Circulating Thyroid Hormone Concentrations Research Articles

273 Effect of dietary iodine supplementation on the growth performance and thyroid hormone concentrations of nursery pigs

Abstract Iodine (I) is critical for growth, development, and thyroid hormone circulation. This study examined the impact of dietary iodine concentration on nursery pig growth performance and thyroid hormone concentrations. Weaned piglets (n =180, 21 ± 3 d of age) were blocked by body weight (BW; 5.4 ± 0.8 kg) and sex (2 barrows and 2 gilts/pen). Pens within a block (n = 9) were randomly assigned to dietary treatments (mg/kg I added): 0 (CON), 0.14 (NRC), 1.4 (NRC10), 14 (NRC100), or 140 (NRC1000). Diets were fed in three phases for 35 d (P1, d 0-10; P2, d 11-21; P3, d 22-35). Piglets were weighed and feed intake recorded on d 0, 7, 10, 14, 21, 28, and 35. Blood was collected on d 21 and 35 for analysis of circulating thyroid hormone concentrations. Data were analyzed as a randomized complete block design via the GLM procedure of SAS. Increasing dietary I concentration linearly increased (P < 0.03) piglet BW on d 10, 21, and 35. On d 35 BW were 19.2 kg CON, 19.9 kg NRC, 20.5 kg NRC10, 21.1 kg NRC100 and 20.2 kg NRC1000. Average daily gain was linearly increased by the addition of I to the diet during P1 (P < 0.02), P2 (P < 0.03) and for the entire 35 d feeding period (P < 0.01). From d 0 to 35, average daily gain (ADG) was (g/d) 384 CON, 405 NRC, 420 NRC10, 440 NRC100, and 407 NRC1000. Average daily feed intake was linearly increased dietary treatment during P1 (P < 0.01), P3 (P < 0.04) and from d 0 to 35 (P < 0.01). From d 0 to 35, average daily feed intake (ADFI) was (g/d) 731 CON, 779 NRC, 791 NRC10, 819 NRC100 and 782 NRC1000. No differences were observed for gain to feed ratio (G:F; P > 0.3) at any time during the study. On d 21, T4 concentrations linearly increased in response to dietary I (P < 0.02), On d 35, T4 and the T4:T3 ratio linearly increased (P < 0.01). On d 35 the T4 values were (nmol/L) 48.4 CON, 51.4 NRC, 58.3 NRC10, 59.3 NRC 100, 59.9 NRC 1000 and the T4:T3 ratio was 36.6 CON, 41.3 NRC, 40.0 NRC10, 45.2 NRC100, and 44.6 NRC1000. Based on the present findings, nursery pigs fed iodine levels above NRC recommendations have improved growth and feed intake and positive impacts on thyroid hormone concentrations. The data from this study indicated that dietary I concentrations 100 times the current NRC resulted in the best piglet performance.

Acute moderate normobaric hypoxia does not modify circulating thyroid hormone concentrations induced by 1 h of head-out cold-water immersion.

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia ([Formula: see text] = 0.21) or normobaric hypoxia ([Formula: see text] = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI.NEW & NOTEWORTHY Acute head-out cold (22°C) water immersion (HOWI) decreased core temperature and increased thermogenesis. This thermogenic response was paralleled by the activation of the hypothalamic-pituitary-thyroid axis, as evidenced by changes in thyroid hormones. However, cold HOWI in combination with moderate normobaric hypoxia did not modify the thermogenic nor the circulating thyroid hormone response. This finding suggests that hypoxia-induced alterations in thyroid hormone concentrations are unlikely to acutely contribute to adaptations resulting from repeated cold-water exposures.

Safety and efficacy of microwave ablation for symptomatic benign thyroid nodules in children.

To evaluate the efficacy and safety of microwave ablation (MWA) for the treatment of symptomatic benign thyroid nodules in children. A retrospective study of MWA for the treatment of 34 symptomatic benign thyroid nodules in 25 children was conducted. Volume reduction ratio (VRR), technique efficacy, symptom score, cosmetic score, and thyroid function were used to evaluate the efficacy of the technique. The associated complications and side effects were recorded. The participants were followed for at least 6months (median 12months, range 6-48months). After MWA treatment, the volumes of the targeted nodules decreased gradually (median volume 5.86mL before MWA and 0.34mL at the final follow-up assessment), the VRR achieved was up to 85.03% at the final follow-up assessment, and the technical efficacy at this time was 91.2%. The subjective and objective nodule-related symptoms were also ameliorated. The circulating hormone concentrations reflecting thyroid function remained within their normal ranges in all the participants after one month of follow-up. The procedure had no major complications. MWA seems to be an effective and safe technique for the treatment of symptomatic benign thyroid nodules in pediatric patients. Microwave ablation is a safe and effective method to treat symptomatic benign thyroid nodules in pediatric patients. This treatment may be selected if the patient or parents are not suitable or refuse to undergo surgery. • Microwave ablation is effective in reducing the volume of benign thyroid nodules and ameliorating nodule-related symptoms in pediatric patients. • Microwave ablation is a safe method in children, with low complications. • Microwave ablation does not affect the circulating thyroid hormone concentrations of children.

Exposure to PFAS in two Alaska Native Communities

Background: Many Arctic Indigenous communities are disproportionately exposed to persistent bioaccumulative toxicants due to global distillation and traditional diets. There is relatively little known about sources of exposure to PFAS in Arctic Indigenous Communities. Aim: The aim of this study was to assess exposure to, and health effects of, PFAS in two Arctic Indigenous communities on Sivuqaq (St. Lawrence Island), Alaska. Methods: Working within an established community-based participatory research program we assessed exposure to PFAS using human serum samples, indoor dust, traditional foods, as well as sentinel fish species. Results: Community members on Sivuqaq have broadly similar PFAS exposures to the U.S. population as measured by NHANES; however, select long chain PFAS such as PFNA and PFUNA appear elevated among Sivuqaq residents. Several PFAS are associated with circulating thyroid hormone concentrations in this this population. PFAS are present in traditional food animals as well as sentinel fish species collected in Sivuqaq. Sentinel fish suggest some aspect of the built environment acts as a point source of PFAS. Fish data also suggest strong species level effects in accumulation of PFAS. Dust concentrations of PFAS are on the low end of those reported and suggest the indoor environment may be a comparatively minor contributor to serum PFAS in this population. Discussion: Alaska Native communities are exposed to PFAS through multiple routes of exposure. This may result in elevated exposure for select PFAS. Serum PFAS are associated with measures of thyroid function.

HPT‐ Axis Activation During Cold Head Out Water Immersion is Not Modified by Moderate Hypoxia

PurposeThe Bajau, an indigenous population renowned for breath‐hold diving, have comparatively large spleen volumes. This adaptation is purportedly indicative of a greater capacity to store red blood cells, which may aid operations in the aquatic environment. Spleen size in the Bajau is associated with the PDE10A genotype that encodes an enzyme that catalyzes the release of thyroxine (T4) from the thyroid gland. T4 is readily released during cold stress as the terminus to activation of the hypothalamus‐pituitary‐thyroid (HPT) ‐axis to increase metabolic rate. T4, and downstream counterpart triiodothyronine (T3), can also stimulate erythropoiesis by increasing erythropoietin production, which can be further promoted with hypoxia. Thus, exposure to cold water may augment erythropoiesis as hypoxia develops during breath‐hold diving via activation of the HPT‐axis. However, interactions between cold exposure and hypoxia on HPT‐axis activation have not been directly explored. Mountaineering expedition studies indirectly suggest that T4 release is elevated by hypoxia. Thus, this study tested the hypothesis that during cold head out water immersion (HOWI) acute hypoxia augments circulating thyroid hormone concentrations compared to normoxia.MethodsIn a randomized crossover single blind design, 12 healthy adults (27 ± 2 y, 2 women) completed one hour of cold (22.0 ± 0.1⁰C) HOWI breathing either normobaric normoxia (FiO2 = 0.21 ± 00, NORM) or normobaric hypoxia (FiO2 = 0.13 ± 00, HYP). Free (f) and total (t) T3 and T4, and thyroid stimulating hormone (TSH) were measured in venous blood samples obtained before (baseline), during (15‐, 30‐, and 60‐min), and 15 min following immersion (post‐). Arterial oxyhemoglobin saturation (SpO2) and rectal temperature were measured continuously. Data are presented as mean ± SD.ResultsSpO2 was lower in HYP (90 ± 3%) compared to NORM (98 ± 1%, p &lt;.001). Rectal temperature did not differ between HYP and NORM (p &gt; .711) but decreased over time in both trials (HYP ‐ baseline: 37.2 ± 0.4⁰C, post‐: 36.4 ± 0.5⁰C, p&lt;.001, NORM ‐ baseline: 37.2 ± 0.4⁰C, post‐: 36.3 ± 0.5⁰C, p &lt;.001). From baseline to post‐HOWI, fT3 (HYP: +0.3 ± 0.4 pg/mL, NORM: +0.4 ± 0.6 pg/mL, p &lt;.001), fT4 (HYP: +1.6 ± 1.7 pg/mL, NORM: +0.7 ± 1.3 pg/mL, p &lt;.001), tT3 (HYP: +0.3 ± 0.5 ng/mL, NORM: +0.2 ± 0.4 ng/mL, p= .053), and tT4 (HYP: +0.6 ± 0.4 µg%, NORM: +0.4 ± 0.5 µg%, p &lt; .001) increased, but the magnitude did not differ between inspirates (p &gt; .165). Relative to baseline, tT4 at 15 min (HYP: ‐0.2 ± 0.3 µg%, NORM: ‐0.3 ± 0.3 µg%, p = .025), and TSH at 30 min (HYP: ‐0.2 ± 0.2 µIU/mL, NORM: ‐0.2 ± 0.3 µIU/mL, p = .029) and 60 min (HYP: ‐0.2 ± 0.2 µIU/mL, NORM: ‐0.3 ± 0.4 µIU/mL, p = .008) of HOWI were lower, but did not differ between inspirates (p = .921).ConclusionsIncreases in circulating thyroid hormone concentrations during one hour of cold HOWI are not modified by normobaric hypoxia. Thus, moderate hypoxia does not likely affect activation of the HPT‐axis during short duration cold exposure. Further investigation is warranted to determine the possibility of circulating thyroid hormones to augment the erythropoietic response to acute hypoxia during cold exposure.

A Study of Thyroid Profile (FT3, FT4, TSH) in Liver Cirrhosis in Jharkhand - A Hospital based Study

in people with liver disorders. Aim: To determine the prevalence of thyroid dysfunction in liver cirrhosis patients. Materials and Methods: This case-control study was carried out in a group of randomly selected liver cirrhosis patients in the Department of Medicine at Rajendra Institute of Medical Sciences (R.I.M.S), Ranchi, Jharkhand (India) between September 2017 to August 2018. The equal number of age (&gt;18 years) and sex-matched cases &amp;controls were included in this study. Radioimmunoassays were used to evaluate early morning fasting blood thyroid-stimulating hormone (TSH), serum total free thyroxine (FT4), and free triiodothyronine (FT3) in 100 index patients with liver cirrhosis who had no history of thyroid disorders. Results: In the cases that were studied, which consisted of cirrhotic patients, males (80%) outnumbered females (20%). The mean age of cases was 47.9 years, and the maximum numbers of the patient were between 41-55 years of age group (47%). Among the cirrhotic patients, the commonest etiology was alcoholic liver disease which contributed to 78% of the total cases studied. The rest of the cases included cirrhotics from other etiologies, which included NAFLD (22%), HBsAg positive individuals (07%), and other cases of cryptogenic origin. The mean FT3, FT4, and TSH values in cases were 2.29±0.83; 1.20±0.55 &amp; 3.76±2.43 respectively &amp; the mean FT3, FT4, and TSH of the control group were 2.95±0.52; 1.40±0.25 &amp; 2.70±0.94 respectively. From these data, we can say that there is significant derangement of thyroid function in liver cirrhosis in favor of hypothyroidism (p&lt;0.05). Conclusion: Hypothyroidism, or abnormalities in circulating thyroid hormone concentrations, is seen in people with alcoholrelated liver cirrhosis and is linked to more severe liver disease

Impaired physiological thermoregulation in postweaning obese female LA/Ntul//-cp (corpulent) rats

Groups of lean and obese female lean, and obese LA/Ntul//cp (corpulent) rats were subjected to measures of thermic responses to feeding, noradrenaline administration, and responses to 14 hours of cold exposure to access their capacity for thermoregulation beginning at 6 to 8 weeks of age. Body weights and adipose tissue mass were greater in the obese than the lean phenotype (p=&lt;0.05). RMR and the dose related thermic responses to norepinephrine (NE) in lean were greater than in obese. Cold exposure at 4°C resulted in decreases in rectal but not core temperature in obese rats, and the thermic responses to 45 minutes of 4°C cold exposure on VO2 were typical but were significantly greater in lean than obese animals at all points measured. Circulating thyroid hormone concentrations were similar in lean and obese rats and T3 but not T4 increased dramatically in both phenotypes following the cold exposure, consistent with phenotype- and IBAT-linked changes in T4-5’ deiodinase and thyroidal activity in this strain. These thermoregulatory changes are consistent with previous studies and may contribute to phenotype mediated aspects of energy metabolism, storage, and adipose tissue deposition and to a phenotype specific selective epigenetic propensity for the expression of obesity during the early postweaning period

Germ Line Mutations in the Thyroid Hormone Receptor Alpha Gene Predispose to Cutaneous Tags and Melanocytic Nevi.

Background: Many physiological effects of thyroid hormone (TH) are mediated by its canonical action via nuclear receptors (TH receptor α and β [TRα and TRβ]) to regulate transcription of target genes. Heterozygous dominant negative mutations in human TRα mediate resistance to thyroid hormone alpha (RTHα), characterized by features of hypothyroidism (e.g., skeletal dysplasia, neurodevelopmental retardation, constipation) in specific tissues, but near-normal circulating TH concentrations. Hitherto, 41 RTHα cases have been recorded worldwide.Methods: RTHα cases (n = 10) attending a single center underwent cutaneous assessment, recording skin lesions. Lesions excised from different RTHα patients were analyzed histologically and profiled for cellular markers of proliferation and oncogenic potential. Proliferative characteristics of dermal fibroblasts and inducible pluripotent stem cell (iPSC)-derived keratinocytes from patients and control subjects were analyzed.Results: Multiple skin tags and nevi were recorded in all cases, mainly in the head and neck area with a predilection for flexures. The affected patients had highly deleterious mutations (p.E403X, p.E403K, p.F397fs406X, p.A382PfsX7) involving TRα1 alone or mild/moderate loss-of-function mutations (p.A263V, p.L274P) common to TRα1 and TRα2 isoforms. In four patients, although lesions excised for cosmetic reasons were benign intradermal melanocytic nevi histologically, they significantly overexpressed markers of cell proliferation (K17, cyclin D1) and type 3 deiodinase. In addition, oncogenic markers typical of basal cell carcinoma (Gli-1, Gli-2, Ptch-1, n = 2 cases) and melanoma (c-kit, MAGE, CDK4, n = 1) were markedly upregulated in skin lesions. Cell cycle progression and proliferation of TRα mutation-containing dermal fibroblasts and iPSC-derived keratinocytes from patients were markedly increased.Conclusions: Our observations highlight frequent occurrence of skin tags and benign melanocytic nevi in RTHα, with cutaneous cells from patients being in a hyperproliferative state. Such excess of skin lesions, including nevi expressing oncogenic markers, indicates that dermatologic surveillance of RTHα patients, monitoring lesions for features that are suspicious for neoplastic change, is warranted.

Per- and Polyfluoroalkyl Substances Are Positively Associated with Thyroid Hormones in an Arctic Seabird.

Per- and polyfluoroalkyl substances (PFAS) are associated with several disrupted physiological and endocrine parameters. Regarding endocrine mechanisms, laboratory studies suggest that PFAS could disrupt the thyroid hormone system and alter circulating thyroid hormone concentrations. Thyroid hormones play a ubiquitous role-controlling thermoregulation, metabolism, and reproduction. However, evidence for disruption of thyroid hormones by PFAS remains scarce in wildlife. The present study investigated the associations between concentrations of PFAS, thyroid hormones, and body condition in an arctic seabird, the black-legged kittiwake (Rissa tridactyla). We collected blood from kittiwakes sampled in Svalbard, Norway (2013 and 2014). Plasma samples were analyzed for total thyroxine (TT4) and total triiodothyronine (TT3) concentrations; detected PFAS included branched and linear (lin) C8 perfluoroalkyl sulfonates (i.e., perfluoroctane sulfonate [PFOS]) and C9 -C14 perfluoroalkyl carboxylates (PFCAs). The dominant PFAS in the kittiwakes were linPFOS and C11 - and C13 -PFCAs. Generally, male kittiwakes had higher concentrations of PFAS than females. We observed positive correlations between linPFOS, C10 -PFCA, and TT4 in males, whereas in females C12-14 -PFCAs were positively correlated to TT3. Interestingly, we observed contrasted correlations between PFAS and body condition; the direction of the relationship was sex-dependent. Although these results show relationships between PFAS and circulating thyroid hormone concentrations in kittiwakes, the study design does not allow for concluding on causal relationships related to effects of PFAS on the thyroid hormone system. Future experimental research is required to quantify this impact of PFAS on the biology of kittiwakes. The apparently different associations among PFAS and body condition for males and females are puzzling, and more research is required. Environ Toxicol Chem 2021;40:820-831. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Study of association between chronic liver disease and thyroid function tests at a tertiary hospital

Background: Among the various functions of liver, one function is synthesis of carrier proteins and metabolism of hormones and liver diseases, have been shown to be associated with various endocrinal disturbances. Aim of the study was to evaluate the spectrum of chronic liver disease and association between thyroid profile and severity of liver damage at a tertiary hospital. Material and Methods: Present study was single-center, hospital based, case-control study, conducted in 88 cases of liver cirrhosis/ chronic liver disease and 88 age/sex matched healthy controls (randomly selected from relatives attending OPD with patients) were studied. Thyroid function tests were done and compared among cases and controls. Results: In present study 88 cases of liver cirrhosis/ chronic liver disease and 88 healthy controls were studied. Mean age and gender were comparable in cases and controls and difference was not statistically significant. Most of cases had alcoholic liver cirrhosis (80.7 %), rest had non-alcoholic liver cirrhosis (12.5%) and chronic viral hepatitis (6.8%). As per Child-Pugh Score, most cases were from Child-Pugh B (42%), followed by Child-Pugh C (31.8%) and Child-Pugh A (26.1%). In present study free T3, free T4 and TSH were compared between cases and controls, abnormal values were noted in cases and statistically significant difference was noted. Serum thyroid profile abnormalities were noted as per advancement in Child-Pugh Score Classes and difference was statistically significant for free T3 and free T4. Conclusion: Thyroid function test abnormalities in circulating thyroid hormone concentrations were noted in patients liver cirrhosis as compared to healthy subjects and severe abnormalities were associated with advanced Child Pugh score.

SAT-117 PREVALENCE OF THYROID HORMONE ABNORMALITIES IN STAGE 5 CHRONIC KIDNEY DISEASE

Kidney and thyroid function are interconnected through several mechanisms. Thyroid hormones are necessary for the maintenance of electrolyte and water. Similarly, kidney is also involved in the regulation of thyroid hormones metabolism. Failure of metabolic, excretory and synthetic functions are commonly associated with the irreversible loss of renal function that ultimately results in uremia or azotemia i.e. retention of urea and other non-protein nitrogenous substances in the blood. CKD affects thyroid function in several ways that include low circulating thyroid hormone concentration, alteration in peripheral hormone metabolism, disturbance in binding them to carrier proteins, possible reduction in tissue thyroid hormone content and increased iodine store in thyroid gland resulting in the reduction of serum triidothyronine (T3) and thyroxin (T4). End stage renal disease is a frequent cause of non-thyroidal illness (NTI) that refers to a syndrome found in seriously ill or starving patients with low fT3, usually elevated reverse T3, normal or low TSH and if prolonged, low fT4 despite patient remaining clinically euthyroid. The aim of the present study was i) to estimate the prevalence of thyroid hormone abnormalities in stage 5 CKD patients and ii) to compare these changes with healthy controls. The present cross-sectional observational study was conducted on thirty eight stage 5 CKD patients and 38 age-sexes matched healthy volunteers as control. The demographic data, medical history, etiology, physical examination and laboratory results were recorded on a special form developed by the researchers. GFR was measured by using Cockcroft-Gault formula. Written informed consent were taken from the study subject. Patient with known history of thyroid function abnormalities and pregnancy were excluded from the study. Serum fT3, fT4 and TSH were measured by using Immunoassay system. The independent sample t test was used to compare stage 5 CKD patient with healthy controls group. Statistical analysis were done by SPSS software (Statistical Package for the Social Sciences, version 21.0, SPSS Inc, Chicago, USA). The level of significance (P) was set to be < 0.05. Seventeen (44.73%)stage 5 CKD patients had low fT3 whereas eleven (28.94%) had low fT4 values that were below the reference range. There were no any reduction in TSH level but two patients (5.26%) had increased TSH values compared to normal limit. Significant differences in the mean level of fT3 and fT4 were seen amongstage 5 CKD patientsandhealthy control group. The mean value of fT3 in stage 5 CKD patients and control group were 2.18 ± 0.56 pg/ml and 2.96 ± 0.49. The P value in both group were < 0.001, which was significant. The mean value of fT4 in stage 5 CKD patients and control group were 0.99 ± 0.22 ng/dl and 1.37 ± 0.48 respectively. Here the P value in both group was < 0.001, which was statistically significant. Mean value of TSH in stage 5 CKD patient (2.71 ± 1.66) and healthy control (2.68 ± 1.41) did not vary with each other. So, TSH value in these two groups were not differed significantly (P > 0.05). From this study, it was concluded that the prevalence of thyroid hormone abnormalities especially low fT3 and fT4 is very common in stage 5 CKD patients. Diabetic nephropathy was among the lead cause of stage 5 CKD.

Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine

Background: Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4). Methods: Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity. Results: Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice. Conclusions: We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment.

Common genetic variations of deiodinase genes and prognosis of brain tumor patients.

Thyroid hormone (TH) metabolism can have prognostic significance in brain tumors. We studied the association of common variations in three deiodinase gene single-nucleotide polymorphisms (SNPs) with circulating TH concentrations and prognosis of brain tumor patients. Patients admitted for glioma and meningioma surgery between January, 2010 and September, 2011 were evaluated for functional status (Barthel Index or BI) and circulating free tri-iodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) concentrations. Ten common SNPs in the DIO1 gene; five SNPs in the DIO2 gene; and one SNP in the DIO3 gene were genotyped. Follow-up continued until November, 2017. In glioblastoma patients, the DIO1 SNP rs2235544 CC genotype was associated with significantly lower risk of death at 2 years when compared to AA + CA genotypes after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, and extent of resection (HR = 0.34, 95% CI: 0.13-0.84, p = 0.019). The TT genotype vs. CC + TC genotypes of the DI02 SNP rs12885300 was associated with increased mortality risk after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, extent of resection, and FT3/FT4 (HR = 3.13, 95% CI: 1.20-8.16, p < 0.019). The C-allele of the DI01 SNP rs2235544 was related to increased circulating free T3/ free T4 ratio in glioma and meningioma patients, indicating greater T4 to T3 conversion. SNPs of DIO1 gene (rs2235544) and DIO2 gene (rs12885300) have independent prognostic significance in glioblastoma patients. The C-allele of the DIO1 (rs2235544) is associated with greater T4 to T3 conversion.

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.

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.

Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women.

Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Total thyroxine (T4 ) concentrations were positively associated with Pd3G and E1 3G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G=11.7μg/mg Cr for women with high T4 vs Pd3G=9.5 and 8.1μg/mg Cr for women with medium and low T4 , respectively) and greater follicular phase maximum E1 3G (E1 3G=41.7ng/mg Cr for women with high T4 vs E1 3G=34.3 and 33.7ng/mg Cr for women with medium and low T4 , respectively). Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.

Elevated aggressive behavior in male mice with thyroid-specific Prkar1a and global Epac1 gene deletion

Alterations in circulating thyroid hormone concentrations are associated with several psychological and behavioral disorders. In humans, behavioral disorders such as anxiety, depression, and attention-deficit hyperactivity disorder can be associated with thyroid disease. The Tpo-Cre;Prkar1aflox/flox;Epac1−/− (R1A-Epac1KO) mice, originally bred to investigate the role of exchange protein directly activated by cAMP (Epac1) in follicular thyroid cancer, displayed self-mutilating and aggressive behaviors during casual observation. To assess these atypical responses, behavioral testing was conducted with the R1A-Epac1KO mice, as well as their single knockout counterparts, the thyroid-specific Prkar1a−/− and global Epac1−/− mice. Mice of all three genotypes demonstrated increased aggressive behavior against an intruder mouse. In addition, Epac1−/− mice increased response to an auditory stimulus, and the Prkar1a−/− and R1A-Epac1KO mice increased swimming behavior in the Porsolt forced swim test. Both Prkar1a−/− mice and R1A-Epac1KO mice have increased circulating thyroxine and corticosterone concentrations. Although hyperthyroidism has not been previously associated with aggression, increased thyroid hormone signaling might contribute to the increased aggressive response to the intruder mouse, as well as the increased swimming response. Mice with a genetic background of Tpo-Cre;Prkar1aflox/flox;Epac1−/− are aggressive, and both the thyroid-specific knockout of Prkar1a and global knockout of Epac1 likely contribute to this aggressive behavior. This study supports the hypothesis that altered thyroid signaling and aggressive behavior are linked.

Incipient iron deficiency in primary hypothyroidism

Background: Hypothyroidism affects around 1% of general population. Anemia in association with hypothyroidism has been studied since 1881. Iron deficiency has multiple adverse affects on thyroid metabolism. It decreases circulating thyroid hormone concentration, blunts thyrotropic response to thyrotropin-releasing hormone (TRH) and decreases serum triiodothyronine (T3). Objectives: To find the prevalence of iron deficiency in primary hypothyroids. Material and Methods: In our study, 70 patients were selected, out of which 50 were females and 20 were males, who were suffering from hypothyroidism. Iron deficiency in the study group was confirmed at baseline using multiple iron status indicators (serum ferritin, serum iron, total iron-binding capacity and percentage saturation). These patients were between age group 18–65 years. Results: In our study, only 14 patients (20%) manifested with anemia (which was defined as HB < 12 gm/dl), whereas the prevalence of iron deficiency (with or without anemia) was 34.2%), in which 28.5% were females and 5.70% were males, thus showing that prevalence of iron deficiency (with or without anemia) can be higher than iron deficiency anemia itself, which is supported by literature. Conclusion: Iron deficiency was present in a significant portion of patients with primary hypothyroidism. It also concluded that frequency of iron deficiency (with or without anemia) was higher than iron-deficiency anemia.

The Effect of Chronic Renal Failure on Thyroid Hormones

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 in thyroid glands.The target of study is to find a relationship between chronic renal failure and thyroid function.In addition, we tried to study the effect of CRF on serum creatinine dependent on the level of thyroid hormones (T3 and T4) and thyroid stimulating hormones(TSH). Forty patients with chronic renal failure (20 male, 20 female) were enrolled in this study in addition to forty healthy individual as control group (20 male, 20 female). The age ranged from (25 -65) years. T4, T3, TSH, urea, uric acid and creatinine were measured in each of the two groups. The results revealed statistically significant reduction in T3 and T4 while there is elevation in TSH, urea,uric acid and creatinine in the patients group compared to the control group.&#x0D; Key word : Chronic Renal Failure,Thyroid Hormones.