Thyroid Hormone Metabolism Research Articles

The role of thyroid hormone in the renal immune microenvironment.

Thyroid hormones are essential for proper kidney growth and development. The kidney is not only the organ of thyroid hormone metabolism but also the target organ of thyroid hormone. Kidney disease is a common type of kidney damage, mainly including different types of acute kidney injury, chronic kidney disease, diabetic nephropathy, lupus nephritis, and renal cell carcinoma. The kidney is often damaged by an immune response directed against its antigens or a systemic immune response. A variety of immune cells in the innate and adaptive immune systems, including neutrophils, macrophages, dendritic cells, T lymphocytes, and B lymphocytes, is essential for maintaining immune homeostasis and preventing autoimmune kidney disease. Recent studies have found that thyroid hormone plays an indispensable role in the immune microenvironment of various kidney diseases. Thyroid hormones regulate the activity of neutrophils, and dendritic cells express triiodothyronine receptors. Compared to hypothyroidism, hyperthyroidism has a greater effect on neutrophils. Furthermore, in adaptive immune systems, thyroid hormone may activate T lymphocytes through several underlying mechanisms, such as mediating NF-κB, protein kinase C signalling pathways, and β-adrenergic receptors, leading to increased T lymphocyte activation. The present review discusses the effects of thyroid hormone metabolism regulation in the immune microenvironment on the function of various immune cells, especially neutrophils, macrophages, dendritic cells, T lymphocytes, and B lymphocytes. Although there are not enough data at this stage to conclude the clinical relevance of these findings, thyroid hormone metabolism may influence autoimmune kidney disease by regulating the renal immune microenvironment.

Assessment of the Predictivity of DIO1-SK Assay to Investigate DIO1 Inhibition in Human Liver Microsomes

Introduction: The European Union Reference Laboratory for alternatives to animal testing (EU RL ECVAM) coordinates the validation of multiple thyroid in vitro assays aiming to set up an in vitro test battery. The validation consists of two independent parts: part 1 (Reproducibility assessment) in which the reproducibility of the method is evaluated by testing a small number of described inhibitors and part 2 (Predictivity assessment) where the predictivity of the method is investigated by testing a blinded set of substances. The deiodinases (DIO) are important regulators of thyroid hormone (TH) metabolism and potential targets for substance-induced thyroid disruption. We previously reported the part 1 results for the Sandell–Kolthoff reaction-based type 1 deiodinase (DIO1-SK) assay and an extensive description of the method. In this study, we report the results of the part 2 testing in the DIO1-SK assay. Methods: A set of 22 test substances consisting of known DIO inhibitors in vitro, as well as substances otherwise interfering with the TH system and substances with no such activities were tested in the standardized DIO1-SK assay. Experiments were performed on blinded substances, which were deblinded after experimental completion, statistically evaluated, and compared to literature data. Finally, an in vitro data interpretation procedure (DIP) was generated. Results and Discussion: Seven test substances produced a maximum DIO1 inhibition >90% and 11 test substances below 20%; they were regarded as inhibitors and noninhibiting substances, respectively. Two test substances, Ketoconazole and Silichristin, were found to be not applicable based on assay interference. Inhibition data were consistent with results of relevant in vitro and computational models. Using the variation of control data, an in vitro DIP was defined categorizing test substances (i) by efficacy using the maximum inhibition data and (ii) by potency using the IC50 data of the test substance.

Thyroid hormone regulates proximodistal patterning in fin rays

Processes that regulate size and patterning along an axis must be highly integrated to generate robust shapes; relative changes in these processes underlie both congenital disease and evolutionary change. Fin length mutants in zebrafish have provided considerable insight into the pathways regulating fin size, yet signals underlying patterning have remained less clear. The bony rays of the fins possess distinct patterning along the proximodistal axis, reflected in the location of ray bifurcations and the lengths of ray segments, which show progressive shortening along the axis. Here, we show that thyroid hormone (TH) regulates aspects of proximodistal patterning of the caudal fin rays, regardless of fin size. TH promotes distal gene expression patterns, coordinating ray bifurcations and segment shortening with skeletal outgrowth along the proximodistal axis. This distalizing role for TH is conserved between development and regeneration, in all fins (paired and medial), and between Danio species as well as distantly related medaka. During regenerative outgrowth, TH acutely induces Shh-mediated skeletal bifurcation. Zebrafish have multiple nuclear TH receptors, and we found that unliganded Thrab-but not Thraa or Thrb-inhibits the formation of distal features. Broadly, these results demonstrate that proximodistal morphology is regulated independently from size-instructive signals. Modulating proximodistal patterning relative to size-either through changes to TH metabolism or other hormone-independent pathways-can shift skeletal patterning in ways that recapitulate aspects of fin ray diversity found in nature.

Thyroid Dysfunction and Chronic Kidney Disease: A Study Among the Northeastern Population of India.

Chronic kidney disease (CKD) is a multifaceted non-communicable disease characterized by a progressive decline in kidney function ultimately requiring renal replacement therapy (RRT) in most patients. Due to the high cost and availability of a limited number of donors, the majority of patients dependon dialysis and conservative management. Thyroid hormones are indispensable for the growth, development, and homeostasis of our body. The kidney plays an important role in the metabolism, degradation, and excretion of thyroid hormones. Various studies have revealed significant dysfunction in thyroid hormone status in CKD patients, but the results are inconsistent. To evaluate and compare the thyroid hormone status in CKD patients with healthy controls along with a comparison of thyroid hormones in CKD patients on regular hemodialysis with those on conservative management. The present cross-sectional study involved 100 subjectsof both sexes between 40 and 70 years of age, out of which 50 were patients of stage 5 CKDwith no previous history of any thyroid disorders, while 50 apparently healthy subjects served as control. Of the CKD patients,52% were on regular hemodialysis while 48% were receiving conservative care. The participants were investigated for various biochemical parameters like blood urea, serum creatinine, total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH). The estimated glomerular filtration rate (eGFR) was calculated using a modification of diet in renal disease (MDRD) 4 variable formula. The thyroid profiles were also compared between patients of CKD receiving conservative management and those on maintenance hemodialysis. Of the total sample, 35 (70%) were male and 15 (30%) were female in each of the case and control groups. The mean ageof CKD patients and the control group was 55.32 ± 9.62 years and 54.48 ± 9.63 years, respectively. TT3 was reduced in all50 CKD patients. TT4 was normal in 31 (62%), reduced in 18 (36%), and high in one (2%) case. TSH was high in 38 (76%) cases, while reduced in one (2%) and normal in 11 (22%) cases. The mean blood level of TT3 and TT4 showed a statistically significant reduction (P < 0.0001 for each), while the TSH level showed a significant increase with a p-value of 0.0002 in CKD patients compared to controls. The mean blood urea and serum creatinine levels were statistically increased in cases than in controls (P < 0.0001). The thyroid hormone status revealed a significant difference between CKD patients on maintenance hemodialysis compared to those on conservative care with a p-value of 0.0005 for TT3, 0.0006 for TT4, and 0.0055 for TSH. Patients with CKD were at risk of thyroid hypofunction irrespective of their mode of treatment. This study highlights the clinically relevant interactions between renal and thyroid function, which may be helpful to clinicians for optimal diagnosis and management of CKD patients.

The impact of lockdown on thyroid hormone metabolism in patients on levothyroxine replacement therapy residing in Adjara

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MiR-24–3p/Dio3 axis is essential for BDE47 to induce local thyroid hormone disorder and neurotoxicity

BDE47 (2,2,4,4-tetrabromodiphenyl ether) is a member of the most important congeners of polybrominated diphenyl ethers (PBDEs) and has been identified as a developmental, reproductive and nervous system toxicant and endocrine system disruptor due to its frequent detection in human tissue and environmental samples. Our preliminary work suggested that high- and low-level of bromodiphenyl ethers have different effects on neuronal cells with differential targets of actions on neural tissues. In this study, we presented the underlying mechanism of BDE47 neurotoxicity from the perspective of thyroid hormone (TH) metabolism using in vitro model of human SK-N-AS neuronal cells. BDE47 could induce local TH metabolism disorder in neuronal cells by inhibiting the expression of the main enzyme, human type III iodothyronine deiodinase (Dio3). Further elucidation revealed that BDE47 effectively up-regulating miR-24–3p, which binds to the 3′-UTR of Dio3 and inhibits its expression. In addition, BDE47 could also inhibit the deiodinase activity of Dio3. Collectively, our study demonstrates the molecular mechanism of BDE47 regulating Dio3-induced TH metabolism disorder through inducing miR-24–3p, providing new clues for the role of miRNAs in neurodevelopmental toxicity mediated by environmental pollutants.

Combined toxicity assessment of a naturally occurring toxin and a triazole fungicide on different biological processes through toxicogenomic data mining with mixtures

Fungicides are widely used to prevent fungal growth and reduce mycotoxin contamination in food, which provides the opportunity for the co-occurrence of mycotoxins and fungicide residues in food and poses a greater risk to human health. To assess the combined effects of a naturally occurring mycotoxin, citrinin (CIT), and a widely used triazole fungicide, triadimefon (TAD) on different biological processes, the comparative toxicogenomics database was used to obtain phenotypes and response genes for CIT or TAD exposure. Then individual and combined exposure models were developed with zebrafish embryos, and the interaction between CIT and TAD was analyzed using the 2 × 2 factorial design approach to observe the toxic effects. Through data mining analysis, our results showed that CIT or TAD exposure is related to different biological phenotypes, such as cell death, regulation of antioxidant systems, and thyroid hormone metabolism. Our results also showed that CIT (4-day LC50 value of 12.7 mg/L) exposure possessed higher toxicity to zebrafish embryos compared with TAD (4-day LC50 value of 29.6 mg/L). Meanwhile, individual exposure to CIT and TAD altered the expression levels of biomarkers related to oxidative stress, inflammation, apoptosis and hypothalamic-pituitary-thyroid (HPT) axis. Notably, combined exposure to CIT and TAD induced changes in the mentioned biological processes and had an interactive effect on the expression of multiple biomarkers. In conclusion, we evaluated the toxic effects of CIT and TAD in isolation and combination by in-vivo experiments, which provide a new methodological basis and reference for future risk assessment and setting of safety limits for foodborne toxicants.

Inflammation, Thyroid Hormone Metabolism, and Treatment Outcome, Among Patients With Treatment Resistant Depression (TRD) Naturalistically Treated With Ketamine or ECT

Inflammation, Thyroid Hormone Metabolism, and Treatment Outcome, Among Patients With Treatment Resistant Depression (TRD) Naturalistically Treated With Ketamine or ECT

Prevalence of thyroid disorder in patients with systemic lupus erythematosus and patients with lupus nephritis

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect many organs. Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with SLE. The interaction between kidney and the thyroid-gland functions has been known for a long time. Thyroid hormones (TH) are necessary for growth and development of the kidney, and for the maintenance of water and electrolyte homeostasis. On the other hand, kidney is involved in the metabolism and elimination of TH. Thyroid disease appears to be more frequent in SLE patients than in the general population. Therefore, screening of thyroid dysfunction in patients with SLE, especially in those with evidence of LN, is recommended. The aim of this work is to study morphological (thyromegaly and thyroid nodules) and functional (hypothyroidism or hyperthyroidism) thyroid disorders in patients with SLE with or without renal affection, and whether LN acts as an independent risk factor of thyroid abnormalities. Patients and methods In total, 60 participants were divided into three groups: group I: 20 patients diagnosed with SLE without evidence of renal affection, group II: 20 patients diagnosed with SLE with evidence of LN, and group III: 20 healthy participants. All were subjected to full history taking, thorough physical examination, laboratory investigations (urea and creatinine), thyroid function, and serological marker serum [antithyroid peroxidase antibody (anti-TPO Ab)]. Ultrasound examination of the thyroid gland was done. Results There was a direct significant relationship between renal function tests, namely urea and creatinine and anti-TPO among cases with SLE, both without and with LN, and an inverse significant relationship between estimated glomerular filtration rate and anti-TPO among both the SLE group and the LN group. Conclusion Screening of thyroid dysfunction in patients with SLE, especially in those with evidence of LN by estimation of thyroid function tests, thyroid autoantibodies, and by ultrasonography, is recommended.

ASSOCIATION OF THYROID HORMONE LEVELS AND CHRONIC KIDNEY DISEASE

Introduction- Normal thyroid hormone metabolism, breakdown, and excretion depend heavily on the kidney. We sought to assess the serum thyroid hormone levels in CKD patients in the current investigation because there is little data on the association between thyroid hormone levels and CKD. Methods- This cross-sectional and time bound study was conducted in department of General Medicine and Nephrology in NIMS&amp;R Hospital, Jaipur for 18 months. Results- Number of patients with low serum T3 levels increased proportionately with decreasing eGFR levels. Serum T4 and TSH levels were not signicantly related to worsening renal function. Conclusion- Low T3 syndrome was the commonest and subclinical hypothyroidism was the second most common thyroid abnormality detected. Hypothyroidism and severity of CKD did not correlate with each other.

Selenium and thyroid diseases.

Selenium, a non-metallic element, is a micronutrient essential for the biosynthesis of selenoproteins containing selenocysteine. In adults, the thyroid contains the highest amount of selenium per gram of tissue. Most known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid and are involved in thyroid hormone metabolism, redox state regulation, and maintenance of cellular homeostasis. Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves' orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto's thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure. In thyroid cancer, various selenium supplements have shown variable anticancer activity. However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease.

Selenium Deficiency Alters Thyroid Hormone Metabolism in Guinea Pigs

In guinea pigs, activity of glutathione peroxidase in most organs is markedly lower than in organs of other rodents despite comparable dietary intakes and tissue levels of selenium. To determine if metabolism of selenium with respect to other selenoproteins also differs in guinea pigs, we measured the effects of selenium intake on thyroid hormone metabolism. Weanling male Hartley Albino guinea pigs were fed a selenium-deficient Torula yeast-based diet, or the same diet supplemented with 0.5 mg selenium/kg diet as sodium selenate for 72 d. Growth was impaired in guinea pigs fed the unsupplemented diet. Activity of glutathione peroxidase was higher in tissues and plasma of supplemented guinea pigs than in selenium-deficient animals. However, it was still far lower than reported values for other rodent species. In selenium deficiency, activity of type 1 5′-iodothyronine deiodinase was 60% less in liver and 45% less in kidney. Concentration of thyroxine was 68% lower in kidney of selenium-deficient animals, and levels of 3,3′,5-triiodothyronine in kidney and plasma were 44 and 31% lower, respectively. Thus, with the exception of thyroxine concentrations, thyroid hormone metabolism responds to selenium deficiency in guinea pigs as it does in rats, although the magnitude of that response is not as great.

Deleting Cellular Retinoic-Acid-Binding Protein-1 (Crabp1) Gene Causes Adult-Onset Primary Hypothyroidism in Mice

Adult-onset primary hypothyroidism is commonly caused by iatrogenic or autoimmune mechanisms; whether other factors might also contribute to adult hypothyroidism is unclear. Cellular Retinoic-Acid-Binding Protein 1 (CRABP1) is a mediator for Non-canonical signalling of all-trans retinoic acid (atRA). CRABP1 Knockout (CKO) mice develop and reproduce normally but begin to exhibit primary hypothyroidism in adults (~3 months old) including increased body weight, decreased body temperature, reduced plasma levels of triiodothyronine and thyroxine, and elevated levels of thyroid-stimulating hormone. Histopathological and gene expression studies reveal significant thyroid gland morphological abnormalities and altered expression of genes involved in thyroid hormone synthesis, transport, and metabolism in the CKO thyroid gland at ~6 months old. These significantly affected genes in CKO mice are also found to be genetically altered in human patients with hypothyroidism which could result in a loss of function, supporting the clinical relevance of CKO mice in humans with hypothyroidism. This study identifies, for the first time, an important role for CRABP1 in maintaining the health of the thyroid gland in adults and reports that CKO mice may provide an experimental animal model for studying the mechanisms underlying the development of adult hypothyroidism in humans.

ATA Centennial Interview Series: Thyroid Hormone Metabolism—A Historical Perspective

In this video, Dr. Val Galton from the Geisel School of Medicine at Dartmouth is interviewed by Dr. Meredith Hartley from the University of Kansas. The conversation focuses on Dr. Galton's experiences as a thyroid researcher and on the ATA Centennial Special Article1 that she coauthored with Dr. Arturo Hernandez titled, “Thyroid Hormone Metabolism: A Historical Perspective.” No competing financial interests exist. Runtime of video: 10 mins 38 secs

Normal thyroid volume in subjects evaluated in a primary ambulatory setting in Liguria.

Ultrasonography (US) is the simplest method of evaluating thyroid volume (TV). The current normal TV in Liguria is not known. The aim of this study was to obtain normative data on TV in Liguria, Italy. From 3552 files of endocrine evaluations registered in a primary outpatient setting, we selected 483 files on euthyroid subjects (383 females and 100 males) with a normal echoic pattern on US. The inclusion criterion was the absence of thyroperoxidase autoantibodies and drugs known to interfere with thyroid hormone secretion or metabolism. TV was calculated by means of US. Anthropometric characteristics, smoking habits and the district where subjects lived were registered. Less than 50% of patients were not taking any drug. The percentage of obesity was similar in both sexes. TSH levels were similar in males and females. Median TV was 8.0 mL (IQR: 6.7-9.8 mL) in females and 11.8 mL (9.3-15.6 mL) in males (P<0.0001). In females, TV was greater (P=0.01) in smokers than in non-smokers. In both sexes, the right lobe was significantly (P<0.0001) larger in volume than the left. Post-hoc analysis did not show any differences among age-groups in either females or males. In females, but not in males, TV differed significantly (P=0.0002) according to the district of residence. A significant positive correlation was found in both groups between TV and weight, height, BMI and BSA. Reference values of TV in the Ligurian population are now available. TV in the general population could be compared with these normative data.

Compensatory mechanisms in response to induced hypothyroidism in the late gestation pig fetus†.

To understand the effect of fetal thyroid gland disruption on development in swine, we evaluated thyroid hormone levels, growth and developmental characteristics, and gene expression associated with thyroid hormone metabolism in late gestation fetuses exposed to methimazole (MMI). Pregnant gilts were given either oral MMI or equivalent sham from gestation day 85-106 (n= 4/group), followed by intensive phenotyping of all fetuses (n= 120). Samples of liver (LVR), kidney (KID), fetal placenta (PLC), and the corresponding maternal endometrium (END) were collected from a subset of fetuses (n= 32). Fetuses exposed to MMI in utero were confirmed hypothyroid, with a significant increase in thyroid gland size, goitrous thyroid histology, and dramatically suppressed thyroid hormone in serum. In dams, no differences in temporal measurements of average daily gain, thyroid hormone, or rectal temperatures relative to controls suggests that MMI had little effect on maternal physiology. However, fetuses from MMI-treated gilts exhibited significant increases in body mass, girth, and vital organ weights, but no differences in crown-rump length or bone measurements suggesting non-allometric growth. The PLC and END showed a compensatory decrease in expression of inactivating deiodinase (DIO3). Similar compensatory gene expression was observed in fetal KID and LVR with a downregulation of all deiodinases (DIO1, DIO2, DIO3). Minor alterations in the expression of thyroid hormone transporters (SLC16A2 and SLC16A10) were observed in PLC, KID, and LVR. Collectively, MMI crosses the PLC of the late gestation pig, resulting in congenital hypothyroidism, alterations in fetal growth, and compensatory responses within the maternal fetal interface.

Evaluation of Interactions Between Thyroid Dysfunction in End-Stage Renal Disease Patients: A Cross-Sectional Study.

Thyroid hormones have a very crucial role in the regulation of metabolism, synthesis of proteins, development, and influencing functions of various other hormones in the human body. While both kidneys play an essential role in the metabolism of thyroid hormone by conversion of thyroxine (T4) to triiodothyronine (T3). In patients with chronic renal failure, frequent abnormal thyroid functions are observed. To evaluate thyroid function in patients of chronic renal failure and to find out their correlation with the severity of the disease. A total of 192 patients were selected for the study after applying inclusion and exclusion criteria. A thyroid function test was done in all enrolled subjects. Serum estimation of T3, T4, and thyroid stimulating hormone (TSH) was done by the chemiluminescent immunoassay (CLIA) method, urea was estimated by the diacetyl monoxide method (DAM, Method), and serum creatinine by Jaffe's method. The results were evaluated for age, sex, and estimated glomerular filtration rate (eGFR) of the patients in view of thyroid dysfunction. Of all 192 patients enrolled in the study, 124 (64.58%) were male and 68 (35.41%) were females. The observed male-to-female ratio was 1.93:1.18. The mean age of the study group (mean +/- standard deviation, SD) in males was 42+/-18 and in females 38+/-11 years (p value = 0.258). Significant reductions of serum T3, T4, and elevation of TSH were noted in both sexes. A reduced level of T3 was observed in 38.54% (42 males and 32 females) patients, reduced T4 in 34.37% (42 males and 22 females) patients, and subclinical hypothyroidism (SCH) in 16.7% (12 males and 20 females) patients. Biochemical overt hypothyroidism was noted in 7.29% (six males and eight females) of patients. Chronic renal failure is a condition of thyroid hypofunction. A higher prevalence of SCH and clinical hypothyroidism is reported here in chronic kidney disease (CKD) patients. The severity of thyroid hypofunction increases with a progressive reduction in eGFR. Hypothyroidism in CKD patients may be due to different onset mechanisms other than anti-thyroid antibodies.

DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis.

Possible triggers and genetic markers involved in pathogenesis of amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH) are currently unknown. This study aimed to analyze the association between polymorphisms in the genes involved in thyroid hormones biosynthesis and metabolism. Thirty-nine consecutive patients with confirmed type 2 amiodarone-induced thyrotoxicosis were enrolled; 39 patients on the same therapy for at least 6 months without thyroid pathology were included as a control group. A comparative study was carried out to determine the distribution and genotypes of polymorphic markers of the (Na)-iodide symporter (NIS) genes (rs7250346, C/G substitution), thyroid stimulating hormone receptor (TSHR) (rs1991517, C/G substitution), thyroid peroxidase (TPO) (rs 732609, A/C substitution), DUOX 1-1 (C/T substitution), DUOX 1-2 (G/T substitution), DUOX 1-3 (C/T substitution), glutathione peroxidase 3 (GPX3) (C/T substitution), glutathione peroxidase 4 (GPX4) (C/T substitution). Statistical analysis was performed using Prism (Version 9.0.0 (86)). This study showed that the risk of AIT2 is 3.18 times higher in the G/T of the DUOX1 gene carriers. This study is the first report of genetic markers associated with amiodarone-related adverse events conducted in humans. The obtained results indicate the necessity for a personalized approach to amiodarone administration.

Repositioning of Cefuroxime as novel selective inhibitor of the thyroid hormone activating enzyme type 2 deiodinase

The iodothyronine deiodinases constitute a family of three selenoenzymes regulating the intracellular metabolism of Thyroid Hormones (THs, T4 and T3) and impacting on several physiological processes, including energy metabolism, development and cell differentiation. The type 1, 2 and 3 deiodinases (D1, D2, and D3), are sensitive, rate-limiting components within the TH axis, and rapidly control TH action in physiological conditions or disease. Notably, several human pathologies are characterized by deiodinases deregulation (e.g., inflammation, osteoporosis, metabolic syndrome, muscle wasting and cancer). Consequently, these enzymes are golden targets for the identification and development of pharmacological compounds endowed with modulatory activities. However, until now, the portfolio of inhibitors for deiodinases is limited and the few active compounds lack selectivity. Here, we describe the cephalosporin Cefuroxime as a novel D2 specific inhibitor. In both in vivo and in vitro settings, Cefuroxime acts as a selective inhibitor of D2 activity, without altering the enzymatic activity of D1 and D3. By inhibiting TH activation in target tissues, Cefuroxime alters the sensitivity of the hypothalamus-pituitary axis and interferes with the central regulation of THs levels, and is thus eligible as a potential new regulator of hyperthyroid pathologies, which affect thousands of patients worldwide.

Selenium, Iodine and Iron–Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism

The adequate availability and metabolism of three essential trace elements, iodine, selenium and iron, provide the basic requirements for the function and action of the thyroid hormone system in humans, vertebrate animals and their evolutionary precursors. Selenocysteine-containing proteins convey both cellular protection along with H2O2-dependent biosynthesis and the deiodinase-mediated (in-)activation of thyroid hormones, which is critical for their receptor-mediated mechanism of cellular action. Disbalances between the thyroidal content of these elements challenge the negative feedback regulation of the hypothalamus-pituitary-thyroid periphery axis, causing or facilitating common diseases related to disturbed thyroid hormone status such as autoimmune thyroid disease and metabolic disorders. Iodide is accumulated by the sodium-iodide-symporter NIS, and oxidized and incorporated into thyroglobulin by the hemoprotein thyroperoxidase, which requires local H2O2 as cofactor. The latter is generated by the dual oxidase system organized as 'thyroxisome' at the surface of the apical membrane facing the colloidal lumen of the thyroid follicles. Various selenoproteins expressed in thyrocytes defend the follicular structure and function against life-long exposure to H2O2 and reactive oxygen species derived therefrom. The pituitary hormone thyrotropin (TSH) stimulates all processes required for thyroid hormone synthesis and secretion and regulates thyrocyte growth, differentiation and function. Worldwide deficiencies of nutritional iodine, selenium and iron supply and the resulting endemic diseases are preventable with educational, societal and political measures.