher in autoimmune thyroid diseases. When it was divided into subgroups according to the disease type and thyroid functions, it was found that there was a significant increase in PLT values only in the hypothyroid-HT groups, whereas there was no difference in the hyperthyroid-Graves’ disease groups (18).
Parallel to our results, in a study from Turkey published in 2023 by Erge et al. that included 68 healthy controls and 128 HT patients, the PLR value was found to be significantly higher in the euthyroid HT and hypothyroid HT patient groups compared to the control group. However, in the same study, unlike our study, a significant difference was also observed between the hypothyroid HT and euthyroid patient subgroups (19). On the other hand, in the study of Onalan et al., the NLR value was reported higher in HT patients, while the PLR value was lower, unlike our study (20).
Several studies have been conducted to investigate the clinical importance of NLR and PLR in patients with HT, the most frequent autoimmune thyroid dysfunction, as well as the prognostic and diagnostic significance of PLR, NLR, and SII in patients with thyroid malignancy (21-24).
He et al.'s retrospective study in patients diagnosed with subacute thyroiditis and Graves' disease, combining 7 parameters originating from hemogram, showed that the combination formula including SII, PLR, and NLR indices could be a new marker for the differential diagnosis of subacute thyroiditis and Graves' disease presenting with thyrotoxicosis. However, it was observed that the indices did not have a significant relationship with clinical results in subacute thyroiditis patients (25).
In the study published by Kırkgoz et al., which evaluated the pediatric patient group, it was found that SII and NLR had no predictive significance, and the PLR value was significantly higher in HT patients (26). According to the results of Arpaci et al.'s research analyzing PLR and NLR values in HT patients, the NLR index was found to be high in the patient group, while the PLR value was found to be low. This contrasting result may be due to the statistically different lymphocyte counts between the patient and control groups. In addition, in the same report, while thyroid antibodies showed an inverse correlation with the PLR, they showed a positive correlation with the NLR (27). In our study, similar to previous reports, SII, PLR, and NLR values and the correlations of these indices with thyroid autoantibody were investigated in hypothyroid patients. SII and PLR results were found to be higher in hypothyroid subgroups compared to healthy controls. While the NLR did not differ between hypothyroidism subgroups, it was found to be higher in all patients group compared to healthy controls. TpoAb, one of the thyroid antibodies, was shown to have a statistically significant correlation with the SII, PLR, and NLR indices. Similarly, TgAb was found to have a linear relationship with SII and NLR.
To the best of our knowledge, our study is the first to evaluate the newly proposed SII, PLR and NLR indices together in adult patients diagnosed with immunogenic and non-immunogenic hypothyroidism and to investigate their diagnostic power in terms of inflammation. However, there are some limitations in our study. Because our study was retrospectively designed, thyroid ultrasonography data were not routinely and adequately obtained from the records, so thyroid function tests and thyroid autoantibodies were utilized in the diagnosis and differential diagnosis of HT. Another limitation is that the study`s retrospective design yielded a simple relationship rather than a causal connection between HT and hemogram indices.
In conclusion, in our study, SII and PLR values were found to be higher in patients with Hashimoto's thyroiditis and non-immunogenic hypothyroidism compared to healthy controls, while NLR were not different between hypothyroidism subgroups. As a result of ROC analysis, SII is the most powerful hemogram-derived parameter for detecting the presence of inflammation in hypothyroid patients. Patients who have abnormalities in these parameters, may have a warning feature to be more careful in terms of possible thyroid disease. Prospectively designed clinical studies with a larger patient population may shed light on determining the clinical significance of these indices.
Conflict of interest
The authors declare that they have no conflict of interest.
References
- 1.Paschou SA, Bletsa E, Stampouloglou PK, Tsigkou V, Valatsou A, Stefanaki K, Kazakou P, Spartalis M, Spartalis E, Oikonomou E, Siasos G. Thyroid disorders and cardiovascular manifestations: an update. Endocrine. 2022;75(3):672–683. doi: 10.1007/s12020-022-02982-4. [DOI] [PubMed] [Google Scholar]
- 2.Schneider SA, Tschaidse L, Reisch N. Thyroid Disorders and Movement Disorders-A Systematic Review. Mov Disord Clin Pract. 2023;10(3):360–368. doi: 10.1002/mdc3.13656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mainetti M, Cozzolino M, Graziani V, Ricciardelli P, Marchetti F. L’encefalopatia di Hashimoto: quando la tiroide… fa sognare Descrizione di un caso clinico pediatrico e revisione della letteratura [Hashimoto's encephalopathy: when the thyroid gland makes you dream. Description of a clinical case and literature review. Recenti Prog Med. 2022;113(4):272–276. doi: 10.1701/3792.37768. [DOI] [PubMed] [Google Scholar]
- 4.Van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, Cassio A, Heinrichs C, Beauloye V, Pohlenz J, Rodien P, Coutant R, Szinnai G, Murray P, Bartés B, Luton D, Salerno M, de Sanctis L, Vigone M, Krude H, Persani L, Polak M. Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021;31(3):387–419. doi: 10.1089/thy.2020.0333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Weetman AP. An update on the pathogenesis of Hashimoto's thyroiditis. J Endocrinol Invest. 2021;44(5):883–890. doi: 10.1007/s40618-020-01477-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ralli M, Angeletti D, Fiore M, D'Aguanno V, Lambiase A, Artico M, de Vincentiis M Greco. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmün Rev. 2020;19(10):102649. doi: 10.1016/j.autrev.2020.102649. [DOI] [PubMed] [Google Scholar]
- 7.Klubo-Gwiezdzinska J, Wartofsky L. Hashimoto thyroiditis: an evidence-based guide to etiology, diagnosis and treatment. Pol Arch Intern Med. 2022;132(3):16222. doi: 10.20452/pamw.16222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Yuan J, Qi S, Zhang X, Lai H, Li X, Xiaoheng C, Li Z, Yao S, Ding Z. Local symptoms of Hashimoto's thyroiditis: A systematic review. Front Endocrinol (Lausanne) 2023;13:1076793. doi: 10.3389/fendo.2022.1076793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Pearce EN, Braverman LE. Environmental pollutants and the thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23(6):801–813. doi: 10.1016/j.beem.2009.06.003. [DOI] [PubMed] [Google Scholar]
- 10.Kim HI, Oh HK, Park SY, Jang HW, Shin MH, Han JM, Bae JC, Kim SW, Kim TH, Chung JH. Non-immüne-related hypothyroidism and its relationship with excess iodine. Eur J Nutr. 2019;58(7):2851–2858. doi: 10.1007/s00394-018-1837-4. [DOI] [PubMed] [Google Scholar]
- 11.Jomrich G, Gruber ES, Winkler D, Hollenstein M, Gnant M, Sahora K, Schindl M. Systemic Immüne-Inflammation Index (SII) Predicts Poor Survival in Pancreatic Cancer Patients Undergoing Resection. J Gastrointest Surg. 2020;24(3):610–618. doi: 10.1007/s11605-019-04187-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Shimizu Y, Ashida R, Sugiura T, Okamura Y, Ito T, Yamamoto Y, Ohgi K, Otsuka S, Notsu A, Uesaka K. Prognostic Impact of Indicators of Systemic Inflammation and the Nutritional Status of Patients with Resected Carcinoma of the Ampulla of Vater: A Single-Center Retrospective Study. World J Surg. 2022;46(1):246–258. doi: 10.1007/s00268-021-06346-3. [DOI] [PubMed] [Google Scholar]
- 13.Bailey-Whyte M, Minas TZ, Dorsey TH, Smith CJ, Loffredo CA, Ambs S. Systemic Inflammation Indices and Association with Prostate Cancer Survival in a Diverse Patient Cohort. Cancers (Basel) 2023;15(6):1869. doi: 10.3390/cancers15061869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Bao Y, Wang L, Du C, Ji Y, Dai Y, Jiang W. Association between Systemic Immune Inflammation Index and Cognitive Impairment after Acute Ischemic Stroke. Brain Sci. 2023;13(3):464. doi: 10.3390/brainsci13030464. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Seo IH, Lee YJ. Usefulness of Complete Blood Count (CBC) to Assess Cardiovascular and Metabolic Diseases in Clinical Settings: A Comprehensive Literature Review. Biomedicines. 2022;10(11):2697. doi: 10.3390/biomedicines10112697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Kurtkulagi O, Tel BMA, Kahveci G, Bilgin S, Duman TT, Ertürk A, Balci B, Aktas G. Hashimoto's thyroiditis is associated with elevated serum uric acid to high density lipoprotein-cholesterol ratio. Rom J Intern Med. 2021;59(4):403–408. doi: 10.2478/rjim-2021-0023. [DOI] [PubMed] [Google Scholar]
- 17.Duman TT, Erge E, Tel BMA, Kiziltunc C, Aktas G. De Ritis score as an inflammatory marker in Hashimoto's thyroiditis. Precision Medical Sciences. 2023;12(4):242–246. [Google Scholar]
- 18.Cao YT, Zhang KY, Sun J, Lou Y, Lv TS, Yang X, Zhang WH, Yu JY, Wu QB, Zhou XQ. Platelet abnormalities in autoimmune thyroid diseases: A systematic review and meta-analysis. Front Immunol. 2022;13:1089469. doi: 10.3389/fimmu.2022.1089469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Erge E, Kiziltunc C, Balci SB, Atak Tel BM, Bilgin S, Duman TT, Aktas G. Novel Inflammatory Marker for the Diagnosis of Hashimoto's Thyroiditis: Platelet-Count-to-Lymphocyte-Count Ratio. Diseases. 2023;11(1):15. doi: 10.3390/diseases11010015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Onalan E, Donder E. Neutrophil and platelet to lymphocyte ratio in patients with hypothyroid Hashimoto's thyroiditis. Acta Biomed. 2020;91(2):310–314. doi: 10.23750/abm.v91i2.8592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Bilge M, Yesilova A, Adas M, Helvaci A. Neutrophil-and Platelet-to Lymphocyte Ratio in Patients with Euthyroid Hashimoto's Thyroiditis. Exp Clin Endocrinol Diabetes. 2019;127(8):545–549. doi: 10.1055/a-0723-3441. [DOI] [PubMed] [Google Scholar]
- 22.Aktas G, Sit M, Dikbas O, Erkol H, Altinordu R, Erkus E, Savli H. Elevated neutrophil-to-lymphocyte ratio in the diagnosis of Hashimoto's thyroiditis. Rev Assoc Med Bras 1992. 2017;63(12):1065–1068. doi: 10.1590/1806-9282.63.12.1065. [DOI] [PubMed] [Google Scholar]
- 23.Figueiredo AA, Esteves S, Moura MM, Marques P, Simões-Pereira J, Leite V. Preoperative serum inflammation-based scores in medullary thyroid cancer. Endocrinol Diabetes Nutr (Engl Ed) 2023;70(1):48–55. doi: 10.1016/j.endien.2022.06.015. [DOI] [PubMed] [Google Scholar]
- 24.Zhang Z, Xia F, Wang W, Huang Y, Li X. The systemic immune-inflammation index-based model is an effective biomarker on predicting central lymph node metastasis in clinically nodal-negative papillary thyroid carcinoma. Gland Surg. 2021;10(4):1368–1373. doi: 10.21037/gs-20-666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.He P, Yang H, Lai Q, Kuang Y, Huang Z, Liang X, Huang H, Qin Y, Luo Z. The diagnostic value of blood cell-derived indexes in subacute thyroiditis patients with thyrotoxicosis: a retrospective study. Ann Transl Med. 2022;10(6):322. doi: 10.21037/atm-22-719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Kirkgoz T, Ozkan B. Could Hematologic Parameters Have a Predictive Role in Pediatric Hashimoto thyroiditis? Izmir Dr Behcet Uz Cocuk Hastanesi Dergisi. 2022;12(2):159–163. [Google Scholar]
- 27.Arpaci D, Gurol G, Ergenc H, Yazar H, Tocoglu AG, Ciftci IH, Tamer A. A controversial New Approach to Address Hematological Parameters in Hashimoto's Thyroiditis. Clin Lab. 2016;62(7):1225–1231. doi: 10.7754/Clin.Lab.2015.150927. [DOI] [PubMed] [Google Scholar]