Thyroid Hormone Production Research Articles

PSIX-8 Increased Expression of ST6GAL1 and Vegfa Mediate the Inflammatory Signaling Pathway in Feline Hyperthyroidism

Abstract Hyperthyroidism in cats is characterized by increased production of thyroid hormones including thyroxine (T4) and triiodothyronine (T3) and decreased levels of thyroid stimulating hormone (TSH). Older cats are at greater risk of developing hyperthyroidism. The common clinical signs include increased appetite, body weight loss, increased thirst and urination, periodic vomiting, and rapid heart rate. While the etiology of this disease in cats is not clear, it is likely multi-factorial and environmental, nutritional, and immunological factors have been implicated. We assessed the levels of inflammatory markers in thyroid tissue from cats housed in the Hill’s colony, at the natural end-of-life after living full lives. Cats that were diagnosed as having hyperthyroidism by a veterinarian (n = 10, 12.1-18.9 yr) had greater circulating fT4 when compared with controls. Control cats showed no signs of hyperthyroidism (n = 10, 10.9 to 18.6 yr). Histopathological analysis of hematoxylin and eosin-stained thyroid sections showed an increase in follicular cells as well as evidence of colloid reabsorption in cats with hyperthyroid when compared with controls. RNA was extracted from samples collected from cats and gene expression was investigated using the NanoString nCounter platform. Analysis was performed using the nSolver software. There was a significant increase in ST6GAL1 sialyltransferase when compared with controls (1.22 fold; P < 0.05). ST6GAL1 is an enzyme that can post-translationally modify glycoproteins by adding α2-6-linked sialic acids to them. ST6GAL1 can also regulate the NFκB inflammatory signaling pathway by promoting its sustained activation that can potentially lead to inflammation. In the present study we also saw a decrease in NFκB1/p105 (-1.14, ns), a protein that is processed to produce p50, an NFκB binding protein, but a small increase in NFκB2/p100 (1.06, ns), a protein that is processed to produce p52 of the NFκB signaling pathway in hyperthyroid cats when compared with controls. NFκB1 is a transcriptional repressor and a decline in its expression has been reported to contribute to increased inflammation. Further, an increase in NFκB2 may lead to increased activation of NFκB signaling as p52/RelB dimer is a transcriptional activator of NFκB signaling. There was also an increase in VEGFA in hyperthyroid when compared with controls (1.79 fold; P < 0.05). VEGF is an angiogenesis factor and increasing evidence indicates that angiogenesis sustains inflammation. VEGF is produced by endothelial cells, macrophages and activated T-cells and is also a potent chemoattractant for monocytes. While VEGF induces several pro-inflammatory genes including IL-8 and MCP-1, both were downregulated in hyperthyroid in the present study, indicating that the effects of VEGF were likely not mediated by pro-inflammatory IL-8 or MCP-1 in feline hyperthyroidism. Our data indicate that the etiology of hyperthyroidism involves multiple inflammatory signaling pathways and these may represent important therapeutic targets for reducing inflammation in feline hyperthyroidism.

In Vitro and In Vivo Supplementation with Curcumin Promotes Hippocampal Neuronal Synapses Development in Rats by Inhibiting GSK-3β and Activating β-catenin.

The human fetal thyroid gland is not capable of producing thyroid hormones independently until 20 weeks of gestation, and if maternal thyroid hormone synthesis is inadequate in early pregnancy, fetal brain and nerve development may be affected by maternal hypothyroidism. Curcumin, which is isolated from turmeric (Curcuma longa), has been shown to be effective in repairing neurological disorders and is effective in relieving nerve damage when consumed over a long period of time. In this experiment, we investigated the effect of curcumin supplementation on synaptic development of rat hippocampal neurons. A cell model of oxidative damage and a young rat model of hypothyroidism were constructed, and model cells and rats were treated with triiodothyronine (T3), tetraiodothyronine (T4), and curcumin, respectively. Damage of nerve cells and animal brain tissues was examined, and the effect of curcumin in alleviating the blocked neurodevelopment was investigated. Further modulation of GSK-3β/β-catenin was performed to investigate the mechanism of action of curcumin. Ultimately, we found that T3-, T4-, and curcumin-treated model cells and young rats had increased numbers of synapses and good neurodevelopment. At the same time, we found that curcumin inhibited the production of GSK-3β and Axin to activate β-catenin. The inhibition of β-catenin weakened the therapeutic effect of curcumin, and the differences between the indicators and the model group disappeared. Both cellular and animal experiments supported that curcumin effectively alleviated the oxidative cell damage caused by thyroxine deficiency and activated the synaptogenic ability of nerve synapses by inhibiting GSK-3β and protecting β-catenin activity.

Towards translating in vitro measures of thyroid hormone system disruption to in vivo responses in the pregnant rat via a biologically based dose response (BBDR) model

Despite the number of in vitro assays that have been recently developed to identify chemicals that interfere with the hypothalamic-pituitary-thyroid axis (HPT), the translation of those in vitro results into in vivo responses (in vitro to in vivo extrapolation, IVIVE) has received limited attention from the modeling community. To help advance this field a steady state biologically based dose response (BBDR) model for the HPT axis was constructed for the pregnant rat on gestation day (GD) 20. The BBDR HPT axis model predicts plasma levels of thyroid stimulating hormone (TSH) and the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroid hormones are important for normal growth and development of the fetus. Perchlorate, a potent inhibitor of thyroidal uptake of iodide by the sodium iodide symporter (NIS) protein, was used as a case study for the BBDR HPT axis model. The inhibitory blocking of the NIS by perchlorate was associated with dose-dependent steady state decreases in thyroid hormone production in the thyroid gland. The BBDR HPT axis model predictions for TSH, T3, and T4 plasma concentrations in pregnant Sprague Dawley (SD) rats were within 2-fold of observations for drinking water perchlorate exposures ranging from 10 to 30,000 μg/kg/d. In Long Evans (LE) pregnant rats, for both control and perchlorate drinking water exposures, ranging from 85 to 82,000 μg/kg/d, plasma thyroid hormone and TSH concentrations were predicted within 2 to 3.4- fold of observations. This BBDR HPT axis model provides a successful IVIVE template for thyroid hormone disruption in pregnant rats.

Effect of in utero and lactational exposure to a thyroid hormone system disrupting chemical on mouse metabolome and brain transcriptome

Mice were exposed to a low dose of the model thyroid hormone disruptor, propylthiouracil. Although this had only a modest effect on maternal thyroid hormones production, postnatal analysis of the pups’ plasma by mass spectrometry and the brain striatum by RNA sequencing gave evidence of low lasting changes that could reflect an adverse effect on neurodevelopment. Overall, these methods proved to be sensitive enough to detect minor disruptions of thyroid hormone signalling in vivo.

The Relationship between Thyrotropin Serum Concentrations and Thyroid Carcinoma.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the pituitary gland and plays a role in regulating the production and secretion of thyroid hormones by the thyroid gland. This precise feedback loop is essential for maintaining a harmonious balance of thyroid hormones in the body, which are vital for numerous physiological processes. Consequently, TSH serves as a significant marker in assessing thyroid function, and deviations from normal TSH levels may indicate the presence of a thyroid disorder. Thyroid cancer (TC) is the malignant tumor within the endocrine system. In recent years, numerous experts have dedicated their efforts to discovering efficacious biomarkers for TC. These biomarkers aim to improve the accurate identification of tumors with a poor prognosis, as well as facilitate active monitoring of tumors with a more favorable prognosis. The role of TSH in the thyroid gland underscores its potential influence on the occurrence and progression of TC, which has garnered attention in the scientific community. However, due to the limited scope of clinical research and the dearth of high-quality foundational studies, the precise impact of TSH on TC remains unclear. Consequently, we present a comprehensive review of this subject, aiming to offer a valuable reference for future research endeavors.

Ayurvedic Management of Hypothyroidism - A Case Report

Hypothyroidism is the significant endocrine problem found in general public. It is characterized by insufficient production of thyroid hormones, leading to abnormal levels. This condition prompts the decrease in Basal metabolic rate of the body. Ayurveda places a significant part to preclude the basic reason and to treat it. In Ayurveda, it tends to be associated with Kapha-vata dosha dushti, Rasavaha Strotasadushti, Medadushti and Agnimandya. In present study, a 22 years old female patient suffering from Sthaulya (~Weight gain), Duarbalya (~Weakness), Twak rukshata (~Dry skin), Kesh patana (hair loss), puffiness around eyes, mood swings, impaired memory, emotional depression, drowsiness, headache, Amalapitta (~Hyperacidity) and lethargy from last three years. She had been taking allopathic medicine without experiencing any satisfactory relief in her symptoms. In the present study, group of Herbo-mineral preparation was prescribed to the patient for a period of 4 months. After four months patient experienced relief, and her allopathic medicine was completely stopped. Keywords: Hypothyroidism, Agnimandya, Sthaulya

FRI565 Spontaneous Conversion Of Long-standing Hypothyroidism To Grave’s Disease: A Case Report

Abstract Disclosure: M. Dominic: None. M. Shakir: None. A. Kakkar: None. O.Z. Syed: None. A. Sood: None. D.A. Alvarez: None. Introduction: Autoimmune thyroid diseases associated with IgG4 include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT involves a combination of antibody-mediated thyroid gland destruction and inhibition of thyroid hormone production through a predominance of TSH receptor-blocking antibodies (TBAb). GD is due to increased thyroid hormone production in response to thyroid-stimulating antibodies (TSAb). Although transition to hypothyroidism in patients with GD is commonly encountered in clinical practice, conversion of primary hypothyroidism to GD is a rare event and is described here. Clinical Case: We describe the case of an 81-year-old female with primary hypothyroidism diagnosed more than 10 years ago. She was briefly treated with desiccated thyroid which was later changed to levothyroxine, and she remained euthyroid for several years on Levothyroxine 88 mcg daily. In 05/2021 her routine blood test showed suppressed TSH of less than 0.01uIU/mL for the first time, and it remained consistently low with elevated free T4 & T3 levels despite gradually reducing levothyroxine dose. Patient also started to have tremors, weight loss and anxiety during this period. She was found to have a hypermetabolic thyroid nodule during a PET-CT for evaluation of newly diagnosed Gastrointestinal Stromal Tumor in 09/2022. Levothyroxine was stopped shortly thereafter, but the hyperthyroid labs persisted, following which TSAb levels were obtained and found positive. She was started on methimazole 10 mg twice daily, which resulted in symptomatic improvement and marked reduction of T3 & T4 levels in one month. Clinical lessons: Over-replacement is the most common cause of hyperthyroid symptoms in patients receiving thyroid hormone replacement. Primary hypothyroidism is usually a permanent condition requiring lifelong therapy. Conversion of this condition to GD is a rare entity and can be missed in clinical practice by being mistaken for levothyroxine over-replacement. Proposed mechanisms for conversion of long-standing hypothyroidism to hyperthyroidism include fluctuating levels of TBAbs and TSAbs, spontaneous development of autoimmunity and rarely, production of TSAbs in patients with established Hashimoto’s thyroiditis. Another proposed theory is initial hypothyroidism due to extensive autoimmune gland damage in patients with GD who later develop hyperthyroidism after tissue recovery. It should be noted that this transition to GD has been reported to occur even 30 years after the diagnosis of hypothyroidism. Thus in patients with well-established hypothyroidism requiring lower thyroid replacement doses than before, and labs showing persistent hyperthyroid picture with no evident cause, a careful evaluation is required to check for conversion to GD in order to start appropriate treatment at the earliest. Presentation: Friday, June 16, 2023

FRI308 A Rare Case Of Plurimorphous Plurihormonal Pituitary Neuroendocrine Tumor With LH Hypersecretion

Abstract Disclosure: A. Jeevananthan: None. L. Gratian: None. Background: Plurimorphous plurihormonal pituitary neuroendocrine tumors (PitNETs) are very rare pituitary tumors that are composed of multiple adenohypophyseal lineages and are associated with high risk of recurrence. Further, gonadotropin excess is exceptionally rare. Here we report a rare case of a plurimorphous plurihormonal PitNET with functional hypersecretion of LH. Clinical Case: A 48-year-old male was incidentally found to have a 13x12x14mm pituitary tumor without evidence of cavernous sinus invasion or mass effect during sinus imaging for workup of chronic sinusitis with polyps. Clinical symptoms at the time were notable for night sweats, hot flashes and 1 year history of erectile dysfunction. Functional testing showed normal prolactin, GH, cortisol, and thyroid hormone production. However, LH was elevated at 10.2 mIU/mL (normal range 1.4-7.77 mIU/mL) and FSH was low at 1.3 mIU/mL (normal range 2.5-17.7 mIU/mL) with normal total testosterone of 565 ng/dL (normal range 240-950 ng/dL) but elevated free testosterone of 22 ng/dL (normal range 4.26-16.4 ng/dL). Interval imaging 17 months later showed an increase in size to 16x16x13mm with deviation of the infundibulum to the left and mild mass effect on the optic chiasm. Thereafter, the patient underwent transsphenoidal surgery with subsequent normalization of FSH to 6.2 mIU/mL and LH to 7.9 mIU/mL. Initial post-operative total testosterone level was low at 29 ng/dL but improved spontaneously to 170 ng/dL six weeks following surgery. Pathology was notable for immunohistochemistry (IHC) that showed SF1 lineage (IHC positive for LH, negative for FSH) and PIT1 lineage (IHC positive for prolactin, rare GH). To our knowledge, this is the first reported case of functional LH hypersecretion due to a plurimorphous plurihormonal PitNET. Conclusion: This case aims to shed light on the first noted case of LH only secreting plurimorphous plurihormonal PitNET. Plurihomonal PitNETs are associated with aggressive course and recurrence. Particularly, this case highlights the need for routine use of immunohistochemical staining for accurate diagnosis of PitNETs to ensure rigorous follow-up. Presentation: Friday, June 16, 2023

FRI538 Discovery And Characterization Of Orally Bioavailable Nonpeptide Thyroid Stimulating Hormone Receptor (TSHR) Antagonists For The Treatment Of Graves’ Disease

Abstract Disclosure: M.A. Fowler: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. C. Regan: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. J. Zhao: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. E. Coutinho: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. B. Fleck: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. A.A. Castellanos: Employee; Self; Crinetics Pharmaceuticals. E. Muller: Employee; Self; Crinetics Pharmaceuticals. M. Johns: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. Y. Tang: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. E. Sturchler: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. M. Chen: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. K. Retting: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. D. Dalvie: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. S. Markison: Employee; Self; Crinetics Pharmaceuticals. Stock Owner; Self; Crinetics Pharmaceuticals. Graves’ disease is an autoimmune condition that affects approximately 1 in 100 people in the United States and 2-3% of the population worldwide. It is characterized by the production of autoantibodies against TSHR, and the pathology of Graves’ disease is driven by TSHR stimulatory antibodies (TSAb) that result in heightened activation of TSHR. This overstimulation results in hyperthyroidism due to excessive production of thyroid hormones. Approximately 30% of Graves’ disease patients also develop thyroid eye disease (TED or Graves’ orbitopathy) due to overactivation of TSHR in orbital fibroblasts leading to excessive production of hyaluronic acid, adipogenesis, cytokine production, and fibrosis. This can cause a myriad of debilitating symptoms including pain, swelling, blurry vision, diplopia, and proptosis. Several treatments for Graves’ hyperthyroidism are available including anti-thyroid drugs, radioactive iodine (RAI), and surgery. RAI and surgery are definitive treatments for Graves’ hyperthyroidism, but often result in hypothyroidism. In addition, none of the current treatments for Graves’ hyperthyroidism are effective in treating TED and, in some cases, such as with RAI, worsen the condition. Blocking TSHR activation directly via a TSHR antagonist may provide an important new therapeutic mechanism to treat patients with Graves’ disease that would effectively treat both the hyperthyroidism and TED. We have identified several potent and orally bioavailable nonpeptide allosteric antagonists with acceptable drug-like properties. One analog, TSHRant-1, demonstrated potent negative allosteric modulator activity at both the human and rat TSHR. To evaluate the in vivo pharmacodynamics of TSHant-1, we developed a rat model of hyperthyroidism. In this model, subcutaneous administration of the TSAb, M22, to female rats resulted in a robust and long-lasting rise in levels of the thyroid hormone thyroxin (T4). Oral administration of TSHRant-1 dose-dependently suppressed M22-stimulated T4, providing evidence that a nonpeptide allosteric antagonist of TSHR may serve as an effective treatment for Graves’ disease and associated orbitopathy (TED). Presentation: Friday, June 16, 2023

SAT591 Abnormal Levels Of Thyroid Hormones During Development Alters The Migration And Activity Of GnRH Reproductive Neurons

Abstract Disclosure: C. Quignon: None. A. Backer: None. S. Wray: None. Clinical studies have shown that thyroid hormones disorders and alteration of thyroid hormone production by environmental endocrine disruptors, have deleterious effects on reproduction. By acting in the brain on the hypothalamic component of the reproductive axis, abnormal levels of thyroid hormones can disturb sex hormones production, oestrus cycles or puberty onset, possibly leading to subfertility. Moreover, in animal models, endocrine disruptors and thyroid hormones have been shown to have long-lasting transgenerational effects with the maternal hormones influencing the development of foetal reproductive functions. Despite clear evidence of an interaction between the thyroid and reproductive systems, the effect of T3, the active form of thyroid hormones, on the GnRH neurons controlling reproduction, have been poorly studied. In this work we investigated how T3 functionally interacts with GnRH neurons and how abnormal concentration of T3 alters the migration of these neurons during development. Calcium imaging was used to study the direct effect of T3 on GnRH neuronal activity in an ex vivo nasal explants model. Acute administration of T3 (30nM) was found to stimulate the activity of GnRH cells. Dual labelling of GnRH and thyroid hormone receptors (TR) showed that the GnRH neurons express both nuclear and membrane receptors. However, the use of an antagonist that specifically blocks the TR nuclear receptors (1-850), didn’t inhibit the T3 stimulatory effect. In contrast, blockage of integrin αV/β3 membrane receptors (with cilengitide), which have been shown to be activated by T3, prevented the T3-induced increase in GnRH neuronal activity. During development GnRH neurons migrate from the nasal placodes into the brain. Acute administration of T3 for 1hr significatively decreased the migration rate of the GnRH neurons in our ex vivo model. To assess the effect of thyroid disruption during pregnancy on the development of reproductive axis in utero, pregnant females mice have been treated with methimazole to induce hypothyroidism from gestational day 6 to 13. E13 embryos have been collected from treated and control dams and the distribution of migrating GnRH neurons will be compared between both groups. Together these studies are the first to report a direct effect of thyroid hormones on GnRH neuronal activity, through the integrin αV/β3 membrane receptors and show that T3 can modulate the migration of GnRH neurons during development. These results will bring new insights on how thyroid disruption by endocrine disruptor chemicals or thyroid diseases, especially during foetal development, can lead to long term reproductive defects. Presentation: Saturday, June 17, 2023

FRI001 Tanycytic Thyroid-stimulating Hormone Receptor Activation Increases Blood-Hypothalamus Barrier Permeability And Induces Appetite In Female Mice

Abstract Disclosure: H.S. Kannangara: None. B. Jocoll: None. S. Miyashita: None. A. Gumerova: None. F. Korkmaz: None. R. Witztum: None. S. Sims: None. U. Cheliadinova: None. G. Pevnev: None. O. Moldavski: None. T. Frolinger: None. T. Yuen: None. V. Ryu: None. M. Zaidi: None. In addition to its well-known action to trigger thyroid hormone production, thyroid-stimulating hormone (TSH) is released in the brain, and its receptor (TSHR) has been found in brain sites, including the tanycytes of the third ventricle, that regulate ingestive behavior and convey metabolic information across the blood-hypothalamus barrier (BHB). Our recent work highlights largely undiscovered role for TSHRs in the tanycytes. Here, we tested the hypothesis that tanycytic TSHR activation triggers rapid remodeling of BHB vascular permeability inducing appetite. We compared hypothalamic vascular permeability of food deprived (FD) and ad libitum fed (AL) Tshr+/- and their wild type (WT) counterparts exploiting transmission electron microscopy studies and immunofluorescence for constitutive tight junction protein Claudin-1 and homodimer glycoprotein MECA-32, primarily expressed in tanycytes and endothelial cells, respectively. Fasting significantly increased the organization of tanycytic honeycomb pattern of Claudin-1 and fenestral MECA-32-associated diaphragms in the median eminence and arcuate nucleus implying decreased BHB vascular permeability in Tshr+/- mice. Transmission electron microscopy confirmed immunofluorescence results. In a separate gain-of-function experiment, TSHR activation by the small molecule MS438 increased BHB vascular permeability as evidenced by decreased Claudin-1 and MECA-32 immunostaining. Tanycytic TSHR activation significantly increased both food foraging and intake as during one-hour refeeding after FD. Surprisingly, refeeding restored neuronal activation marker c-Fos expression in the paraventricular nucleus of the hypothalamus, parabrachial nucleus and nucleus of the solitary tract, though failed to do so in the paraventricular nucleus and nucleus of the solitary tract of MS438-injected mice. Collectively, these data infer that modulation of tanycytic TSHRs plays an important role in BHB plasticity in relation with ingestive behavior. Presentation: Friday, June 16, 2023

Association of severe autoimmune hypothyroidism with reversible proteinuria: A case report

Hypothyroidism is a prevalent medical condition characterized by an underactive thyroid gland, resulting in insufficient thyroid hormone production. This hormone plays an important role in regulating the body's metabolism, so when its levels are low, it can lead to various metabolic disturbances. In this article, we present a case report of a 50-year-old female with severe hypothyroidism who exhibited several symptoms of renal impairment and hypothyroidism. She had proteinuria along with elevated lipid levels. Following a diagnosis of Hashimoto's thyroiditis, the patient was treated with levothyroxine, resulting in a remarkable reversal of her proteinuria and other symptoms. The lipid profile also showed significant improvement without the need for cholesterol-lowering medications. This case report highlights the importance of recognizing and managing thyroid dysfunction in patients with renal abnormalities. It provides valuable insights into the complex interplay between thyroid function, renal abnormalities, and lipid levels.

Oxidation of anti-thyroid drugs and their selenium analogs by ABTS radical cation

Lactoperoxidase was previously used as a model enzyme to test the inhibitory activity of selenium analogs of anti-thyroid drugs with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a substrate. Peroxidases oxidize ABTS to a metastable radical ABTS•+, which is readily reduced by many antioxidants, including thiol-containing compounds, and it has been used for decades to measure antioxidant activity in biological samples. We showed that anti-thyroid drugs 6-n-propyl-2-thiouracil, methimazole, and selenium analogs of methimazole also reduced it rapidly. This reaction may explain the anti-thyroid action of many other compounds, particularly natural antioxidants, which may reduce the oxidized form of iodine and/or tyrosyl radicals generated by thyroid peroxidase thus decreasing the production of thyroid hormones. However, influence of selenium analogs of methimazole on the rate of hydrogen peroxide consumption during oxidation of ABTS by lactoperoxidase was moderate. Direct hydrogen peroxide reduction, proposed before as their mechanism of action, cannot therefore account for the observed inhibitory effects. 1-Methylimidazole-2-selone and its diselenide were oxidized by ABTS•+ to relatively stable seleninic acid, which decomposed slowly to selenite and 1-methylimidazole. In contrast, oxidation of 1,3-dimethylimidazole-2-selone gave selenite and 1,3-dimethylimidazolium cation. Accumulation of the corresponding seleninic acid was not observed.

Iodine-induced thyroid dysfunction: a scientometric study and visualization analysis.

Iodine is essential in thyroid hormone production. Iodine deficiency is associated with serious complications (i.e miscarriage and stillbirth), whereas excess can cause thyroid dysfunction (i.e hyperthyroidism, hypothyroidism, thyroid autoimmunity). We conducted this scientometric study to visualize hot spots and trends in iodine-induced thyroid dysfunction over past two decades. The aim of this paper was to help scholars quickly understand the development and potential trend in this field, and guide future research directions. Articles on iodine-induced thyroid dysfunction from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) using the following search terms: (((((TS=(hypothyroid*)) OR TS=(hyperthyroid*)) OR TS= ("TSH deficiency")) OR TS= ("thyroid stimulating hormone deficiency")) AND TS=(Iodine)) NOT TS=(radioiodine). Only publications in English were selected. CiteSpace, VOSviewer, Tableau, Carrot2, and R software were used to analyze the contribution and co-occurrence relationships of different countries, institutes, keywords, references, and journals. A total of 2986 publications from 115 countries and 3412 research institutions were included. From 2000 to 2022, research on iodine-induced thyroid dysfunction progressed over a three-stage development period: initial development (2000-2009), stable development (2010-2016), and rapid development (2016-2022) period. The Journal of Clinical Endocrinology and Metabolism had the most co-citations followed and China Medical University (n=76) had the most publications. The top three clusters of co-citation references were isolated maternal hypothyroxinemia, subclinical hyperthyroidism, and brain development. Various scientific methods were applied to reveal acknowledge structure, development trend and research hotspots in iodine-induced thyroid dysfunction. Our scientometric analysis shows that investigations related to pregnant women, epidemiology surveys, and iodine deficiency are promising topics for future iodine-induced thyroid dysfunction research and highlights the important role of iodine on thyroid function.

REVIEW OF SARS-CORONAVIRUS-2 REPERCUSSIONS ON THYROID GLAND IN THE CONTEXT OF HYPERTHYROIDISM

The thyroid gland may generate, store, and release hormones (such as Triiodothyronine and Thyroxin also called T3 and T4 hormones respectively) into the bloodstream and let them go to the body's cells. Every enzymatic process in the production and secretion of thyroid hormones is controlled by Thyroid stimulating hormone (TSH). All people worldwide are susceptible to thyroid disease, which is often accompanied by hyperthyroidism and hypothyroidism. The thyroid's structural proximity to the upper airways, a main route for coronavirus entry, holds up the idea that the thyroid gland might be a target for Covid-19 or SARS-CoronaVirus-2. When the thyroid gland makes and secretes too much thyroid hormone, it is referred to as hyperthyroidism and if the patients do not take any precautions, hyperthyroidism may lead to cardiac hypertrophy. The Covid-19 epidemic had a substantial influence on our daily lives and has unexpectedly changed the way of medical research. This review aimed to discuss the effects of SARS-CoronaVirus-2 on the Thyroid Gland in the Context of Hyperthyroidism and related causing diseases, highlighting the common causing diseases of hyperthyroidism along with their treatments. We also highlight the impact of SARS-CoronaVirus-2 and its mRNA immunization. So that future studies should focus on the number of important advances and improved drug management in the treatment of Thyroid relating diseases, which may or may not be triggered by the coronavirus and its immunization.

Clinical study to evaluate the efficacy of Commiphora muku (Muqil) on thyroid function in hypothyroidism

Background: Hypothyroidism is a common endocrine disorder in which there is deficient production of thyroid hormone. Even though hormone replacement therapy is the mainstay treatment of hypothyroidism, but due to adverse effects on long term use, safe and effective Unani herbal drugs need to be researched. A decrease in serum concentrations of thyroid hormone causes an increased secretion of thyroid stimulating hormone (TSH), thus resulting in elevated serum TSH concentration. Methods: The methods used to determine thyroid dysfunction are still serum thyroid stimulating hormone and the main circulating thyroid hormones thyroxine and triiodothyronine either as total or estimated free concentrations, and it is indeed the improved assay sensitivities and specificities that have made it possible to diagnose these milder forms. TSH, T3 and T4 with safety parameters tests were done before treatment and after completion of treatment in both the groups in order to make the proper diagnosis, to exclude other systemic ailments and to assess the efficacy/safety of the proposed herbal drug. Results: The effects of test drug on lowering the raised serum TSH are attributed to the thyroid activities of the test drug which shoes highly significance p<0.01 before and after intervention. In respect of thyroxin there were no significant results between the test and control group. Conclusions: The study concluded that the efficacy of Commiphora mukul (Muqil) on thyroid function was designed to explore the role of Unani herbal drugs in the management of hypothyroidism on Unani principles is effective, safe and cost effective.

Changes in TSH suppression during pregnancy reveals novel mechanism for increased thyroid hormone production: comparison between euthyroid and thyroidectomized pregnant women

Changes in TSH suppression during pregnancy reveals novel mechanism for increased thyroid hormone production: comparison between euthyroid and thyroidectomized pregnant women

Exogenous corticosterone administration during pregnancy in mice alters placental and fetal thyroid hormone availability in females

IntroductionMaternal prenatal psychological stress is associated with adverse pregnancy outcomes and increased risk of adverse health outcomes in children. While the molecular mechanisms that govern these associations has not been fully teased apart, stress-induced changes in placental function can drive sex-specific phenotypes in offspring. We sought to identify and examine molecular pathways in the placenta that are altered in response to maternal prenatal stress. MethodsWe previously employed a mouse model of maternal prenatal stress where pregnant dams were treated with stress hormone (CORT) beginning in mid-gestation. Using this model, we conducted RNAseq analysis of whole placenta at E18.5. We used qRT-PCR to validate gene expression changes in the placenta and in a trophoblast cell line. ELISAs were used to measure the abundance of thyroid hormones in maternal and fetal serum and in the placenta. ResultsDio2 was amongst the top differentially expressed genes in response to exogenous stress hormone. Dio2 expression was more downregulated in placenta of female fetuses from CORT-treated dams than both control placenta from females and placenta from male fetuses. Consistent with Dio2's role in production of bioactive thyroid hormone (T3), we found that there was a reduction of T3 in placenta and serum of female embryos from CORT-treated dams at E18.5. Both T3 and T4 were reduced in the fetal compartment of the placenta of female fetuses from CORT-treated dams at E16.5. Exogenous stress hormone induced reduction in thyroid hormone in females was independent of circulating levels of TH in the dams. DiscussionThe placental thyroid hormone synthesis pathway may be a target of elevated maternal stress hormone and modulate fetal programming of health and disease of offspring in a sex-specific fashion.

A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang.

Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the development of thyroid dysfunction. We recruited 183 participants with cretinism and 119 healthy participants from the Xinjiang Uyghur Autonomous Region and randomly selected 29 tag single nucleotide polymorphisms (tSNPs) in TSHB, PAX8, TPO, NKX2-5, and TSHR in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis. Using the chi-squared test, a single SNP was found to be associated with cretinism (recessive model: rs3754363, OR = 0.46, 95% CI = 0.27-0.80, P = 0.00519; genotype model: P = 0.01677). We stratified neurological, myxedematous, and mixed type and determined that another SNP was associated with a higher risk when comparing myxedematous type to the neurological type (rs2277923). rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.

The efficacy of iodinated ethyl esters of safflower seed oil (Carthamus tinctorius L.) in the control of iodine deficiency in sheep

Iodine is an essential component of the thyroid gland hormones (T3 and T4), necessary for mammalian life. Iodine deficiency leads to inadequate thyroid hormone production, and all the consequences of iodine deficiency stem from the associated hypothyroidism. Iodized oil is made by treating a fatty vegetable oil with iodine or hydriodic acid and is an effective long-term means of iodine supplementation. The type and fatty acids profile in the parent oil, as well as the way iodine is trapped, affect the physicochemical properties and effectiveness of the product. This research was conducted to study the effect of iodinated safflower oil on preventing iodine deficiency disorders (IDD) in livestock, compared with a commercial iodine supplement. Iodinated fatty acid ethyl esters prepared from safflower seed oil (IFAEESSO). Thirty Farahani ewes with a history of iodine deficiency were divided into three groups, including control and two treatment groups. The treatment groups received 390 mg of iodine by an intramuscular injection of 1.26 ml of IFAEESSO (n = 10) or 1.5 ml of Depodine® (n = 10), respectively. Serum iodine, thyrotropin stimulating hormone (TSH), T3 and T4 concentrations were assayed at baseline and every 30-day intervals over six months period. Iodine supplementation resulted in a significant increase in serum inorganic iodine over five months with Depodine and IFAEESSO (P < 0.01). Serum T3 and T4 concentrations also increased in treatment groups (P < 0.01), while the concentration of TSH didn’t change. The mean T4 and T3 concentrations were 3.16 μg /dl and 53.89 ng /dl in the control group, which increased to 3.50 μg /dl and 58.88 ng/dl for Depodine and 3.88 μg /dl and 63.55 ng/dl for IFAEESSO, respectively. The serum inorganic iodine and thyroid hormone concentrations were significantly higher in the IFAEESSO group than in the Depodine group (P < 0.01). IFAEESSO is an effective supplement against IDD and more efficient than that of Depodine to increase serum iodine concentration, and thyroid hormone production.