Lipid Metabolism in Pregnancy Women with Hypothyroidism and Potential Influence on Pregnancy Outcome.

Thyroid hormone (TH) is essential for maintaining normal physiological processes during pregnancy, including the metabolism of energy materials in both the mother and fetus and the growth and development of fetal bone and nervous system. TH can act on the liver, fat, and other tissues and organs to participate in lipid synthesis and breakdown through multiple pathways. Consequently, abnormal thyroid function is often accompanied by lipid metabolism disorders. Both clinical and subclinical hypothyroidism, as well as dyslipidemia during pregnancy, have been shown to be associated with an increased risk of multiple adverse pregnancy outcomes. Recently, there has been an increased interest in studying the alteration of lipidomic and hypothyroidism (both clinical and subclinical hypothyroidism) during pregnancy. Studies have suggested that altered lipid molecules might be used as potential biomarker and associated with adverse maternal and neonatal outcome. Thus, we summarized the associations between lipid metabolism and clinical or subclinical hypothyroidism during pregnancy in this review. Then, we discussed the underlying mechanisms of thyroid dysfunction and lipid metabolism. In addition, we reviewed the possible effect of dyslipidemia on pregnancy and neonatal outcome. However, the relationship between hypothyroidism during pregnancy and changes in the lipid profile and how to intervene in the occurrence and development of adverse pregnancy outcomes require further study.

First trimester sCD40L levels associated with adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.

Backgrounds: It remained unclear whether isolated positive thyroid peroxidative antibodies (TPOAb) were associated with adverse maternal and neonatal outcomes. The purpose of this study was to observe adverse neonatal outcomes among euthyroid pregnant women with positive TPOAb and to investigate the underlying risk factors. Methods: Euthyroid pregnant women with TPOAb positivity were enrolled and followed up in our study. Adverse neonatal outcomes such as preterm birth, low birth weight, and fetal macrosomia were observed. Clinical data in the first trimester were collected and compared between groups with or without adverse neonatal outcomes. Maternal serum soluble CD40 ligand (sCD40L) was also measured at the same time. Results: A total of 176 euthyroid pregnant women with TPOAb positivity were finally enrolled and analyzed in our study. Thirty-nine (22.16%) euthyroid women with TPOAb positivity were found to have adverse neonatal outcomes. Thirteen participants received assisted reproductive technology (ART) in our study, and seven participants were in the adverse neonatal outcome group. Preterm birth, low birth weight, and fetal macrosomia were the most common comorbidities. The proportion of receiving ART and the levels of sCD40L and platelet were significantly higher in the adverse neonatal outcome group (all P < 0.05). Multivariate regression analysis showed that sCD40L and receiving ART were the independent risk factors for adverse neonatal outcomes. The odds ratio values of sCD40L higher than 5.625 ng/ml were 2.386 [95% confidence interval (CI) = 1.017 to 5.595; P = 0.046] for overall adverse neonatal outcome, 3.900 (95% CI = 1.194 to 12.738; P = 0.024) for preterm birth, and 3.149 (95% CI = 0.982 to 10.101; P = 0.054) for low birth weight. Conclusions: Approximately one of the four euthyroid women with TPOAb positivity might have adverse neonatal outcomes. Measurement of sCD40L in first trimester might have a predictive value for adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.

Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis.

Background: In recent years, a large amount of clinical evidence and animal experiments have demonstrated the unique advantages of mineralocorticoid receptor antagonists (MRA) for treating chronic kidney disease (CKD). Aims: Accordingly, the present study aimed to systematically assess the second-generation selective MRAs eplerenone's safety and effectiveness for treating CKD. Methods: Four databases (PubMed, The Cochrane Library, Embase, and Web of Science) were searched for randomized controlled trials (RCT) correlated with eplerenone for treating CKD up to September 21, 2022. By complying with the inclusion and exclusion criteria, literature screening, and data extraction were conducted. Results: A total of 19 randomized controlled articles involving 4501 cases were covered. As suggested from the meta-analysis, significant differences were reported with the 24-h urine protein (MD = -42.23, 95% confidence interval [CI] = -76.72 to -7.73, P = 0.02), urinary albumin-creatinine ratio (UACR) (MD = -23.57, 95% CI = -29.28 to -17.86, P < 0.00001), the systolic blood pressure (SBP) (MD = -2.73, 95% CI = -4.86 to -0.59, P = 0.01), and eGFR (MD = -1.56, 95% CI = -2.78 to -0.34, P = 0.01) in the subgroup of eplerenone vs placebo. The subgroups of eplerenone vs placebo (MD = 0.13, 95% CI = 0.07 to 0.18, P < 0.00001) and eplerenone vs thiazide diuretic (MD = 0.18, 95% CI = 0.13 to 0.23, P < 0.00001) showed the significantly increased potassium levels. However, no statistical significance was reported between the eplerenone treatment groups and the control in the effect exerted by serum creatinine (MD=0.03, 95% CI = -0.01 to 0.07, P = 0.12) and diastolic blood pressure (DBP) (MD = 0.11, 95% CI = -0.41 to 0.63, P = 0.68). Furthermore, significant risks of hyperkalemia were reported in the eplerenone group (K+ ≥ 5.5 mmol/l, RR = 1.70, 95%CI = 1.35 to 2.13, P=<0.00001; K+≥6.0 mmol/l, RR = 1.61, 95% CIs = 1.06 to 2.44, P = 0.02), respectively. Conclusions: Eplerenone has beneficial effects on CKD by reducing urinary protein and the systolic blood pressure, but it also elevates the risk of hyperkalemia.

DRESS/DiHS syndrome induced by Propylthiouracil: a case report.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome. CASE PRESENTATION: A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later. CONCLUSIONS: Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.

sCD40L Is Increased and Associated with the Risk of Gestational Diabetes Mellitus in Pregnant Women with Isolated TPOAb Positivity.

Background: Autoimmune disorders are associated with gestational diabetes mellitus (GDM) in pregnant women who were positive for thyroid peroxidase antibody (TPOAb). Soluble CD40 ligand (sCD40L) and soluble interleukin-2 receptor (sCD25) are abnormally expressed in autoimmune diseases and are reliable markers of inflammation. The purpose of this study was to evaluate sCD40L and sCD25 in early pregnancy and investigate their correlation with GDM and TPOAb. Methods: A total of 126 pregnant women in the first trimester were enrolled for analysis: 93 were positive for TPOAb and 33 were negative for TPOAb. Demographical and clinical data in early pregnancy were collected. A total of 123 participants underwent a 75 g oral glucose tolerance test in the second trimester. Serum sCD40L and sCD25 levels were measured by ELISA. Results: The incidence of GDM was 24.4% in pregnant women with isolated TPOAb positivity in our study. Both sCD40L and sCD25 were positively correlated with TPOAb (r = 0.476, P < 0.001; r = 0.188, P < 0.05). sCD40L was highest in (P < 0.001) Ab-positive women with GDM group (P < 0.05). After adjusting for TPOAb, age, TSH, FT4, triglycerides, and low-density lipoprotein cholesterol, multivariate logistic regression analysis showed that sCD40L was an independent risk factor for GDM in pregnant women with TPOAb positivity (odds ratio = 3.235, 95% confidence interval 1.024-10.218, P < 0.05). Conclusions: About a quarter of pregnant women with isolated positive TPOAb might have GDM. sCD40L was an independent risk factor for GDM in women with isolated TPOAb positivity.

Efficacy and safety of eplerenone treatment for patients with diabetic nephropathy: A meta-analysis.

Diabetic nephropathy (DN), which is correlated with an increased risk of cardiovascular disease, significantly elevates the morbidity and mortality of patients with diabetes. Recently, the benefits of mineralocorticoid receptor antagonists in chronic kidney disease (CKD), such as their anti-inflammatory and anti-fibrotic properties, have been discovered. Thus, the present meta-analysis aimed to systematically assess the efficacy and safety of eplerenone treatment in patients with DN. Six electronic databases-PubMed, The Cochrane Library, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), and CBM(Chinese BioMedical Literature Database)-were searched to retrieve randomized controlled trials that assessed eplerenone treatment in patients with DN and were published up to July 31, 2021. Eight randomized controlled trials involving 838 patients were included. Between the eplerenone treatment groups and controls, significant differences were identified in 24-h urine protein levels (mean difference [MD], -19.63 [95% CI, -23.73 to -15.53], P < 0.00001), microalbuminuria (MD, -7.75 [95% CI, -9.75 to -5.75], P < 0.00001), urinary albumin-creatinine ratio (MD, -48.29 [95% CI, -64.45 to -32.14], P < 0.00001), systolic blood pressure (SBP) (MD, -2.49 [95% CI, -4.48 to -0.50], P = 0.01), serum potassium levels (MD, 0.19 [95% CI, 0.13 to 0.24], P < 0.00001), and levels of the renal fibrosis indicator laminin (MD, -8.84 [95% CI, -11.93 to -5.75], P < 0.00001). However, for the effect of estimated glomerular filtration rate (MD, 1.74 [95% CI, -0.87 to 4.35], P = 0.19) and diastolic blood pressure (MD, -0.51 [95% CI, -1.58 to 0.57], P = 0.36), the differences between the two groups were not significant. In addition, no noticeable difference was identified in the adverse events of hyperkalemia and cough between them. These findings suggest that eplerenone exerts beneficial effects on DN by significantly reducing urinary albumin or protein excretion, SBP, and laminin levels, without increasing the incidence of hyperkalemia and other adverse events.

[High expression of ICOS on CD4+ T cells and ICOSL on CD19+ B cells in peripheral blood and its positive correlation with TRAb in Graves' disease].

Objective To detect the expression of inducible co-stimulator and inducible co-stimulator ligand (ICOS/ICOSL) on peripheral lymphocytes in patients with Graves' disease (GD) and its clinical significance. Methods A total of 105 untreated GD patients and 67 healthy controls were enrolled in our study. 19 GD patients treated with anti-thyroid drugs were followed up in the outpatient department until TRAb were negative. The peripheral blood mononuclear cells (PBMCs) were separated and analyzed with PCR. ICOS expression on CD4+/CD8+ T cells and ICOSL expression on CD19+ B cells were detected by flow cytometry. The correlations between the expression of ICOS/ICOSL with thyroid parameters and TRAb were analyzed. Results The expression of both ICOS and ICOSL mRNA in PBMCs of the untreated GD patients were significantly higher than those in the healthy controls. Compared with healthy controls, ICOS expression on CD4+ T cells and ICOSL expression on CD19+ B cells were up-regulated significantly in the GD patients. Correlation analysis showed that ICOS expression on CD4+ T cells was positively correlated with the level of free triiodothyronine (FT3) in the GD patients. In the group of GD patients with high TRAb titers in serum, ICOSL expression on CD19+ B cells notably increased as compared with that in the patients with low TRAb. ICOS expression on CD4+ T cells and ICOSL expression on CD19+ B cells were recovered in the GD patients with negative TRAb. Conclusion The expression of ICOS on the surface of CD4+ T cells and ICOSL on CD19+ B cells in peripheral blood of patients with Graves's disease are significantly increased.With the decrease of TRAb level, the expression levels of ICOS on the surface of CD4+ T cells and ICOSL on CD19+ B cells are restored.