Low Thyroid Hormone Levels Research Articles

Effects of repetitive transcranial magnetic stimulation on cognitive function and hormone levels in early stroke patients with low thyroid hormone levels.

This study aimed to observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function and thyroid hormone levels in early older stroke patients with low thyroid hormone levels, and to investigate the correlation between the changes in thyroid hormone levels and the improvements in cognitive function after stroke. Forty older stroke patients who met the inclusion criteria were recruited and randomized into a magnetic-stimulation group (rTMS group) and a sham-stimulation group (Sham group). The rTMS group received low-frequency true stimulation and the Sham group received low-frequency sham stimulation. Patients' cognitive scores, activity of daily living(ADL) scores, and their levels of triiodothyronine (T3), free triiodothyronine (FT3), thyroxin (T4), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were assessed before the intervention, after the 4-week intervention, and after an additional 4 weeks of follow-up; Repeated measurement analysis of variance was used to compare the changes of each index in the two groups at different times and the correlations between patiens' cognitive function scores and their changing hormone levels were subsequently investigated. Thirty-one patients were included in this study: 16 patients in rTMS group and 15 patients in the Sham group. Repeated-measures ANOVA showed that patients' T3,FT3 and TSH levels tended to increase at 4-week intervention and at the follow up (p < 0.05), and that the rTMS group had a better effect on improving T3 than the Sham group (Fgroup = 5.319, p = 0.028); The cognitive scale at different time points in both groups showed an upward trend (p < 0.05), and the MoCA, DSF, DSB scores in the rTMS group were statistically higher than those in the Sham group at the end of the 4-week intervention and at the follow-up (p < 0.05); The changes in the levels of T3 before and after 4-week intervention were positively correlated with the changes in the MoCA scores (r = 0.638, p < 0.05). And the difference in T3 level change was positively correlated with the difference in delayed recall, attention and naming score change (r = 0.562, p < 0.05; r = 0.562, p < 0.05; r = 0.531, p < 0.05); and the difference in FT3 level change was positively correlated with the visuospatial and executive function (r = 0.514, p < 0.05). Repetitive transcranial magnetic stimulation improved cognitive function and elevated T3 levels in older patients with post-stroke cognitive dysfunction who had low thyroid hormone levels. Within the normal range, increases in T3 levels are positively correlated with changes in cognitive function.

8490 The mRNA for the Nonsyndromic Deafness Gene Atp2b2 Is Reduced Following Developmental Hypothyroidism

Abstract Disclosure: E.A. Gregersen: None. R.P. Peeters: None. D. Forrest: None. D.S. Sharlin: None. Thyroid hormone (TH) is essential for auditory system development. In rodent models, low levels of TH during the early postnatal period delay cochlear tissue remodeling and alter ion channel function required for normal auditory function. TH receptors are ligand-dependent transcription factors that regulate gene expression. Considering this, auditory deficits observed in hypothyroidism are thought to be largely the result of altered expression of specific TH target genes. However, few TH-regulated genes in the developing cochlea have been reported. TH is reported to impact calcium signaling in several tissues, but whether regulators of calcium signaling are altered following developmental hypothyroidism in the cochlea is largely unexplored. In this report, we investigated the spatial and temporal expression of the ATPase, Ca++ transporting, plasma membrane 2 (Atp2b2) gene in a mouse model of developmental hypothyroidism. Timed-pregnant dams were treated with thyroid gland inhibitors to induce developmental TH insufficiency from embryonic day 12.5 (E12.5) through post-natal day 15 (P15). Untreated timed-pregnant dams served as euthyroid controls. Control and experimental cochleae were collected over a developmental period ranging from embryonic day 18.5 (E18.5) through P15. Cochleae were then processed to detect Atp2b2 mRNA by in situ hybridization or quantitative real-time PCR. In situ hybridization showed that Atp2b2 localizes to inner and outer hair cells as expected, but Atp2b2 was also observed at lower levels in the greater epithelial ridge and spiral ganglion. Quantification of Atp2b2 mRNA revealed an effect of postnatal day and treatment on Atp2b2. In euthyroid animals, Atp2b2 expression gradually increased until P10, then decreased slightly by P15. In hypothyroid animals, Atp2b2 mRNA was consistently decreased (2-2.5 fold). Hypothyroidism similarly impacted expression regardless of sex. The reduction in Atp2b2 mRNA expression in the hypothyroid animals suggests that Atp2b2 is developmentally regulated in part by thyroid hormone signaling. This study characterizes the relationship between TH and Atp2b2 expression during early cochlear development while providing insight into abnormal cochlear development due to hypothyroidism. Presentation: 6/3/2024

9370 Thinking Outside the Box: A Rare Case of Using Plasmapheresis Treatment of Amiodarone-Induced Thyrotoxicosis in Preparation For CABG

Abstract Disclosure: K. Shaik: None. A. Kartoumah: None. J. Alsheikh: None. A. Nayeem: None. M.H. Horani: None. Introduction: Amiodarone, a standard treatment for arrhythmias, poses a risk of disrupting thyroid function and causing amiodarone-induced thyrotoxicosis (AIT). In critical cases where AIT is refractory to first-line treatment, plasmapheresis can be a vital option to rapidly lower thyroid hormone levels, which is essential for pre-surgical stabilization. This case report describes plasmapheresis in managing AIT in a patient undergoing coronary artery bypass grafting, highlighting its role in preventing potential thyrotoxic crises. Case Presentation: A 75-year-old male with a past medical history of diabetes mellitus, coronary artery disease, arrhythmias treated with amiodarone, and a ninety-pack-year history of tobacco presented to the ED with complaints of chest pressure and dyspnea. Initial troponin levels were normal at 24 ng/mL but trended upward toward 66 ng/mL. In the ED, he was not tachycardic and denied recurrent pain, fever, or chills. A CT angiogram of his chest showed no pulmonary embolus. The patient was found to have low TSH (0.005), and his T3 and T4 were both elevated (3.89/1.96, respectively), confirming thyrotoxicosis; however, he was negative for Graves’ disease. While in the hospital, his amiodarone was discontinued, and he was started on prednisone 10 mg for 14 days and methimazole 5 mg for 14 days. He was ultimately discharged on the same prednisone and methimazole regimen and told to follow up with outpatient endocrinology. However, the patient reappeared a week later with dyspnea on exertion; blood work performed after admission revealed a higher free T4 at 2.87. The patient was admitted, and angiography showed three-vessel disease; however, a coronary artery bypass graft (CABG) procedure was delayed over the concern of a potential thyroid storm. Thus, CABG was planned for when free T4 was less than 2, and the patient underwent two rounds of plasmapheresis, which initially decreased free T4 to 1.7 and finally to 1.4. Ultimately, a CABG was performed and well tolerated. Discussion: Amiodarone-induced thyrotoxicosis (AIT) poses a challenge in patient management, especially in patients requiring urgent surgeries. Plasmapheresis is shown to be a valuable option for rapidly lowering thyroid hormone levels and stabilizing the patient in the pre-operative stages. This case demonstrates the effectiveness of plasmapheresis in reducing free thyroxine levels, facilitating a safe and successful CABG. Due to its ability to quickly remove circulating thyroid hormones, plasmapheresis has excellent potential in managing refractory AIT. It is crucial to carefully time plasmapheresis relative to surgery and monitor for complications throughout. Further research is required to optimize proper plasmapheresis protocols in AIT. Conclusion: This case study highlights plasmapheresis as a promising adjunctive therapy in managing AIT and preventing potential thyrotoxic crises. Presentation: 6/1/2024

Autoimmune Hypothyroidism Associated with Helicobacter Pylori Infection

Objective: The study aimed to investigate the correlation between Helicobacter pylori (H. pylori) and thyroid autoimmunity. Material and Methods: To demonstrate the possible correlation between H. pylori infection and autoimmune hypothyroidism, 200 individuals were enrolled in this research (100 patients with active H. pylori infection and 100 healthy controls). All of them were tested for serum levels of thyroid hormones, thyroid stimulating hormone (TSH), and autoantibodies, as well as Helicobacter pylori-Immunoglobulin G (H. pylori-IgG) and cytotoxin-associated gene A-Immunoglobulin G (cagA-IgG) antibodies. Results: The study found that H. pylori infection was associated with higher levels of TSH, thyroperoxidase and thyroglobulin (TPO and TG) (p-value&lt;0.000, 0.001 and 0.006, respectively) and a significant decrease in the levels of free-thyroid hormone (FT3 and FT4) (p-values=0.008 and 0.007 respectively) in patients compared with the control group. Moreover, using Pearson’s correlation tests, significant proportional correlations were found between H. pylori IgG and TSH (r=0.302, p-value=0.001), and a significant negative correlation was found between anti-H. pylori-IgG and with FT3 and FT4 (r=-0.261, p-value=0.003 and r=-0.260, p-value=0.003, respectively). Moreover, Spearman’s correlation results showed that H. pylori IgG was positively linked to TPO (r=0.531, p-value&lt;0.001) and TG (r=0.320, p-value=0.001). Conclusion: The current investigation found that H. pylori infection was linked to higher concentrations of thyroid autoantibody and TSH and lower levels of thyroid hormones, suggesting that the bacterium may play a role in the development of subclinical autoimmune hypothyroidism.

Thyroid hormones and oxidative stress moderated the association between urinary phthalate metabolites and cardiovascular risk factors

While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations.

Low triiodothyronine is associated with high risk of malnutrition and poor functional status in subacute stroke patients

Background and AimsStroke patients may exhibit low thyroid hormone (TH) levels and disease-related malnutrition, both potentially affecting clinical status; their relationships remain unexplored. This study aimed to evaluate TH concentrations in subacute stroke patients and investigate the relationships between TH levels, nutritional risk, and functional status. Methods and ResultsEarly subacute stroke patients admitted to a rehabilitation unit were assessed using various nutritional screening tools (Geriatric Nutritional Risk Index-GNRI, Prognostic Nutritional Index-PNI, and Controlling Nutritional Status-CONUT score) and with the Global Leadership Initiative on Malnutrition (GLIM) criteria.Thyroid-Stimulating Hormone (TSH), free Tetraiodothyronine-Thyroxine (fT4) and free Triiodothyronine (fT3) levels were determined. Functional and cognitive status was evaluated using different scales. Associations between altered THs and nutritional status were examined through univariate/multivariate analyses and ROC analyses.Among 264 patients (age 72.0±10.5 yrs), significant correlations emerged between fT3 and nutritional risk and functional tests (mostly p<0.001). The prevalence of high nutritional risk determined by GNRI, PNI and CONUT increased from higher to lower fT3 tertiles. Lower fT3 levels were observed in patients at high nutritional risk and with GLIM-based malnutrition. fT3 exhibited reasonable predictive power for high nutritional risk (particularly PNI: AUC 0.769, 95%CI 0.702-0.836, p<0.001). Multivariate logistic regression identified nutritional risk (p<0.001) and time from stroke onset as predictors of low fT3 values. ConclusionAltered fT3 levels in early subacute stroke patients correlate with high nutritional risk and poor functional status. Low fT3 values upon admission for stroke rehabilitation may serve as a further parameter to be considered in patients at high nutritional risk.

Thyroid Hormone and Diabetes Mellitus Interplay: Making Management of Comorbid Disorders Complicated.

Insulin and thyroid hormones play important roles in our body. Insulin helps regulate the glucose level while the thyroid hormones affect various cells and tissues, metabolizing protein, lipids, and glucose. Hyperthyroidism and thyrotoxicosis are potential hazards for type 2 diabetes mellitus. There is a high prevalence of hypothyroidism being more common compared to hyperthyroidism coexisting with diabetes mellitus. Thyroid hormones affect glucose metabolism through its action on peripheral tissues (gastrointestinal tract, liver, skeletal muscles, adipose tissue, and pancreas). High-level thyroid hormone causes hyperglycemia, upregulation of glucose transport, and reduction in glycogen storage. The reverse is observed during low levels of thyroid hormone along with insulin clearance. The net result of thyroid disorder is insulin resistance. Type 2 diabetes mellitus can downsize the regulation of thyroid stimulating hormones and impair the conversion of thyroxine to triiodothyronine in peripheral tissues. Furthermore, poorly managed type 2 diabetes mellitus may result in insulin resistance and hyperinsulinemia, contributing to the proliferation of thyroid tissue and an increase in nodule formation and goiter size. Although metformin proves advantageous for both type 2 diabetes mellitus and thyroid disorder patients, other antidiabetics like sulfonylureas, pioglitazone, and thiazolidinediones may have adverse effects on thyroid disorders. Moreover, antithyroid drugs such as methimazole can weaken glycemic control in individuals with diabetes. Thus, an interplay between both endocrinopathies is observed and individualized care and management of the disorder needs to be facilitated.

The Causes of Thyrotoxicosis, Clinical Features, and Treatment Strategies in a Former Iodine Deficient Area

Thyrotoxicosis is a hypermetabolic condition caused by excess thyroid hormones in the circulation with/without increased production from the thyroid gland. In this prospective study, we aimed to investigate the causes of thyrotoxicosis, clinical features, and treatment strategies in a former iodine-deficient area. Thyroid function tests, antithyroid and antithyroid receptor antibodies, and routine thyroid ultrasonography was obtained, and a thyroid scintigraphy/radioactive iodine uptake test was performed on need. A statistically significant difference was found between toxic multinodular goiter (TMNG) and Graves’ disease (GD) groups when mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values were analyzed. TSH levels were significantly lower in GD patients compared to those in TMNG and TNG patients, but free triiodothyronine (FT3) and free thyroxine (FT4) values were higher. A high level of TSH receptor antibody (TRAb) was observed in patients with normal antithyroid peroxidase (Anti-TPO). TRAb levels were found to be high. Anti-TPO and anti-thyroglobulin (Anti-Tg) levels were observed to be positively correlated with sT3 and sT4 levels. TMNG is the leading cause of thyrotoxicosis; despite sufficient iodide intake in our former iodine-deficient region, TMNG is characteristically seen in older patients with much lower thyroid hormone levels than GD. According to the study results, the diagnosis of patients with thyrotoxicosis, their clinical presentation, the treatment they will receive, early detection of postoperative complications were predicted

SMIM1 absence is associated with reduced energy expenditure and excess weight

Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Thyroid Function and Sleep Patterns: A Systematic Review.

Hypothyroidism, defined as a low metabolic function of the thyroid gland that results in low thyroid hormone levels, and insomnia, a condition with the inability to sleep, are two distinct conditions with little overlap that have been extensively established. Both conditions have been studied independently in terms of epidemiology, pathophysiology, diagnosis, and management. The exact causal relationship between the two conditions has yet to be elucidated, and a direct underlying pathophysiology has not been pinpointed. To gain further insight into the relationship between hypothyroidism and insomnia, we performed a systematic review to explore this relationship using predetermined guidelines. Out of 59 studies assessed, four studies evaluated the mechanisms of these two potentially comorbid conditions. Our findings suggest that hypothyroidism and insomnia may have a bidirectional relationship, with symptomatic overlap that is tied to increased metabolic comorbidities and hormonal dysregulation. These findings warrant further research to verify these early findings and gain further insight into the relationship between these conditions. A better understanding of the pathophysiology of overlap between these two conditions will help improve diagnosis and target treatment more effectively.

#339 Thyroid hormone levels critically contribute to ADPKD progression

Abstract Background and Aims Thyroid hormone (TH) signaling plays a crucial role in the regulation of the cell differentiation state, cell cycle and metabolism in various organs. Low TH levels are observed in most patients with chronic kidney disease, and correlate with cell de-differentiation and reactivation of the cell cycle. Despite this knowledge, possible alterations of TH signaling in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and the capacity of TH to modulate anti-cystogenic and renoprotective pathways have not yet been studied. In this study we aimed to (i) investigate the role of TH signaling in the pathogenesis of ADPKD in patients and experimental models, and (ii) assess whether the pharmacological modulation of this pathway with TH (T3, T4) and TH analogs could arrest or reverse ADPKD progression. Method Ninety patients with a diagnosis of ADPKD based on renal ultrasonography findings or genetic testing were included in the study and divided into five subgroups of chronic kidney disease stages, according to the KDIGO classification. Serum TH was measured using ELISA and chemiluminescent immunoassays. The correlation between TH levels and renal function parameter (eGFR) in these patients was assessed using linear regression. 3D polycystic tubules were engineered from patient-derived cells as previously described (Benedetti et al. 2016). For the in vivo experiments, PCK rats—an animal model of ADPKD—were treated with T4 (10 μg/kg) or vehicle by gavage from 4 to 11 weeks of age. Age-matched SD rats were followed for the same length of time and used as controls. Results The analysis of patients’ data showed a strong linear correlation between the levels of FT3 and eGFR, and corresponding inverse correlation between rT3 (the inactivated form of T3) and eGFR. Treating patients-derived tubules with THs strongly inhibited cyst formation and growth. Interestingly, the results were validated in engineered polycystic tubules from three ADPKD patients with different mutations (missense, splice-site and stop-gain) in the PKD1 gene, further confirming that T4 plays an essential role in the cystogenesis and, presumably, progression of the disease in humans. Treating PCK rats—an animal model of ADPKD—with T4 resulted in a significant increase in T4 serum levels and a simultaneous reduction in the size of the macrocystic area compared to vehicle-treated PCK rats. Most importantly, T4 serum levels positively correlated with a reduction in both the size of the macrocystic area and loss of protein into the urine, indicating that TH signaling plays a role in the growth of cysts, and that exogenous T4 can slow down cystogenesis and improve renal function. Interestingly, our mechanistic studies revealed that T4 exerts its anti-cystogenic effects, at least partially, by binding to the membrane receptor αvβ3 and activating the MAPK cascade. Conclusion These results suggest that TH signaling plays a role in the progression of ADPKD and timely administration of T4, ideally at a relatively early stage of the disease, could delay progression or even reverse key clinical features of ADPKD.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Blood count, endocrine, immunologic, renal, and hepatic markers in a case-control animal study of induced periodontitis in female rodents.

Introduction: Periodontitis is a non-communicable chronic inflammatory disease with a systemic burden. Animal models of induced periodontitis help elucidate the mechanisms by which periodontal inflammation drives systemic effects. Studying this systemic involvement over longer follow-up periods may provide a strong foundation for future research on the association between diseases and periodontitis, particularly in female rats. Therefore, we aimed to compare blood, endocrine, immunologic, renal, and hepatic markers in a rat model of induced periodontitis in females with their control counterparts. Methods: Experimental periodontitis was induced in 20 female Wistar rats by the application and maintenance of silk ligatures on the upper molars. The rats were then assessed for macroscopical analysis, complete blood count, and biochemical, endocrine, and immunologic markers at 21, 28, 42, and 56days. Results: Chronic periodontal inflammation was observed after 42days of exposure to the ligatures. Additionally, it was also possible to notice significant systemic manifestations, such as the reduction of triiodothyronine and thyroxine levels, along with an increase in the expression of alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase. Discussion: The study's findings imply that certain changes can be underscored to highlight a reduced risk of conception. Notably, previous investigations have indicated that subfertile women exhibit lower levels of thyroid hormones and elevated lactate dehydrogenase expression. Despite the absence of preclinical data delineating a possible association between periodontitis and female infertility, the results of this study may prove to be a crucial contribution to both the scientific and medical fields.

Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice

Thyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. We explored these genes and created an expression panel that assesses liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH action under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state.

Thyroid hormone may predict treatment failure in Kawasaki disease.

In systemic inflammatory conditions, inflammatory cytokines can cause low thyroid hormone levels. There are no reports discussing the relation between thyroid hormone levels and response to treatment for Kawasaki disease. We investigated 67 patients who underwent treatment in the acute phase of Kawasaki disease. We divided patients into two groups based on their response to initial intravenous immunoglobulin (IVIG) treatment: the responder group (n = 40), and the non-responder group (n = 27). The serum levels of the thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were compared before and after treatment in all patients, and between responder and non-responder groups. The FT3, FT4, and TSH levels were low before the initial treatment and increased significantly after treatment (p < 0.05). The FT3, FT4, and TSH levels before treatment were significantly lower in the non-responder group than in the responder group (p < 0.05). Logistic regression analysis suggested that the addition of pre-treatment FT4 values to Gunma score was useful in predicting treatment failure. Thyroid hormone and TSH levels were lower in the non-responder group than in the responder group in the initial IVIG treatment for Kawasaki disease. This study suggests that Kawasaki disease in the acute phase is associated with low thyroid hormone levels and TSH. It is possible that these hormone levels predict response to the initial IVIG.

Single-nucleus transcriptome inventory of giant panda reveals cellular basis for fitness optimization under low metabolism

BackgroundEnergy homeostasis is essential for the adaptation of animals to their environment and some wild animals keep low metabolism adaptive to their low-nutrient dietary supply. Giant panda is such a typical low-metabolic mammal exhibiting species specialization of extremely low daily energy expenditure. It has low levels of basal metabolic rate, thyroid hormone, and physical activities, whereas the cellular bases of its low metabolic adaptation remain rarely explored.ResultsIn this study, we generate a single-nucleus transcriptome atlas of 21 organs/tissues from a female giant panda. We focused on the central metabolic organ (liver) and dissected cellular metabolic status by cross-species comparison. Adaptive expression mode (i.e., AMPK related) was prominently displayed in the hepatocyte of giant panda. In the highest energy-consuming organ, the heart, we found a possibly optimized utilization of fatty acid. Detailed cell subtype annotation of endothelial cells showed the uterine-specific deficiency of blood vascular subclasses, indicating a potential adaptation for a low reproductive energy expenditure.ConclusionsOur findings shed light on the possible cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas and helped to understand physiological adaptation response to nutrient stress.

Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease.

The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-β in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-β agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-β agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-β agonists have on hepatic lipid metabolism.

Severe hypothyroidism as the cause of rhabdomyolysis and acute kidney injury – a case report

Hypothyroidism is a set of clinical symptoms associated with a deficiency of thyroid hormones. Musculoskeletal symptoms, i.e. stiffness, pain or muscle fatigue, are among the many manifestations of the disorder. Rhabdomyolysis, a syndrome accompanying muscle tissue damage, which leads to acute kidney injury, may be a complication of hypothyroidism. In this paper, we present a case of a 35-year-old patient with hypothyroidism due to Hashimoto’s disease, with a 4-year history of diagnosis for periodic pain and muscle weakness in the lower extremities. The patient presented to the hospital due to the recurring symptoms. One month before admission, she had discontinued thyroid hormone supplementation. Laboratory tests showed unquantifiable low levels of free thyroid hormones, elevated creatine kinase levels, and elevated kidney function parameters. Non-compliance can lead to potentially life-threatening complications in hypothyroid patients. Prompt diagnosis and implementation of treatment can lead to symptom resolution.

Effect of Ayurveda formulations in Primary Hypothyroidism with respect to prakriti - A multi-center clinical study

Primary hypothyroidism is defined as low levels of blood thyroid hormone due to destruction of the thyroid gland. Based on the signs and symptoms in Ayurvedic classics, Hypothyroidism can be described as kapha-medo vridhi and dhātvāgnimāndhya and considered as a condition called galaganda. Ayurveda stresses the importance of prakriti as a prognostic factor in the management of diseases. With due consideration, this study is intended to evaluate the effect of three commonly used indigenous formulations viz., Hamsapathyadikashaya, Kanchanaraguggulu and Bhallatakalehya in primary hypothyroidism when administered with respect to dehaprakriti of the individuals.

The isl2a transcription factor regulates pituitary development in zebrafish.

ISL LIM homeobox 2, also known as insulin gene enhancer protein ISL-2 (ISL2), is a transcription factor gene that participates in a wide range of developmental events. However, the role of ISL2 in the hypothalamus-pituitary-thyroid axis is largely unknown. In the present study, we characterized the expression patterns of ISL2 and revealed its regulative role during embryogenesis using zebrafish. We used the CRISPR/Cas9 system to successfully establish homozygous ISL2-orthologue (isl2a and isl2b) knockout zebrafish. Moreover, we utilized these knockout zebrafish to analyze the pituitary and thyroid phenotypes in vivo. For further molecular characterization, in situ hybridization and immunofluorescence were performed. The isl2a mutant zebrafish presented with thyroid hypoplasia, reduced whole-body levels of thyroid hormones, increased early mortality, gender imbalance, and morphological retardation during maturity. Additionally, thyrotropes, a pituitary cell type, was notably decreased during development. Importantly, the transcriptional levels of pituitary-thyroid axis hormones-encoding genes, such as tshba, cga, and tg, were significantly decreased in isl2a mutants. Finally, the thyroid dysplasia in isl2a mutant larvae may be attributed to a reduction in proliferation rather than changes in apoptosis. In summary, isl2a regulates the transcriptional levels of marker genes in hypothalamus-pituitary-thyroid axis, and isl2a knockout causing low thyroid hormone levels in zebrafish. Thus, isl2a identified by the present study, is a novel regulator for pituitary cell differentiation in zebrafish, resulting in thyroid gland hypoplasia and phenotypes of hypothyroidism.