A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

About half of patients with Graves’ disease develop an orbitopathy related to an inflammatory expansion of the periorbital adipose tissue and muscles. We used a targeted metabolomic approach measuring 188 metabolites by mass spectrometry to compare the metabolic composition of tears in patients with active (n = 21) versus inactive (n = 24) thyroid-associated orbitopathy. Among the 44 metabolites accurately measured, 8 showed a significant alteration of their concentrations between the two groups. Two short-chain acylcarnitines, propionylcarnitine and butyrylcarnitine, and spermine showed increased concentrations in the tears of patients with active orbitopathy, whereas ornithine, glycine, serine, citrulline and histidine showed decreased concentrations in this group. In addition, the ratio putrescine/ornithine, representing the activity of ornithine decarboxylase, was significantly increased in patients with active compared to inactive orbitopathy (p = 0.0011, fold change 3.75). The specificity of this candidate biomarker was maintained when compared to a control group with unclassified dry eye disease. Our results suggest that the stimulation of ornithine decarboxylase by TSH receptor autoantibodies in orbital fibroblasts could lead to increased synthesis of spermine, through the increased activity of ornithine decarboxylase, that may contribute to periorbital expansion in Graves’ ophthalmopathy.

Graves’ disease combined with acute myocarditis and thyrotoxic periodic paralysis in a male:a case report and review of the literature

Graves’ disease is the most common reason for hyperthyroidism which manifest as multi-system changes.Among these clinical manifestations acute myocarditis and thyrotoxic periodic paralysis are very rare and patients who are combined with both two haven’t been reported yet.The etiology may attribute to autoimmunity.

Autoimmune Polyglandular Syndrome Type 3-D

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by the presence of autoantibodies against cell nuclei and involves many organ systems in the body. The etiopathology of SLE is thought to involve complex and multifactorial interactions between genetic variation and environmental factors. Hyperthyroidism is a disease due to increased thyroid hormone function followed by signs and symptoms that affect the body's metabolic system. Graves' disease is an autoimmune disease characterized by the presence of antibodies to TSHR (TRAb). Several coexisting autoimmune diseases have been classified under different syndromes. Case Presentation: A woman, 29 years-old, came to office with complaint of chest palpitation. Patient had history of fever, joint pain, hair loss, and malar rash. Patient had been diagnosed with hyperthyroidism for 4 years and regularly taking propylthiouracil 100 mg and propranolol 10 mg. Titer ANA Test 1/100, Anti ds-DNA 68.08, C3-Complement 93 (N: 83-193), C4-Complement 11.2 (N: 15-57), Free T3 7.79 (N: 1.71-3.71), Free -T4 2.50 (N: 0.70-1.48), TSHs 0.0001 (N: 0.350-4.94), TRAb 3.38 (N: < 1.75). Patient was diagnosed with systemic lupus erythematosus (SLE) and graves’ disease. Patient treated with methimazole 10 mg, propranolol 10 mg, myfortic 360 mg, and methylprednisolone 4 mg. Conclusion: Autoimmune Polyendocrine Syndromes (APS) was at first characterized as different endocrine organ diseases related to an immune system disease in a subject. Hence, affiliation between illnesses in APS was noted not to be irregular but in specific combinations in which a few non-endocrine immune system diseases were moreover portion of the disorders.

Reversal of Graves’ Disease with a Whole Foods Plant Based Diet: A Case Report

The benefits of a whole-food, plant-based diet (WFPBD) include, but are not limited to, improvement of cardiovascular health, decreased inflammation, as well as enhanced endocrine system function. We present the case of a 51-year-old pre-diabetic female with a 22-year history of Graves’ disease who reversed her conditions following the ini- tial 28-week WFPBD period. In this time, she was able to reduce her thyroid stimu- lating immunoglobulin (TSI) and hemoglobin A1c (HbA1c) levels and discontinue methimazole and cetirizine intake. It was also found that maintaining vitamin D levels are beneficial for promoting a more balanced immune response to help lower thyroid antibodies.

Hyperthyroidism in Graves’ disease causes sleep disorders related to sympathetic hypertonia

Context It is well known that Graves’ disease (GD) causes sleep disorders (SD). However, the characteristics and associated factors of SD and its clinical course post-hyperthyroidism normalization remain unclear. Objective To clarify the characteristics and associated factors of subjective SD and its clinical course after GD treatment. Design, setting, and study participants From November 2017 to October 2020, we enrolled 72 participants (22 newly diagnosed with GD with untreated hyperthyroidism, 20 previously diagnosed with GD with normal thyroid function, and 30 normal controls) with no other underlying sleep disorder-related diseases. We compared the groups at enrollment and conducted prospective observations after 12 months of treatment on participants with newly diagnosed GD. Main outcome measures Differences and changes in the Pittsburgh Sleep Quality Index (PSQI) global and component sleep quality scores. Results PSQI global sleep quality scores (p = 0.036) and sleep disturbance scores (p = 0.011) were significantly different among the three groups, and were highest in the untreated hyperthyroidism group. Multiple regression analysis demonstrated that free thyroxine level, which was positively correlated with sympathetic tone (ST) as evaluated by pulse rate and urinary total metanephrines, was associated with poorer PSQI global sleep quality scores independently of other factors (p = 0.006). Prospective observation showed that PSQI global sleep quality scores (p = 0.018) and sleep disturbance scores (p = 0.011) significantly improved with thyroid function normalization and ST attenuation. Conclusions Hyperthyroidism caused by GD augmented ST and exacerbated subjective SD. Normalization of hyperthyroidism caused by GD improved subjective SD.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome

Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.