Progression To Hypothyroidism Research Articles

Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study.

Multiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism. To investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran's Q statistics were utilized to gauge the heterogeneity of the instrumental variables. The results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74-0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01-1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88-0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81-0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02-1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01-1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84-0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy. The findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.

A Feedback Loop Involving Exosomal miR-146a and NG2 to Propel the Development and Progression of Hypothyroidism.

Background: Thyrotropin receptor (TSHR) plays a central role in maintaining thyroid function and TSHR impairment causes hypothyroidism, which is often associated with metabolic disarrangement. The most common type of hypothyroidism is autoimmune disease-related and the mechanism, particularly with respect to the role of microRNAs (miRNAs), has not been delineated. Methods: Serum from 30 patients with subclinical hypothyroidism (SCH) and 30 healthy individuals were collected and exosomal miR-146a (exo-miR-146a) was examined, followed by extensive mechanistic investigation using various molecular and cellular experimental approaches and genetic-knockout mouse models. Results: Our clinical investigation showed that exo-miR-146a was systemically elevated in the serum of patients with SCH (p = 0.04) compared with healthy individuals, prompting us to investigate the biological effects of miR-146a in cells. We found that miR-146a could target and down-regulate neuron-glial antigen 2 (Ng2), with consequent down-regulation of TSHR. We next generated a thyroid-specific Ng2 knockout (Thy-Ng2-/-) mouse model and found a significant down-regulation of TSHR in Thy-Ng2-/- mice, accompanied by the development of hypothyroidism and metabolic disorders. We further found that a decrease in NG2 resulted in decreased receptor tyrosine kinase-linked downstream signaling and down-regulation of c-Myc, consequently resulting in up-regulation of miR-142 and miR-146a in thyroid cells. Up-regulated miR-142 targeted the 3'-untranslated region (UTR) of TSHR messenger RNA (mRNA) and post-transcriptionally down-regulated TSHR, explaining the development of hypothyroidism above. Local up-regulation of miR-146a in thyroid cells augments the earlier cited processes initiated by systemically elevated miR-146a, thereby forming a feedback loop to propel the development and progression of hypothyroidism. Conclusions: This study has uncovered a self-augmenting molecular loop initiated by elevated exo-miR-146a to suppress TSHR through targeting and down-regulating NG2, thereby initiating and propelling the development and progression of hypothyroidism.

Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis-A meta-analysis of randomized controlled trials.

IntroductionRecent evidence suggested that vitamin D deficiency was associated with Hashimoto's thyroiditis (HT) pathogenesis and thyroid hypofunction. This study aimed to investigate whether vitamin D supplementation would be effective in the prevention and progression of hypothyroidism in patients with HT.MethodsPubMed, Embase and the Cochrane library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to August 2021.ResultsA total of 7 cohorts of patients from six clinical trials with 258 patients with HT were included. Significant difference was found (WMD = 19.00, 95% CI: 12.43, 25.58, p < 0.001; I 2 = 90.0%, p heterogeneity < 0.001) between the vitamin D group and control group in serum 25‐hydroxyvitamin D level. And the combined results indicated vitamin D supplementation significantly reduced the level of thyroid peroxidase antibodies (TPO‐Ab) compared to the control group (WMD = −158.18, 95% CI: −301.92, −14.45, p = 0.031; I 2 = 68.8%, p heterogeneity = 0.007). Whereas no significant differences were found on the levels of thyroid‐stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) compared to the control group (p > 0.05).What is New and ConclusionOur study demonstrated that vitamin D treatment might significantly increase the serum 25(OH)D levels and produce changes in TPO‐Ab titres.No significant association was found between serum vitamin D treatment and the levels of TG‐Ab, TSH, FT3 and FT4, suggesting that vitamin D is not associated with the function of the thyroid in patients with HT.

Status of Serum Zinc Level in Hypothyroid Patients with Normal Serum Albumin Level: A Case Control Study

INTRODUCTION: Decreased thyroid hormone synthesis and low levels of circulating thyroid hormones result in clinical hypothyroidism causing many metabolic processes to slow down. Zinc is essential for many biochemical processes and cell proliferation. Thyroid hormones influence Zinc metabolism by affecting absorption and excretion.&#x0D; MATERIAL AND METHODS: This case-control study was conducted in subclinical hypothyroidism (n=30), overt hypothyroidism (n=30) and compared with age and sex matched euthyroid controls (n=30) attending UCMS-TH. Serum free T3 (fT3), free T4 (fT4) and Thyroid Stimulating Hormone (TSH) were estimated by ELISA. The serum Zinc and Albumin were estimated by colorimetric Nitro-PAPS and BCG dye binding method respectively.&#x0D; RESULTS: The overall frequency of Zinc deficiency has been observed 12 (40%) in overt hypothyroidism, 9 (30%) in subclinical hypothyroidism and two (6.66%) in euthyroid controls. A significant association between serum Zinc with fT3, fT4 levels (p=0.0046) and with TSH level (p-value=0.030) was observed in all cases. The positive correlation of serum Zinc with fT3 level (r=0.217, p=0.04), fT4 level (r=0.267, p=0.011) while serum negative correlation with TSH level (r=-0.234, p=0.026) and Albumin (r=-0.039, p=0.713) were observed. The odds ratio shows 9.33 times Zinc deficiency likely to occur in overt hypothyroidism (CI: 1.86-46.68; p-value=0.0065) whereas 6.0 times in subclinical hypothyroidism (CI:1.17- 30.72; p-value=0.0315) than euthyroid controls.&#x0D; CONCLUSION: The significant difference in Zinc deficiency was observed in overt hypothyroid patients. However, non-significant difference in sub-clinical hypothyroidism as compared to euthyroid controls was found in all groups having normal albumin level. This may conclude that with progression of hypothyroidism there is significant decrease in Zinc with normal albumin. Hence, there is association between thyroid profile and serum Zinc status.

Role of Changes in Some Adipokines with Obesity in Relation to Thyroid Function in Early Diagnosed Patients with Subclinical Hypothyroidism

AbstractBackground: Thyroid hormones can influence energy metabolism. Many patients of obesity have subclinical hy-pothyroidism and vice versa.Aim of Study: To evaluate the relation of changes in the level adipocyte hormones in obesity and in relation to hy-pothyroid state in early diagnosed patients with subclinical hypothyroidism.Material and Methods: This work includes 90 females divided into 3 groups each 30 persons (Group I) normal control, (Group II) obese females and (Group III) obese females with early diagnosed subclinical hypothyroidism: BMI were measured and blood samples were collected from all subjects and subjected to determine fasting blood glucose, triglyceride, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDH), TSH, FT4, FT3, insulin level and Inter-leukin-6 (IL-6). Vaspin, lipocalin 2 and apelin were measured and HOMA IR (homeostatic model assessment) was calculated.Results: In obese patients' body mass index, TSH, fasting blood glucose, fasting insulin, HOMA IR, Interleukin-6, total cholesterol, triglyceride, low-density lipoprotein and apelin, lipocalin 2, vaspin showed a significant increase with a further significant increase in obese with hypothyroidism compared to control group. A significant decrease in high density lipo-protein in obese females with further significant decrease in obese with hypothyroidism, however, the level of FT3 and FT4 are insignificantly reduced in both obese and obese with hypothyroidism compared to control group.Conclusion: It is concluded that obesity released adipok-ines and inflammation may be part of the axis that has a pathogenic role in the development and progression of hy-pothyroidism in obese subjects. This open a new point of view that disruption of thyroid function may be one of sec-ondary effect of obesity and that disruption of adipocyte secretion of vaspin, lipocalin 2 and apelin may be implicated in some of the metabolic changes associated with obesity and aggravated with hypothyroid state.

Changes in intra-and extracellular Ca2+ concentration and prostaglandin E2 synthesis in osteoblasts of the femoral bone in experimental hyper-and hypothyroidism

Subclinical form of hypothyroidism was not associated with considerable changes in Ca(2+) content in osteoblasts and blood plasma and in the content of ATP and prostaglandin E2. Activation of prostaglandin E2 synthesis in response to binding of extracellular Ca(2+) in osteoblasts in the absence of ATP was less pronounced (by 11%) compared to the control. Progression of hypothyroidism and development of clinical signs of the disease were accompanied by a decrease in Ca(2+) content in osteoblasts and plasma by 45 and 12%, respectively, and ATP content in osteoblasts by 30%, and by activation of prostaglandin E2 synthesis by 117%. Moreover, the synthesis of prostaglandins in response to binding of extra- and intracellular Ca(2+) also considerably changed. Hyperthyroidism (2 months) was characterized by a moderate decrease in plasma content of Ca(2+) by 15% and ATP by 25%, together with an increase in prostaglandin E2 level by 55.5%. The release of prostaglandin E2 in response to chelation of extracellular Ca(2+) increased even more markedly, but somewhat decreased in response to addition of 5 mM ATP due to compensation of metabolic acidosis.