Circulating Thyroid Hormone Levels Research Articles

Thyrotoxic Valvulopathy in a 7-year-Old Child: Case Report and Literature Review

Introduction: Children with thyrotoxicosis may present rarely with valvulopathies. This disease is a syndrome complex of hyperdynamic status due to systemic manifestation of elevated circulating thyroid hormone levels. 
 Case Reports: O.C, a 7-year-old female child presented with abdominal pain that started seven days ago, passage of loose stool that started five days ago and weight loss that started five days ago. Salient findings at presentation were tachycardia, anterior neck swelling that moves with swallowing with a grade 3/6 pan-systolic murmur maximal at the apex. A diagnosis of hyperthyroidism at risk of thyrotoxicosis was made based on supported laboratory evidence. Echocardiography done showed severe mitral regurgitation. She is on Tabs Carbimazole and Propranolol. She has improved remarkably and has been on follow up.
 Conclusion: Hyperthyoidism affects multiple organ systems in the body and the heart is not spared. Most of the cardiac manifestations are functional and occur as a result of the hyperfunctioning gland. A high index of suspicion is required, as many of the patients present with only the consequences of hyperthyroidism.

Bone loss after discontinuation of denosumab: the devil is in the details.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.

Regulation of circulating thyroid hormone levels by hypothalamic tanycytes and hypophysial pars tuberalis-specific cells and their morphological and gene- and protein-expression changes under different photoperiods.

Thyroid hormone in the hypothalamus acts as a key determinant of seasonal transitions. Thyroid hormone-levels in the brain are mainly regulated by the hypothalamic tanycytes and pituitary pars tuberalis (PT)-specific cells. TSHβ produced by the PT-specific cells stimulates Dio2 expression and decreases Dio3 expression of the tanycytes. Both tanycytes and PT-specific cells in photosensitive animals exhibit remarkable changes of morphological appearance and expressions of genes and proteins under different photoperiods. Long photoperiods induce increased gene- and protein-expressions and active features. Short photoperiods cause the decreased gene- and protein-expressions and inactive features. In the PT, expressions of TSHβ, common α-subunit of glycoprotein hormones (α-GSU), and MT1 receptor of melatonin receptors and eyes absent 3 change under different photoperiods. Diurnal rhythms of α-GSU mRNA expression are observed in the PT of Djungarian hamsters. Hes1, Nkx2.1, and LIM homeodomain gene 2 (Lhx2) are involved in the differentiation of PT. In the hypothalamic tanycytes, expressions of Dio2, Dio3, vimentin, serine/threonine kinase 33, GPR50, Nestin, Retinoid signaling genes (retinaldehyde dehydrogenase 1, cellular retinol binding protein 1, and Stra6), monocarboxylate transporter 8, and neural cell adhesion molecule change under different photoperiods. Rax, Lhx2, Nfia/b/x, and fibroblast growth factor 10 are involved in the differentiation of tanycytes.

FRI488 The Effect Of Thyroid Stimulating Hormone On Brown Adipose Tissue In Humans

Abstract Disclosure: L. Salej: None. S.D. Kodani: None. N. Chaves: None. K.N. Youssef: None. R. Monahan-Earley: None. H. Halle: None. H. Shaelah: None. P. Annie: None. J.A. Parker: None. A.M. Cypess: None. G. Kolodny: None. Y. Tseng: None. B.C. James: None. A. Gavrila-Filip: None. Obesity and diabetes are two main public health concerns due to their high impact on global morbidity and mortality. In an effort to find new treatment strategies, highly active metabolic tissues such as brown adipose tissue (BAT) have been studied as potential targets. Animal studies have shown that TSH may have a direct local effect on BAT mass and activity by stimulating local T3 production via increased deiodinase-2 (DIO2) expression and also by increasing the expression of uncoupling protein-1 (UCP-1), the key molecule in BAT thermogenesis. We hypothesized that high circulating TSH levels could increase BAT activity by increasing local T3 production and generating a local tissue "thyrotoxicosis". We studied 7 patients with thyroid cancer who underwent thyroid surgery and required recombinant TSH (rhTSH) administration for standard follow-up procedures. Each patient underwent 2 PET-CT scans for assessment of BAT volume and activity, first one day after the rhTSH administration (high TSH state) and then 1-3 months later on suppressive thyroid hormone (TH) treatment (low TSH state). Indirect calorimetry and serum thyroid function tests, fasting glucose, insulin, HbA1c, and lipid panel were measured. Our results show that there was a statistically significant difference in TSH levels (p = 0.0095), with stable circulating T4 and T3 between the low and high TSH states. There was no statistically significant difference in the BAT volume and activity (SUVmax) between the high TSH and low TSH states. Age was a significant predictor of BAT SUVmax (p = 0.008; coeff = -0.39, CI = -0.65-0.13), while BMI was a significant predictor for resting energy expenditure (REE) (p = 0.04; coeff = -203.95, CI = -396.12 - -10.78). Based on these findings, along with those from our previous study[1] showing that circulating TH levels may not be directly correlated with BAT function, we have extended our study to assess the intracellular thyroid hormone status in BAT. We have collected deep peri-thyroidal adipose tissue and subcutaneous white adipose tissue (WAT) as a control group from patients undergoing thyroid surgery. In these samples, we will measure mRNA expression of TSH receptors, TH receptors, β-adrenergic receptors, DIO2 and UCP-1 and evaluate for correlations with circulating TSH and TH levels as well as different metabolic parameters to get a deeper insight into BAT function in humans. Reference: 1. Gavrila A et al. Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status. Thyroid. 2017 Jan 1;27(1):1-10. Presentation: Friday, June 16, 2023

FRI471 Regulation Of Adult Thyroid Hormone Homeostasis By Early Postnatal Hyperthyroidism In Male Mice

Abstract Disclosure: D. Kovári: None. A. Szilvásy-Szabó: None. V. Penksza: None. B. Gereben: None. C. Fekete: None. The thyroid hormone (TH) negative feedback regulation enables the hypothalamic-pituitary-thyroid (HPT) axis to maintain the relatively steady circulating TH levels. Internal and external factors influence the development of this feedback regulation and consequently evoke life-long changes of the HPT axis activity. The aim of our study was to reveal how perinatal alteration of TH status influences TH homeostasis of adult mice. Mice were treated with 1µg/bwg thyroxine (T4) or vehicle subcutaneously every day between postnatal day (P) 2-6 and sacrificed at adulthood. Early postnatal hyperthyroidism resulted in central hypothyroidism in adults, characterized by decreased thyrotropin releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and lower serum free T4 level, accompanied by unchanged thyrotropin stimulating hormone β (TSHβ) mRNA expression in the pituitary and serum free triiodothyronine level. The two main regulators of the HPT axis are the hypophysiotropic TRH neurons and tanycytes. Tanycytes affect the feedback regulation of TRH neurons by type 2 deiodinase (D2) mediated TH activation. To understand how postnatal T4 treatment results in central hypothyroidism in adult mice, tanycytes and TRH neurons of the PVN were isolated by laser capture microdissection from control and postnatally T4 treated adult mice. Postnatal T4 treatment did not change D2 expression in the tanycytes. Furthermore, using Thyroid Hormone Action Indicator (THAI) mice, we showed that the treatment did not influence TH action in the mediobasal hypothalamus of adult mice. These data together indicate that tanycytes are not involved in mediation of the postnatal T4 treatment induced effects. In contrast, the early postnatal T4 treatment markedly changed the transcriptome of TRH neurons in the PVN of adult mice. The expression of TH receptors, most TH receptor-related coregulators, TH transporters and genes involved in the synthesis of TRH were decreased. Despite of the central hypothyroidism, the energy expenditure of these mice were not decreased and TH action also remained unchanged in most tissues indicating that the peripheral tissues are able to compensate the effect of the generated mild hypothyroidism. These results indicate that alteration of TH levels during the early postnatal period can cause life-long effects on the activity of the HPT-axis likely via epigenetic regulation of TRH neurons. Presentation: Friday, June 16, 2023

FRI480 Uncovering The Mystery Of Macro TSH

Abstract Disclosure: F. Anwar: None. Z.I. Saeed: None. Introduction: An isolated elevation in TSH level, while uncommon, may result in incorrect diagnosis and improper treatment. We present a case of suspected hypothyroidism that was later found to be caused by macroTSH in the blood. Clinical Case: A 21-year-old asymptomatic female was diagnosed with hypothyroidism and started on levothyroxine at age 16 when routine lab work revealed TSH of 34.2 MCU (0.550-4.780 MCU) and free T4 of 1.1 ng/dl (0.89-1.76 ng/dl). She denied any personal or family history of thyroid disorders in the past. Patient later reported symptoms including palpitations and weight loss leading to discontinuation of levothyroxine. Repeat lab work showed TSH of 0.112 MCU and free T4 of 1.71 ng/dl. After discontinuing levothyroxine, TSH levels were found in range of 89.26 MCU to 106 MCU (0.550-4.780 MCU). Free T4 levels remained normal, even when tested using dialysis method. Total T3 level also remained normal at 87 ng/dl (80-200 ng/dl). TPO antibodies were slightly elevated at 9.3 IU/mL (0.0-9.0 IU/ml), TSI and TSH receptor antibodies were negative. Patient's high TSH level, lack of symptoms, and normal free T4 levels prompted the use of different assays to test TSH. We contacted Mayo Clinic Lab for further testing. One assay (Roche Elecsys) showed TSH level of 90.8 mIU/L, but this result was not significantly changed when sample was incubated with a commercial heterophile antibody blocking reagent. Another assay (Beckman Coulter Access TSH) produced a significantly different but still elevated result of 43.1 mIU/L. For research purposes, the sample was further tested for macroTSH using polyethylene glycol (PEG) precipitation, which resulted in TSH level of 5.8 mIU/L which was reduced from 90.8 mIU/L (94% reduction). These results were higher than the mean +/- 2 standard deviations of the control group (range 0% to 65% reduction in TSH with PEG in controls). This suggested presence of macroTSH, although the assay's performance characteristics and reference ranges had not been established at the time of testing for this patient. Patient's TSH levels remain high and she was advised not to begin the medication unless circulating thyroid hormone levels are abnormal. Conclusion: Macro TSH is a combination of monomeric TSH and anti-TSH antibodies, similar to macro-prolactin. It is considered inactive and has an estimated prevalence of 0.6-1.6%. In a review of over 150 patients, more than 50% of documented thyroid interferences, including macro TSH, led to incorrect diagnosis and improper treatment. This case demonstrates the significance of identifying macro TSH to avoid misdiagnosis and inappropriate management of euthyroid patients with isolated TSH elevation. Presentation: Friday, June 16, 2023

OR26-06 Cardiovascular Morbidity And Mortality In Patients With Resistance to THYROID Hormone (RTH): A Linked Record Study

Abstract Disclosure: O. Okosieme: None. D. Usman: None. P. Taylor: None. C. Dayan: None. G. Lyons: None. C.M. Moran: None. V.K. Chatterjee: None. A. Rees: None. Introduction: Individuals with Resistance to Thyroid Hormone β (RTH-β) may develop cardiac disease, including cardiomyopathy or arrhythmia. Long-term survival outcomes in this group of patients have not been systematically evaluated. Objectives: We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTH-β in endocrine clinics in Wales. Methods: In a retrospective cohort study using linked datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank, Welsh patients with genetically-proven RTH-β were identified from laboratory records (n=55), matched to population controls by age and sex (n=2750), and linked to outcomes in SAIL. We used Kaplan-Meier and Cox regression models to analyse the association of RTH-β with all-cause mortality, acute myocardial infarction, atrial fibrillation, heart failure, strokes and major adverse cardiovascular events (MACE; a composite of cardiovascular death, acute myocardial infarction, heart failure, and strokes). We also investigated any association between baseline thyroid hormone concentrations and outcomes using restricted cubic splines. Results: Compared to controls, patients had an increased risk of all-cause mortality (Hazard ratio [HR] 2.84, 95% Confidence Interval [95%CI] 1.59-5.08), MACE (HR 3.49, 95%CI 2.04-5.99), atrial fibrillation (HR 10.56, 95%CI 4.72-23.63), and heart failure (HR 6.35, 95%CI 2.26-17.86). Positive associations between FT4 concentration at diagnosis and subsequent cardiovascular morbidity or death were observed, with a 7% increased risk of death per pmol/L increase in FT4. The relationship between FT4 and outcomes was non-linear, with increased risk associated with FT4 concentration exceeding 30 pmol/L. When compared to no intervention, treatment with antithyroid drugs, radioiodine/surgical ablation or levothyroxine, alone or in combination, did not effectively control thyroid hormone excess in the long-term. Conclusion: Patients with RTH-β have increased mortality and cardiovascular outcomes that correlates with high, circulating thyroid hormone levels. Ideal future therapies would target both thyroid hormone excess and tissue resistance and could potentially reduce cardiovascular risk in this disorder. Presentation: Saturday, June 17, 2023

Circulating Thyroid Hormone Levels among Patients with Cardiovascular, Gastrointestinal, and Hypertensive Disorders in the Population of Peshawar, Khyber Pakhtunkhwa: An Analytical Comparison

This research set out to determine the levels of TSH, T4, and T3 in various age groups, genders, and conditions such as heart disease, gastroenteritis, and hypertension. Chemiluminiscence immunoassay (CLIA) was used to measure the serum levels of TSH, T4, and T3 in stomach, heart, and hypertension patients of various age groups and genders. Gender differences were seen in thyroid hormone levels. Based on our findings, women have a wider TSH range than men. Women's mean T3 values are nearly identical to those of men, whereas women's T4 values are higher than men's. Hormone levels vary significantly across people with heart disease, hypertension, and gastrointestinal disorders. While the values of T3 and T4 are normal, the mean TSH value in several patients was somewhat higher than the normal range. Hormone levels are influenced by age in a similar manner.

Management of Hyperthyroidism during Pregnancy: A Systematic Literature Review

In pregnancy, several physiological changes affect maternal circulating thyroid hormone levels. The most common causes of hyperthyroidism in pregnancy are Graves' disease and hCG-mediated hyperthyroidism. Therefore, evaluating and managing thyroid dysfunction in women during pregnancy should ensure favorable maternal and fetal outcomes. Currently, there is no consensus regarding an optimal method to treat hyperthyroidism in pregnancy. The term "hyperthyroidism in pregnancy" was searched in the PubMed and Google Scholar databases to identify relevant articles published between 1 January 2010 and 31 December 2021. All of the resulting abstracts that met the inclusion period were evaluated. Antithyroid drugs are the main therapeutic form administered in pregnant women. Treatment initiation aims to achieve a subclinical hyperthyroidism state, and a multidisciplinary approach can facilitate this process. Other treatment options, such as radioactive iodine therapy, are contraindicated during pregnancy, and thyroidectomy should be limited to severe non-responsive thyroid dysfunction pregnant patients. In light of this events, even in the absence of guidelines certifying screening, it is recommended that all pregnant and childbearing women should be screened for thyroid conditions.

Changes in Thyroid Function in Patients Undergoing Cardiac Surgery Using Cardiopulmonary Bypass

INTRODUCTION: After open heart surgery (OHS) using cardiopulmonary bypass (CPB), abnormalities in the circulating thyroid hormone levels are found in the absence of primary thyroid disease; this is collectively called the sick euthyroid syndrome (SES). AIMS ANDOBJECTIVES: To study thyroid function test in patients planned for cardiac surgery under cardiopulmonary bypass. MATERIALS AND METHODS: This study included a total of 150 patients, of any age, either sex, planned for cardiac surgery under cardiopulmonary bypass (like Valve replacement, CABG, myxoma excision, congenital Heart Diseases like ASD, VSD, TOF). To assess the levels of thyroid hormone, TSH, TT3 and TT4 were measured. The blood samples were collected at regular intervals: preoperatively, on 2nd postoperative day and on 7th postoperative day. CONCLUSION: In our study the levels of thyroid hormone (TT4 and TT3) decreased significantly after cardiopulmonary bypass. Keywords: Open Heart Surgery (OHS), Cardiopulmonary Bypass (CPB), Sick Euthyroid Syndrome (SES)

Vandetanib downregulates type 2 deiodinase in fibro/adipogenic progenitors.

Treatment with tyrosine kinase inhibitors (TKIs) has been associated with alterations in circulating thyroid hormone levels, possibly related to perturbations in peripheral thyroid hormone metabolism. In this study, we evaluated the effect of the multi-kinase inhibitor vandetanib on the expression of the three deiodinase selenoenzymes, responsible for the thyroid hormone activation (type 1 and type 2 deiodinases) or for its inactivation (type 3 deiodinase). Here, we show that the multi-kinase inhibitor vandetanib determines a strong cell-specific downregulation of type 2 deiodinase (D2) expression and a significant reduction in D2 enzymatic activity. This occurs in the diffused population of fibro/adipogenic progenitors, which reside in different tissues - including the muscles - and normally express D2. Given the widespread diffusion of mesenchymal cells within the body, our results may explain at least partially the alterations in thyroid hormone levels that occur in vandetanib-treated patients. Our findings represent a step forward into the understanding of the mechanisms by which TKIs induce hypothyroidism and identify a resident cell population in which such an effect takes place.

Subclinical hypothyroidism in children and adolescents as mild dysfunction ofthe thyroid gland: asingle-center study.

Subclinical hypothyroidism (SH) is a biochemical diagnosis made when a serum thyroid-stimulating hormone (TSH) is ele-vated with circulating thyroid hormone levels within their reference ranges. Aim of our prospective non-randomized study was to evaluate the course of SH. All patients with suspicion of SH referred to the Endocrinology Outpatient Clinic between 2014 and 2018 were recruited to prospective study. A total of 130 patients with SH were recruited for this study. Thirty-five (26.9%) patients were followed up without levothy-roxine (L-T4) (SH-T0 group) and therapy with L-T4 was randomly introduced in 95/130 (73.1%) SH children (SH-T1 group). We did not find statistical differences in hSDS and BMI Z-score between the SH-T0 and SH-T1 groups (p = 0.761 and p = 0.843, respectively). Introducing L-T4 in patients with short stature did not affect the linear growth at the end of FU ex-pressed as hSDS. OH developed in six children (6.3%) in the SH-T1 group. After conducting a multivariate logistic regres-sion, we found that the baseline TSH concentration and BMI Z-score are possible predictors of OH. Our study confirmed a low risk of progression of SH to overt hypothyroidism. The majority of patients remains SH or resolved for nor-mal thyroid function. The L-T4 therapy did not effect on linear growth and body weight. The main predictor of worsening to hypothyroidism were a higher TSH level and Z-score BMI.

Type 2 Deiodinase A/G (Thr92Ala) Polymorphism and Circulating Thyroid Hormone Level of Childbearing Age Women in Area Replete with Iodine Deficiency Disorders

BACKGROUND: Iodothyronine deiodinase (DIO) is an enzyme that regulates thyroid hormone activity. DIO consists of three types: deiodinase 1 (D1), 2 (D2), and 3 (D3). D2 is a gene that plays an important role in regulation of the biochemistry of the thyroid hormone in several tissues. D2 also plays a role in the production of triiodothyronine and controlling thyroid hormone signals. This study measured the observation that about 15% of the normal population show that D2 gene polymorphism (Thr92Ala) potentially affects the activity of D2. AIM: This study aimed to determine D2 polymorphisms and their association with thyroid hormone levels in women of childbearing age in replete iodine deficiency disorder areas. METHODS: Total number of subjects was 131. Analysis of serum TSH, T3, fT3, T4, and fT4 levels was done using ELISA. Polymorphism of Thr92Ala was analyzed by PCR-RFLP method. RESULTS: The results showed that the frequencies of the genotypes Thr92Ala were AA 16.79%, AG 41.22%, and GG 41.99%, whereas the allele frequency A 37.5% and G 62.5% (p HWE = 0.171). In this study, we found no differences of TSH and thyroid hormone level between group of each allel. Mean of TSH and thyroid hormone level was on normal range. CONCLUSION: This D2 polymorphism is associated with fT4 levels rather than fT3 but not statistically significant. Heterozygous alleles at D2 AG have higher TSH levels compared with homozygous alleles.

ODP452 A Case of Thymic Hyperplasia in Graves’ Disease

Abstract Introduction We report a case of a patient with Graves’ Disease (GD) associated with thymic hyperplasia (TH) which regressed with treatment of GD. The association between these two conditions is under recognized. The causative mechanisms between TH associated with GD are still under investigation. Case Description A 39-year-old male patient presented with hemoptysis, dyspnea, palpitations, tremors and unintentional weight loss. His TSH was suppressed to < 0. 005 and free T4 was elevated to 5.51. As part of his work up a CT scan was performed which revealed a prominent anterior mediastinal mass. He was started on Methimazole and Atenolol. Lab work confirming positive TSI and TRAB antibodies consistent with Graves’ disease. At follow up, he opted for radioactive iodine ablation therapy with 20mCi. He had failure of therapy and was resumed on Methimazole. He ultimately underwent total thyroidectomy with subsequent thyroid hormone replacement with Levothyroxine 150mcg daily. His thyroid function tests normalized, and his symptoms resolved. A repeat CT thorax was performed which showed complete resolution of his mediastinal mass, consistent with GD associated TH. Conclusions GD associated TH was first described in 1914. Data supports TSH receptor antibody mediated thymic enlargement1. TH can be classified in two morphological types, lymphoid hyperplasia unassociated with thymic enlargement and true TH in which an increase in thymic volume is evident 2. Thymic cortical tissue expansion seems to be due to a hyperthyroid state involving increased levels of thymulin, a protein involved in lymphocyte differentiation whereas lymphoid hyperplasia correlates with the immune process in GD 2. Antithyroid drug therapy reduces circulating thyroid hormone levels causing a generalized immunosuppressive effect. This reduces hyperplasia of lymphatic organs including the thymus 3. There are no current guidelines for the management and surveillance of thymic hyperplasia in GD as the course and timeline of regression of TH can vary widely. Thymic biopsies are performed frequently to rule out malignancy, however, it is important to raise awareness that GD associated TH has a benign course and generally resolves with management of the underlying GD 3. It is imperative to avoid unnecessary invasive procedures and their subsequent complications in such GD patients.

Oxidative Stress Is a Potential Cost of Synchronous Nesting in Olive Ridley Sea Turtles.

Olive ridley sea turtles, Lepidochelys olivacea, exhibit a polymorphic reproductive behavior, nesting solitarily or in mass aggregations termed “arribadas”, where thousands of individuals nest synchronously. Arribada nesting provides fitness benefits including mate finding during nearshore aggregations and predator satiation at the time of hatching, but it is unknown if such benefits come with a physiological cost. We used plasma metabolite profiling, stable isotope analysis, biochemical and endocrine assays to test whether metabolic parameters differ between nesting modes, and if arribada nesting is associated with increased levels of oxidative damage compared to solitary nesting. Arribada nesters were bigger and had higher circulating thyroid hormone levels than solitary nesters. Similarly, pathways related to phospholipid and amino acid metabolism, catabolic processes, and antioxidant defense were enriched in individuals nesting in arribada. Stable isotope signatures in skin samples showed differences in feeding zones with arribada nesters likely feeding on benthic and potentially more productive grounds. Arribada nesters had increased levels of plasma lipid peroxidation and protein oxidation products compared to solitary nesters. These results suggest that metabolic profiles differ between nesting modes and that oxidative stress is a trade-off for the fitness benefits associated with arribada nesting.

Clinical Manifestation and Diagnosis of a Thyroid Adenoma in a 3-year-old Horse

Hyperthyroidism in horses is a rare disorder in young horses that causes diverse findings such as weight loss, tachypnea, aggression, change in appetite and cachexia. In this report, the clinical manifestation and methods that used in the diagnosis of thyroid adenoma are presented. It was learned that a 3-year-old male Thoroughbred horse became aggressive and had been losing weight despite an adequate diet and appetite. During the inspection, a palpable, painless and moving mass was detected caudal to the larynx, on the left side. For further diagnosis, hemogram, serum biochemistry, urine dipstick analysis and ultrasonographic examination were performed. In serum biochemistry, high HDL, LDH, triglyceride, AST, direct bilirubin, creatine kinase and fT3; low TSH, fT4 and ferritin levels were determined. Ultrasonographic examination revealed that the left thyroid tissue was 2.83 cm x 4.81 cm in size. In the microscopic examination of the aspirate, it was observed that follicles were rich in cytoplasm and surrounded by cuboidal epithelial cells of varying sizes. Dilatation was observed in some follicles, while others were small or even atrophic. As a result, high fT3 and low TSH levels were consistent with the fact that the gland was overactive, the circulating thyroid hormone level was high, and the pineal gland produced less TSH by the feedback mechanism, all of which indicated hyperthyroidism. In addition, it was concluded that thyroid adenoma can also be seen in young horses, may cause clinical symptoms, ultrasonographic examination, microscopic examination of the aspirate and comprehensive serum biochemistry analysis are sufficient for diagnosis.

Risk Assessment of the Insecticide Movento 100 SC with the Active Substance Spirotetramat

Movento 100 SC is a new insecticide containing the active substance spirotetramat. The intended use is in stone fruit, pome fruit, vegetables and ornamentals outdoors, and lettuce, tomatoes and cucumbers in greenhouses.
 VKM was requested by the Norwegian Food Safety Authority to consider possible health risk for operators related to the properties of Movento 100 SC; in particular the relevance of the effects of spirotetramat on thyroid hormones, brain, thymus and body weight observed in dogs, and the reproductive effects of spirotetramat observed in rats. VKM was also asked to consider the fate and behaviour of Movento 100 SC with the active ingredient spirotetramat in the environment, and the ecotoxicological effects and risks related to its use. The risk assessment was finalized in a meeting on May 24. 2013, by VKM’s Scientific Panel on Plant Protection Products.
 VKM’s conclusions are as follows:
 Health:
 VKM concludes that spirotetramat shows toxic effects in dogs and rats that could be relevant for humans. Thyroid and thymus glands are target organs in the oral subchronic toxicity studies of spirotetramat in dogs, and effects are observed from 19 mg/kg bw/day (600 ppm). Decreases in circulating thyroid hormone levels were detected in all three studies carried out with dogs (28-, 90-days and 1-year) and should be considered toxicologically relevant. The opinion of the Panel is that it cannot be excluded that the observed brain dilatation in dogs is treatment-related, and relevant to humans.
 Furthermore, VKM concludes that the reproductive effect observed in rats could be relevant for humans.
 VKM proposes a NOAEL of 5 mg/kg bw/day (200 ppm) for spirotetramat based on a 1- year toxicity study in dogs, and a NOAEL of 100 mg/kg bw/day based on the acute neurotoxicity study in rats.
 VKM supports/proposes:
 
 ADI: 0.05 mg/kg bw/day.
 AOEL: 0.05 mg/kg bw/day.
 ARfD: 1 mg/kg bw/day.
 
 Risk calculations show minimal risk if personal protective equipment is used.
 Environment:
 VKM concludes that spirotetramat and its metabolites are not expected to accumulate in soil. It is not expected that spirotetramat or any of its metabolites will reach concentrations in groundwater above the threshold level of 0.1 μg/L when the formulation Movento 100 SC is applied according to the intended use.
 VKM concludes that use of Movento 100 SC with the active substance spirotetramat according to the proposed application scheme in Norway represents a minimal risk of adverse effects on terrestrial mammals, birds, earthworms, and soil microorganisms. However, in-field effects on sensitive species of predatory mites in the crop cannot be excluded.
 The risk of adverse effects on bees is minimal providing that spirotetramat is not used on crops during flowering or when bees are actively foraging.
 For aquatic organisms in surface water, the risk is considered minimal, provided that a 5 m buffer zone to open water is used.

Low-grade systemic inflammation in subclinical hypothyroidism

Background: Hypothyroidism is the deficiency in the production of thyroid hormones to meet the requirements of peripheral tissues. Subclinical hypothyroidism (SCH) is defined biochemically as normal serum free thyroxin concentration in the presence of an elevated serum thyroid-stimulating hormone (TSH) concentration. SCH may be associated with low-grade systemic inflammation (increased high sensitivity-C reactive protein (hs-CRP), one possible explanation may be that TSH in adipocytes promotes the release of interleukin-6 (IL-6). Studies have confirmed inflammatory biomarkers like hs-CRP and IL-6 to be a predictor of cardiovascular (CV) events. However, the treatment of SCH remains subject to debate. Conclusions: It is increasingly evident that SCH has prognostic values and crucial clinical effects, which leads to the view of SCH not being a compensated biochemical change sensu strictu. Even a modest but consistent fluctuation in the circulating thyroid hormone levels can create a response from the human heart. Well-timed treatment should be considered as a precaution to avoid the unfavourable CV diseases. The inflammatory biomarkers, namely CRP and IL-6 are exceptionally robust markers of cardiovascular risk. Thus, using these biomarkers may be helpful in assessing the cardiovascular risk in patients with subclinical hypothyroidism.

Unraveling the Role of Thyroid Hormones in Seasonal Neuroplasticity in European Starlings (Sturnus vulgaris).

Thyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starlings employing in situ hybridization methods. Thyroid hormone transporter LAT1 expression in the song nucleus HVC was elevated during the photosensitive phase, pointing toward an active role of thyroid hormones during this window of possible neuroplasticity. In contrast, DIO3 expression was high in HVC during the photostimulated phase, limiting the possible effect of thyroid hormones to maintain song stability during the breeding season. Next, we studied the effect of hypothyroidism on song behavior and neuroplasticity using in vivo MRI. Both under natural conditions as with methimazole treatment, circulating thyroid hormone levels decreased during the photosensitive period, which coincided with the onset of neuroplasticity. This inverse relationship between thyroid hormones and neuroplasticity was further demonstrated by the negative correlation between plasma T3 and the microstructural changes in several song control nuclei and cerebellum. Furthermore, maintaining hypothyroidism during the photostimulated period inhibited the increase in testosterone, confirming the role of thyroid hormones in activating the hypothalamic–pituitary–gonadal (HPG) axis. The lack of high testosterone levels influenced the song behavior of hypothyroid starlings, while the lack of high plasma T4 during photostimulation affected the myelination of several tracts. Potentially, a global reduction of circulating thyroid hormones during the photosensitive period is necessary to lift the brake on neuroplasticity imposed by the photorefractory period, whereas local fine-tuning of thyroid hormone concentrations through LAT1 could activate underlying neuroplasticity mechanisms. Whereas, an increase in circulating T4 during the photostimulated period potentially influences the myelination of several white matter tracts, which stabilizes the neuroplastic changes. Given the complexity of thyroid hormone effects, this study is a steppingstone to disentangle the influence of thyroid hormones on seasonal neuroplasticity.

No effect of thyroid hormones on 5-year mortality in patients with subjective cognitive decline, mild cognitive disorder, and Alzheimer's disease.

The present study aimed to investigate differences in circulating thyroid hormone levels, gender, education, depressive symptoms, and cognitive performance among patients with cognitive impairment, and also to examine their associations, as well as that of cognitive decline, with 5‐year mortality. Between 1998 and 2017, a hospital‐based, single‐centre (Neurology Department of the General Hospital in Vienna, Austria), retrospective follow‐up study enrolled 2102 patients with mild to severe cognitive impairment (grouped into subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease). Cox proportional hazards models were used to calculate hazard ratios (HRs), with 95% confidence intervals (CIs), as well as to calculate stepwise adjustments for demographic variables (age, gender, and education), depressive symptoms (Geriatric Depression Scale, GDS‐15), and neuropsychological abilities (four domains of a neuropsychological test battery of Vienna, NTVB). In univariate analyses, total triiodothyronine (TT3) levels differed significantly between Alzheimer's disease and mild cognitive impairment patients (p diff = .001). No other differences in cognitive impairment subgroups with any of the measured thyroid hormones were observed. Furthermore, in multivariate models, circulating TT3 was not associated with mortality (multivariable‐adjusted HR per unit increase in TT3 = 0.56; 95% CI = 0.29–1.07). In multivariate models, we observed significantly lower 5‐year mortality among women (HR = 0.56; 95% CI = 0.43–0.73) and those who scored higher on any of the four domains of the NBTV (e.g., attention and perceptual speed, HR = 0.63; 95% CI = 0.54–0.72); we also observed significantly higher 5‐year mortality among patients with depressive symptoms (HR per one point score increase in GDS‐15 = 1.06; 95% CI = 1.02–1.10), regardless of cognitive impairment subgroup. Among patients with various degrees of cognitive impairment, we found no associations of thyroid hormone levels with 5‐year mortality. Gender, neuropsychological abilities, and depressive symptoms were each significant predictors of 5‐year mortality. These results suggest that a neurocognitive test performance could serve as an important predictor of 5‐year mortality among patients with cognitive impairment, although further studies with a more complete adjustment for comorbidities are needed to confirm these findings.