Circulating Thyroid Hormone Research Articles

Status of Serum Zinc Level in Hypothyroid Patients with Normal Serum Albumin Level: A Case Control Study

INTRODUCTION: Decreased thyroid hormone synthesis and low levels of circulating thyroid hormones result in clinical hypothyroidism causing many metabolic processes to slow down. Zinc is essential for many biochemical processes and cell proliferation. Thyroid hormones influence Zinc metabolism by affecting absorption and excretion.
 MATERIAL AND METHODS: This case-control study was conducted in subclinical hypothyroidism (n=30), overt hypothyroidism (n=30) and compared with age and sex matched euthyroid controls (n=30) attending UCMS-TH. Serum free T3 (fT3), free T4 (fT4) and Thyroid Stimulating Hormone (TSH) were estimated by ELISA. The serum Zinc and Albumin were estimated by colorimetric Nitro-PAPS and BCG dye binding method respectively.
 RESULTS: The overall frequency of Zinc deficiency has been observed 12 (40%) in overt hypothyroidism, 9 (30%) in subclinical hypothyroidism and two (6.66%) in euthyroid controls. A significant association between serum Zinc with fT3, fT4 levels (p=0.0046) and with TSH level (p-value=0.030) was observed in all cases. The positive correlation of serum Zinc with fT3 level (r=0.217, p=0.04), fT4 level (r=0.267, p=0.011) while serum negative correlation with TSH level (r=-0.234, p=0.026) and Albumin (r=-0.039, p=0.713) were observed. The odds ratio shows 9.33 times Zinc deficiency likely to occur in overt hypothyroidism (CI: 1.86-46.68; p-value=0.0065) whereas 6.0 times in subclinical hypothyroidism (CI:1.17- 30.72; p-value=0.0315) than euthyroid controls.
 CONCLUSION: The significant difference in Zinc deficiency was observed in overt hypothyroid patients. However, non-significant difference in sub-clinical hypothyroidism as compared to euthyroid controls was found in all groups having normal albumin level. This may conclude that with progression of hypothyroidism there is significant decrease in Zinc with normal albumin. Hence, there is association between thyroid profile and serum Zinc status.

Case study: Thyrotoxicosis on women with complete hydatidiform molar pregnancy

Thyrotoxicosis defined as a clinical manifestation of excess circulating thyroid hormone. Epidemiologic investigation reports 0.2% of thyrotoxicosis is caused by hydatidiform mole. The New England Trophoblastic Disease Centre (NETDC) mentioned that 20% of hydatidiform mole cases have thyrotoxicosis as one of its complications. The basic pathogenesis of thyrotoxicosis is the similarity of the HCG subunit to TSH which results in excessive stimulation of thyroid hormone. We present thethyrotoxicosis case in a 15-weeks pregnant woman with complete hydatidiform mole. The patient admitted to the hospital with blackish-red coloured bleeding and several hyperthyroidism complaints, laboratory test showed elevated levels of HCG and thyroid hormone and decreased TSH. Imaging studies done with ultrasound showed with snowflake pattern. The patient then treated with thyroid hormone suppressant therapy before the hydatidiform mole evacuation. Normalization of thyroid hormone levels should be made immediately before the mole evacuation to avoid life-threatening thyroid storm complications.

Evolution of circulating thyroid hormone levels in preterm infants during the first week of life: Perinatal influences and impact on neurodevelopment

Evolution of circulating thyroid hormone levels in preterm infants during the first week of life: Perinatal influences and impact on neurodevelopment

Differential Diagnosis of Thyrotoxicosis

Hyperthyroidism is characterized by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. Thyrotoxicosis is characterized by low serum thyroid-stimulating hormone (TSH) level and elevated serum levels of free thyroxine or free triiodothyronine, or both. Therefore, thyrotoxicosis is divided into two subtypes: thyrotoxicosis with hyperthyroidism such as Graves’ disease and Plummer’s disease, and thyrotoxicosis without hyperthyroidism such as painless and subacute thyroiditis. Here, I describe the differential diagnosis of hyperthyroidism; differentiation between Graves’ disease and Plummer’s disease; differentiation between Graves’ disease with and without thyroid storm. Further, I show the differentiation among Graves’ disease, painless thyroiditis and subacute thyroiditis. I believe that the proper diagnosis leads to appropriate treatment and management of thyrotoxicosis. J Endocrinol Metab. 2019;9(5):127-132 doi: https://doi.org/10.14740/jem600

Unraveling the Molecular Basis for Successful Thyroid Hormone Replacement Therapy: The Need for New Thyroid Tissue- and Pathway-Specific Biomarkers.

Thyroid function is conventionally assessed by measurement of thyroid-stimulating hormone (TSH) and free circulating thyroid hormones, which is in most cases sufficient for correct diagnosis and monitoring of treatment efficiency. However, several conditions exist, in which these parameters may be insufficient or even misleading. For instance, both, a TSH-secreting pituitary adenoma and a mutation of thyroid hormone receptor β present with high levels of TSH and circulating hormones, but the optimal treatment is substantially different. Likewise, changes in thyroid hormone receptor α signaling are not captured by routine assessment of thyroid status, as serum parameters are usually inconspicuous. Therefore, new biomarkers are urgently needed to improve the diagnostic management and monitor treatment efficiency for e. g., replacement therapy in hypothyroidism or thyroid hormone resistance. By comparing animal models to human data, the present minireview summarizes the status of this search for new tissue- and pathway-specific biomarkers of thyroid hormone action.

Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

BackgroundSymptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression.MethodsPost-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI).ResultsTreatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877).ConclusionsThis study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients.Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

Thyroid Dysfunction and Type 2 Diabetes Mellitus: Screening Strategies and Implications for Management.

Diabetes mellitus (DM) and thyroid dysfunction (TD) often tend to coexist in patients. Both hypothyroidism and hyperthyroidism are more common in type 2 diabetes mellitus (T2DM) patients than in their nondiabetic counterparts. Current guidelines are neither clear nor specific about the frequency of thyroid function monitoring in T2DM patients. Circulating thyroid hormones affect several different organs and cells, have a major impact on glucose, lipid, and protein metabolism, and can worsen glycaemic control in T2DM. Hyperthyroidism and thyrotoxicosis can worsen subclinical DM and cause hyperglycaemia in T2DM patients, increasing the risk of diabetic complications. T2DM reduces thyroid-stimulating hormone levels and impairs the conversion of thyroxine (T4) to triiodothyronine (T3) in the peripheral tissues. Poorly managed T2DM can lead to insulin resistance and hyperinsulinaemia, which causes thyroid tissue proliferation and increases nodule formation and goitre size. In addition, while metformin can be beneficial in both T2DM and TD patients, other antidiabetics such as sulfonylureas, pioglitazone, and thiazolidinediones can negatively impact TD. Antithyroid drugs such as methimazole can impair glycaemic control in T2DM patients. Thyrovigilance in T2DM patients and diabetovigilance in TD patients may therefore be necessary to facilitate individualized care and management.Funding: Abbott India Ltd.

Environmental exposure to pesticides and risk of thyroid diseases

Occupational and environmental exposure to pesticides has been associated with thyroid dysfunction, particularly changes in circulating thyroid hormone levels (T3, T4) and thyroid stimulating hormone (TSH). This study assessed the association between environmental exposure to pesticides and the risk of developing thyroid diseases. A population-based case-control study was carried out among Spanish populations living in areas categorized as of high or low pesticide use according to agronomic criteria, which were used as surrogates for environmental exposure to pesticides. The study population consisted of 79.431 individuals diagnosed with goiter, thyrotoxicosis, hypothyroidism, and thyroiditis (according to the International Classification of Diseases, Ninth Revision) and 1.484.257 controls matched for age, sex and area of residence. Data were collected from computerized hospital records for the period 1998 to 2015. Prevalence rates and risk of having thyroid diseases were significantly higher in areas with higher pesticide use, with a 49% greater risk for hypothyroidism, 45% for thyrotoxicosis, 20% for thyroiditis and 5% for goiter. Overall, this study indicates an association between increased environmental exposure to pesticides as a result of a greater agricultural use and diseases of the thyroid gland, thus supporting and extending previous evidence. This study also provides support to the methodology proposed for real-life risk simulation, thus contributing to a better understanding of the real life threat posed by exposure to multiple pesticides from different sources.

TRAbs at diagnosis may better predict disease severity and relapse in younger patients with Graves′ disease

Thyrotropin receptor antibodies (TRAbs) are pathognomonic for Graves′ disease. Previous studies have linked serum titers of TRAbs to severity of Graves′ disease and likelihood of Graves′ disease relapse. However, we know little about factors that may be involved in the impact of TRAbs on Graves′ disease patients. In December 2018, The Journal of Clinical Endocrinology & Metabolism online published an article [Bano A, Gan E, Addison C, et al. Age may influence the impact of TRAbs on thyroid function and relapse-risk in patients with Graves′ disease. J Clin Endocrinol Metab, 2019, 104(5): 1378-1385. DOI: 10.1210/jc.2018-01738]. With the permission of the original journal, we translated the article into Chinese. This article aimed to investigate the association of TRAbs at diagnosis with thyroid hormones and risk of relapse, and to study the influencing factors on these associations. The results showed that TRAbs at diagnosis were positively associated with circulating thyroid hormone levels and risk of relapse, and these associations were influenced by age, but not by sex, race, smoking or thyroid peroxidase antibody levels. This study indicates TRAbs at diagnosis can better predict severity of elevated thyroid hormone levels and risk of relapse in younger patients with Graves′ disease. Key words: TSH receptor antibody; Graves′ disease; Age; Relapse; Predictive value

SUN-557 Thymic Hyperplasia in Graves' Disease: A Case Series

Background: Thymic hyperplasia (TH) is a known, but often under-recognized finding associated with Graves' disease (GD). The exact pathophysiology of GD-related TH is poorly understood, but is thought to be benign. Limited case reports or series indicate resolution or improvement of TH following successful treatment of GD. Although TH is often incidentally found, discovery can be alarming resulting in potentially inappropriate intervention. Therefore, increased awareness regarding GD-related TH is necessary to avoid this. Aim: To describe the natural history of GD-related TH and assess for risk factors which may be associated with the development of TH. Methods: Retrospective review of patients referred to a tertiary referral center with GD with an anterior mediastinal mass on computed tomography (CT) scan suspected to be TH. Clinical Cases: In total, six patients (30-51 years of age) were discovered to have an anterior mediastinal mass on CT scan at time of GD diagnosis. The majority were women (5/6). Although three patients had a family history of thyroid autoimmunity, only one patient had a co-existing autoimmune condition (Vitiligo). Two patients were active smokers. All patients presented to the emergency room with significant thyrotoxic symptoms including tachycardia (107-170 beats per minute) and weight loss (18.3 ± 11.8 kg) with four requiring admission. One patient presented with thyroid storm. Laboratory testing revealed high circulating thyroid hormone levels at diagnosis with mean free T4 level of 4.24 ± 1.56 ng/dL (0.6-1.76) as well as high mean thyroid-stimulating immunoglobulin activity level of 306.2% (≤122). Clinically significant Graves'-associated orbitopathy was observed in 67% of patients. Tachycardia was the cited reason for requested CT imaging in all patients. The size of thymus glands varied with the largest measuring 9cm x 1cm x 5cm. All thymic masses were consistently characterized as homogeneous without discrete lesions or calcifications. Though only two patients received follow-up chest imaging, both patients demonstrated > 50% reduction in thymus size at six months and no patients underwent biopsy or surgical excision. All but one of our patients required definitive therapy for poorly controlled hyperthyroidism on thionamides (Three had surgery of whom two had severe Graves' orbitopathy and two underwent radioactive iodine therapy). Conclusions: While the true incidence of GD-associated TH is unknown, increased use of imaging modalities may result in further incidental discoveries. Therefore, clinicians need to be aware of the association between benign TH and GD to avoid unnecessary invasive interventions. Furthermore, our findings suggest that GD-related TH may be a marker of GD severity with a lower likelihood of GD remission using thionamides necessitating definitive therapy.

THYROID HORMONES AND CARDIOVASCULAR HOMEOSTASIS; A REVIEW

Two iodinated hormones, 3,5,3-triiodothyronine (T3) and 3,5,3,5-tetraiodothyronine; also known as thyroxine (T4) are secreted by thyroid gland.Thyroid hormones interact with specific receptors on myocardial and vascularendothelial tissues to induce chemical changes and these tissues are verysensitive for a small fluctuation in circulating thyroid hormones. The obtaineddata from different experimental and clinical studies revealed significance ofnormal thyroid hormones to maintain the cardiovascular homeostasis. Evensubtle fluctuation in the concentration of thyroid hormone as in subclinicalhypothyroidism or hyperthyroidism could significantly affect the cardiovascularsystem. In this review article we will understand how thyroid hormones interactswith specific receptors on myocytes and induces many genomic as well as nongenomicalterations directly and indirectly including due to dyslipidemia, bloodpressure changes and endothelial dysfunction. Key Words: Hormones, Homeostasis, Cardiovascular, Hypothyroidism,Hyperthyroidism

Effect of acute aerobic exercise on arterial stiffness and thyroid-stimulating hormone in subclinical hypothyroidism.

Acute exercise has been reported to increase thyroid hormone levels and decrease arterial stiffness in healthy young subjects. However, the effect of acute aerobic exercise on circulating thyroid hormone levels and arterial stiffness in patients with subclinical hypothyroidism remains unclear. The aim of this study was to investigate the effects of acute aerobic exercise on arterial stiffness and thyroid hormone levels, and any relationship between these endpoints, in patients with subclinical hypothyroidism. We studied patients with untreated subclinical hypothyroidism (n = 53, 65 ± 12years old) compared with euthyroid subjects (n = 55, 64 ± 10years old). Exercise analysis was performed with a ramp cycle ergometer test. Arterial stiffness (cardio-ankle vascular index, CAVI) was measured at baseline and 5min after exercise. We collected participant blood samples for serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurements before and 5min after exercise. The CAVI and serum TSH levels significantly decreased after exercise in the subclinical hypothyroidism group (CAVI; 8.1 ± 1.6 vs. 8.5 ± 1.5, p < 0.001, TSH; 6.7 ± 1.4 vs. 7.6 ± 1.2 μIU/ml, p < 0.001) and euthyroid group (CAVI; 7.6 ± 1.0 vs. 8.3 ± 0.9, p < 0.001, TSH; 2.2 ± 1.1 vs. 2.4 ± 1.2 μIU/ml, p = 0.005). The changes in CAVI from baseline compared with after exercise were lower, in absolute values, in the subclinical hypothyroidism group than in the euthyroid group (subclinical hypothyroidism group vs euthyroid group; ΔCAVI: - 0.4 ± 0.6 vs. - 0.7 ± 0.7, p = 0.012). The changes in serum TSH from baseline to after exercise were higher, in absolute values, in the subclinical hypothyroidism group than in the euthyroid group (subclinical hypothyroidism group vs euthyroid group; Δ serum TSH: - 1.3 ± 1.4 vs. - 0.3 ± 0.5, p < 0.001). The changes in CAVI from baseline to after exercise were negatively correlated with changes in TSH (r = - 0.32, p = 0.038) in the subclinical hypothyroidism group. In conclusion, acute aerobic exercise decreased both arterial stiffness and serum TSH levels in patients with subclinical hypothyroidism and euthyroid subjects. While the absolute change in arterial stiffness decreased, the absolute change in serum TSH levels increased in patients with subclinical hypothyroidism compared with euthyroid subjects. These data suggest that subclinical hypothyroidism reduces CAVI during acute aerobic exercise. Further changes in absolute levels of serum TSH in subclinical hypothyroidism may result in reduced CAVI improvement by acute aerobic exercise.

The Effect of Chronic Renal Failure on Thyroid Hormones Specificity Measured fT3 in a Sample of Iraqi Patients

Background: Chronic renal failure (CRF) affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store. Objective: To evaluate of thyroid Gland Function in patients with chronic renal failure and an attempt to find a relationship between chronic renal failure and thyroid dysfunctions. Subjects and Methods: A total number of 96 subjects with age range from 15-67 years old (56 males and 40 females) were included in this study. Total number was divided into two groups according to their number Group A. Study group: haemodialysis (HD) consists of 48 patients and Group B. Control group: consists of 48 subjects. T3, T4, TSH, fT3, Urea, Creatinine, Albumin and TSP were measured in each of the two groups. Results: The results revealed statistically significant reduction serum level of tT3 , fT3 more than tT4 in Chronic Renal Failure group in comparison with normal levels in control group while there is no statistically significant difference seen between case and control groups in regard to TSH. Conclusion: There is a decrease serum level of tT3 , tT4 and fT3 but the decreased of tT3 and fT3 more than tT4 in Chronic Renal Failure group in comparison with normal levels in control group.

Reverse triiodothyronine (rT3) attenuates ischemia-reperfusion injury

Hypothyroidism has been associated with better recovery from cerebral ischemia-reperfusion (IR) injury in humans. However, any therapeutic advantage of inducing hypothyroidism for mitigating IR injury without invoking the adverse effect of whole body hypothyroidism remains a challenge. We hypothesize that a deiodinase II (D2) inhibitor reverse triiodothyronine (rT3) may render brain specific hypometabolic state to ensue reduced damage during an acute phase of cerebral ischemia without affecting circulating thyroid hormone levels. Preclinical efficacy of rT3 as a neuroprotective agent was determined in rat model of middle cerebral artery occlusion (MCAO) induced cerebral IR and in oxygen glucose deprivation/reoxygenation (OGD/R) model in vitro. rT3 administration in rats significantly reduced neuronal injury markers, infarct size and neurological deficit upon ischemic insult. Similarly, rT3 increased cellular survival in primary cerebral neurons under OGD/R stress. Based on our results from both in vivo as well as in vitro models of ischemia reperfusion injury we propose rT3 as a novel therapeutic agent in reducing neuronal damage and improving stroke outcome.

Role of Selenium Intake for Risk and Development of Hyperthyroidism

To investigate the importance of dietary selenium (Se) for hyperthyroidism. We performed a more in-depth analysis of a large cross-sectional study of 6152 participants from two counties within the Shaanxi Province, China. These counties are characterized by different habitual Se intake. We investigated the effects of a different dietary Se supply (0.02, 0.18, 0.6, or 2.0 ppm Se) on disease development in a mouse model of Graves disease (GD). The cross-sectional study revealed a comparable prevalence of hyperthyroidism, irrespective of Se intake, in both counties. However, an unexpected sex-specific difference was noted, and Se deficiency might constitute a risk factor for hyperthyroidism, especially in males. In a mouse model, pathological thyroid morphology was affected, and greater Se intake exerted some protecting effects on the pathological distortion. Circulating thyroid hormone levels, malondialdehyde concentrations, total antioxidant capacity, and the titer of GD-causing TSH receptor autoantibodies were not affected by Se. Expression analysis of the transcripts in the spleen indicated regulatory effects on genes implicated in the immune response, erythropoiesis, and oxygen status. However, the humoral immune response, including the CD4/CD8 or T-helper 1/T-helper 2 cell ratio and the concentration of regulatory T cells, was similar between the experimental groups, despite the difference in Se intake. Our data have highlighted a sexual dimorphism for the interaction of Se and thyroid disease risk in humans, with indications of a local protective effects of Se on thyroid gland integrity, which appears not to be reflected in the circulating biomarkers tested.

Surgical management of hyperthyroidism: about 60 cases

L'hyperthyroïdie englobe plusieurs maladies caractérisées par un niveau élevé d'hormones thyroïdiennes circulantes. La thyroïdectomie en est un des principaux traitements. L'objectif de notre étude est d'évaluer, à travers une étude rétrospective, les particularités épidémiologiques, cliniques, thérapeutiques, et évolutives des patients ayant bénéficié d'une prise en charge chirurgicale d'une hyperthyroïdie dans le service d'ORL à l'hôpital militaire Avicenne de Marrakech. Soixante patients ont été colligés avec une prédominance féminine et une moyenne d'âge de 52 ans. La clinique a été dominée par les signes de thyrotoxicoses qui ont été retrouvés chez tous les patients. L'exploration a permis d'identifier 47 cas de goitre multihétéronodulaire toxique ou prétoxique (soit 78.33% des cas), 5 cas de maladies de Basedow (soit 8.33%) et 8 cas d'adénome toxique (soit 13.33%). Une préparation médicale a été de mise chez tous nos patients. Une thyroïdectomie totale a été réalisée chez 50 patients (soit 83.33%) et une loboisthmectomie chez 10 patients (soit 16.33%). En post-opératoire, des complications sont été colligés: un cas de paralysie laryngée transitoire (1,6% des cas), neuf cas d'hypoparathyroïdie transitoire (15% des cas), un cas d'hypoparathyroïdie définitive (1,6% de cas), et un seul cas d'hématome compressif (1,6% de cas). La chirurgie des goitres toxiques réputés hémorragiques et adhérents, doit être réalisée par un chirurgien expérimenté qui doit doubler de vigilance pour minimiser la morbidité représentée essentiellement par la paralysie laryngée et l'hypoparathyroïdie.

Evaluating Iodide Recycling Inhibition as a Novel Molecular Initiating Event for Thyroid Axis Disruption in Amphibians.

The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces available iodide for thyroid hormone synthesis, which leads to hormone insufficiency in tissues and subsequent negative developmental consequences. IYD activity is especially critical under conditions of lower dietary iodine and in low iodine environments. Our objective was to evaluate the toxicological relevance of IYD inhibition in a model amphibian (Xenopus laevis) used extensively for thyroid disruption research. First, we characterized IYD ontogeny through quantification of IYD mRNA expression. Under normal development, IYD was expressed in thyroid glands, kidneys, liver, and intestines, but minimally in the tail. Then, we evaluated how IYD inhibition affected developing larval X. laevis with an in vivo exposure to a known IYD inhibitor (3-nitro-l-tyrosine, MNT) under iodine-controlled conditions; MNT concentrations were 7.4-200 mg/L, with an additional 'rescue' treatment of 200 mg/L MNT supplemented with iodide. Chemical inhibition of IYD resulted in markedly delayed development, with larvae in the highest MNT concentrations arrested prior to metamorphic climax. This effect was linked to reduced glandular and circulating thyroid hormones, increased thyroidal sodium-iodide symporter gene expression, and follicular cell hypertrophy and hyperplasia. Iodide supplementation negated these effects, effectively rescuing exposed larvae. These results establish toxicological relevance of IYD inhibition in amphibians. Given the highly conserved nature of the IYD protein sequence and scarcity of environmental iodine, IYD should be further investigated as a target for thyroid axis disruption in freshwater organisms.

Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China.

Pregnant women are highly vulnerable to iron deficiency (ID) due to the increased iron needs during pregnancy. ID decreases circulating thyroid hormone concentrations likely through impairment of iron-dependent thyroid peroxidase. The present study aimed to explore the association between ID and hypothyroxinemia in a retrospective cohort of pregnant women in China. To investigate the relationship between ID and hypothyroxinemia, 723 pregnant women were retrospectively analyzed, including 675 and 309 women in the second and third trimesters, respectively. Trimester-specific hypothyroxinemia was defined as free thyroxine (fT4) levels below the 2.5th percentile of the reference range with normal serum thyrotropin (TSH) or TSH higher than the 97.5th percentile of the reference range in each trimester of pregnancy. Serum TSH, fT4, thyroid peroxidase antibodies, thyroglobulin antibodies, serum ferritin, soluble transferrin receptor, and urinary iodine concentrations were measured. Serum ferritin, soluble transferrin receptor, and total body iron were used to indicate the nutritional iron status. Cross-sectional multiple linear regression analysis showed that iron status was positively associated with serum fT4 levels in the first and second trimesters of pregnancy, but not in the third trimester. Logistic regression analysis showed that ID was an independent risk factor for hypothyroxinemia (odds ratio = 14.86 [confidence interval 2.31-95.81], p = 0.005 in the first trimester and odds ratio = 3.36 [confidence interval 1.01-11.21], p = 0.048 in the second trimester). The prospective analysis showed that pregnant women with ID during the first trimester of pregnancy had lower serum fT4 levels and a higher rate of hypothyroxinemia in the second or third trimester than those without ID. ID appears to be a risk factor to predict hypothyroxinemia in the first and second trimesters of pregnancy, but not in the third trimester. Pregnant women with ID in the first and second trimesters should be regarded as a high-risk group for maternal hypothyroxinemia.

Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives

Perfluoroalkyl substances (PFASs) are known to accumulate in traditional food animals of the Arctic, and arctic indigenous peoples may be exposed via consumption of subsistence-harvested animals. PFASs are suspected of disrupting thyroid hormone homeostasis in humans. The aim of this study is to assess the relationship between serum PFASs and thyroid function in a remote population of Alaska Natives.Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska. The concentrations of 13 PFASs, as well as free and total thyroxine (T4), free and total triiodothyronine (T3), and thyrotropin (TSH) were quantified in serum samples. The relationships between circulating concentrations of PFASs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations.Several PFASs, including perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively associated with TSH concentrations when modeled individually. PFOS and PFNA were significantly associated with free T3 and PFNA was significantly associated with total T3 in models with PFAS*sex interactive terms; these associations suggested negative associations in men and positive associations in women. PFASs were not significantly associated with concentrations of free or total T4.Serum PFASs are associated with circulating thyroid hormone concentrations in a remote population of Alaska Natives. The effects of PFAS exposure on thyroid hormone homeostasis may differ between sexes.

Leptin regulation of core body temperature involves mechanisms independent of the thyroid axis

The ability to maintain core temperature within a narrow range despite rapid and dramatic changes in environmental temperature is essential for the survival of free-living mammals, and growing evidence implicates an important role for the hormone leptin. Given that thyroid hormone plays a major role in thermogenesis and that circulating thyroid hormone levels are reduced in leptin-deficient states (an effect partially restored by leptin replacement), we sought to determine the extent to which leptin's role in thermogenesis is mediated by raising thyroid hormone levels. To this end, we 1) quantified the effect of physiological leptin replacement on circulating levels of thyroid hormone in leptin-deficient ob/ob mice, and 2) determined if the effect of leptin to prevent the fall in core temperature in these animals during cold exposure is mimicked by administration of a physiological replacement dose of triiodothyronine (T3). We report that, as with leptin, normalization of circulating T3 levels is sufficient both to increase energy expenditure, respiratory quotient, and ambulatory activity and to reduce torpor in ob/ob mice. Yet, unlike leptin, infusing T3 at a dose that normalizes plasma T3 levels fails to prevent the fall of core temperature during mild cold exposure. Because thermal conductance (e.g., heat loss to the environment) was reduced by administration of leptin but not T3, leptin regulation of heat dissipation is implicated as playing a uniquely important role in thermoregulation. Together, these findings identify a key role in thermoregulation for leptin-mediated suppression of thermal conduction via a mechanism that is independent of the thyroid axis.