Thyroid Hormone Production Research Articles

Hypothyroidism is Strongly Correlated with Mean Platelet Volume and Red Cell Distribution Width

Abstract: Objective: Hypothyroidism is characterized with insufficient production and release of thyroid hormones, and cause a variety symptoms including cold intolerance, constipation, deceleration in movement, and hair loss. It is associated with increased inflammatory burden. Therefore, we aimed to observe red cell distribution width (RDW) and mean platelet volume (MPV) levels, novel predictors of inflammation, in patients with hypothyroidism and to compare to those in healthy subjects. Materials and Methods: The subjects with hypothyroidism that show up in internal medicine outpatient clinics of Abant Izzet Baysal University Hospital between January 2020 and January 2021 were enrolled to the retrospective study. Healthy volunteers were enrolled as control subjects. MPV and RDW of the study groups were compared. Results: The median RDW level of hypothyroid and control groups were 13.3 (10-20.7) % and 15.3 (11.8-21.3) %, respectively (p<0.001). The median MPV level of hypothyroid and control groups were 10.2 (6.4-12.4) fL and 8.1 (5.4-11.5) fL, respectively (p<0.001). MPV levels greater than 9.47 fL have 80% sensitivity and 72% specificity in predicting hypothyroidism (AUC: 0.66 [95% CI: 0.58-0.74]; p<0.001). RDW levels greater than 13.4% have 80% sensitivity and 50% specificity in predicting hypothyroidism (AUC: 0.67 [0.82 [95% CI: 0.59-0.75]; p<0.001). Conclusion: We suggest that elevated MPV and reduced RDW levels should alert physicians for hypothyroidism in otherwise healthy subjects. Keywords: Hypothyroidism, Red cell distribution width, Mean platelet volume, Inflammation, Thyroid hormones, Predictor, Retrospective study.

Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease

BackgroundGraves’ disease is an autoimmune disorder characterised by excessive production of thyroid hormones, which induces increased cellular metabolism in most tissues and increased production of reactive oxygen species (ROS). The aim of this work was to analyse the effect of ROS on cell viability and the expression of catalase (CAT), glutathione peroxidase-1 (GPx-1), superoxide dismutase (SOD-1) and DNA methyltransferase-1 (DNMT-1) in peripheral blood mononuclear cells (PBMC) from patients with newly diagnosed Graves’ disease or treated with methimazole. Patients and methodsFor this study, women patients with newly diagnosed Graves’ disease (n=18), treated with methimazole (n=6) and healthy subjects (n=15) were recruited. ROS were evaluated by flow cytometry, and the viability/apoptosis of PBMC was analysed by flow cytometry and fluorescence microscopy. Genomic expression of CAT, GPx-1, SOD-1 and DNMT-1 was quantified by real-time PCR. ResultsWe found high levels of ROS and increased expression of CAT, GPx-1, SOD-1 and DNMT-1 in PBMC from patients with newly diagnosed Graves’ disease. Methimazole treatment reversed these parameters. Cell viability was similar in all study groups. ConclusionsROS induces the expression of CAT, GPx-1, and SOD-1. The activity of these enzymes may contribute to the protection of PBMC from the harmful effect of free radicals on cell viability. Increased expression of DNMT-1 may be associated with aberrant methylation patterns in immunoregulatory genes contributing to autoimmunity in Graves’ disease.

​Comparative Gross Anatomical and Biometrical Studies on Thyroid Gland of Buffalo, Sheep and Goat

Background: The thyroid gland is vital endocrine gland which secretes three hormones i.e. thyroxin (T4), triiodothyronine (T3) and Calcitonin hormones. The thyroxin (T4) and triiodothyronine (T3) hormones are biologically active and are required for maintenance of normal levels of metabolic activity. The thyroid also produces calcitonin from the parafollicular cells which act directly on osteoclast to decrease the bone resorption which lower the blood calcium level. Deficient or excessive production of thyroid hormones may lead to serious pathological states with outward symptoms. Methods: The gross anatomical and biometrical studies were conducted on thyroid gland of buffalo, sheep and goat (n=12) collected immediately after slaughtering from slaughter house and local meat shop. The weight of thyroid gland was measured by weighing balance, volume by water displacement method, length and width of lateral lobes and isthmus by calibrated scale and inelastic thread and thickness of lateral lobes and isthmus was measured by digital vernier calliper. The data was analysed statistically. Result: The lateral lobes were roughly triangular in buffalo and elongated in sheep and oval in goat. The surfaces were granular and rough in buffalo but smooth in sheep and goat. It extended from thyroid cartilage to 2nd tracheal ring in buffalo, 1st to 6th tracheal ring in sheep and 1st to 7th tracheal ring in goat. The left lobe was larger than the right lobe in all the three species studied. The thyroid gland was biggest in buffalo followed by goat and smallest in sheep. The density of isthmus was more than the lobes in sheep and goat but not in buffalo.

Isotopic Tracing of Perchlorate Sources in the Environment

Perchlorate (ClO4−) is an emerging persistent pollutant that is ubiquitous in the environment at trace concentrations. Perchlorate ingestion poses a risk to human health because it interferes with thyroidal hormone production. The identification of perchlorate sources in groundwater is a primary concern. Chlorine and multi-oxygen isotopic tracing of perchlorate (δ37Cl, 36Cl/Cl, δ18O, and Δ17O) can provide a unique tool for identifying the origin and transport of perchlorate in groundwater. Along with the kinetic fractionation of chlorine and oxygen isotopes, the Δ17O value, 36Cl/Cl ratio, and ε18O/ε37Cl (the fractionation coefficient of oxygen and chlorine isotopes) are constant, potentially indicating the biodegradation of perchlorate, without disguising its source information. Therefore, comprehensive characterization of stable chlorine and poly-oxygen isotopes is expected to provide direct evidence for identifying the source of perchlorate in groundwater. However, further studies are needed to increase the amount of isotopic data of different perchlorate sources, to make the end-member model available to broader regions. It is critically important to understand the range of values and differences of isotopes among natural perchlorate sources and the perchlorate formation mechanisms.

A Study and Report on the Role of Clinical Pharmacy Services Provided by the Doctor of Pharmacy in the Management of Thyroid Disorders (Hyperthyroidism and Hypothyroidism) to a Tertiary Care Hospital

Thyroid hormones affect the function of virtually every organ system. In children, thyroid hormone is critical for normal growth and development but in adults, the main role of these thyroid hormones is to maintain stability. The main thyroid hormones which play such an important are the Thyroxine (T4) and Triiodothyronine (T3) hormones. Hence, Thyroid disorders encompass a variety of disease states affecting thyroid hormone production or secretion that result in alteration in the metabolic stability. Hyperthyroidism and Hypothyroidism are the clinical and biochemical syndromes resulting from increased and decreased thyroid hormone production, respectively. Thyroid disorder/ disease is more or less considered to be a type of chronic disease, henceforth Clinical Pharmacy and the Clinical Pharmacists play a vital role in helping such patients to cope up and also overcome the disorder. Clinical pharmacy is the branch of pharmacy and is the practice of pharmacy that helps the pharmacists provide services to promote rational and economical drug therapy that is appropriate,safe and cost effective which in turn optimizes the use of medication and promote wellness,health and disease prevention.Clinical pharmacists provide care for patients in all health care settings. Clinical pharmacists often work in collaboration with physicians,nurse practitioners and other health care practitioners. There are various Clinical Pharmacy services that can be offered to various outpatients and inpatients such as pharmacovigilance services, development and management of hospital formulary, patient counselling and education along with discharge medication, drug information services, poison centre, and ward round participation. Aim: The main aim of this article is to determine the role of the Clinical Pharmacy Services for the management of thyroid disorders mainly Hyperthyroidism and Hypothyroidism. To ensure safe, effective, economic and patient friendly with the knowledge inputs of each professional practice. Objectives: To study the Role of the Clinical Pharmacy Services/ Doctor of Pharmacy profession in the management of Thyroid Disorders. To monitor drug therapy efficiently, to attain desired pharmacological effect of the drug, to reduce risk of toxicity and thereby improving the health-related quality of life (HRQOL) of the patient . Methodology: The details regarding his/her condition of thyroid disorder were collected from the patients’ case sheets, medication charts, drug and poison information queries, ADR reporting forms, drug interaction forms etc either present in the nursing stations or through direct interaction with the patient. In regards to this, appropriate patient counselling was also given to patients according to his/ her condition of thyroid. Discussion and results: The sample size for the study conducted was taken to be around 120 patients and the role of all related Clinical Pharmacy Services/ activities such as monitoring for drug therapy, adverse drug reactions, medication errors, providing drug and poison information to the concerned patients or caregivers and thus providing patient counselling for improvement of health and quality of life for patients, for the management of Hyperthyroidism and Hypothyroidism is determined. Conclusion: It is concluded that the management of thyroid disorders is rather a burden on individual patients and this can be overcome by providing the Clinical Pharmacy Services to patients suffering from thyroid disorders, which can be provided by the Doctor of Pharmacy Professionals thereby improving the quality of life of patient so that their ability to manage thyroid conditions is improved to the optimum maximum level.

Clinical Profile of Patients with Hyperthyroidism in Zagazig University Hospitals

Hyperthyroidism is a condition that occurs due to over production of thyroid hormones by the thyroid gland . It can be categorized according to thyroid hormone levels into overt and subclinical hyperthyroidism. Also could be classified into, normal (or high) and low thyroid radioactive iodine uptake according to radioiodine uptake. So, the aim of this study was to evaluate the difference in the clinical profile between hyperthyroid patients and its relation to thyroid scan imaging. Also to avoid prescribing antithyroid medications to patients with thyroiditis, this could lead to hypothyroidism . Materials and methods: This is a prospective cohort study for patients with hyperthyroidism. Patients have been enrolled from Endocrinology Outpatient Clinic at Zagazig University Hospitals in the period from December 2018 to October 2020. Results: patients were divided into two major groups, overt hyperthyroidism (group 1) and subclinical hyperthyroidism (group 2). All patients of group (1) had abnormal thyroid gland examination but, only 50 % of group (2) patients had showed abnormal gland examination (p= <0.001). 83 .3% of patients of group (1) had high thyroid uptake and 62.5 % of patients of group (2) had high thyroid uptake (p=0.108). There was highly statistical significance between the two groups as regard F. T4( P = <0.001) and F .T3 (p = < 0.001 ) , but no difference in TSH( p =0.223) . Conclusion: The thyroid scan had cross linkage with abnormal thyroid function ,

Hyperthyroidism in adolescents.

The term 'hyperthyroidism' refers to a form of thyrotoxicosis due to inappropriate high synthesis and secretion of thyroid hormone(s) by the thyroid. The leading cause of hyperthyroidism in adolescents is Graves’ disease (GD); however, one should also consider other potential causes, such as toxic nodular goitre (single or multinodular), and other rare disorders leading to excessive production and release of thyroid hormones. The term 'thyrotoxicosis' refers to a clinical state resulting from inappropriate high thyroid hormone action in tissues, generally due to inappropriate high tissue thyroid hormone levels. Thyrotoxicosis is a condition with multiple aetiologies, manifestations, and potential modes of therapy. By definition, the extrathyroidal sources of excessive amounts of thyroid hormones, such as iatrogenic thyrotoxicosis, factitious ingestion of thyroid hormone, or struma ovarii, do not include hyperthyroidism. The aetiology of hyperthyroidism/and thyrotoxicosis should be determined. Although the diagnosis is apparent based on the clinical presentation and initial biochemical evaluation, additional diagnostic testing is indicated. This testing should include: (1) measurement of thyroid-stimulating hormone receptor (TSHR) antibodies (TRAb); (2) analysis of thyroidal echogenicity and blood flow on ultrasonography; or (3) determination of radioactive iodine uptake (RAIU). A 123I or 99mTc pertechnetate scan is recommended when the clinical presentation suggests toxic nodular goitre. A question arises regarding whether diagnostic workup and treatment (antithyroid drugs, radioiodine, surgery, and others) should be the same in children and adolescents as in adults, as well as whether there are the same goals of treatment in adolescents as in adults, in female patients vs in male patients, and in reproductive or in postreproductive age. In this aspect, different treatment modalities might be preferred to achieve euthyroidism and to avoid potential risks from the treatment. The vast majority of patients with thyroid disorders require life-long treatment; therefore, the collaboration of different specialists is warranted to achieve these goals and improve patients’ quality of life.

Management of Feline Hyperthyroidism and the Need to Prevent Oxidative Stress: What Can We Learn from Human Research?

Feline hyperthyroidism is a clinical syndrome related to an excessive production of thyroid hormones, and it is considered as a spontaneous animal model for human thyrotoxicosis. Many shared features between the feline and the human disease have been identified so far, including pathogenesis, clinical signs, and treatment options. Although methimazole is considered the first-choice drug in both species, several side effects have been described. Furthermore, methimazole could interfere with the oxidative status, already perturbated by the disease. It has been reported in humans that dietary management, mainly through antioxidant supplementation, could mitigate this oxidative burden. The purpose of the review is to describe current therapeutic options in the course of feline hyperthyroidism and to summarize the state of the art relationship between dietary antioxidants administration and the reduction of methimazole side-effects in humans to support the use of this approach also in cats.

Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn.

BackgroundSeveral factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels.MethodsThis prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels.ResultsSubjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L [13.2 μg/L (1.3 - 46.5) vs 19.7 μg/L (2.4 - 48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05).ConclusionsOur results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.

Thyroid Hormones in the Human Body: A review

Thyroid gland is an essential endocrine gland that is present in the human body. This review highlights the production, regulation and disease conditions of the thyroid hormones. The thyroid gland is controlled with the help of hypothalamus and the pituitary gland that is present in the brain. The production of thyroid hormones involves five main steps such synthesis of thyroglobulin (TG), iodide uptake, iodination of thyroglobulin, storage and release. The two important hormones produced by the thyroid gland are Thyroxine (T4) and Triiodothyronine(T3). These two hormones are iodine containing derivatives. Deficiency of iodine in the body results in the reduction of T3 and T4 production. Excess and deficiency of these two hormones result in the major diseases like Hyper and Hypothyroidism. The synthetic forms of Thyroxine(T4) and Triiodothyronine(T3) used in the Pharmaceutical field are Levothyroxine and Liothyronine. Women are most commonly prone to these thyroid diseases comparatively to men. Undiagnosed disease conditions may become fatal. Levothyroxine therapy is commonly used for thyroidism which is a similar synthetic thyroid hormone. Also natural thyroid hormones that are obtained from the dried thyroid glands of animals are available. Thyroid function test and the measurement of T3, T4 plasma level becomes essential for the identification and regular maintenance of thyroid hormones in the body and human well-being.&#x0D;

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring.Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns.Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders.Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83–68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70–8.23) μIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27–13.53) μg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36–12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6–24.9) μg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19–24.9).Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

The Influence of Oxidative Stress on Thyroid Diseases.

Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate the oxidative profile in patients with thyroid diseases compared to the healthy population. This opens up a new perspective for investigating the role of elevated parameters of oxidative stress and damage in people with thyroid diseases, especially of neoplastic nature. An imbalance between oxidants and antioxidants is observed at different stages and in different types of thyroid diseases. The organ, which is part of the endocrine system, uses free radicals (reactive oxygen species, ROS) to produce hormones. Thyroid cells release enzymes that catalyse ROS generation; therefore, a key role is played by the internal defence system and non-enzymatic antioxidants that counteract excess ROS not utilised to produce thyroid hormones, acting as a buffer to neutralise free radicals and ensure whole-body homeostasis. An excess of free radicals causes structural cell damage, undermining genomic stability. Looking at the negative effects of ROS accumulation, oxidative stress appears to be implicated in both the initiation and progression of carcinogenesis. The aim of this review is to investigate the oxidation background of thyroid diseases and to summarise the links between redox imbalance and thyroid dysfunction and disease.

XB130 Deficiency Causes Congenital Hypothyroidism in Mice due to Disorganized Apical Membrane Structure and Function of Thyrocytes.

Background: Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. Methods:Xb130-/- mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. Results:Xb130-/- mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of Xb130-/- mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal Xb130-/- mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. Conclusion: XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.

Selenium Nanoparticles as a Natural Antioxidant and Metabolic Regulator in Aquaculture: A Review.

Balanced aquafeed is the key factor for enhancing the productivity of aquatic animals. In this context, aquatic animals require optimal amounts of lipids, proteins, carbohydrates, vitamins, and minerals. The original plant and animals’ ingredients in the basal diets are insufficient to provide aquafeed with suitable amounts of minerals. Concurrently, elements should be incorporated in aquafeed in optimal doses, which differ based on the basal diets’ species, age, size, and composition. Selenium is one of the essential trace elements involved in various metabolic, biological, and physiological functions. Se acts as a precursor for antioxidative enzyme synthesis leading to high total antioxidative capacity. Further, Se can enhance the immune response and the tolerance of aquatic animals to infectious diseases. Several metabolic mechanisms, such as thyroid hormone production, cytokine formation, fecundity, and DNA synthesis, require sufficient Se addition. The recent progress in the nanotechnology industry is also applied in the production of Se nanoparticles. Indeed, Se nanoparticles are elaborated as more soluble and bioavailable than the organic and non-organic forms. In aquaculture, multiple investigations have elaborated the role of Se nanoparticles on the performances and wellbeing of aquatic animals. In this review, the outputs of recent studies associated with the role of Se nanoparticles on aquatic animals’ performances were simplified and presented for more research and development.

Urinary Iodine Status at Delivery in Rural Pregnant Mothers from KONKAN Region of India (BKLWHANC-2)

Adequate iodine is necessary in pregnancy for normal maternal as well as fetal thyroid function. Fetus cannot produce thyroid hormone so it is exclusively dependent on mother. During pregnancy, iodine demand is increased by 50%. An adequate intake of dietary iodine in pregnancy is essential for the normal neurodevelopment of the offspring. We measured urinary iodine concentrations in 220 pregnant women who reported for delivery at a rural hospital in the KONKAN region of the State of Maharashtra, India. The mean age and gestation at delivery were 26.9 years and 38.2 weeks respectively. The observed median UIC was 84.6μg/l. Urinary iodine of mother was not associated with neonatal anthropometric measurements (weight, length and head circumference). We have found low median UIC levels at delivery among pregnant women. The increased demand in pregnancy could be met by iodine supplementation or increasing iodine content in the salt. The burden of poor iodine status in pregnant women will further adversely affect the fetal neurodevelopment. There should be universal screening of every pregnant woman for the identification of iodine status. A simple strategy of improving iodine content in the salt beyond the current recommendation for pregnant women might be beneficial for mother as well as fetus but continuous monitoring for adequate iodine is warranted.

Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production.

Thyroid hormone receptor β (THRB) is posttranslationally modified by small ubiquitin-like modifier (SUMO). We generated a mouse model with a mutation that disrupted sumoylation at lysine 146 (K146Q) and resulted in desumoylated THRB as the predominant form in tissues. The THRB K146Q mutant mice had normal serum thyroxine (T4), markedly elevated serum thyrotropin-stimulating hormone (TSH; 81-fold above control), and enlargement of both the pituitary and the thyroid gland. The marked elevation in TSH, despite a normal serum T4, indicated blunted feedback regulation of TSH. The THRB K146Q mutation altered the recruitment of transcription factors to the TSHβ gene promoter, compared with WT, in hyperthyroidism and hypothyroidism. Thyroid hormone content (T4, T3, and rT3) in the thyroid gland of the THRB K146Q mice was 10-fold lower (per gram tissue) than control, despite normal TSH bioactivity. The expression of thyroglobulin and dual oxidase 2 genes in the thyroid was reduced and associated with modifications of cAMP response element–binding protein DNA binding and cofactor interactions in the presence of the desumoylated THRB. Therefore, thyroid hormone production had both TSH-dependent and TSH-independent components. We conclude that THRB sumoylation at K146 was required for normal TSH feedback regulation and TH synthesis in the thyroid gland, by a TSH-independent pathway.

P–421 Down-expression of glycolytic pathway-related protein A1 is associated with the pathogenesis of recurrent pregnancy loss

Abstract Study question How does glycolytic pathway-related protein A1 (GPRPA1) relate to the pathogenesis of recurrent pregnancy loss (RPL)? Summary answer GPRPA1 was found as a substrate of ITI-H4 to modulate the inflammatory response and was down-expressed in the sera of RPL patients. What is known already Thus far, the pathogenesis of RPL was not fully understood. In a previous study, the short isoform ITI-H4 cleaved by kallikrein B1 was detected in the sera of RPL patients and would be an important inflammatory factor for RPL by increasing pro-inflammatory cytokines. GPRPA1, a new binding partner of ITI-H4, was known to relate with pre-eclampsia and human decidualization by regulating angiogenesis and glycolysis. Also, GPRPA1 affects placental cell motility and cancer cell proliferation. Study design, size, duration Through immunoprecipitation (IP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analyses, we found new binding partners of ITI-H4. Of these, GPRPA1 was selected, and direct binding between GPRPA1 and ITI-H4 was confirmed by IP and GST pull-down assay. Differential expression of GPRPA1 in sera and cellular functions of GPRPA1 in the placental cell line were investigated by molecular and cellular analyses. Participants/materials, setting, methods The Flag-tagged full-length ITI-H4 and the short isoform ITI-H4 were transfected into HEK293T cells and IP has proceeded with the Flag antibody. Spots showing differential expression were analyzed by MALDI-TOF/MS analysis and peptide sequence alignment was performed. The binding between GPRPA1 and ITI-H4 was confirmed using IP and GST pull-down assay. The effects of GPRPA1 on cellular functions in the placental cell were investigated by CCK–8 assay, invasion assay, and colony-forming assay. Main results and the role of chance Through IP, MALDI-TOF/MS analysis, and peptide sequence alignment, we found new substrates of ITI-H4 related to glycolysis, T cell activation, and production of thyroid hormones. Of these, we selected GPRPA1 which is secreted in the serum to utilize a serum biomarker of RPL. GPRPA1 directly binds to the full-length ITI-H4 and also binds to the short isoform ITI-H4 shown by IP and GST pull-down assay. Besides, GPRPA1 as a protein kinase increases serine phosphorylation of ITI-H4 and inhibits the cleavage by KLKB1. GPRPA1 is expressed significantly lower in the sera of PRL patients than the control group and knockdown of GPRPA1 negatively regulates cell motility in the placental cell. Therefore, down-expressed GPRPA1 would be one of the causes of RPL and can be utilized as a serum biomarker of RPL. Limitations, reasons for caution Additional in vivo study is needed to specifically investigate the effect of GPRPA1 on the pathogenesis of RPL. Wider implications of the findings: By investigating the cellular functions of GPRPA1 in the placental cell, we found that it is an important key factor for the pathogenesis of RPL, and down-regulation of GPRPA1 can be utilized as a biomarker of RPL. Trial registration number Not applicable

AYURVEDIC PERSPECTIVE OF SUBCLINICAL HYPOTHYROIDISM

Thyroid gland is one of the important glands of the endocrine system and thyroid disorders are the most common disorders amongst the general population worldwide, as well as in india. Hypothyroidism is caused by inadequate function of the thyroid gland called as primary hypothyroidism or by insufficient stimulation by thyroid- stimulating hormones called as secondary hypothyroidism. Current view the thyroid gland is a butterfly shaped gland. It is located inferior to the larynx and anterior to the trachea. It has two lobes connected by the isthmus. It is made of microscopic spherical masses called follicles. A secretary substance is present in the follicle called colloid. Colloid is made of a glycoprotein called as thyroglobulin. Thyroglobulin produces thyroid hormones. They are triiodothyronine (t3), tetraiodothyronine (t4) and calcitonin. Ayurvedic perspective of subclinical hypothyroidism. Management of hypothyroidism with synthetic thyroid hormone derivatives may bring the value of tsh, t3 and t4 to normal range but the daily intake of medicine for lifetime, the known side-effects thereafter and increase in the dosage with time as the disease become chronic, is troublesome for the patients. Also the quality of life of the patients taking medicine regularly for long durations is compromised.

Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk.

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the “0“ time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α–dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

45-Year-Old Woman With Fever and Malaise

45-Year-Old Woman With Fever and Malaise