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Objective: This study aimed to investigate the changes in thyroid hormones in the serum of patients with polycystic ovary syndrome (PCOS) and their correlation with insulin resistance. Design: This is a retrospective study. Participants: 84 patients having insulin resistance and 76 patients without insulin resistance were included. 90 women without history of PCOS were selected as a healthy control group. Settings: This study was conducted at Shijiazhuang Fourth Hospital. Methods: Blood samples were collected from each group on days 3–5 of their menstrual cycle, and their triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were analyzed and compared between groups. Results: We investigated the changes of serum thyroid hormones in patients with PCOS and their correlation with insulin resistance. We found that serum levels of T3 and T4 were significantly decreased, while TSH levels were significantly increased in PCOS patients compared with HCs. Moreover, we found that patients with insulin resistance had significantly lower levels of serum T3 and T4 and higher levels of TSH compared to those PCOS participants without insulin resistance. Limitations: This study was a retrospective and single-center study, which had selection bias, information bias, and confounding variables may affect the accuracy and reliability of the conclusion. Conclusions: Insulin resistance negative correlates with their serum T3, T4, and positive correlates with their TSH levels. Our results develop a combined test model with the serum T3, T4, and TSH levels for the clinical diagnosis of insulin resistance in PCOS women. [ABSTRACT FROM AUTHOR]

Context: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. Objective: We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status. Methods: We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. Results: Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. Conclusion: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The thyroid gland secretes thyroxine (T 4) and tri-iodothyronine (T 3) in response to thyroid-stimulating hormone (TSH) released from the anterior pituitary gland. Iodine is essential for the synthesis of thyroid hormones. T 4 and T 3 increase basal metabolic rate, heat production and help to maintain normal growth and development. The parathyroid glands are essential for maintaining normal levels of serum calcium, which is necessary to maintain normal cellular function via calcium acting as a secondary messenger. Calcium is also involved in the coagulation of blood, transmission of nerve impulses and muscular contraction. Calcium is provided by various dietary sources and plasma levels are altered by varying absorption in the gut, mobilization from bone and excretion by the kidney. [ABSTRACT FROM AUTHOR]

Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy. It applies to non‐pregnant adults and is focussed on care delivered within the UK National Health Service, although it may be relevant in other healthcare environments. The statement emphasises several key clinical practice points for patients dissatisfied with treatment for hypothyroidism. Firstly, it is important to establish a diagnosis of overt hypothyroidism; patients with persistent symptoms during thyroid hormone replacement but with no clear biochemical evidence of overt hypothyroidism should first have a trial without thyroid hormone replacement. In those with established overt hypothyroidism, levothyroxine doses should be optimised aiming for a TSH in the 0.3–2.0 mU/L range for 3 to 6 months before a therapeutic response can be assessed. In some patients, it may be acceptable to have serum TSH below reference range (e.g. 0.1–0.3 mU/L), but not fully suppressed in the long term. We suggest that for some patients with confirmed overt hypothyroidism and persistent symptoms who have had adequate treatment with levothyroxine and in whom other comorbidities have been excluded, a trial of liothyronine/levothyroxine combined therapy may be warranted. The decision to start treatment with liothyronine should be a shared decision between patient and clinician. However, individual clinicians should not feel obliged to start liothyronine or to continue liothyronine medication provided by other health care practitioners or accessed without medical advice, if they judge this not to be in the patient's best interest. [ABSTRACT FROM AUTHOR]

Background: Low thyroxine (T4) levels have been observed in critically ill patients; however, controversial results regarding T4 supplemental therapy are reported. The association between serum free T4 (FT4) levels and mortality in critically ill patients has not been fully established and needs to be clarified. Methods: Data from the Medical Information Mart for Intensive Care (MIMIC)-IV were collected and analyzed. The association between FT4 level and 30-day mortality after ICU admission was analyzed using Kaplan-Meier curves, spline smoothing fitting, martingale residuals of the null Cox model, and restricted cubic spline (RCS). Logistic regression, Cox regression, and receiver operating characteristic curve (ROC) were used to uncover the relationship and predictive value of serum FT4 and 30-day mortality in critically ill patients. Results: In the final analysis, 888 patients were enrolled, and the serum FT4 levels were divided into four groups. A significant difference in 30-day mortality was observed between the four groups. Kaplan-Meier curves also presented significantly higher 30-day mortality in groups 1 and 2 (p < 0.0001). Further multivariance logistic regression showed that group 1 with FT4 levels lower than 0.7 mg/dl can predict 30-day mortality (odds ratio (OR) = 3.30, 95% confidence interval (CI) = 1.04-11.31). Spline smoothing fitting analysis showed a "V"-shaped line between 30-daymortality and FT4 level within 0-3 mg/dl. Further RCS analysis showed that the risk of death decreased rapidly as FT4 levels increased when serum FT4 levels were lower than 1.2 mg/dl and started to become flat afterward. The area under the ROC of the lower FT4 level to predict 30-day mortality was 0.833 (95% CI = 0.788-0.878). Both multivariant Cox regression and logistic regression showed that FT4 levels lower than 1.2 mg/dl can independently predict 30-day mortality when adjusted for other potential confounders (HR = 0.34, 95% CI = 0.14-0.82; OR = 0.21, 95% CI = 0.06-0.79, respectively), but its predictive power disappeared when adjusted for T3 or total T4. Conclusion: Serum FT4 levels were significantly negatively associated with 30-day mortality when they were lower than 1.2 mg/dl and could predict the risk of 30-day mortality. A higher FT4 level is potentially related to increased 30-day mortality. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice. Main text: There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures. Conclusion: Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals. [ABSTRACT FROM AUTHOR]

Sepsis is one of the most serious problems in intensive care units due to its high morbidity and mortality. Objective of the study to compare the healing effects of Activated Protein C and Tri-Iodothyronine in the late period of experimental sepsis. Twenty-four Wistar Albino male rats were divided into 4 groups, including the control group, septic group, Activated Protein C (APC), and Tri-Iodothyronine (T3) treatment groups. Leukocyte, thrombocyte, IL-1, IL-6, TNF-α, and antithrombin-III levels were investigated. Histopathological evaluation was performed by taking the liver, lung and intestinal tissue samples. The APC and T3 replacement groups were compared with the septic rat group, and it was observed that they preserved thrombocyte levels and antithrombin III levels, suppressed interleukin levels, and limited the effects of inflammatory responses in the liver, intestine and lung tissue. Leukocyte levels were found to be significantly higher in the T3 replacement group than in the septic group, while there was no significant difference between the APC group and the septic group. Our study showed that both activated protein C and Tri-iodothyronine can be effective in the host's response to infection in the late period of sepsis, alone and in a single dose. [Med-Science 2022; 11(1.000): 259-66]

Thyroid hormones and Cortisol level are the essential biomarkers in the assessment of stress condition. This study was done to estimate the metabolic hormonal profile of Tharparkar and Sahiwal during heat stress condition. The experiment was conducted on two groups consisting of Tharparkar and Sahiwal animals (5 in each group) and the experimental period comprised a 7-day acclimatization period, a heat exposure period of 21 days at control (25 °C), moderate (35 °C) and severe (42 °C) heat stress within a 9–10-day recovery period between each exposure. The hormonal concentrations of T3, T4 and cortisol were determined in serum. The serum concentration of Thyroxine (T4) and tri-iodothyronine (T3) decreases whereas cortisol level increases in both the breeds when subjected to heat stress. However, the serum level of T4 was significantly (p < 0.05) more declined in Sahiwal as compared to Tharparkar but there was no significant difference found between the two breeds in serum T3 levels. The cortisol levels were elevated in both breeds during heat stress but significantly (p < 0.05) more elevated in the Sahiwal. Hence, observations of these hormonal profiles suggest a better thermo-adaptability in Tharparkar as compared to Sahiwal. [ABSTRACT FROM AUTHOR]

According to studies, a pathophysiological feature of schizophrenia may be a dysregulation of the inflammatory immune response. Conversely, antipsychotic medications have been found to have an immunosuppressive effect in patients with schizophrenia; however, this has not been consistently observed in different studies. The purpose of the following study is to compare the effects of risperidone with aripiprazole on thyroid function as it relates to inflammatory markers (CRP). This study was based on a randomized controlled trial. A total of thirty rats were recruited for the experiment and were kept in the artificial, and optimal environment. The rats were divided into three groups; each group has an equal number of rats which was 10 rats each. The first group was the control group which received the placebo, in the second group, there were 10 rats too, which was known as the risperidone group. Each rat received 20mg/kg/day through I/V. The third group is known as the aripiprazole group which received the drug from the intravenous route, 10mg/kg//day. In the results, the summarized values represented that all the mean values before and after the treatment remained less than 3.0. From the results and other evidence, it can be said that although the subjects who receive the following results do not require regular or frequent monitoring of thyroid hormones in long-term use and in the use of the drug in higher concentration there must be a check as long term use is associated with hyperthyroidism. [ABSTRACT FROM AUTHOR]

A genetic deficiency of the solute carrier monocarboxylate transporter 8 (MCT8), termed Allan–Herndon–Dudley syndrome, is an important cause of X-linked intellectual and motor disability. MCT8 transports thyroid hormones across cell membranes. While thyroid hormone analogues improve peripheral changes of MCT8 deficiency, no treatment of the neurological symptoms is available so far. Therefore, we tested a gene replacement therapy in Mct8 - and Oatp1c1 -deficient mice as a well-established model of the disease. Here, we report that targeting brain endothelial cells for Mct8 expression by intravenously injecting the vector AAV-BR1- Mct8 increased tri-iodothyronine (T3) levels in the brain and ameliorated morphological and functional parameters associated with the disease. Importantly, the therapy resulted in a long-lasting improvement in motor coordination. Thus, the data support the concept that MCT8 mediates the transport of thyroid hormones into the brain and indicate that a readily accessible vascular target can help overcome the consequences of the severe disability associated with MCT8 deficiency. [ABSTRACT FROM AUTHOR]

Abstract Background Data regarding the relation between both subclinical thyroid dysfunction, thyroid autoantibodies and clinical outcomes in stroke patients are limited. This study aimed to evaluate subclinical thyroid dysfunction and thyroid autoantibodies production in acute stroke patients and their relation to long term stroke outcome. We recruited 138 patients who were subjected to thorough general, neurological examination and brain imaging. Blood samples were collected for measurement of levels of serum thyroid function [free tri-iodothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH)], thyroid autoantibodies within 48 h after hospital admission. FT4 and TSH after 1 year were done. The stroke severity was assessed at admission by the National Institutes of Health Stroke Scale (NIHSS). The stroke outcome was assessed at 3 months and after 1 year by the modified Rankin Scale (mRS). We divided the patients into two groups according to thyroid autoantibodies (positive and negative groups). Results Subclinical hyperthyroidism was found in 23% of patients, and subclinical hypothyroidism in 10% of patients. Euthyroidism was detected in 67% of patients. 34% patients had positive thyroid autoantibody. Positive thyroid autoantibodies were commonly found in those with subclinical hyperthyroidism (28%), followed by subclinical hypothyroidism (21%) and euthyroidism (14%). 73% and 59% of stroke patients had poor outcomes (mRS was > 2) at 3 months and 1 year respectively with no significant difference between ischemic and hemorrhagic stroke patients. In the positive group final TSH level, NIHSS score at admission, and disability at 1 year were significantly higher compared with the negative group. Poor outcome was significantly associated with higher NIHSS score at admission, positive thyroid autoantibodies, subclinical hyperthyroidism, and atrial fibrillation. Conclusions Subclinical thyroid dysfunction could be found in stroke patients with positive thyroid autoantibodies. Subclinical hyperthyroidism and thyroid autoantibodies were associated with a poor outcome at 1 year in first-ever acute stroke patients especially in those presented with atrial fibrillation and higher NIHSS score at admission.

Sepsis is one of the most serious problems in intensive care units due to its high morbidity and mortality. Objective of the study to compare the healing effects of Activated Protein C and Tri-Iodothyronine in the late period of experimental sepsis. Twenty-four Wistar Albino male rats were divided into 4 groups, including the control group, septic group, Activated Protein C (APC), and Tri-Iodothyronine (T3) treatment groups. Leukocyte, thrombocyte, IL-1, IL-6, TNF-a, and antithrombin-III levels were investigated. Histopathological evaluation was performed by taking the liver, lung and intestinal tissue samples. The APC and T3 replacement groups were compared with the septic rat group, and it was observed that they preserved thrombocyte levels and antithrombin III levels, suppressed interleukin levels, and limited the effects of inflammatory responses in the liver, intestine and lung tissue. Leukocyte levels were found to be significantly higher in the T3 replacement group than in the septic group, while there was no significant difference between the APC group and the septic group. Our study showed that both activated protein C and Tri-iodothyronine can be effective in the host's response to infection in the late period of sepsis, alone and in a single dose. [ABSTRACT FROM AUTHOR]

Background: Data regarding the relation between both subclinical thyroid dysfunction, thyroid autoantibodies and clinical outcomes in stroke patients are limited. This study aimed to evaluate subclinical thyroid dysfunction and thyroid autoantibodies production in acute stroke patients and their relation to long term stroke outcome. We recruited 138 patients who were subjected to thorough general, neurological examination and brain imaging. Blood samples were collected for measurement of levels of serum thyroid function [free tri-iodothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH)], thyroid autoantibodies within 48 h after hospital admission. FT4 and TSH after 1 year were done. The stroke severity was assessed at admission by the National Institutes of Health Stroke Scale (NIHSS). The stroke outcome was assessed at 3 months and after 1 year by the modified Rankin Scale (mRS). We divided the patients into two groups according to thyroid autoantibodies (positive and negative groups). Results: Subclinical hyperthyroidism was found in 23% of patients, and subclinical hypothyroidism in 10% of patients. Euthyroidism was detected in 67% of patients. 34% patients had positive thyroid autoantibody. Positive thyroid autoantibodies were commonly found in those with subclinical hyperthyroidism (28%), followed by subclinical hypothyroidism (21%) and euthyroidism (14%). 73% and 59% of stroke patients had poor outcomes (mRS was > 2) at 3 months and 1 year respectively with no significant difference between ischemic and hemorrhagic stroke patients. In the positive group final TSH level, NIHSS score at admission, and disability at 1 year were significantly higher compared with the negative group. Poor outcome was significantly associated with higher NIHSS score at admission, positive thyroid autoantibodies, subclinical hyperthyroidism, and atrial fibrillation. Conclusions: Subclinical thyroid dysfunction could be found in stroke patients with positive thyroid autoantibodies. Subclinical hyperthyroidism and thyroid autoantibodies were associated with a poor outcome at 1 year in first-ever acute stroke patients especially in those presented with atrial fibrillation and higher NIHSS score at admission. [ABSTRACT FROM AUTHOR]

Introduction: the outbreak and rapid spread of the novel SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), has evolved into an unprecedented global pandemic. The infection impairs several human organs and systems, however, it is not clear how it affects thyroid function. The study therefore aimed at measuring plasma levels of thyroid hormones and Hs-CRP in COVID-19 patients and apparently healthy uninfected controls to assess the possible effect of SAR-CoV-2 infection on thyroid function. Methods: in this cross-sectional study carried out between May-August 2020, 90 consenting participants comprising 45 COVID-19 patients and 45 apparently healthy uninfected controls were recruited. Plasma FT3, FT4, TSH and Hs-CRP were measured using Enzyme Linked Immunosorbent Assay (ELISA) method. Data was analysed using SPSS version 20 and statistical significance set at p < 0.05. Results: the mean plasma FT3 and TSH concentrations were significantly higher in COVID-19 patients compared to controls (p < 0.001, p < 0.001 respectively). Euthyroidism was observed in all uninfected controls, whereas 35 (77.8%) COVID-19 patients were euthyroid. Sick euthyroid and subclinical hypothyroidism was observed in 7 (15.6%) and 3 (6.7%) COVID-19 patients, respectively. Conclusion: though there was a preponderance of euthyroidism among COVID-19 patients, significantly higher mean plasma levels of TSH and FT3, sick euthyroid syndrome and subclinical hypothyroidism observed among some COVID-19 patients may be indicative of disease-related thyroid function changes. Hence, there is need to pay attention to thyroid function during and after treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Purpose The aims of this study were to evaluate the visual evoked potential (VEP) changes in thyroid ocular disorders and to correlate between VEP latencies and thyroid hormones. Patients and methods The study participants were divided into four groups. Group 1 comprised 50 patients (100 eyes) with subclinical hypothyroidism (29 patients had recent hypothyroidism without treatment, and 21 patients had controlled hypothyroidism with treatment). Group 2 comprised 35 patients (70 eyes) with overt hypothyroidism (20 patients had recent hypothyroidism without treatment, and 15 patients had controlled hypothyroidism with treatment). Group 3 comprised 35 patients (70 eyes) with hyperthyroidism (18 patients had recent hyperthyroidism without treatment, and 17 patients were under treatment). Group 4 comprised 70 patients (140 eyes) with normal thyroid functions as a control group. Flash and pattern VEP and thyroid hormone assay were performed for all patients. Results There was an increase in the latencies of VEP without statistically significant change in amplitudes in thyroid disorders (groups 1, 2, and 3) compared with the normal control group (group 4). The increase in latencies in group 1 was statistically insignificant (P>0.1), while, in groups 2 and 3, it was statistically significant (P

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Abstract Endocrine disrupting chemicals (EDCs) include a wide array of pollutants, such as some metals and other toxic elements, which may cause changes in hormonal homeostasis. In addition to affecting physiology of individuals directly, EDCs may alter the transfer of maternal hormones to offspring, i.e. causing transgenerational endocrine disruption. However, such effects have been rarely studied, especially in wild populations. We studied the associations between environmental elemental pollution (As, Cd, Cu, Ni, Pb) and maternally-derived egg thyroid hormones (THs) as well as nestling THs in great tits (Parus major) using extensive sampling of four pairs of polluted and reference populations across Europe (Finland, Belgium, Hungary, Portugal). Previous studies in these populations showed that breeding success, nestling growth and adult and nestling physiology were altered in polluted zones compared to reference zones. We sampled non-incubated eggs to measure maternally-derived egg THs, measured nestling plasma THs and used nestling faeces for assessing local elemental exposure. We also studied whether the effect of elemental pollution on endocrine traits is dependent on calcium (Ca) availability (faecal Ca as a proxy) as low Ca increases toxicity of some elements. Birds in the polluted zones were exposed to markedly higher levels of toxic elements than in reference zones at the populations in Finland, Belgium and Hungary. In contrast to our predictions, we did not find any associations between overall elemental pollution, or individual element concentrations and egg TH and nestling plasma TH levels. However, we found some indication that the effect of metals (Cd and Cu) on egg THs is dependent on Ca availability. In summary, our results suggest that elemental pollution at the studied populations is unlikely to cause overall TH disruption and affect breeding via altered egg or nestling TH levels with the current elemental pollution loads. Associations with Ca availability should be further studied. Graphical abstract Image 1 Highlights • We studied element-associated transgenerational endocrine disruption in wild populations. • We sampled four pairs of metal-polluted and reference sites across Europe. • Eggs and nestling plasma of Parus major were analysed for thyroid hormones and nestling faeces for toxic elements. • We found no general association between toxic element exposure, egg and nestling plasma thyroid hormones. • The effect of cadmium and copper on egg thyroid hormones depended on calcium availability. [ABSTRACT FROM AUTHOR]

Background: The health benefits of soy are widely reported but there are queries on the effect of soy isoflavones on thyroid function and the underlying mechanism of action.Materials and Methods: We examined the effect of soy isoflavones on reverse tri-iodothyronine (or 3,3′,5′-tri-iodothyronine; rT3) in two studies comprising 400 patients: 200 men (study 1; 3 months) and 200 post-menopausal women (study 2; 6 months) who were randomized to consume 15 g soy protein with 66 mg of isoflavones (SPI) daily, or 15 g soy protein alone without isoflavones (SP) daily.Results: SPI supplementation increased rT3 serum concentration in both men 0.41 (0.12) vs. 0.45 (0.14) nmol/L and women 0.33 (0.12) vs. 0.37 (0.09) nmol/L at 3 months compared to SP that was not seen at 6 months. Thyroid stimulating hormone (TSH) serum concentrations increased while free thyroxine (fT4) concentrations decreased with 3 months of SPI compared to SP supplementation for both men and women. rT3 correlated with TSH in both studies (p = 0.03) but not with either fT3 or fT4. fT3 levels did not differ between the SPI and SP preparations.Conclusion: Soy isoflavones transiently increased rT3 levels within 3 months though reverted to baseline at 6 months. The mechanism for this would be either rT3 degrading deiodinase 1 and/or deiodinase 2 activities are transiently inhibited at 3 months, or inhibition of deiodinase 3, which generates rT3 from T4 is induced at 6 months. These changes were mirrored in the TSH concentrations, suggesting that short-term high dose isoflavone transiently impairs thyroid function in the first 3 months and may impact on general health during this period.ISRCTN Registry: ISRCTN 90604927; ISRCTN34051237.

Objective: Low tri-iodothyronine (T3) syndrome is a predictor of poor prognosis in patients with stroke. Poststroke cognitive impairment (PSCI) is a common and important complication after stroke. The association between low T3 syndrome and PSCI is unclear. We aimed to explore the potential relationship between low T3 syndrome and PSCI in the acute phase of ischemic stroke at a 1-month follow-up visit.Methods: In total, 314 ischemic stroke patients were consecutively enrolled in the study and followed up at 1 month. Thyroid hormones were measured within 24 hours after admission. Cognitive function was evaluated by the Mini-Mental State Exam (MMSE) 1 month after acute ischemic stroke. Cognitive impairment was defined as an MMSE score of less than 27. Cognitive impairment severity was categorized as severe, mild, or none (MMSE score <23, 23-26, or ≥27, respectively).Results: According to the MMSE score, 182 participants (58.0%) had cognitive impairment 1 month after stroke. Patients with low T3 syndrome were more prone to have cognitive impairment than patients with normal levels of T3 (p < 0.001). After adjusting for potential confounders in our logistic model, low T3 syndrome was independently associated with PSCI (odds ratio 4.319, 95% confidence interval 1.553-12.013, p = 0.005).Conclusion: Low T3 syndrome in the acute phase of ischemic stroke was associated with a higher prevalence of 1-month PSCI, independently of established risk factors. [ABSTRACT FROM AUTHOR]

Background: The health benefits of soy are widely reported but there are queries on the effect of soy isoflavones on thyroid function and the underlying mechanism of action. Materials and Methods: We examined the effect of soy isoflavones on reverse tri-iodothyronine (or 3,3′,5′-tri-iodothyronine; rT3) in two studies comprising 400 patients: 200 men (study 1; 3 months) and 200 post-menopausal women (study 2; 6 months) who were randomized to consume 15 g soy protein with 66 mg of isoflavones (SPI) daily, or 15 g soy protein alone without isoflavones (SP) daily. Results: SPI supplementation increased rT3 serum concentration in both men 0.41 (0.12) vs. 0.45 (0.14) nmol/L and women 0.33 (0.12) vs. 0.37 (0.09) nmol/L at 3 months compared to SP that was not seen at 6 months. Thyroid stimulating hormone (TSH) serum concentrations increased while free thyroxine (fT4) concentrations decreased with 3 months of SPI compared to SP supplementation for both men and women. rT3 correlated with TSH in both studies (p = 0.03) but not with either fT3 or fT4. fT3 levels did not differ between the SPI and SP preparations. Conclusion: Soy isoflavones transiently increased rT3 levels within 3 months though reverted to baseline at 6 months. The mechanism for this would be either rT3 degrading deiodinase 1 and/or deiodinase 2 activities are transiently inhibited at 3 months, or inhibition of deiodinase 3, which generates rT3 from T4 is induced at 6 months. These changes were mirrored in the TSH concentrations, suggesting that short-term high dose isoflavone transiently impairs thyroid function in the first 3 months and may impact on general health during this period. ISRCTN Registry: ISRCTN 90604927; ISRCTN34051237. [ABSTRACT FROM AUTHOR]

Introduction Thyroid Function Tests (TFTs) are among the most commontly ordered tests. Significant overuse of TFTs can occur when instead of using a single TSH test to screen for thyroid disease a full panel (TSH plus FT4 and FT3) is ordered. The aim of our study was to evaluate the effectiveness of the application of a scientifically-established laboratory-controlled algorithm for TFTs to physician's orders for inpatients and to address potential pitfalls of such an approach. Materials and methods We collected and analyzed Laboratory Information System data of the TFTs performed between April 2009 and March 2016 in a 739-bed tertiary teaching hospital. Between April 2013 and March 2016, we applied a laboratory controlled algorithm for inpatient TFT assays after TSH and did not perform further tests, unless a justified bypass was requested by the treating physician. Results Algorithm application led to significant reductions of TFTs executed per TSH ordered. Compared to the four years preceding the intervention, executed FT4/TSH tests decreased from 93 to 18%, FT3/TSH from 92 to 18%, anti-TG/TSH from 18 to 4% and anti-TPO/TSH from 11 to 3%. Simultaneously, FT4, FT3, anti-TG, and anti-TPO tests ordered in outpatients also displayed a significant gradual decrease. Conclusions Hospital-based laboratories can safely apply a generally accepted TFTs algorithm on physician's orders without any compromise in diagnostic/therapeutic accuracy, thus achieving significant direct cost-reduction and increased physician awareness on current TFT ordering practices. Such an approach, combined with collaboration with ordering physicians, can safeguard patients from the consequences of low-value care practices. [ABSTRACT FROM AUTHOR]

Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection (P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function. [ABSTRACT FROM AUTHOR]

Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH), pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction.

Background: Thyroid disorders are common in clinical medicine and laboratory confirmation is essential, especially in cases where overt signs and symptoms are absent. The measurement of thyroid-stimulating hormone (TSH) is recommended as the best indicator of thyroid function and is utilized along with thyroxine (T4) and in some circumstances triiodothyronine (T3). Aim: The aim is to evaluate the relationship between TSH and free T4 (FT4), and TSH and FT3. Methods: Thyroid function tests (TFTs) - TSH, FT4, and FT3 - performed in the Chemical pathology laboratory from February to December 2015 were retrieved from the laboratory information management system. Results were classified based on TSH results into suppressed, mildly suppressed, normal, mildly elevated and elevated, and correlated with FT3 and FT4 results. Results were also categorized as overt hyperthyroidism, subclinical hyperthyroidism, normal, subclinical hypothyroidism, overt hypothyroidism, and "others" and compared based on age and gender. Results: FT4 and FT3 correlate best with TSH at suppressed and elevated levels. Mean TSH was significantly higher in males than in females only in those with normal FT4 and TSH. TSH was significantly higher in the 41-60 age group, with females in this group having significantly higher levels as compared to males. Conclusions: There is an inverse correlation between FT4 and TSH, and FT3 and TSH, especially significant at suppressed and elevated levels of TSH. Highest TSH levels were observed in women in the 41-60 age cohort. [ABSTRACT FROM AUTHOR]

Background In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear. Material and methods We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters. Results TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes. Discussion This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the relationship between Ginger administration and thyroid gland function. Ginger was orally administered daily to male albino rats at a dose level of either 50 or 100 mg/kg for one month. Blood samples and thyroid glands were collected after 15 and 30 days and also 10 days after stopping Ginger administration for hormonal analysis and histopathological examination. It was found that T3 elevated significantly 15 days after administration regardless of the dose. Moreover, this elevation became non-significant after 30 days. Interestingly, this change in T3 is reversible and returned to normal level after stopping Ginger administration. Regarding to T4, both doses of Ginger elevated T4 after 15 and 30 days. Likewise, T4 decreased and returned to normal level after stopping Ginger administration. Both dose level, 50 and 100 mg/kg of Ginger elevated TSH after 15 and 30 days, but this elevation after 100 mg/kg was less potent. During the recovery period, almost no change in TSH level was observed. The effect of Ginger for a long period has a deleterious effect on thyroid follicles which appear dilated and empty from colloidal materials. [ABSTRACT FROM AUTHOR]

Reduced triiodothyronine (T3) concentrations were implicated in worse prognosis of brain tumor patients. In this study we investigated the association of normal and abnormal thyroid hormone concentrations with health-related quality of life (HRQoL) of patients with primary brain tumors. Sixty-three patients (67% women and a mean age of 55.5 ± 13.8 years) before brain tumor surgery were evaluated for: (1) HRQoL using the EORTC questionnaire for cancer patients (QLQ-C30) and the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20); (2) functional status (Barthel Index); and (3) clinical disease severity. Blood samples were obtained for assessment of thyroid hormone concentrations before surgery. After adjusting for the brain tumor histological diagnosis, patients' age, gender and functional status, lower thyroid stimulating hormone (TSH) concentrations were associated with poor levels of functioning on the QLQ-C30 scales: physical functioning (β = 0.395, p < 0.001), role functioning (β = 0.334, p = 0.003) and cognitive functioning (β = 0.327, p = 0.009), and with greater QLQ-BN20 fatigue symptom severity (β = −0.406, p < 0.001). Lower free T3 concentrations were associated with worse HRQOL on the QLQ-C30 global health status (β = 0.302, p = 0.017), emotional functioning (β= 0.422, p < 0.001) and cognitive functioning (β= 0.259, p = 0.042) domains, and with greater symptom severity on the QLQ-BN20 fatigue (β = −0.238, p = 0.041), motor dysfunction (β = −0.283, p = 0.013) and weakness of legs (β = −0.269. p = 0.027) domains. In conclusion, reduced T3 and TSH hormone concentrations are associated with impaired emotional and physical aspects of HRQoL of primary brain tumor patients independent of brain tumor histological diagnosis, patients' age, gender and functional status. Assessment for thyroid axis dysfunction should be addressed and appropriately managed in neuro-oncology patient care. [ABSTRACT FROM AUTHOR]

Background Intracranial neurosurgical disorders are important causes of mortality and disability worldwide. Low tri-iodothyronine (T3) syndrome is a common complication in critically ill patients and is associated with a poor prognosis. Methods We performed a systematic review of clinical studies analyzing the prevalence of low T3 syndrome and the association of serum T3 concentrations with disease severity and outcomes in patients with traumatic brain injury (TBI), hydrocephalus, aneurysmal subarachnoid hemorrhage (SAH), and brain tumors. Results The greatest prevalence rate of low T3 syndrome was reported in severe TBI patients (up to 67%), followed by patients with brain tumors (54%), aneurysmal SAH (up to 43%), and hydrocephalus (33%). A lower than normal serum T3 concentration was associated with greater disease severity, worse health status, complicated clinical course, and worse hospital discharge outcomes for TBI, aneurysmal SAH, and brain tumor patients. Lower T3 concentrations were also associated with greater long-term mortality and increased disability in TBI and aneurysmal SAH patients. Conclusions Low T3 syndrome is a common complication in patients suffering from intracranial neurosurgical disorders and is associated with greater disease severity, complicated clinical course, and greater mortality and handicap rates. However, it remains unclear if low T3 syndrome can impact the findings of currently available clinical prognostic models and if management of low T3 syndrome can improve outcomes in neurosurgical patients. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones are controlled by the hypothalamic-pituitary-thyroid (HPT) axis through a complex network of regulatory loops, involving the hormones TRH, TSH, FT4, and FT3. The relationship between TSH and FT4 is widely used for diagnosing thyroid diseases. However, mechanisms of FT3 homeostasis are not well understood., Objective: We used mathematical modelling to further examine mechanisms that exist in the HPT axis regulation for protecting circulating FT3 levels., Methods: A mathematical model consisting of a system of four coupled first-order parameterized non-linear ordinary differential equations (ODEs) was developed, accounting for the interdependencies between the hormones in the HPT axis regulation. While TRH and TSH feed forward to the pituitary and thyroid, respectively, FT4 and FT3 feed backward to both the pituitary and hypothalamus. Stable equilibrium solutions of the ODE system express homeostasis for a particular variable, such as FT3, if this variable stays in a narrow range while certain other parameter(s) and system variable(s) may vary substantially., Results: The model predicts that (1) TSH-feedforward protects FT3 levels if the FT4 production rate declines and (2) combined negative feedback by FT4 and FT3 on both TSH and TRH production rates keeps FT3 levels insensitive to moderate changes in FT4 production rates and FT4 levels. The optimum FT4 and FT3 feedback and TRH and TSH-feedforward ranges that preserve FT3 homeostasis were found by numerical continuation analysis. Model predictions were in close agreement with clinical studies and individual patient examples of hypothyroidism and hyperthyroidism., Conclusions: These findings further extend the concept of HPT axis regulation beyond TSH and FT4 to integrate the more active sister hormone FT3 and mechanisms of FT3 homeostasis. Disruption of homeostatic mechanisms leads to disease. This provides a perspective for novel testable concepts in clinical studies to therapeutically target the disruptive mechanisms., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: JWD is co-owner of the intellectual property rights for the patent ‘System and Method for Deriving Parameters for Homeostatic Feedback Control of an Individual’ (Singapore Institute for Clinical Sciences, Biomedical Sciences Institutes, Application Number 201208940-5, WIPO number WO/2014/088516). All other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© The Author(s), 2023.)

Objectives: The objective of this research was to elucidate some of the major relation of thyroid dysfunctions, keeping in view the various selected demographic details of included patients. Methods: This study was approved by the ethical committee of Post Graduate Medical Institute (PGMI) Hayatabad Medical Complex Peshawar, and was conducted in the Institute of Radioactive Nuclear Medicine (IRNUM) Peshawar. The blood samples were collected, followed by their analysis for triiodothyronine (T3), tetraiodothyronine (T4) and thyroid stimulating hormone (TSH). Results: The results obtained regarding the demographical aspects of the patients revealed that female gender has categorically significantly high percentage of occurrence of thyroid abnormality as compared to male gender (75.8% vs. 24.2%). Results regarding locality distribution of the patients depicted that majority of those belonged to the local population of Peshawar and Charsadda region. Conclusion: In Pakistan especially Khyber Pakhtunkwa (KPK), thyroid diseases are more common in females as compared to males. The most probable causes could be lactation and pregnancy. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction is a common accompaniment to severe sepsis. Clinical management of the same complicating pregnancy presents unique challenges balancing maternal and fetal well-being. Can short-term intravenous (IV) tri-iodothyronine (T3) be used in the management of these patients? T3 has been reported in varied clinical settings to favorably affect cardiac lusitropy, inotropy, and chronotropy without significant side effects. We report a case of acute severe left ventricular dysfunction in a pregnant woman with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation managed with short-term IV T3. Hemodynamic stability was rapidly achieved and the improvement in contractility imaged in real time by transesophageal echocardiography. < Learning objective: Tri-iodothyronine (T3) rapidly affects cardiac inotropy, lusitropy, chronotropy, and systemic vascular resistance. Widespread application of intravenous T3 for treatment of heart failure is currently limited by a paucity of scientific literature. Selective short-term intravenous T3 use is an underutilized adjunct in the management of acute left ventricular dysfunction.> [ABSTRACT FROM AUTHOR]

Background: Transient thyroid dysfunction occurs in children after cardiopulmonary bypass (CPB). We demonstrated significant benefits of acute postoperative tri-iodothyronine (T3) treatment for recovery and myocardial function. Now we report the long-term neurodevelopment of these children. Methods: Twenty-eight children (70% of the original study population) could be recruited for a follow-up examination (median age 10.7 years, range 10-19.6 years) retaining the double-blind, randomized, placebo-controlled protocol. Cognitive function and motor development were tested, as were growth and thyroid and cardiac functions. Results: The median full-scale intelligence quotient of all children was within the reference range and similar in the placebo and T3 groups. Tests for motor and cognitive functions, growth, and thyroid and cardiac functions revealed concurrent results. Conclusions: Overall intellectual development is preserved in adolescents treated with CPB in infancy irrespectively of low postoperative thyroid hormone concentrations. While acute postoperative T3 treatment in children after CPB improves recovery, no significant long-term effects on neurodevelopment could be detected. We therefore speculate that transient postoperative thyroid dysfunction by means of nonthyroidal illness syndrome is predominantly mediated by extranuclear, nongenomic mechanisms and thus acutely affects the cardiovascular system but not the development of the central nervous system mediated by genomic mechanisms. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Preeclampsia is an important cause of maternal and prenatal morbidity and mortality in the developing countries. Changes in thyroid function/antibodies profiles in preeclamptic women are controversial and were never investigated before in Sudan. A case-control study was conducted at Medani Hospital, Sudan, to investigate thyroid function/antibodies in preeclampsia. The sociodemographic, medical history was gathered using questionnaires. Thyroid hormones [thyroid-stimulating hormone (TSH), free tri-iodothyronine (T3), and free thyroxine (T4)] and anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG) antibodies were measured using ELISA. The three groups [controls, mild, and severe preeclampsia (SP) (55 women in each arm)] were matched in age and parity. While median (interquartile range) of TSH was significantly lower, both free T3 and free T4 levels were significantly higher in women with preeclampsia than in the healthy controls. There was no significant difference in the TSH levels in women with MP and SP. In comparison with women with MP, women with SP had significantly higher levels of free T3 and significantly lower levels of free T4. While anti-TPO antibodies were significantly higher, anti-TG antibodies were significantly lower in women with preeclampsia. Likewise, anti-TPO antibodies were significantly higher and anti-TG antibodies were significantly lower in women with SP than in women with MP. In linear regression, preeclampsia was significantly associated with TSH (-0.675 IU/ml, P=0.009), free T3 (0.977 pg/ml, P<0.001), and free T4 (0.186 ng/dl, P<0.001) levels. In contrast to anti-TG antibodies and TSH, Sudanese patients with preeclampsia had higher levels of T3 and T4 hormones and anti-TPO antibodies irrespective of parity, gestational age, and hemoglobin levels. [ABSTRACT FROM AUTHOR]

ABSTRACT An increase in energy intake and/or a decrease in energy expenditure lead to fat storage, causing overweight and obesity phenotypes. The objective of this review was to analyse, for the first time using a systematic approach, all published evidence from the past 8 years regarding the molecular pathways linking non-shivering thermogenesis and obesity in mammals, focusing on mechanisms involved in brown adipose tissue development. Two major databases were scanned from 2006 to 2013 using 'brown adipose tissue' AND 'uncoupling protein-1' AND 'mammalian thermoregulation' AND 'obesity' as key words. A total of 61 articles were retrieved using the search criteria. The available research used knockout methodologies, various substances, molecules and agonist treatments, or different temperature and diet conditions, to assess the molecular pathways linking non-shivering thermogenesis and obesity. By integrating the results of the evaluated animal and human studies, our analysis identified specific molecules that enhance non-shivering thermogenesis and metabolism by: ( i) stimulating 'brite' (brown-like) cell development in white adipose tissue; ( ii) increasing uncoupling protein-1 expression in brite adipocytes; and ( iii) augmenting brown and/or brite adipose tissue mass. The latter can be also increased through low temperature, hibernation and/or molecules involved in brown adipocyte differentiation. Cold stimuli and/or certain molecules activate uncoupling protein-1 in the existing brown adipocytes, thus increasing total energy expenditure by a magnitude proportional to the number of available brown adipocytes. Future research should address the interplay between body mass, brown adipose tissue mass, as well as the main molecules involved in brite cell development. [ABSTRACT FROM AUTHOR]

Objective: Patients treated for childhood craniopharyngioma often develop hypothalamic obesity (HO), which has a huge impact on the physical condition and quality of life of these patients. Treatment for HO thus far has been disappointing, and although several different strategies have been attempted, all interventions had only transient effects. Since thyroid hormones increase energy expenditure metabolism (thyroid hormone induced thermogenesis), it was speculated that treatment with tri-iodothyronine (T3) may be beneficial. In 2002, a case report was published on reduction of body weight after T3 treatment for HO. No studies have been reported since. Recent experimental studies in rodents showed that T3 increases brown adipose tissue (BAT) activity via (pre)sympathetic pathways between the hypothalamus and BAT. Our aim was to investigate whether T3 treatment increases BAT activity in a patient with HO resulting from (treatment of) childhood craniopharyngioma. Methods: Thyroxine treatment for central hypothyroidism was switched to T3 monotherapy. Serum T3 and free thyroxine (FT4) concentrations were measured twice weekly for 2 months. 123I-MIBG and 18F-FDG-PET after induction of non-shivering thermogenesis for the assessment of sympathetic and metabolic activity of BAT as well as indirect calorimetry for assessment of resting energy expenditure were performed before and during T3 treatment. Results: No change in sympathetic and metabolic BAT activity, energy expenditure, or BMI was seen during T3 treatment despite the expected changes in thyroid hormone plasma concentrations. Conclusion: We conclude that T3 monotherapy does not seem to be effective in decreasing HO in childhood craniopharyngioma. [ABSTRACT FROM AUTHOR]

Bipolar disorders of types I and II, even when treated by currently standard options, show a marked excess of depressive morbidity. Treated, type I patients in mid-course or from the onset of illness are ill, overall, 50 % of weeks of follow-up, and 75 % of that unresolved morbidity is depressive. Currently widely held impressions are that bipolar depression typically is poorly responsive to antidepressants, that treatment-resistant depression (TRD) is characteristic of the disorder, and that risk of mania with antidepressant treatment is very high. However, none of these views is supported consistently by available research. TRD may be more prevalent in bipolar than unipolar mood disorders. Relatively intense research attention is directed toward characteristics and treatments of TRD in unipolar depression, but studies of bipolar TRD are uncommon. We found only five controlled trials, plus 10 uncontrolled trials, providing data on a total of 13 drug treatments, all of which involved one or two trials, in 87 % as add-ons to complex, uncontrolled regimens. In two controlled trials, ketamine was superior to placebo but it is short-acting and not orally active; pramipexole was weakly superior to placebo in one controlled trial; three other drugs failed to outperform controls. Other pharmacotherapies are inadequately evaluated and nonpharmacological options are virtually untested in bipolar TRD. The available research supports the view that antidepressants may be effective in bipolar depression provided that currently agitated patients are excluded, that risk of mania with antidepressants is only moderately greater than risk of spontaneous mania, and that bipolar TRD is not necessarily resistant to all treatments. [ABSTRACT FROM AUTHOR]

Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH), pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction. [ABSTRACT FROM AUTHOR]

Abstract: The interactions between kidney and thyroid functions have been known for many years, but how the thyroid affects the kidney function is largely unknown. Here we analyzed the role of T3 on the tubular epithelial-to-mesenchymal transition (EMT), which is recognized to play pivotal roles in the process of renal fibrosis. T3 was found to significantly inhibit the TGFβ1 induced EMT in human proximal tubular epithelial cell line HK-2. Meanwhile, T3 induced the expression of miR34a. Molecularly, the T3 receptor could directly bind the T3R recognition motif at the −1505 to −1526bp and −604 to −609bp regions in the miR34a promoter and transcriptionally activate the expression of miR34a upon T3 treatment. Inhibition of the miR34a by miR34a knockdown nearly blocked the effects of T3 on EMT. Taken together, our study here revealed that thyroid hormone T3 could inhibit TGFβ1 induced renal tubular epithelial to mesenchymal transition by increasing miR34a expression. [Copyright &y& Elsevier]

Timely diagnosis and treatment of thyroid dysfunction is compelling given the prevalence and severity of the disease. It requires reliance on adequate laboratory testing of serum TSH as a hallmark in combination with free thyroxine/triiodothyronine. Free hormone methods have to accommodate variations in the concentration and binding capacity of binding proteins. This is a challenge because none of the methodologies developed so far measures the actual unbound hormone in serum. The indirect methods provide an approximation while the direct ones estimate the free hormone concentration either in the presence of the protein-bound counterpart, or after physical separation of the free from bound fraction. The ongoing controversy on the validity and lack of comparability of methodologies points to their imperfectness to reflect real in-vivo free hormone concentrations. Therefore, laboratories and clinicians should know the window of validity and limitations of their methods. The recently developed reference measurement system is a key advance towards improved standardization and clinical validity of free thyroid hormone measurements. [Copyright &y& Elsevier]

Objective: The aim of this study in pregnant women with hypothyroidism treated by levothyroxine is to examine the interrelations between thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free tri-iodothyronine (FT3), and examine whether in such patients the treatment is adequate. Methods: This was a retrospective cross-sectional study. Maternal serum concentrations of FT3, FT4 and TSH were measured at 11–13 weeks in 164 singleton pregnancies from women with hypothyroidism before pregnancy receiving treatment with thyroxine. The values were compared to the results in 4,318 normal singleton pregnancies. Results: In the hypothyroid group, compared to the normal group, there was an increase in median TSH (1.990 vs. 1.007 MoM) and FT4 (1.052 vs. 0.992 MoM) and decrease in FT3 (0.901 vs. 0.991 MoM). Serum FT4 was at or above the 2.5th centile in 158 (96.3%) cases but TSH was above the 97.5th centile in 48 (29.3%) and FT3 was below the 2.5th centile in 49 (29.9%) cases. In both the hypothyroid and unaffected groups there were significant associations between TSH and FT4, TSH and FT3 and between FT3 and FT4. Conclusions: In a high proportion of pregnant women with hypothyroidism treated with levothyroxine there is evidence of persistent hypothyroidism because the treatment is inadequate in correcting the levels of FT3. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153), a di- ortho-substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose–anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153–treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153–treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10–16, 16–64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Roux-en-Y gastric bypass (RYGB) produces rapid and dramatic weight loss in very heavy obese patients. Up to 20% cannot sustain their weight loss beyond 2 to 3 y after surgery. Methods: To identify putative etiologic factors producing post-RYGB weight regain, a literature survey of metabolic changes in very obese and a review of our diet-induced obese RYGB rat model data was done. Results: Weight regain suggests an imbalance in physiologic mechanisms regulating appetite and metabolic rate. Weight regain occurred in 25% of our rats, produced by return to presurgical energy intake levels. The 75% of rats that sustained weight loss secreted a significantly larger amount of peptide YY (PYY) while suppressing leptin secretion; those that failed were unable to develop or sustain a sufficiently large plasma PYY:leptin ratio. Metabolic consequences of this failure included reversal of initial postsurgical increases in peripheral fatty acid oxidation, anorexigenic activity in the hypothalamic arcuate nucleus and paraventricular nucleus, and the expression of uncoupling protein-2 in adipose tissues, and decreases in hepatic lipogenesis, free tri-iodothyronine secretion, expression of orexigenic activity in the arcuate nucleus and paraventricular nucleus, expression of adenosine monophosphate kinase in adipose tissues, skeletal muscle mitochondrial mass, and endocannabinoid content and appetite. Conclusion: Weight regain after RYGB occurs in approximately 20% of patients and constitutes a serious complication. Weight regain–promoting consequences are attributed to a failure to sustain elevated plasma PYY concentrations, indicating that combining RYGB with pharmacologic stimulation of PYY secretion in patients after RYGB who exhibit inadequate PYY concentration may increase long-term success of surgical weight reduction in morbidly obese adults. [Copyright &y& Elsevier]

Abstract: Conjugation reactions are important pathways in the peripheral metabolism of thyroid hormones. Rat cardiac fibroblasts produce and secrete glucuronidated thyroxine (T4G) and 3,3′,5-triiodothyronine (T3G). We here show that, compared to fibroblasts from other anatomical locations, the capacity of cardiofibroblasts to secrete T4G and T3G is highest. H9c2(2-1) myotubes, a model system for cardiomyocytes, take up T4G and T3G at a rate that is 10–15 times higher than that for the unconjugated thyroid hormones. T3 and T4, and their glucuronides, stimulate H9c2(2-1) myoblast-to-myotube differentiation. A substantial β-glucuronidase activity was measured in H9c2(2-1) myotubes, and this confers a deconjugating capacity to these cells, via which native thyroid hormones can be regenerated from glucuronidated precursors. This indicates that the stimulatory effects on myoblast differentiation are exerted by the native hormones. We suggest that glucuronidation represents a mechanism to uncouple local thyroid hormone action in the heart from that in other peripheral tissues and in the systemic circulation. This could represent a mechanism for the local fine-tuning of cardiac thyroid hormone action. [Copyright &y& Elsevier]

Background: Tri-iodothyronine (T3) has been shown to be a hepatic mitogen. We investigated whether exogenous application of T3 improves liver regeneration after 70% partial hepatectomy (PH) and confers a survival advantage after 90% subtotal hepatectomy (SH) in rats and whether this is associated with the stimulation of angiogenesis. Methods: Rats were subjected to PH or SH 10 days after injection of a single dose of T3. Liver body weight ratio (LBR), hepatic proliferation (Ki-67), biochemical markers as well as vascular endothelial growth factor (VEGF) expression were assessed by immunohistochemistry. Gene expression of pathogenic relevant genes was determined by customized cDNA arrays and quantitative RT-PCR. Results: T3-treated rats showed an increased LBR and Ki-67 index after PH and SH, which reached statistical significance compared to placebo-treated rats (p < 0.05). On the transcriptional level, T3-treated rats had an increased expression of VEGF as demonstrated by immunohistochemistry, which was associated with a higher expression of its receptor Flt-1. Conclusions: Exogenous administration of T3 ameliorates liver regeneration after 70% PH and 90% SH, possibly due to stimulation of angiogenesis. Therefore, its clinical use might be of interest due to its excellent general practicability. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]