Relationship Between Leukopenia and Intercellular Adhesion Molecules in Graves’ Disease

Gao, Yue; Hj, Shen; Zhou, Ping; Hu, Howard; Tang, Jih-Luh; Ll, Peng; Ji, Tong

doi:10.7727/wimj.2013.113

Cited by 6 publications

(10 citation statements)

References 21 publications

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“…Only one study 11 reported that morning ANCs were repeated in several instances. Preexisting diseases (ie infections, cancer, haematological or rheumatological disorders) or the use of drugs (including iron and methotrexate) potentially influencing the development of neutropenia were reported in some studies 10,12,13,18,20‐24 as exclusion criteria of hyperthyroid patients. Smoking habits were explored in only two studies 10,13 .…”

Section: Resultsmentioning

confidence: 99%

“…Neutropenia (ANC < 1.8 × 10 9 /L) was found in 103 cases who were all affected by hyperthyroidism due to Graves’ disease. In the study by Gao et al, 24 the cut‐off to define neutropenia was 1.5x10 9 /L.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, RAI therapy resolved both Graves’ hyperthyroidism and neutropenia 11,12,23 . Instead, Gao et al 24 surprisingly obtained the resolution of neutropenia by using prednisone in 32 hyperthyroid patients; however, these authors did not state if the glucocorticoid treatment was able to lead to resolution of the hyperthyroid state. Therefore, all neutropenic patients under ATD therapy did not have a worsening of their baseline ANC values neither developed agranulocytosis.…”

Section: Resultsmentioning

confidence: 99%

“…Another mechanism could consist of an immune‐mediated shortened survival of peripheral neutrophils: interestingly, the study by Weitzman et al 32 provided evidence that TRAb, in addition to the 'conventional' antineutrophil antibodies, could bind the neutrophil TSH receptor so that they could mediate the low ANC in some GD patients. Yet, the reduction in circulating neutrophils could be due to abnormal distribution and margination 24 . In particular, Gao et al 24 postulated that Graves’ disease caused an increase in the level of adhesion molecules (ie E‐selectin) with subsequent higher distribution of leucocytes at the edge of the pool.…”

Section: Discussionmentioning

confidence: 99%

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Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis

Scappaticcio

Maiorino

Maio

et al. 2020

Clinical Endocrinology

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Background and Objective Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new‐onset hyperthyroidism. The aim of this systematic review and meta‐analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting. Methods A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non‐English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta‐analysis was performed with DerSimonian and Laird method (random‐effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I2 statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two‐sided P‐value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included. Results The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta‐analysis. Results of the meta‐analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves’ hyperthyroidism was 10% (CI 5%‐19%, I2 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 109/L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable. Conclusions Graves’ disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis

Scappaticcio

Maiorino

Maio

et al. 2020

Clinical Endocrinology

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“…Graves disease is often associated with leukopenia, mainly agranulocytosis and the speci c mechanisms thought to be involved includes marrow depression, anti-neutrophil antibodies etc. [28] It has been suggested that a cross antigenicity between TSH receptors and polynuclear neutrophils, a decreased circulating time of granulocytes and reduced marrow granulocyte reserve are the causes of neutropenia in thyrotoxicosis. [29,30] However, these still remain controversial .When slight leucopenia, neutropenia and thrombocytopenia are common manifestations of Graves disease even in untreated cases and believed to be an autoimmune process, use of anti-thyroid medications mainly Thiamazole could cause serious life-threatening agranulocytosis.…”

Section: Discussionmentioning

confidence: 99%

Ophthalmopathy and other influential factors for liver abnormalities in patients with Graves’ disease

Pudasaini

Yang

Ma³

2020

Preprint

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Background - Abnormal liver function tests (LFTs) is a common phenomenon in patients having Grave’s disease that tends to affect the treatment choice. Only few data on factors and biochemical indexes that contributes to such abnormalities in Graves patients are documented till date. Objective - The objective of this study was to explain the potent factors including ophthalmopathy for hepatic dysfunction evoked by Grave's disease alone. Method - A cohort of 263 patients who were newly diagnosed and untreated for Grave’s disease were studied. Clinical characteristics and all the biochemical values were collected and further analysis was done. These patients were further divided into two groups: group A with abnormal LFTs and group B with normal LFTs. Data were analyzed by using tests like the independent samples t- tests, chi-square tests and logistic regression tests. Result - Among them, 175(66.53%) were found to have at least one LFT abnormality. The frequencies of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γ-GGT), total bilirubin (TBIL) and direct bilirubin (DBIL) were 54.9% (96/175), 29.7% (52/175), 29.7% (52/175), 38.3% (67/175), 33.1% (58/175) and 34.3% (60/175) respectively of which ALT was the commonest abnormality In the univariate analysis, group A patients had higher FT3 and FT4 than group B while group B had higher white blood cells (WBC) count mainly granulocyte % and ophthalmopathy than group A. Results of multivariate logistic regression identified FT3 and ophthalmopathy as independent factors predicting abnormal LFTs [odds ratio (OR) = 1.062, 95% confidence interval (CI) = 1.028–1.096 and OR = 0.355, 95% CI = 0.195–0.647 respectively] . Conclusion - While FT3 value > 5.70 pmol/L showed consistent association with liver function abnormality in patients with Graves, in contrast, ophthalmopathy showed inverse association with liver function abnormalities.

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Association between radioactive iodine uptake and neutropenia in untreated Graves’ disease

Yang

Pan

et al. 2023

Endocrine Connections

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Objective: Neutropenia is a complication of Graves' disease (GD) but there is currently no means by which to predict its occurrence. This study aimed to investigate the risk factors for development of neutropenia in untreated GD. Methods: This was a retrospective cohort study. Between January 1, 2010, and July 31, 2020, 1000 patients with new-onset or relapsing GD without treatment were enrolled in the study and divided into two groups: neutropenia group (neutrophil count <2×109/L) and non-neutropenia group (neutrophil count ≥2×109/L). Clinical characteristics of subjects were compared between the two groups and logistic regression analysis applied to determine risk factors for neutropenia. To further explore the correlation of radioactive iodine uptake(RAIU) with neutropenia, subjects were first classified according to quartile of 3hRAIU and 24hRAIU prior to logistic regression analysis. Results: Of all patients recruited, 293 (29.6%) were diagnosed with neutropenia. Compared with non-neutropenic patients, those with neutropenia had a higher level of free thyroxine (FT4) (56.64±31.80 vs. 47.64±39.64, P=0.001), 3hRAIU (55.64±17.04 vs. 49.80±17.21, P<0.001;) and 24hRAIU (67.38±12.54 vs. 64.38±13.58, P<0.001). Univariate logistic regression analysis revealed that FT4、3hRAIU、24hRAIU、creatinine (Cr) and low density lipoprotein (LDL) were risk factors for development of neutropenia in Graves' disease. After adjusting for confounding factors of age, BMI, and sex, we determined that 3hRAIU and 24hRAIU (Model 1: OR=1.021,95%CI 1.008-1.033,P=0.001; Model2: OR=1.023, 95%CI 1.007-1.039,P=0.004), but not FT4, were associated with development of neutropenia. Conclusions: RAIU is associated with neutropenia in patients with untreated Graves' disease.

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Relationship Between Leukopenia and Intercellular Adhesion Molecules in Graves’ Disease

Abstract: Objective: Changes in soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin levels as well as leukocyte count were examined in this study to explore the relationship between leukopenia and ICAMs in Graves' disease (GD)

Cited by 6 publications

References 21 publications

Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis

Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis

Ophthalmopathy and other influential factors for liver abnormalities in patients with Graves’ disease

Association between radioactive iodine uptake and neutropenia in untreated Graves’ disease

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