High Thyroid Hormone Levels Research Articles

Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation

High levels of thyroid hormones are linked to increased risk and advanced stages of breast cancer. Our previous work demonstrated that the biologically active triiodothyronine (T3) facilitates mitochondrial ATP production by upregulating Ca2+ handling proteins, thereby boosting mitochondrial Ca2+ uptake and Krebs cycle activity. In this study, different cell types were utilized to investigate whether T3 activates a Ca2+-induced signaling pathway to boost cancer cell proliferation. Using live-cell imaging, biochemical assays, and molecular profiling, differences in intracellular signaling among MCF7 and MDA-MB-468 breast cancer cells, non-cancerous breast cells hTERT-HME1, and PC3 prostate carcinoma cells, previously found to be insensitive to thyroid hormones in terms of proliferation, were investigated. Our findings revealed that T3 upregulates 1,4,5-trisphosphate receptor 3 via thyroid hormone receptor α. This boosts mitochondrial Ca2+ uptake, reduction equivalent yield, and mitochondrial ATP production, supporting the viability and proliferation of breast cancer cells without affecting non-cancerous hTERT-HME1 or PC3 prostate carcinoma cells. Understanding the interplay between T3 signaling, organellar interaction, and breast cancer metabolism could lead to targeted therapies that exploit cancer cell vulnerabilities. Our findings highlight T3 as a crucial regulator of cancer metabolism, reinforcing its potential as a therapeutic target in breast cancer.Graphical

Causal linkage of Graves’ disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes

BackgroundAging is an irreversible progressive decline in physical function. Graves’ disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated.MethodsWe used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes.ResultsF-statistics of the five IVs were greater than 10, and the R2 values ranged from 0.033 to 0.156 (R2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer’s disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004).ConclusionsGD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer’s disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.

The influence of triiodothyronine on the immune response and extracellular matrix remodeling during zebrafish heart regeneration

Damage to the human heart is an irreparable process that results in a permanent impairment in cardiac function. There are, however, a number of vertebrate species including zebrafish (Danio rerio) that can regenerate their hearts following significant injury. In contrast to these regenerative species, mammals are known to have high levels of thyroid hormones, which has been proposed to play a role in this difference in regenerative capacity. However, the mechanisms through which thyroid hormones effect heart regeneration are not fully understood. Here, zebrafish were exposed to exogenous triiodothyronine (T3) for two weeks and then their hearts were damaged through cryoinjury to investigate the effect of thyroid hormones on ECM remodeling and the components of the immune response during heart regeneration. Additionally, cardiac fibroblasts derived from trout, another species of fish known to display cardiac regenerative capacity, were exposed to T3in vitro to analyze any direct effects of T3 on collagen deposition. It was found that cryoinjury induction results in an increase in myocardial stiffness, but this response was muted in T3 exposed zebrafish. The measurement of relevant marker gene transcripts suggests that T3 exposure reduces the recruitment of macrophages to the damaged zebrafish heart immediately following injury but had no effect on the regulation of collagen deposition by cultured trout fibroblasts. These results suggest that T3 effects both the immune response and ECM remodeling in zebrafish following cardiac injury.

Differential Regulation of Opsin Gene Expression in Response to Internal and External Stimuli.

Determining how internal and external stimuli interact to determine developmental trajectories of traits is a challenge that requires the integration of different subfields of biology. Internal stimuli, such as hormones, control developmental patterns of phenotypic changes, which might be modified by external environmental cues (e.g. plasticity). Thyroid hormone (TH) modulates the timing of opsin gene expression in developing Midas cichlid fish (Amphilophus citrinellus). Moreover, fish reared in red light accelerate this developmental timing compared to fish reared in white light. Hence, we hypothesized that plasticity caused by variation in light conditions has coopted the TH signaling pathway to induce changes in opsin gene expression. We treated Midas cichlids with TH and crossed this treatment with two light conditions, white and red. We observed that not only opsin expression responded similarly to TH and red light but also that, at high TH levels, there is limited capacity for light-induced plasticity. Transcriptomic analysis of the eye showed that genes in the TH pathway were affected by TH, but not by light treatments. Coexpression network analyses further suggested that response to light was independent of the response to TH manipulations. Taken together, our results suggest independent mechanisms mediating development and plasticity during development of opsin gene expression, and that responses to environmental stimuli may vary depending on internal stimuli. This conditional developmental response to external factors depending on internal ones (e.g. hormones) might play a fundamental role in the patterns of phenotypic divergence observed in Midas cichlids and potentially other organisms.

Proportion of hydatidiform molar gestations among patients undergoing uterine evacuation for missed abortions, associated demographics and risk factors -Experience at a single center over 18 months

Objectives: Gestational trophoblastic diseases represent a significant obstetric morbidity among women of reproductive age, with a potential to impact women’s health substantially. Molar pregnancies present as clinical aberrations in embryogenesis and placentation during the first trimester of pregnancy. Cases with missed abortions and spontaneous incomplete abortions requiring uterine evacuation, could be an opportunity to look for molar pregnancies through histopathology which otherwise could be missed. We aim to study the proportion of hydatidiform molar gestations among patients undergoing uterine evacuation in cases of missed abortion and to evaluate the demographic and risk factors associated with hydatidiform molar gestations. Material and Methods: A prospective observational, descriptive study was conducted at the Department of Obstetrics and Gynecology of a tertiary care teaching hospital over a period of 18 months. Data was collected using a pre-tested study questionnaire which included the objectives, besides the inclusion and exclusion criteria. The abortus and uterine evacuated tissue was sent for histopathologic examination by a single histopathologist. Analysis of various epidemiological characteristics and risk factors was done using the Statistical Package for the Social Sciences software version 21. Results: Out of 67 patients presenting with missed abortions or incomplete abortions during the study period, five had hydatidiform molar gestations; an incidence of 7.5%. Upon histological examination 3 (4.5%) patients had a complete mole, 2 (3%) had a partial mole while 62 (92.5%) had non-molar histopathology. Eleven (16.4%) of the study participants had a history of previous spontaneous pregnancy loss/recurrent pregnancy losses. Three among five cases detected to have molar gestations had a history of prior spontaneous abortions (60%), and the difference observed was statistically significant (P = 0.019; Odds Ratio [95% Confidence interval] 10.25 [1.459–70.257]). Hyperthyroidism and high levels of serum beta-human chorionic gonadotrophin (β-HCG) were associated with molar gestations and this was statistically significant. Conclusion: The risk of developing molar gestation is higher in patients who had previous first-trimester losses. Importantly, this should be a differential diagnosis in instances with elevated β-HCG and high thyroid hormone levels. Histopathological examination of products of conception should be considered as an essential assessment in all presentations of spontaneous abortions requiring uterine evacuation.

TSH receptor antibody as a predictor of difficult robotic thyroidectomy in patients with Graves’ disease

Thyroidectomy in Graves’ disease can be challenging due to greater thyroid size and vascularity. While thyroid stimulating hormone receptor antibody (TRAb) level is associated with disease severity and thyroid vascularity, its impact on operative outcomes remains unclear. This study aimed to compare challenging factors for robotic thyroidectomy (RT) and open thyroidectomy (OT) in Graves’ disease patients, including TRAb as a predictive factor for difficult thyroidectomy. This retrospective study included Graves’ disease patients who underwent total thyroidectomy between September 2013 and January 2023. The clinical characteristics and operative outcomes were compared between patients who received OT and bilateral axillo-breast approach RT. Factors affecting operation time and estimated blood loss (EBL) were evaluated in both groups using regression analyses. A total of 85 patients received either OT (n = 48) or RT (n = 37). Median thyroid volumes in the OT and RT groups were 72.4 g and 57.6 g, respectively. Operation time was affected by thyroid volume in both groups. Additionally, higher thyroid hormone levels and bilateral central neck node dissection prolonged operation time in the RT group. EBL was marginally associated with thyroid volume in the OT group. However, in the RT group, TRAb level was independently associated with greater EBL (p = 0.04), while no significant association was found with thyroid volume. Predictive factors for difficult thyroidectomy differed by operation approaches. TRAb significantly predicted intraoperative bleeding in RT, while this association was absent in OT. Caution is warranted when performing RT on Graves’ disease patients with high TRAb levels.

Cardioprotective effects of losartan and diminazene against the ischemia/reperfusion injury in hyperthyroidism rats.

Hyperthyroidism is a condition where the thyroid gland produces high levels of thyroid hormone. Heart diseases are one of the main complications of hyperthyroidism. Several studies have shown that losartan (LOS) and diminazene aceturate (DIZE) possess cardioprotection effects against cardiac hypertrophy, ischemic heart disease, and heart failure. The research aimed to investigate the cardioprotection of LOS, DIZE, and their combination in the case of levothyroxine (LT4)-induced cardiomyopathy in rats. Hyperthyroidism was induced by LT4 in drinking water (12mg/L) for 28 days. LOS (10mg/kg, orally) and/or DIZE (15mg/kg, subcutaneously) were administrated in rats with hyperthyroidism for 28 days. Decreased serum creatine kinase myoglobin and lactate dehydrogenase levels and cardiac hypertrophy by DIZE and combination therapy in hyperthyroidism rats have been reported. Cardiac hemodynamic findings showed that DIZE and its combination with LOS decreased the LT4-mediated left ventricular developed pressure (LVDP), rate pressure product (RPP), and RPP recovery percentage. Elevated cardiac oxidative stress and inflammation were confirmed by decreasing cardiac superoxide dismutase (SOD) activity and increasing the total oxidative stress and tumor necrosis factor-alpha (TNF-α) levels. SOD activity and TNF-α level were reversed by LOS and DIZE administration, respectively. Generally, DIZE and combination therapy with LOS improved cardiac dysfunction caused by hyperthyroidism in rats, whereas LOS alone has not been able to effectively respond to this dysfunction.

OR14-03 The Thyroid Hormone Receptor Beta Genotype Of The Fetus Influences The Maternal Thyroid Function During Pregnancy

Abstract Disclosure: F. Salas Lucia: None. X. Liao: None. H. Jiang: None. A.M. Dumitrescu: None. S. Refetoff: None. J. Anselmo: None. When women with resistance to thyroid hormone beta (RTHβ) are pregnant, their high serum thyroid hormone (TH) levels are perceived as normal by affected fetuses (AfFe) carrying the same THRB mutation as their mothers. On the contrary, normal fetuses (NlFe) that do not carry the maternal THRB mutation are exposed to supraphysiologic TH levels and have unfavorable outcomes. This shows the impact maternal TH levels have on the fetus. However, whether the fetus might influence the maternal thyroid function remains unknown. To explore this possibility, we studied the maternal thyroid function tests (TFT) TSH, FT3, and FT4 throughout the pregnancies from 8 women harboring the R243Q THRB mutation (AfMo) during a total of 10 pregnancies: 6 carrying AfFe and 4 NlFe fetuses. Cord blood TFT from 3 of the NlFe and 3 AfFe at birth were also obtained. In addition, 8 pregnancies from 7 normal mothers (NlMo) carrying 4 AfFe who inherited the THRB mutation from the father and 4 NlFe were also evaluated for TFT. Cord blood from these pregnancies was not available. Results were compared to those in pregnancies of normal WT women. In all RTHβpregnancies, the maternal TSH values were within the range of pregnancies in WT women (0.35-4.94 mU/L) with an hCG-mediated nadir at the end of the first trimester. Maternal FT4 and FT3 values in RTHβpregnancies were above the upper limit of normal (ULN) of 100, peaking during weeks 5-16 (150±20% and 175±15% ULN, respectively) and progressively decreasing afterward. We found differences in maternal TFTdepending on the THRB genotype of the fetus. From weeks 25-32, the AfMo carrying an AfFe exhibited lower FT4 than when carrying a NlFe (96±2 vs. 108±5.3% ULN; p<0.05). Similarly, from weeks 25-40, the AfMo carrying an AfFe exhibited lower FT3 values than when carrying a NlFe ULN (110±11 vs. 134±13% ULN; p<0.05). While gestational age at delivery was similar in all RTHβ pregnancies, the NlFe had a lower birth body weight than the AfFe (2.3±0.1 vs. 3.1±0.2 kg; p<0.01). Cord blood TSH in NlFe was undetectable (<0.1 mU/L) but was 9.51 mU/L (2.2-10; range in normal neonates) in AfFe, which indicates that the thyroid function in NlFe could be restricted during pregnancy, but not in AfFe. Cord blood FT4 levels were similar in NlFe and AfFe (98.4±16.4 vs. 89.5±9.4% ULN). However, FT3 levels were significantly higher in NlFe than in AfFe (67.7±3.0 vs. 42.0±9.6% ULN; p<0.05) and represented ∼68, and ∼42% of the serum maternal FT3 level at birth, respectively. NlMo carrying either AfFe or NlFe showed similar TSH and FT3 levels during pregnancies. However, from weeks 33 to 40, FT4 levels were lower when carrying an AfFe than when carrying a NlFe (51.8±2.8 vs. 62.5±3.2% ULN; p<0.001). Our findings indicate that maternal thyroid function are influenced by THRB genotype of the fetus. The quantitation of placental and fetal TH transporters, deiodinases, and TH metabolites could provide insights into the mechanisms involved. Presentation: Friday, June 16, 2023

Activation of Toll-like receptor 4 by thyroid hormone triggers abnormal B-cell activation.

Breakdown of tolerance and abnormal activation of B cells is an important mechanism in the pathogenesis of Graves' disease (GD). High levels of thyroid hormones (THs) play important roles in GD progression. However, the interactions between THs and abnormal activation of B cells remain elusive. This study aimed to explore the effect of high levels of THs on TLR4 expression and abnormal B cell differentiation. Blood samples were collected from patients with GD and healthy controls (HCs) to evaluate the frequency of B cells, their subsets, and TLR4 expression in B cells. A high-level T3 mouse model was used to study the interaction between THs and the TLR4 signalling pathway. We found that the frequencies of CD19+ , CD19+ TLR4+ , CD19+ CD86+ , and CD19+ CD138+ B cells were significantly higher, as were the expression levels of MRP8/MRP14 and MRP6 and MRP8, MRP14, and MRP6 messenger RNA (mRNA) in peripheral blood mononuclear cells in patients with GD. In high-level T3 mice models, the serum MRP8/MRP14 and MRP6 levels and the TLR4 mRNA expression in PBMCs were significantly higher. TLR4 mRNA, protein expression, and cytokines downstream of TLR4, such as myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB, were also increased in mouse spleen mononuclear cells. The present study indicated that high levels of T3 can induce abnormal differentiation and activation of B cells by promoting TLR4 overexpression and provide novel insights into the roles of THs in the pathogenesis of GD.

Exploring the prevalence and causes of normal Tc 99m thyroid uptake in thyrotoxic patients A retrospective study at a regional hospital of nuclear medicine in Oman

This study focuses on assessing the prevalence of normal Technetium-99m (Tc-99m) Thyroid uptake scans among thyrotoxic patients at a specific medical facility in Oman, named "Royal hospital-nuclear medicine department". Thyrotoxicosis is a condition characterized by high levels of thyroid hormones in the body which is usually reflects as a high uptake in Tc-99m Thyroid Pertechnetate uptake scan. However, in some cases the scan shows normal thyroid activity which may lead to misdiagnosis or delayed treatment.

P435 THE IMPORTANCE OF CORRELATION BETWEEN HEART FAILURE AND THYROID: A CASE REPORT

Abstract A 39–year–old African man was admitted to our department within a four days symptoms of short of breath, cough, tachycardia and lower limb edema. He also complained headache for about a month. He denied fever, chest pain and loss of consciousness. Clinical and family history were unremarkable. Blood tests showed moderate microcytic anemia ( Hb 9.6 g/dl, MCV 93.3 fL), hypoalbuminemia ( Albumin: 3.20 g/dl), elevated levels of LDH ( LDH: 246 U/L), mild C–reactive protein (CRP) and pro–Brain Natriuretic Peptide (pro–BNP) increase (CRP: 1.14 mg/dl); (PRO–BNP: 1133 pg/mL) and negative troponin. Given the clinical picture suggestive of heart failure, we immediately started diuretic therapy with benefit. Chest–x ray revealed a modest thickening of the pulmonary interstitium, electrocardiogram (ECG) a sinus rhythm and early repolarization changes. Chest CT highlighted a bilateral apical–basal pleural effusion, a bilateral hilar ectasia and interstitial markings due to stasis. He underwent an ultrasound of the abdomen that was normal. Thyroid function tests showed high levels of thyroid hormones with suppressed TSH and elevated levels of Ab anti–receptor TSH ( FT3: 8.73 pg/mL; FT4: 2.35 ng/dL; TSH<0.01 mUI/ml; TRAB: 3.62 UI/L). Thyroid ultrasound showed a multinodular goiter. The patient began therapy with Tapazole. Echocardiogram didn’t show any evidence of acute heart disease and systolic function was normal. After discharge he performed a heart MRI with evidence of no alteration of global systolic function, of regional left and right ventricular kinetics or of pathological areas of delayed enhancement in relation to myocardial edema/fibrosis/necrosis. Hyperthyroid patients can show signs and symptoms of heart failure that are due to the hyperdynamic circulatory state and/or to the frequent pulmonary arterial hypertension and our case report demonstrates that this clinical status tends to improve with the restoration of euthyroidism, but if left untreated, can worsen over the time leading to heart failure.

Higher thyroid hormone has a negative association with lower limb lean body mass in euthyroid older adults: Analysis from the Baltimore Longitudinal study of aging.

Background: Hyperthyroidism is associated with lower lean body mass, as a result of catabolic actions of thyroid hormone. Therefore, higher thyroid hormone levels could be a factor in the development of sarcopenia and age associated functional decline. The relationship between thyroid hormone and muscle mass in ambulatory, euthyroid older adults is not known. Method: We used mixed-effects models to estimate the cross-sectional relationships (accounting for inter-person variability) between thyroid axis hormone measures and lower limb composition or sarcopenia at visits in the Baltimore Longitudinal Study of Aging (BLSA) at which DEXA scans were available and both thyrotropin (TSH) and free thyroxine (FT4) were in the reference range. Analyses were adjusted for levothyroxine use, age, race, sex, BMI, smoking, alcohol intake, cholesterol, and systolic blood pressure. Results: 1442 euthyroid participants (median age 68, 50% female, and 69% white) contributed to 5306 visits from 2003 to 2019. FT4 was negatively associated with lower limb lean mass (beta: 88.49; 95% Confidence Interval (CI): 122.78, -54.20; p < 0.001) and positively associated with sarcopenia (OR: 1.11%, 95% CI: 1.01, 1.22) in the whole cohort. Additionally, higher FT4 was associated with lower leg lean mass (beta: 66.79; 95% CI: 102.24, -31.33; p < 0.001) and sarcopenia (OR:1.09%, 95% CI:1.01, 1.18) in older adults, but not in younger adults alone. Conclusion: In euthyroid older adults, higher FT4 is associated with lower leg lean mass and higher odds of sarcopenia. Understanding the relationship between thyroid hormone and sarcopenia is needed to improve clinical decision-making and avoid functional decline from excess thyroid hormone use in older adults.

Characterizing the Interplay of Lymphocytes in Graves' Disease.

Graves' disease (GD) is a thyroid-specific autoimmune disease with a high prevalence worldwide. The disease is primarily mediated by B cells, which produce autoantibodies against the thyroid-stimulating hormone receptor (TSHR), chronically stimulating it and leading to high levels of thyroid hormones in the body. Interest in characterizing the immune response in GD has motivated many phenotyping studies. The immunophenotype of the cells involved and the interplay between them and their secreted factors are crucial to understanding disease progression and future treatment options. T cell populations are markedly distinct, including increased levels of Th17 and follicular helper T cells (Tfh), while Treg cells appear to be impaired. Some B cells subsets are autoreactive, and anti-TSHR antibodies are the key disease-causing outcome of this interplay. Though some consensus across phenotyping studies will be discussed here, there are also complexities that are yet to be resolved. A better understanding of the immunophenotype of Graves' disease can lead to improved treatment strategies and novel drug targets.

Thyroid status of the organism against the background of induction of the liver monooxygenase system

Zixor induction occurred only with an increase in the amount of free T3. Free T4 levels even tended to decline. At the same time, the same trend was observed in the amount of TTG. Our research shows that there is a relationship between the functional status of the liver monooxygenase system and the amount of thyroid hormones in the body. However, the question of the degree of closeness of this connection, that is, whether this connection is direct or indirect, remains open. So far, studies show that the high activity of the monooxygenase enzyme system of the endoplasmic reticulum of hepatocytes is accompanied by high levels of thyroid hormones - triiodothyronine and thyroxine

Induced Overexpression of B Cell-Activating Factor by Triiodothyronine Results in Abnormal B Cell Differentiation in Mice

Breakdown of tolerance and abnormal activation in B cells is an important mechanism in the pathogenesis of Graves’ disease (GD) and high levels of thyroid hormones (THs) can drive the progression of GD. However, the interactions between THs and abnormal activation of B cells in the context of GD are not well understood. The aim of this study was to investigate B cell-activating factor (BAFF) mediating the cross talk between THs and B cells and the possible underlying mechanisms. A high-level triiodothyronine (T3) mouse model was used to verify T3-mediated induction of overexpression of BAFF and B cell abnormal differentiation. The possible promotion of BAFF overexpression in the mice spleen macrophages during polarization to M1 by T3 was also studied. We showed that high levels of T3 can induce BAFF overexpression and lead to abnormal differentiation of B cells in the mice. While the overexpression of BAFF was observed across many tissue types in the mice, high levels of T3 could induce M1 macrophages polarization by IFN (interferon-gamma)-γ in the spleen of the mice, which in turn generated BAFF overexpression. Our findings provide a novel insight into the interactions between the endocrine and immune systems, as well as provide insight into the role of TH in the pathogenesis of GD.

High levels of thyroid hormones promote recurrence of Graves' disease via overexpression of B-cell-activating factor.

BackgroundElevated thyroid hormone (TH) levels have been suggested to be associated with the pathological progression of Graves' disease (GD). However, direct evidence from clinical studies remains unclear.MethodsPeripheral blood samples were collected from patients with or without the recurrence of Graves' hyperthyroidism (GH) and healthy donors. Thyroid tissue samples were obtained from patients with benign thyroid nodules. To assess the differentiation of autoreactive B cells, the expression of B‐cell‐activating factor (BAFF) and the proportion of CD11c+/–IgG+/− subsets of B cells stimulated by high levels of triiodothyronine (T3) in vivo and in vitro were examined by ELISA, flow cytometry, western blotting, and qRT‐PCR.ResultsSerum BAFF levels in patients with GD were significantly and positively correlated with FT3, FT4, and TRAb levels. Furthermore, the ratio of abnormally differentiated CD11c+ autoreactive B cells positively correlated with BAFF and TRAb. High levels of triiodothyronine (T3) induced BAFF overexpression in thyroid follicular cells and mononuclear cells of the normal thyroid in vitro, thereby promoting the differentiation of CD11c+IgG+ autoreactive secretory B cells (ASCs). However, the precise knockdown of BAFF expression significantly inhibited the abnormal differentiation of ASCs.ConclusionThe pathological progression of GD was prolonged and exacerbated by autoimmune positive feedback modulation caused by high TH levels. BAFF could be considered a potential target for localized thyroid immunosuppressive treatment of Graves' hyperthyroidism recurrence.

Diabetic ketoacidosis as first presentation of latent autoimmune diabetes in adults in a patient with hashitoxicosis as first presentation of Hashimoto’s thyroiditis: a case report

BackgroundLatent autoimmune diabetes in adults is an infrequent form of autoimmune diabetes mellitus, while Hashimoto’s thyroiditis, the most common thyroid disease in adults, rarely manifests as thyrotoxicosis. The concurrent initial presentation of these two autoimmune disorders is extremely rare.Case presentationA 29-year-old male of Albanian descent presented after being hospitalized owing to diabetic ketoacidosis. The diagnosis of type 1 diabetes mellitus was placed, and intensified insulin therapy was initiated. Medical history was not of significance except a 5 kg weight loss within 2 months. The patient presented with recurrent episodes of hypoglycemia, and the doses of preprandial and basal insulin were reduced. The differential diagnosis included type 1 diabetes mellitus “honeymoon” period or another type of diabetes mellitus. His serological tests only revealed positive autoantibodies against glutamic acid decarboxylase 65 and C-peptide. The diagnosis leaned toward latent autoimmune diabetes in adults, and the therapeutic approach involved cessation of preprandial insulin therapy, regulation, and subsequent discontinuation of basal insulin and introduction of metformin. Two years later, basal insulin was reintroduced along with a glucagon-like peptide-receptor agonist and metformin. Further physical examination during the initial visit disclosed upper limb tremor, lid lag, excessive sweating, increased sensitivity to heat, and tachycardia. Laboratory tests were indicative of hashitoxicosis (suppressed level of thyroid-stimulating hormone, high levels of total and free thyroid hormones, positive anti-thyroglobulin and anti-thyroid peroxidase, and negative anti-thyroid-stimulating hormone receptor). Thyroid-stimulating hormone level was spontaneously restored, but an increase was observed during follow-up. Levothyroxine was administrated for 2 years until the patient had normal thyroid function.ConclusionsThe prevalence of thyroid autoantibodies in patients with latent autoimmune diabetes in adults ranges from 20% to 30%. This correlation can be attributed to genetic involvement as well as disorders of immune tolerance to autoantigens. Hence, this report gives prominence to the holistic approach and consideration of comorbidities in patients with diabetes mellitus.

Epidemiology of Thyroid Cancer.

Epidemiology of Thyroid Cancer.

Is there an association between thyroid dysfunction and breast cancer?

Objective: The association between thyroid disease and breast cancer risk remains unclear. A cross-sectional study was carried out to find the association between hypothyroidism, hyperthyroidism, and breast cancer. Materials and Methods: The study included 71 diagnosed cases of breast cancer patients belonging to stage III of the disease. The mean age of controls and patients was 43-45 years. Their level of thyroid hormones was estimated. On the bases of high and low levels of thyroid hormone, women were divided into group one (hypothyroidism n= 56) and group two (hyperthyroidism n=15). Levels of neutrophils, lymphocytes, and hematocrit were estimated by the SWISS MAX analyzer. The level of thyroid hormones, TSH, 8OHG, Isoprostane, and 4-HNE was estimated by the technique of ELISA. The level of MDA was estimated spectrophotometrically. Results: It was observed that body weight was high in hypothyroid females (group 1) Levels of neutrophils, lymphocytes, and monocytes were significantly higher in group 1 of the breast cancer afflicted women, as compared to the controls and group 2. The level of thyroid hormones FT3, FT4, and TSH was also higher in group 1. The level of MDA, isoprostane, and 4-HNE was significantly high in both women with hypo and hyperthyroidism as compared to controls. Conclusions: We found an increased risk of breast cancer in women with hyporhyroidism and a slightly decreased risk in women with hyperthyroidism indicating an association between thyroid function level and breast cancer risk. Key Words: breast cancer, hypo, and hyperthyroidism, MDA, HNE, and Isoprostane

Hydrogen Attenuates Thyroid Hormone-Induced Cardiac Hypertrophy in Rats by regulating angiotensin II type 1 receptor and NADPH oxidase 2 mediated oxidative stress

Cardiac hypertrophy occurs as a result of high levels of thyroid hormone, which may contribute to heart failure and is closely related to oxidative stress. Hydrogen is a good antioxidant. In this study, we found that intragastric levothyroxine administration for two weeks caused obvious cardiac hypertrophy without reduced systolic function. Additionally, hydrogen inhalation ameliorated the levothyroxine-induced metabolic increase and cardiac hypertrophy in rats. Serum brain natriuretic peptide expression was also attenuated by hydrogen treatment. However, hydrogen had no significant effect on levothyroxine -induced serum troponin I and serum thyroid hormone changes.Hydrogen treatment also reduced the levothyroxine-induced increase in cardiac malondialdehyde, 8-hydroxy-2-deoxyguanosine and serum hydrogen peroxide levels and upregulated superoxide dismutase and glutathione peroxidase activity. Additionally, western blotting results showed that hydrogen inhalation inhibited the expression of cardiac nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), angiotensin II type 1 receptor, sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospho-phospholamban and α-myosin heavy chain proteins. In conclusion, the present study revealed a protective effect of hydrogen on levothyroxine -induced cardiac hypertrophy by regulating angiotensin II type 1 receptors and NOX2-mediated oxidative stress in rats.