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| Receiver operating characteristic (ROC) curve for the discrimination of patients with Graves' disease from healthy controls and patients with subacute thyroiditis. *The detailed indicator combination formula is presented in the text. Eo, eosinophils; fT 3 , free triiodothyronine; fT 4 , free thyroxine; Mo, monocytes.
Source publication
Background: Thyrotoxicosis is commonly classified into several entities according to different etiologies. Identifying the causes of thyroid dysfunction is critical for the subsequent selection of treatment. The free triiodothyronine to free thyroxine ratio (fT3/fT4) is widely used but is still a controversial diagnostic measurement. Methods: A tot...
Context in source publication
Context 1
... obtain the optimal diagnostic cut-off value of all proposed indexes, ROC curve analysis of all untreated thyrotoxicosis patients and healthy control population were performed as shown in Figure 1. Among four individual indexes (Mo, Eo, fT 3 , and fT 4 ), fT 3 with an optimal cut-off at 10.770 showed the highest sensitivity and specificity of 82.56 and 76.19%, respectively. ...
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Objective
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Methods
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Citations
... An unexpected finding was the significant decrease in eosinophils in the TT group. There is some evidence suggesting that the eosinophil count and eosinophil/monocyte indices can serve as an alternative marker to differentiate between DT and autoimmune hyperthyroidism (36,37). More specifically, an elevated eosinophil level is associated with Graves' disease while a low eosinophil/monocyte index ratio suggests DT. ...
Background
Immune-related endocrinopathies are common after immune checkpoint inhibitor (ICI) therapy, among which destructive thyroiditis is the most prevalent. Improved survival outcomes have been associated with immune-related adverse events. We aimed to compare the clinical course and biochemical parameters of two subtypes of ICI-related destructive thyroiditis: a transient thyrotoxicosis that reverts to either euthyroidism (TT; transient thyroiditis) versus progression to permanent hypothyroidism (PH), and to identify prognostic markers in cancer patients receiving ICI therapy who developed DT.
Methods
This retrospective observational study included 124 patients who developed a transient thyrotoxicosis due to a destructive thyroiditis after ICI therapy from January 1, 2016 to April 30, 2021 at the Montefiore Medical Center. Patients were categorized as either TT or PH based on spontaneous renormalization of the TSH or the permanent need for thyroid hormone replacement, respectively. Thyroid hormone and antibody levels, serum inflammatory markers, eosinophils, and metabolic uptake of the thyroid on PET imaging, each corresponding closest to a suppressed TSH, were characterized. Survival from TT and PH were also analyzed.
Results
Of the 124 patients, 53 developed PH and 71 developed TT. The PH group developed thyrotoxicosis at a median of 42 days from the first ICI dose while the TT group took significantly longer at 56 days. Thyroidal PET uptake was increased in 18.9% of the PH group versus 6.0% of the TT group (P=0.04). Three different survival models consistently demonstrated a trend towards increased survival in the PH group, compared to the TT group.
Conclusion
Our results suggest that PH developing after ICI-induced destructive thyroiditis may be associated with a more robust inflammatory and antitumor response to ICI therapy. The results suggests that PH may be a potential clinical predictor of improved survival.
... In that study, individuals with GD and SAT were grouped into 2 as moderate and severe. MER was elevated in the severe GD group compared to moderate GD study population, but the statistical significance has not been revealed [21]. Additionally monocyte and eosinophil concentrations of patients with moderate and severe course were not identified in their study leading to the fact that it is not clear whether the MER was high in severe GD due to high monocyte or low eosinophil levels. ...
Prognostic parameters are crucial in the choice of treatment in Graves' disease (GD), thus,these parameters may not be easily achievable in all situations. However hematological parameters is important in inflammation and easy to obtain. In this study we aimed to elucidate whether these parameters could determine the prognosis in patients with Graves Disease. This retrospective analysis consisted of 114 individuals with a diagnosed with GD. The enrolled patients were treated with anti-thyroid drugs for an average of 14 months and the mean follow-up period after treatment discontinuation was 17.4 months. After the follow-up period subjects have been segmented to 2 groups as: Group 1 relapsed (n:61) and Group 2 non-relapsed (n:53). The neutrophil to lymphocyte ratio (NLR) of the relapsing individual was statistically significantly higher compared to other group, while the eosinophil to monocytes ratio (EMR) was lower. In the multiregression analysis, both parameters were found to be independent risk factors in predicting relapse [(OR=3.1, p:0.026 for NLR) (OR=1.5, p<0.001 for EMR)]. In addition, a value of 0.17 EMR had 70% sensitivity and 80% specificity in determining recurrence. EMR was found to be an independent predictor of prognosis with high specificity. The calculation of EMR before initiating treatment could provide beneficial outcomes for the choice of treatment in patients with GD.
... We believe that the monocyte elevation is correlated with the monocyte/macrophage stimulation seen in SAT. Similarly, the monocyte-eosinophil ratio (Mo/Eo) combined with fT3 to fT4 ratio (fT4/fT3) has been suggested as a potentially useful parameter in SAT [11]. As expected, we found the classical inflammatory markers, ESR and CRP, higher in our patients than in the control group. ...
Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid gland. Although its etiology is not fully understood, it is believed to occur shortly after viral infections and is mostly associated with human leukocyte antigen (HLA)-B*35. Cellular immunity is prominent in SAT. Neopterin is produced by activated monocytes/macrophages and is a marker of cellular immunity. Its production is stimulated by interferon gamma (IFN-γ), provided mainly by activated helper T lymphocytes type 1 (Th1) in the adaptive immune system. Therefore, with these cells’ activation, an increase in serum neopterin levels is expected. We aimed to evaluate neopterin levels in demonstrating cellular immunity in SAT and compared 15 SAT patients with 16 healthy controls. Since all SAT patients were in the active thyrotoxic phase, we found a significant difference in thyroid functions, classical inflammatory markers, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were markedly elevated in the patient group. Although we expected to find an increase considering that cellular immunity is at the forefront in the pathogenesis of SAT, we found serum neopterin levels significantly lower in the patient group than in the control group. There is an increase in CD8+ T cells in the thyroid tissue in SAT. The possible relationship with HLA-B*35- MHC class I in SAT, and the antigen presentation to CD8+ T cells may be the reason why we observed low serum neopterin levels in patients due to the cytokine imbalance. Neopterin provides unique and independent data from classical acute phase response indicators.
... Many authors analyzed the usefulness of several surrogate markers based on simple blood count analysis. The potential usefulness of such parameters as platelet-lymphocyte ratio (PLR) [39][40][41][42], monocyte-eosinophil ratio (Mo/Eo) combined with free triiodothyronine (FT3) to free thyroxine (FT4) ratio (FT4/FT3) [43], neutrophil-lymphocyte ratio (NLR) [39,41,42] has been postulated. Taşkaldiran et al. observed that in Turkish patients with SAT, PLR and NLR were significantly higher than in patients with GD, thyroid adenomas or in healthy control groups [39]. ...
... Taking into account the discrepancies in the obtained results, we can conclude that NRL and PLR can be useful in differential diagnosis of SAT and GD and in the follow up of SAT treatment, but currently no universal cut-off value can be unequivocally recommended. Hu et al. evaluated other potential markers and reported that Mo/Eo and FT4/FT3 ratios were significantly higher in SAT than in GD, and the cut-off values for fT4/fT3, Mo/Eo ratios and Mo/ Eo ratio + fT4/fT3 for diagnosing GD were ≤ 2.841, ≤ 8.813 and > 0.644, respectively [43]. Although still no universal cutoff values of the proposed markers can be recommended for general population, such surrogate tools might be helpful in the initial differential diagnosis of SAT in resource-limited settings. ...
Subacute thyroiditis (SAT) is a thyroid inflammatory disease, whose pathogenesis and determinants of the clinical course were unclear for many decades. The last few years have brought many clinically significant new data on the epidemiology, pathogenesis and management of SAT. Several human leukocyte antigen (HLA) alleles were demonstrated not only to increase the risk of SAT, but also to correlate with SAT clinical course and determine the risk of recurrence. The world-wide epidemic of the coronavirus disease 19 (COVID-19) has provided new observations that the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can be a potent SAT-triggering factor, and that the clinical course of SAT in patients affected by COVID-19 is different from a typical one. Additionally, many new trends in the clinical course are emerging. In the last years, painless course of SAT is more and more often described, constituting a special challenge in patients hospitalized due to COVID-19. Despite an excellent availability of diagnostic methods, several difficulties in SAT differential diagnosis can be currently encountered and the proper diagnosis and treatment is frequently delayed. False positive diagnoses of SAT in patients with malignancies of poor prognosis constitute a life-threatening problem. Taking into account all the new aspects of SAT pathogenesis and of its clinical course, the new – modified – SAT diagnosis criteria have been proposed.
... Additionally, we found that an MLR of o0.21 could discriminate distant metastasis from lymph node metastasis, with a sensibility of 80% and an accuracy of 58%. A small number of studies have demonstrated the relationship between these ratios and benign thyroid diseases such as Graves' disease (GD), Hashimoto's thyroiditis (HT), toxic adenoma (TA), and subacute thyroiditis (SAT) (26)(27)(28)(29)(30). Hu et al. (28) proposed combining thyroid hormones (free thyroxine and triiodothyronine) and the eosinophil-to-monocyte ratio to distinguish GD from SAT. Taskaldiran et al. (30) retrospectively analyzed NLR and PLR in patients with GD, SAT, and TA and suggested that high PLR and NLR may be useful in differentiating SAT from GD and TA. ...
... Additionally, we found that an MLR of o0.21 could discriminate distant metastasis from lymph node metastasis, with a sensibility of 80% and an accuracy of 58%. A small number of studies have demonstrated the relationship between these ratios and benign thyroid diseases such as Graves' disease (GD), Hashimoto's thyroiditis (HT), toxic adenoma (TA), and subacute thyroiditis (SAT) (26)(27)(28)(29)(30). Hu et al. (28) proposed combining thyroid hormones (free thyroxine and triiodothyronine) and the eosinophil-to-monocyte ratio to distinguish GD from SAT. Taskaldiran et al. (30) retrospectively analyzed NLR and PLR in patients with GD, SAT, and TA and suggested that high PLR and NLR may be useful in differentiating SAT from GD and TA. Another interesting retrospective study performed by Kim et al. (29) reported that elevated NLR was an independent prognostic factor for relapse in patients with GD. ...
Objective:
This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC).
Methods:
This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively.
Results:
PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity).
Conclusion:
Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.
... RAIU is also contraindicated during pregnancy, breastfeeding, or after recent iodine exposure (1). Thyroid stimulating hormone (TSH) receptor antibodies (TRAb) is useful for diagnosis of GD but is negative in some GD patients (7). Therefore, it is necessary to find a reliable alternative biomarker that can quickly clarify the 2 types of thyrotoxicosis. ...
Background:
Both subacute thyroiditis (SAT) and Graves' disease (GD) can lead to thyrotoxicosis, but the methods to distinguish these two diseases are relatively complex. Therefore, it is necessary to find biomarkers which can quickly and efficiently identify the two kinds of thyrotoxicosis. Blood cell-derived indexes are widely used to evaluate systemic inflammation. We aimed to evaluate the diagnostic value of blood cell-derived indexes in SAT patients with thyrotoxicosis.
Methods:
Totally 139 SAT patients with thyrotoxicosis, 146 GD patients, and 100 euthyroid individuals were enrolled in the study. Complete blood cell (CBC) count, thyroid function, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), aggregate inflammation systemic index (AISI), and mean platelet volume to platelet ratio (MPR) were evaluated in all subjects. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the capacity of blood cell-derived indexes in differentiating SAT patients with thyrotoxicosis from GD patients. We also evaluated the association between blood cell-derived indexes and other laboratory indicators and clinical outcomes in SAT patients.
Results:
NLR, PLR, MLR, SII, SIRI, and AISI were significantly higher in the SAT group. MPR was significantly lower in the SAT group. A formula including NLR, PLR, MLR, SII, SIRI, AISI and MPR was developed. The combination formula with an optimal cutoff of 0.426 showed the better diagnostic value [area under the curve (AUC) =0.921; 95% confidence interval (CI): 0.891-0.950; P<0.001; sensitivity, 87.1%; specificity, 83.6%]. However, thyroid function, erythrocyte sedimentation rate (ESR), thyroid peroxidase antibodies (TPOAb), and blood cell-derived indexes, were not found to be significantly associated with hypothyroidism and recurrence.
Conclusions:
We developed a formula combining 7 blood cell-derived indexes. The combination formula could be a novel biomarker to distinguish SAT patients with thyrotoxicosis from GD patients. However, we did not find significant association between the blood cell-derived indexes and clinical outcomes in SAT patients.
... In accordance to previous data, we proved that there were no statistically significant differences in basophil and eosinophil counts in GD patients with and without GO compared to controls [44,48]. Some reports suggested increased percentage of eosinophil in peripheral blood in GD patients compared to healthy individuals, but it might be associated with concomitant Th-2-predominant disorders [48][49][50]. ...
... In accordance to previous data, we proved that there were no statistically significant differences in basophil and eosinophil counts in GD patients with and without GO compared to controls [44,48]. Some reports suggested increased percentage of eosinophil in peripheral blood in GD patients compared to healthy individuals, but it might be associated with concomitant Th-2-predominant disorders [48][49][50]. ...
Graves’ orbitopathy (GO) is an autoimmune disease with a chronic inflammatory background. Smoking behavior is the main environmental factor responsible for the transition of this major extra thyroidal manifestation of Graves’ disease (GD) from the subclinical to the overt form. Complete blood count-derived parameters are suggested to be novel inflammatory indices. The aim of this retrospective study was to investigate the association between neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte ratios (PLR) with selected clinical parameters and smoking status in 406 GD patients with (n = 168) and without GO (n = 238). The control group consisted of 100 healthy individuals. The activity of GO was graded according to Clinical Activity Score. Significantly higher white blood cells (WBC), neutrophil, and NLR (p < 0.05) values were observed in GD patients with GO compared with those without GO. PLR values were significantly higher in GO patients than in the controls. WBC (6.81 ± 1.56 vs. 5.70 ± 1.23) and neutrophils (3.89 ± 1.06 vs. 3.15 ± 0.95) count was higher in active GO patients than in those with inactive GO. Positive correlation (p < 0.05) between CAS score and WBC, neutrophil and monocyte count, and NLR was found. Smoking was associated with higher WBC (p = 0.040), neutrophil (p = 0.049), PLR (p = 0.032) values. Multivariate analysis revealed that WBC, NLR may be risk factors for GO development. WBC, neutrophil, NLR and PLR values seem to be useful tools in the assessment of inflammation in GD.
Purpose
This study aims to show the relationship between neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR), with clinicopathological characteristics in patients with differentiated thyroid cancer (DTC).
Methods
This is a retrospective study involving 390 DTC patients who had complete blood cell count available at the time of the surgery. NLR, PLR, and MLR were calculated, risk of cancer-related death, structural recurrence, and response to therapy were assessed by the 8th edition of the tumor-node-metastasis (TNM), American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively.
Results
PLR was higher in distant metastasis (133.15±43.95 vs 119.24±45.69, p = 0.0345), lower in disease-free versus persistent disease or death (117.72±44.70 vs 131.07±47.85, p = 0.0089). In MLR, patients ≥55 had a higher score than < 55 years old (0.26±0.10 vs 0.24±0.12, p = 0.0379). Higher MLR (OR 8.775; 95% CI = 1.532–50.273; p = 0.0147), intermediate (OR 4.892; 95% CI = 2.492–9.605; p ≤ 0.0001) and high ATA risks (OR 5.998; 95% CI = 3.126–11.505; p ≤ 0.0001) were risk factors associated with active disease. NLR was not significant. ROC curve cut-off values for NLR, PLR, and MLR were able to discriminate distant from lymph node metastasis (NLR > 1.93 sensitivity 73.3%, specificity 58.7%; PLR > 124.34 sensitivity 86.7%, specificity 69.2%; MLR > 0.21 sensitivity 80%, specificity 45.2%).
Conclusion
Cut-off values of NLR, PLR, and MLR discriminated the presence of distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was an associated factor with disease-free status and higher in DTC patients with distant metastasis, persistency, and disease-related death. MLR was a risk factor of active disease.
