Altered Thyroid Status Research Articles

Thyroid status in premenopausal and postmenopausal women – A biochemical study on insulin resistance in non obese, overweight and obese type 2 diabetics

BackgroundInsulin resistance with altered thyroid status in women is observed in type 2 diabetics and varies with advancing age and estrogen profile. We compared thyroid status between premenopausal and postmenopausal women in obese, non obese and overweight type 2 diabetes. MethodologyWe included 301type 2 diabetics who were segregated into premenopausal (n = 100) 33.2% and postmenopausal (n = 201) 66.8% among three sub groups (Non obese, overweight and Obese).Anthropometry, fasting blood glucose, lipid profile, glycated hemoglobin, homeostasis model assessment of insulin resistance, liver function tests, Free T4, T3, TSH, Zn2+and Mg2+ were enabled. ResultsNon obese type 2 diabetics were segregated into two groups n = 21 (29.2%)- premenopausal with mean age of 41.48 ± 4.30 and n = 51 (70.8%) - post menopausal with mean age of 58.49 ± 7.32 There were significant differences in WHR, HbA1c, HDL with p < 0.05 and ALP with p < 0.01; Overweight type 2 diabetics n = 55 (37.9%) -premenopausal with mean age of 41.96 ± 3.80 and n = 90 (62.1%)- post menopausal with mean age of 57.80 ± 7.20. There were significant differences in Urea, Zinc, Total protein, Albumin with p < 0.05 and T4, TSH with p < 0.01. Obese Type 2 diabetics n = 24 (28.6%) -premenopausal with mean age of 42.00 ± 4.30 and n = 60 (71.4%) -post menopausal with mean age of 57.80 ± 7.20. There were significant differences in Urea, Magnesium, Triacylglycerols, and VLDL with p < 0.05, Insulin and HOMA-IR with p < 0.01. ConclusionAnthropometry specified classification of type 2 diabetics in pre and postmenopausal women reflects thyroid status.

Red palm oil supplementation does not increase blood glucose or serum lipids levels in Wistar rats with different thyroid status.

Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status. We induced hypothyroidism and hyperthyroidism in rats by oral administration of either methimazole or mixture of thyroid hormones. Different thyroid status (EU - euthyroid, HY - hypothyroid and HT - hyperthyroid) was characterized by different serum thyroid hormones levels (total and free thyroxine and triiodothyronine), changes in the activity of a marker enzyme of thyroid status - liver mitochondrial glycerol-3-phosphate dehydrogenase, and altered absolute and relative heart weights. Fasting blood glucose levels were higher in HT rats in comparison with EU and HY rats, but the changes caused by RPO supplementation were not significant. The achievement of the HY status significantly increased serum levels of total cholesterol, as well as with high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol: 2.43+/-0.15, 1.48+/-0.09, 0.89+/-0.08 mmol/l, compared to EU: 1.14+/-0.06, 0.77+/-0.06, 0.34+/-0.05 mmol/l and HT: 1.01+/-0.06, 0.69+/-0.04, 0.20+/-0.03 mmol/l, respectively. RPO supplementation did not increase significantly levels of blood lipids but tended to increase glutathione levels in the liver. In conclusion, RPO supplementation did not induce the presumed deterioration of glucose and lipid metabolism in rats with three well-characterized alterations in thyroid status.

Thyroid function in type 2 diabetes mellitus

Background: Type 2 Diabetes Mellitus (T2DM) and thyroid disorder are common endocrine disorders that affect major population worldwide. Subclinical hypothyroidism is common among T2DM.Objectives: To observe thyroid stimulating hormone (TSH), total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) levels in newly diagnosed T2DM.Methods: This cross sectional study was conducted from July 2014 to June 2015. For this, 50 newly diagnosed T2DM patients aged 30 to 50 years of both sexes were enrolled from the Out Patient Department of Endocrinology, Rangpur Medical College and Diabetic Association, Rangpur. Fifty age matched non-diabetic healthy subjects of both sexes constituted control. Serum TSH, TT4 , FT4, TT3, FT3 levels were estimated to observe thyroid function. All these hormones were estimated by ELISA method. For statistical analysis independent sample “t” test was performed.Results: Serum TSH was significantly higher (p&lt;0.001) and serum TT4, FT4, FT3 levels were significantly lower (p&lt;0.001) in T2DM compared to control. Eight (16%) of T2DM were hypothyroid.Conclusion: From this study it can be concluded that altered thyroid status leading to hypothyroidism may be associated with T2DM.Bangladesh Soc Physiol. 2017, December; 12(2): 61-64

The effect on the altered thyroid status for ovarian tumor xenografts in rats

Our study examined the effect of induced hypo- and hyperthyroidism on ovarian cancer (OC). The intraperitonealxenograft model of OCperformed the standard technique. Using propylthiouracil(2,0 mg per 100 g of animal weight once a day) and L-thyroxine(200 µg per 100 g of animal weight once a day)we found that altered thyroid status significantly influenced the ovary tumor xenograftsdevelopment. The median survival life expectancy was 9,6 and 17,6 daysin the euthyroidcontrol group and the hypothyroidgroup, respectively (p?= 0.02). Induced hypothyroidismleads to thelifetime increase of rats with intraperitonealxenograftof OC by 83.3%. It was shown that hyporthyroidism was associated with the aggressiveness decrease of OC. Ourevidence confirms previous clinical and epidemiologicaldata.Thyroid status can be anindepending prognostic factor for patients with OC, as well as induced hypotyroidism opens new opportunities for the palliative treatment of OC.

Thyroid Hormone Signaling in the Development of the Endochondral Skeleton.

Thyroid hormone (TH) is an established regulator of skeletal growth and maintenance both in clinical studies and in laboratory models. The clinical consequences of altered thyroid status on the skeleton during development and in adulthood are well known, and genetic mouse models in which elements of the TH signaling axis have been manipulated illuminate the mechanisms which underlie TH regulation of the skeleton. TH is involved in the regulation of the balance between proliferation and differentiation in several skeletal cell types including chondrocytes, osteoblasts, and osteoclasts. The effects of TH are mediated primarily via the thyroid hormone receptors (TRs) α and β, ligand-inducible nuclear receptors which act as transcription factors to regulate target gene expression. Both TRα and TRβ signaling are important for different stages of skeletal development. The molecular mechanisms of TH action in bone are complex and include interaction with a number of growth factor signaling pathways. This review provides an overview of the regulation and mechanisms of TH action in bone, focusing particularly on the role of TH in endochondral bone formation during postnatal growth.

Лекарственное моделирование тиреоидного статуса и длительность жизни крыс с перевитой асцитной опухолью яичника

Медикаментозное торможение функции тиреоидных гормонов (пропилтиоурацил, 2 мг на 100 г массы животного 1 раз в сутки внутрижелудочно) вызывает увеличение продолжительности жизни крыс с перевитым раком яичников на 83,3 %: медиана продолжительности жизни 17,6 и 9,6 дней у крыс в гипо- и эутиреоидной группах соответственно, p = 0,02. Выявленный феномен подтверждает ранее полученные клинические и эпидемиологические данные о влиянии тиреоидного статуса на риск возникновения и/или течения солидных новообразований. Полученные данные могут явиться основной для определения тиреоидного статуса как независимого прогностического фактора для течения рака яичников, а также открывают новые возможности для паллиативной терапии новообразований.

Changes in Acid Labile Subunit (ALS) and Insulin-Like Growth Factor 1 (IGF-1) Concentration in Hyperthyroidism before and After Medical Treatment: A Prospective Controlled Study

Background:The relationship of altered thyroid status with GH and components of insulin-like Growth factor (IGF-1) axis is complex and not fully understood. We aimed to evaluate changes in Acid labile subunit (ALS) and IGF-1 in hyperthyroidism, before and after normalization of thyroid status. Methods:Thirty-four hyperthyroid patients matched with 36 normal controls were studied. The patients and controls were assessed at baseline and the patients were followed up prospectively and re-assessed after 6 months of treatment with antithyroid drug (ATD) (carbimazole). On each occasion, blood was collected for measurement of ALS, IGF-1, glucose, insulin, intact proinsulin and thyroid function. Results: Pre-treatment levels of ALS (p=0.012) and IGF-1 (p=0.007) were significantly lower in patients than controls. Five to 10 weeks post-treatment with ATD, all patients were restored to euthyroidism. ALS and IGF-1 levels increased significantly to similar levels of controls after 6 months of ATD. Within the patients, ALS (p=0.049) and IGF-1 (p=0.001) correlated inversely with free T3, whereas, only IGF-1 (p=0.005) correlated inversely with free T4. Conclusion:These results demonstrate that untreated hyperthyroidism is associated with reduction in ALS and IGF-1. Due to the fact that ALS and IGF-1 were related inversely with thyroid status and their concentrations were normalized with euthyroidism, it would be possible to consider their reductions as helpful markers of altered thyroid status, namely hyperthyroidism.

Effects of thyroid status on glycated hemoglobin.

Introduction:Glycated hemoglobin (HbA1c) can be altered in different conditions. We hypothesize that HbA1c levels may change due to altered thyroid status, possibly due to changes in red blood cell (RBC) turnover.Objectives:The objective of this study was to determine the effects of altered thyroid status on HbA1c levels in individuals without diabetes, with overt hyper- and hypo-thyroidism, and if present, whether such changes in HbA1c are reversed after achieving euthyroid state.Methods:Euglycemic individuals with overt hypo- or hyper-thyroidism were selected. Age- and sex-matched controls were recruited. Baseline HbA1c and reticulocyte counts (for estimation of RBC turnover) were estimated in all the patients and compared. Thereafter, stable euthyroidism was achieved in a randomly selected subgroup and HbA1c and reticulocyte count was reassessed. HbA1c values and reticulocyte counts were compared with baseline in both the groups.Results:Hb A1c in patients initially selected was found to be significantly higher in hypothyroid group. HbA1c values in hyperthyroid patients were not significantly different from controls. HbA1c reduction and rise in reticulocyte count were significant in hypothyroid group following treatment without significant change in glucose level. Hb A1c did not change significantly following treatment in hyperthyroid group. The reticulocyte count, however, decreased significantly.Conclusion:Baseline HbA1c levels were found to be significantly higher in hypothyroid patients, which reduced significantly after achievement of euthyroidism without any change in glucose levels. Significant baseline or posttreatment change was not observed in hyperthyroid patients. Our study suggests that we should be cautious while interpreting HbA1c data in patients with hypothyroidism.

THYROID STATUS AND ITS CORRELATION WITH THE FUNCTIONAL ACTIVITY OF IMMUNOCYTES

Pathogenesis studies in thyroid autoimmune diseases take a specific place among endocrine disorders, due to high prevalence of these pathologies, thus representing an urgent problem of the modern medicine. Their triggering mechanisms of their are still unknown. Changes of thyroid status in cases of nonthyroid pathology, e.g., during development of «nonthyroidal syndrome», may launch synthesis of some functionally opposite cytokines by immunocytes, with subsequent loss of tolerance to thyroid autoantigens. One may suggest that mast cells may potentially influence secretory activity of thyrocytes via Toll-like receptors, and, therefore, induce synthesis of opposite cytokines, with subsequent loss of auto-tolerance. The mast cells found in thyroid gland affected by an autoimmune disorder may also regulate functional activity of immunocytes and hormone-secreting cells due to molecular effects of secretable substances. The mechanisms prevailing in autoimmune thyroid disease are, however, widely unknown. These effects may involve either primary activation of mast cells by thyroid hormones, or secondary changes of thyroid status. To address these issues, we studied some features of mast cells response and production of functionally opposite cytokines (IL-1β, IL-10, IFNγ, TNFα) in experimental thyrotoxicosis and hypothyroidism. To boost the immune response, a subgroup of experimental animals with thyrotoxicosis was treated with recombinant interleukin-2. Specific changes of IFNγ/IL-10 ratio depending on thyroid status confirmed a role of opposite cytokine balance for development of different pathological variants. A significant increase in the Th1-marker cytokines revealed at the organ level in cases of thyrotoxicosis argued for direct involvement of thyroid hormones into the immune regulation, as confirmed by a focal infiltration of a thyroid gland with mast cells, along with significant increase in pro-inflammatory cytokines at systemic and organ levels. A hypothesis on possible reception of thyroid hormones by immune cells is in accordance with intensive correlations between the levels of opposite cytokines in target organ and contents of thyroid hormones in peripheral blood. A regulatory role of interleukin-2 was suggested as a factor of keeping balance for opposite cytokines and changing vector of immune response in case of altered thyroid status. The results of our study presume an important role of mast cells and balance of opposite cytokines in pathogenesis of thyroid dysfunction. Further studies are required, in order to clarify the mechanisms of interaction between thyroid hormones and immune cells.

Effects of altered thyroid states on oxidative stress parameters in rats.

Thyroid hormones are effective on oxidant-antioxidant balance by leading basal metabolic rate. In this study, the effects of altered thyroid states on low density lipoprotein (LDL) oxidation and oxidative stress parameters were investigated in an experimental animal model. Thirty female Wistar Albino rats were equally divided into 3 groups as follows: control group; hypothyroid group (methimazole (75 mg/100 g was added to diet); hyperthyroid group [L-thyroxine (0.4 mg/100 g was added to diet)]. Oxidized LDL (ox-LDL) levels, thyroid, and lipid parameters were determined in serum. Also lipid peroxidation (LPO), sialic acid (SA) and glutathione levels (GSH), as well as superoxide dismutase (SOD) and catalase (CAT) activities were determined in tissue samples. A significant increase in lipid parameters was observed in hypothyroid group, whereas these parameters were decreased in hyperthyroid group compared to control group. For ox-LDL levels, a significant increase was observed both in hypothyroid and hyperthyroid groups. In brain, liver and kidney tissues, LPO and SA levels were increased, whereas GSH levels were decreased both in hypothyroid and hyperthyroid groups. The SOD and CAT activities were significantly decreased in hypothyroid group, however, they were increased in hyperthyroid group compared to control group. Both hypothyroid and hyperthyroid conditions modify the oxidant-antioxidant state in serum and tissues. Increased SOD and CAT activities in hyperthyroid group suggest that elevated thyroid hormones can reduce oxidative stress by maintaining antioxidant defense and they might have a protective effect on some tissues against oxidants.

Hypothyroidism and possible association with Metabolic Syndrome

Background: Thyroid dysfunctions are the most common forms of endocrine disorder in our country, Thyroid hormones perform a wide array of metabolic functions including regulation of lipids, carbohydrates, protein and electrolytes and mineral metabolism, Thyroid hormones are major regulatory hormones that controls the rate of metabolic function and alteration in the levels of thyroid hormones may be associated with metabolic syndrome Aim: The study was performed to investigate the association between Altered thyroid state i.e hypothyroidism and metabolic syndrome. Materials and Methods: The study was done on patients with symptoms of hypothyroidism or follow up cases of hypothyroidism having metabolic syndrome. T3, T4 and TSH and were analyzed by enzyme linked fluorescent assay (ELFA) technique using Vidas auto analyzer from Biomeriuex, France. Fasting blood sugar and lipid profile were estimated by Erba Chem 7 semi-auto analyzer. The data was analyzed using SPSS-17 software package. Results: The percentage of metabolic syndrome and hypothyroidism in each age group were determined and we have found that the percentage of metabolic syndrome is increasing with age and is highest 60 % in the age group of 61-75 years, both T3, T4 are comparably decreased but TSH is on the higher side in metabolic syndrome as compared to non-metabolic syndrome Conclusion: Patients having Thyroid dysfunction should regularly be checked for parameters of metabolic syndrome: Early detection of thyroid dysfunction and treatment can prevent the complications of metabolic syndrome.

Cardiac connexin-43 and PKC signaling in rats with altered thyroid status without and with omega-3 fatty acids intake.

Thyroid hormones are powerful modulators of heart function and susceptibility to arrhythmias via both genomic and non-genomic actions. We aimed to explore expression of electrical coupling protein connexin-43 (Cx43) in the heart of rats with altered thyroid status and impact of omega-3 polyunsaturated fatty acids (omega-3) supplementation. Adult male Lewis rats were divided into following six groups: euthyroid controls, hyperthyroid (treated with T(3)) and hypothyroid (treated with methimazol) with or without six-weeks lasting supplementation with omega-3 (20 mg/100 g/day). Left and right ventricles, septum and atria were used for immunoblotting of Cx43 and protein kinase C (PKC). Total expression of Cx43 and its phosphorylated forms were significantly increased in all heart regions of hypothyroid rats compared to euthyroid controls. In contrast, the total levels of Cx43 and its functional phosphorylated forms were decreased in atria and left ventricle of hyperthyroid rats. In parallel, the expression of PKC epsilon that phosphorylates Cx43, at serine 368, was increased in hypothyroid but decreased in hyperthyroid rat hearts. Omega-3 intake did not significantly affect either Cx43 or PKC epsilon alterations. In conclusion, there is an inverse relationship between expression of cardiac Cx43 and the levels of circulating thyroid hormones. It appears that increased propensity of hyperthyroid while decreased of hypothyroid individuals to malignant arrhythmias may be in part attributed to the changes in myocardial Cx43.

Altered thyroid status affects myocardial expression of connexin-43 and susceptibility of rat heart to malignant arrhythmias that can be partially normalized by red palm oil intake.

We aimed to study the impact of altered thyroid status on myocardial expression of electrical coupling protein connexin-43 (Cx43), the susceptibility of rats to ventricular fibrillation (VF) and the effects of antioxidant-rich red palm oil (RPO). Adult male and female euthyroid, hyperthyroid (treated with T3/T4), hypothyroid (treated with methimazole) Wistar rats supplemented or not with RPO for 6weeks were used. Function of isolated perfused heart and VF threshold were determined. Left ventricular tissue was used for assessment of mRNA and protein levels of Cx43, its phosphorylated forms and topology. Protein kinase C signaling (PKC) and gene transcripts of some proteins related to cardiac arrhythmias were assessed. Hyperthyroid state resulted in decrease of total and phosphorylated forms of Cx43 and suppression of PKC-ε expression in males and females, decrease of Cx43 mRNA in females, decrease of VF threshold and increase of functional parameters in male rat hearts. In contrast, hypothyroid status resulted in the increase of total and phosphorylated forms of Cx43, enhancement PKC-ε expression in males and females, increase of Cx43 mRNA in females, increase of VF threshold and decrease of functional parameters in male rat hearts. Function of the heart was partially normalized by RPO intake, which also enhanced myocardial Cx43 and PKC-ε expression as well as increased VF threshold in hyperthyroid male rats. We conclude that there is an inverse relationship between myocardial expression of Cx43, including its functional phosphorylated forms, and susceptibility of male rat hearts to VF in condition of altered thyroid status. RPO intake partly ameliorated adverse changes caused by excess of thyroid hormones.

Effect of neonatal hypothyroidism on prepubertal mouse testis in relation to thyroid hormone receptor alpha 1 (THRα1)

Thyroid hormones (THs) are important for growth and development of many tissues, and altered thyroid status affects various organs and systems. Testis also is considered as a thyroid hormone responsive organ. Though THs play an important role in regulation of testicular steroidogenesis and spermatogenesis, the exact mechanism of this regulation remains poorly understood. The present study, therefore, is designed to examine the effect of neonatal hypothyroidism on prepubertal Parkes (P) strain mice testis in relation to thyroid hormone receptor alpha 1 (THRα1). Hypothyroidism was induced by administration of 6-propyl-2-thiouracil (PTU) in mother’s drinking water from birth to day 28; on postnatal day (PND) 21 only pups, and on PND 28, both pups and lactating dams were euthanized. Serum T3 and T4 were markedly reduced in pups at PND 28 and in lactating mothers, while serum and intra-testicular testosterone levels were considerably decreased in pups of both age groups. Further, serum and intra-testicular levels of estrogen were significantly increased in hypothyroid mice at PND 28 with concomitant increase in CYP19 expression. Histologically, marked changes were noticed in testes of PTU-treated mice; immunohistochemical and western blot analyses of testes in treated mice also revealed marked decrease in the expression of THRα1 at both age groups. Semiquantitative RT-PCR and western blot analyses also showed reductions in both testicular mRNA and protein levels of SF-1, StAR, CYP11A1 and 3β-HSD in these mice. In conclusion, our results suggest that neonatal hypothyroidism alters localization and expression of THRα1 and impairs testicular steroidogenesis by down-regulating the expression SF-1, thereby affecting spermatogenesis in prepubertal mice.

Effect of polybrominated diphenyl ether (BDE-209) on testicular steroidogenesis and spermatogenesis through altered thyroid status in adult mice

Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), have been widely used in many products to minimize the risk of fire, mainly by mixing in polymer products. BDE-209, a congener of PBDEs having structural similarity with thyroid hormones, acts as an endocrine disruptor by interfering with thyroid homeostasis. However, little is known about the effect of BDE-209 exposure on testicular steroidogenesis and spermatogenesis. This study was therefore conducted in adult mice to examine the effect of BDE-209 on testicular steroidogenesis and spermatogenesis in relation to thyroid status, and to explore possible mechanism(s) of its action. Adult Parkes strain male mice were orally gavaged with 750 and 950mg/kg BW of BDE-209 in corn oil for 35days. Significant reductions were noted in the levels of serum total T3, T4 and testosterone in mice treated with 950mg/kg BW of BDE-209 compared to controls; histologically, testes showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; further, number and viability of spermatozoa were also adversely affected in cauda epididymidis of these mice. Semiquantitative RT-PCR and western blot analyses also showed significant reductions in both testicular mRNA and protein levels of steroidogenic factor 1 (SF-1), steroidogenic acute regulatory (StAR) protein, cytochrome P450scc (CYP11A1), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) in 950mg dose treated-mice compared to controls. Immunohistochemical and immunoblot analyses further revealed a marked decrease in proliferating cell nuclear antigen (PCNA) positive cells in testes of 950mg dose of BDE-209-treated mice. However, 750mg dose of BDE-209 had no effect on the above parameters. In conclusion, our results suggest that exposure of BDE-209 to adult mice causes reduction in serum levels of thyroid hormones and altered thyroid status may partly result into impairment of testicular steroidogenesis because of down-regulated expression of SF-1, thereby causing suppression of spermatogenesis.

Altered thyroid hormone production induced by long-term exposure to low doses of the endocrine disruptor dichlorodiphenyltrichloroethane

Endocrine disruptors are exogenous substances that enter the body and exhibit hormone-like action thus disrupting the homeostatic action of endogenous hormones. The most wide-spread disruptor is dichlorodiphenyltrichloroethane (DDT). The aim of this study was to investigate changes in thyroid hormone production induced by prolonged exposure to low doses of DDT. The experiment was performed on male Wistar rats treated with daily doses of DDT 1.89 ± 0.86 μg/kg and 7.77 ± 0.17 μg/kg for six and ten weeks. After six weeks there was a dose dependent increase of serum total thyroxine, total triiodthyronine, and thyroid peroxidase. Subsequently, concentration of free thyroxine decreased. These data indicate that impaired production of thyroxine by follicular thyrocytes, rather than decreased deiodinase activity and blood transport proteins is the major cause of altered thyroid status induced by DDT.

Circulating Irisin Concentrations in Rat Models of Thyroid Dysfunction — Effect of Exercise

ObjectivesThe speculation that the myokine irisin could regulate whole body energy expenditure led to the anticipation that irisin may have therapeutic potential in metabolic diseases. Regulation of irisin under conditions of metabolic derangements in altered thyroid status, and the changes in irisin response to exercise remain to be investigated. MethodsSerum irisin concentration was measured in sixty male Wistar rats subjected to either sedentary life or 8-week chronic swimming exercise after induction of hyper- or hypothyroidism (10 rats/group). The effect of acute exercise on serum irisin was assessed in 10 additional rats subjected once to forced swimming against a load (5% of body weight) and compared to sedentary rats. ResultsSerum irisin was significantly higher in both sedentary hyper- and hypothyroid rats (by 45%, p<0.001, and 30%, p<0.001, respectively) versus euthyroid controls. Serum irisin also increased after acute exercise (p<0.001 versus sedentary control). Chronic training episodes failed to significantly alter serum irisin in all thyroid hormone profiles. Serum irisin correlated positively with serum creatine kinase (r=0.45, p<0.001) and with muscle and liver concentrations of malondialdehyde (r=0.50 and r=0.47 respectively, p<0.001 for both), and negatively with muscle and liver content of reduced glutathione (r=−0.34, p=0.003 and r=−0.28, p=0.018 respectively) in pooled groups. However, significance of these associations was waived when analyzing each group separately. Serum irisin was not associated with skeletal muscle mass, insulin resistance, blood glucose, lipids or TSH. ConclusionsBoth hyper- and hypothyroidism are associated with up-regulation of serum irisin in male rats, possibly as a response to oxidative damage and/or myopathy observed in both conditions. Acute exercise, which is also associated with oxidative stress, increases serum irisin. No obvious association was detected linking serum irisin to metabolic abnormalities in thyroid dysfunction.

Detection of 3,5-Diiodothyronine in Sera of Patients with Altered Thyroid Status Using a New Monoclonal Antibody-Based Chemiluminescence Immunoassay

3,5-Diiodo-L-thyronine (3,5-T2), a potential metabolite of 3,3',5-triiodothyronine (T3), exerts marked metabolic actions without the undesirable cardiac and central side effects of T3. So far the lack of reliable quantification methods for endogenous 3,5-T2 in human serum has limited further insight into its physiological and pathophysiological roles in endocrine homeostasis and disease status. Monoclonal anti-3,5-T2 antibodies (3,5-T2 mAbs) were produced in mice. We developed a competitive chemiluminescence immunoassay (CLIA) with one selected mAb and optimized it for high sensitivity, linearity, recovery, and low cross-reactivity to structurally related thyroid hormones (THs) and thyronamines. The CLIA was then used to investigate the origin and action of 3,5-T2 in humans under physiological and pathophysiological conditions in comparison with THs. Patient analysis included individuals with confirmed hypo- or hyperthyroidism and a separate population of thyroidectomized patients on L-thyroxine (T4) replacement therapy. 3,5-T2 is stable in human serum after storage at 4°C or room temperature as well as several freeze-thaw cycles. The immunoassay did not show any significant cross-reactivity with naturally occurring TH metabolites in physiological and pathophysiological concentrations. The assay shows a lower detection limit of 0.2 nM 3,5-T2 and an upper detection limit of 10.0 nM. The newly established CLIA generates reliable results after spiking exogenous 3,5-T2 or by linear dilution of sera. Intra-assay variation is between 4.1% and 9.0%. Overall mean of variation between different assays is 5.6%-12.9%. 3,5-T2 serum concentrations do not differ in hyperthyroid (0.31 ± 0.02 nM, n=24) compared to hypothyroid (0.43 ± 0.04 nM, n=31) individuals. 3,5-T2 was detectable and elevated in serum from thyroidectomized and T4-substituted patients (0.48 ± 0.03 nM, n=100) in comparison to a sex- and age-matched control group (0.29 ± 0.01 nM, n=99). The established CLIA is highly specific, sensitive, precise and accurate for 3,5-T2 detection in human serum. Because 3,5-T2 is not regulated in conditions of an altered thyroid state, it is most likely that serum 3,5-T2 concentrations are not directly dependent on feedback regulation via the hypothalamic-pituitary axis. In addition 3,5-T2 is present in thyroidectomized individuals on T4 substitution, and it is elevated after T4 substitution compared with healthy controls. We conclude that these data support extrathyroidal production of 3,5-T2 from T4.

A Case Report of Reversible Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is mostly an idiopathic disease with a progressive and irreversible course. It carries poor prognosis and outcome. Rarely, a reversible metabolic etiology that is amenable to specific therapy is identified. Alteration in thyroid status can lead to changes in systolic and diastolic function of left ventricle. Heart is sensitive to thyroid hormone changes, and cardiac disorders are commonly associated with both hyper and hypothyroidism. Diastolic dysfunction is the most common abnormality reported in hypothyroidism. In systolic function, prolonged systolic time interval or normal cardiac function has been reported by most workers. DCM is a rare presentation of hypothyroidism. Here, we report a case of 40-year-old female diagnosed with DCM due to hypothyroidism

The impact of high fat diets on physiological changes in euthyroid and thyroid altered rats

The association of adverse health with high fat intake has long been recognized. However, the lack of research focusing on the interrelationship of thyroid and liver function, and the pathogenesis of a high fat diet leaves these topics poorly understood. The objective of this study was to evaluate and compare the physiological changes in euthyroid and thyroid altered animal model fed saturated and unsaturated high fat diets. To achieve this objective adult male Sprague Dawley rats (n = 100) were fed one of five diets; a control or one of four test diets containing 25% saturated or unsaturated, and 37% saturated or unsaturated fats for a period of eight weeks. Each experimental group consisted of ten euthyroid and ten thyroid altered animals. An altered thyroid state was chemically induced with the addition of 0.05% propylthiouracil (PTU) in the drinking water. Euthyroid animals fed high fat diets increased in body weights and body lengths, compared to thyroid altered animals (P < 0.05). Alanine aminotransferase (ALT) and asparte aminotransferase (AST) levels increased across all experimental groups. HbA1C values and urinary glucose values were within normal range for all animals. Liver morphology showed increased hepatic stellate (ito) and vacuole cells in thyroid altered animals. These findings suggest that altered thyroid status negatively impacts growth and weight gain, and simultaneously affected lipid metabolism, resulting in abnormal liver morphology.