Plasma Free T4 Research Articles

Predictors of Serum TSH in a Healthy Adult Sample of the Lebanese Population

Purpose: Measuring thyroid-stimulating hormone (TSH) is essential for diagnosing and monitoring thyroid diseases. The aim of this study is to determine the factors predicting TSH variability. Materials and Methods: Plasma TSH, free T3 (FT3), total T3 (TT3), free T4 (FT4), anti-peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TgAb) were measured in 301 healthy Lebanese adults (198 women and 103 men) aged 18 to 65 years. Measurements were performed on the Cobas Roche automate. Age, sex, Body Mass Index (BMI), arterial blood pressure and the presence of dyslipidemia were collected from the population. Results: The mean age of the population was 38.98 ± 13.28 years and the mean BMI 25.36 ± kg/m². There was no correlation between TSH and FT4, while a positive correlation was found between TSH and TT3, FT3, TPOAb and TgAb (respectively p <0.001, p=0.002, p<0.0001and p< 0.0001). TSH was not associated with age or gender but was positively correlated with BMI (p=0.053) and systolic blood pressure (p=0.03).In a multiple linear regression analysis, the independent predictors of TSH were FT4, FT3 and TPOAb. In addition, FT4, TPOAb, and dyslipidemia were independently associated with the TSH 97.5th percentile. Conclusion: Our study showed that the main predictors of TSH are FT4, FT3 and TPOAb. This finding supports the role of TSH in enhancing T3 production as well as the main role of TPOAb in predicting the rise in TSH.

Sensitivity and specificity of clinical diagnosis of Graves’ disease and non-Graves’ disorders compared to serum TSH receptor antibodies

Background and objective: Sensitivity and specificity of clinical diagnosis of different hyperthyroid conditions were studied and compared with serum thyrotropin receptor antibodies test, as a standard test for diagnosing Graves' disease. This study aimed to assess the degree of sensitivity and specificity of clinical diagnosis of hyperthyroid conditions compared to the thyrotropin receptor antibodies test, which was selected as a standard test for diagnosis of Graves’ disease in the study. Methods: We studied patients presenting to endocrine outpatient clinics and other outpatient settings in Erbil city, presenting with clinical features of thyrotoxicosis. Serum or plasma thyroid-stimulating hormone, free T4, and thyrotropin receptor antibodies measurements were done for all the patients. Thyroid peroxidase antibodies and thyroid ultrasonography were done for most patients. Radioactive thyroid uptake was available for a limited number of patients. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and accuracy index of clinical diagnosis of the thyrotoxicosis cases were calculated. Results: A total of 150 patients were included in our study, female 102, males 48, mean age 38 (range 16-78) years, pretest diagnosis of (Graves’ disease N=58, and non-Graves’ disease N=92 and posttest diagnosis of (Graves’ disease n= 59 vs. non-Graves’ disease=91). Sensitivity of 74.6%, specificity (84.60%), positive predictive value (75.9%), negative predictive value (83.7%), positive likelihood ratio (4.847), negative likelihood ratio (0.30), and accuracy index (80.7%) of the clinical diagnosis were estimated. Conclusion: The study showed that clinical diagnosis of Graves' disease and non-Graves’ disease disorders, using thorough clinical examination and primary essential investigations, has high sensitivity and specificity index. However, the serum thyrotropin receptor antibodies test remains the standard method in the differential diagnosis of Graves' disease. Other studies are needed to study ultrasound and scintigraphy compared to the thyrotropin receptor antibodies test.

A prospective study on thyroid functions in chronic kidney disease patients: In tertiary care centre

Background and Objectives: Unusual thyroid function tests are frequent in chronic kidney disease patients. The kidneys play an important role in thyroid hormone metabolism by converting T4 to T3 (the active metabolite). Low plasma free T3 in ESRD is a marker of inflammation and endothelial activation, and it has been linked to an increased risk of death from any cause. The present study has been conducted to look for biochemical abnormalities in thyroid function tests in chronic kidney disease, as well as to correlate the severity of CKD and changes in thyroid indices. Methods: In a cross-sectional study, thyroid function tests [TT3, TT4, FT4, TSH] were estimated by CLIA in 60 patients of chronic kidney disease who were in various stages. Symptoms of hypothyroidism, thyroid hormone abnormalities and CKD stage were analyzed using Chi-square test and ANOVA tests. Results: Among the mean age was 48.8 ± 12.2 years, of which 38 were male and 22 females. The mean value of TT3 in CKD stage 3, 4, 5 were 1.01±0.39; 1.05± 0.6; 0.95±1.09 µg/mL respectively. (p= 0.02 Significant). The mean value of TT4 in CKD stage 3, 4, 5 were 6.3± 2.4; 5.5± 1.5; 5.11 ± 1.01 µIU/ml, respectively. (p=0.71 Not significant). Conclusions: Total T3 and total T4 levels were found to decrease progressively as the stage of CKD increased. There was no statistically significant relationship between TT4 and CKD stage. The prevalence of thyroid dysfunction and the stage of chronic kidney disease were found to be significantly related. The severity of renal failure increases the prevalence of thyroid hormone abnormalities; the levels of thyroid profile, i.e. T3, T4, and TSH, decrease as the severity of renal failure increases. Thyroid hormone abnormalities could represent a risk factor for cardiovascular disease and might also be implicated in kidney disease progression.

Maternal selenium deficiency in mice promotes sex-specific changes to urine flow and renal expression of mitochondrial proteins in adult offspring.

Selenium deficiency during pregnancy can impair fetal development and predispose offspring to thyroid dysfunction. Given that key selenoproteins are highly expressed in the kidney and that poor thyroid health can lead to kidney disease, it is likely that kidney function may be impaired in offspring of selenium‐deficient mothers. This study utilized a mouse model of maternal selenium deficiency to investigate kidney protein glycation, mitochondrial adaptations, and urinary excretion in offspring. Female C57BL/6 mice were fed control (>190 µg selenium/kg) or low selenium (<50 µg selenium/kg) diets four weeks prior to mating, throughout gestation, and lactation. At postnatal day (PN) 170, offspring were placed in metabolic cages for 24 hr prior to tissue collection at PN180. Maternal selenium deficiency did not impact selenoprotein antioxidant activity, but increased advanced glycation end products in female kidneys. Male offspring had reduced renal Complex II and Complex IV protein levels and lower 24 hr urine flow. Although renal aquaporin 2 (Aqp2) and arginine vasopressin receptor 2 (Avpr2) mRNA were not altered by maternal selenium deficiency, a correlation between urine flow and plasma free T4 concentrations in male but not female offspring suggests that programed thyroid dysfunction may be mediating impaired urine flow. This study demonstrates that maternal selenium deficiency can lead to long‐term deficits in kidney parameters that may be secondary to impaired thyroid dysfunction. Considering the significant burden of renal dysfunction as a comorbidity to metabolic diseases, improving maternal selenium intake in pregnancy may be one simple measure to prevent lifelong disease.

A Study of thyroid dysfunction in chronic kidney disease Patients in a tertiary Care Hospital - A Prospective study

Background: Abnormal thyroid function tests are frequently observed in patients of chronic kidney disease. Kidneys plays a significant role in thyroid hormone metabolism by conversion of T4 to T3 (the active metabolite). Low plasma free T3 in ESRD is a marker of the inflammation and endothelial activation and is known to predict all cause mortality.Aim & objective of the study: The present study was done look for the biochemical abnormalities of thyroid function tests in chronic Kidney Disease and to correlate the severity of CKD and alterations of thyroid indices.Methods: In a cross-sectional study, thyroid function test [TT3, TT4, FT3, FT4, TSH] were estimated by CLIA in 60 patients of chronic Kidney Disease who were in various stages. Symptoms of hypothyroidism, thyroid hormone abnormalities and chronic renal failure patients with different CKD stage were analyzed using Chi square test and ANOVA tests.Results: Among the mean age was 54.2 ± 12.5 years of which 45 were male and 15 females. The mean value of TT3 in CRF stage 3, 4, 5 were 110.6 ± 17.8; 94.9 ± 29.4; 77.9 ± 29.5 ng/mL respectively (p= 0.02 Significant). The mean value of FT3 in CRF stage 3, 4, 5 were 2.52 ± 0.31; 2.08 ± 0.54; 1.89 ± 0.61 pg/mL respectively (p=0.03 Significant). The mean value of TT4 in CRF stage 3, 4, 5 were 6.47 ± 0.67; 5.12 ± 1.16; 4.41 ± 1.52 µg/dL respectively (p=0.0 significant). The mean value of FT3 in CRF stage 3, 4, 5 were 1.19 ± 0.15; 1.02 ± 0.22; 0.98 ± 0.21 pg/dL respectively (p=0.07 Not significant).Conclusions: Total T3, total T4 and free T3 were found to be progressively decreased as stage of CKD increased. There was no significant correlation between FT4 and CKD stage. There was a significant correlation between the prevalence of thyroid dysfunction and the stage of chronic kidney disease. Higher the degree of renal insufficiency, the higher was the prevalence of thyroid hormone abnormalities, the levels of thyroid profile i.e T3, T4 decreases and TSH increases as severity of renal failure increases. Thyroid hormone abnormalities could represent a risk factor for cardiovascular disease and might also be implicated in kidney disease progression.

Association of subclinical hypothyroidism with metabolic syndrome in females of reproductive age

Background and objective: The association of metabolic syndrome and subclinical hypothyroidism is a matter of debate. Both confer an increased risk for cardiovascular disease and type 2 diabetes mellitus, and previous studies showed overlap between features of both conditions. This study aimed to evaluate the association of subclinical hypothyroidism with metabolic syndrome in young women. Methods: This case control study was conducted in the internal medicine consultation department of Rizgary Teaching Hospital Erbil, Iraq, from May 2017 to May 2018. Sixty eight consecutive women with the metabolic syndrome as per the Harmonizing definition were compared to 95 age matched women with no metabolic syndrome as a control group. Detailed history and physical examination with blood pressure and waist circumferences recorded and appropriate fasting blood samples were tested for plasma glucose, lipid profile, TSH, free T3, and free T4. Results: Subclinical hypothyroidism was present in 10 (14.7%) of the 68 women with metabolic syndrome and four women (4.2%) of the 95 control group with a significant difference (P = 0.018). Central obesity, hypertriglyceridemia, and low levels of high density lipoprotein were present in 9 (17.3%), 9 (23.1%), and 10 (16.4%) women with subclinical hypothyroidism with a significant difference for each association (P = 0.013, 0.001 and 0.006, respectively). Conclusion: There is a significant association between subclinical hypothyroidism and metabolic syndrome in young women.

Clinical Importance of Free Thyroxine Concentration Decline After Radiotherapy for Pediatric and Adolescent Brain Tumors.

Clinical significance of a decline in free T4 (FT4) concentrations across the reference range in children with brain tumors treated with radiation therapy (RT) is uncertain. To study trends in FT4 in children after RT and risk factors and health outcomes associated with plasma FT4 concentrations. Longitudinal, single-center retrospective cohort study. Low-grade glioma or ependymoma patients (n = 267; age ≤25 years) who received RT (50.4 to 59.4 Gy) at a single institution (1996 to 2016) and followed with serial FT4 measurements. A linear mixed-effects model with a random intercept was used to investigate risk factors for longitudinal changes in FT4 concentrations. A two-stage mixed-effects model examined associations between clinical outcomes and plasma FT4 concentrations. FT4 concentrations declined over time after RT (P < 0.001). Females (P < 0.001) and younger patients (P < 0.001) demonstrated greater declines in FT4 concentrations over time. The rate of weight gain, but not of height loss, increased with a higher FT4 decline rate (P < 0.001). At last follow-up, patients with lower baseline FT4 concentrations had increased risk of glucose disorder (OR, 19.73; P = 0.002) or dyslipidemia (OR, 19.40; P = 0.003) but not high fat mass (P = 0.18). Lower baseline FT4 concentrations were not associated with impaired scores for intelligence, attention, memory, or psychosocial functioning. FT4 concentrations significantly decline in children with brain tumor after RT. Variation and trends in FT4 concentration are associated with physical health outcomes. Future studies should assess whether continuous FT4 concentrations and trends, rather than population-based cut-off values, can distinguish between euthyroid and hypothyroid states.

Determination of thyroid hormones in human hair with online SPE LC–MS/MS: Analytical protocol and application in study of burnout

Thyroid hormones (THs) play a key role within the endocrine system. Incorporated biomarkers in hair can reflect endogenous excretion patterns over several months. We present an online solid phase extraction-liquid chromatography-mass spectrometry (online SPE-LC–MS/MS) method for quantification of THs in human hair and test it in the volunteers suffering from different severity of burnout symptom. THs were extracted from 7.5 mg hair by methanol incubation. Extracts were analyzed with LC–MS/MS in positive electrospray ionization mode. Burnout symptoms were assessed with the Maslach Burnout Inventory-General Survey (MBI-GS). THs levels were determined in 208 hair samples from adults and related to individual MBI-GS score. Intra- and inter-day coefficients of variance were between 3.1% and 10.2%. The recoveries of this method were between 88.5% and 102.1%. Hair T4 levels correlated significantly with total and free T4 in plasma. Participants with high degree of burnout had significantly higher hair T4 levels and lower T3/T4 ratio compared to those with no or moderate degree of burnout. A trend towards higher hair T3 levels was observed in subjects with high burnout score. Hair T4 levels showed a significant positive relationship with MBI-GS score, whereas no significant correlation emerged for hair T3 levels. The negative correlation between T3/T4 ratio and MBI-GS score was also significant. We have developed an online SPE-LC–MS/MS method for measurement of THs in human hair, allowing high analytical specificity and sensitivity. The novel finding of hair THs levels from individuals suffering from chronic stress in burnout underscores the relevance of this method for medical and psychological research.

Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period.

Background Polychlorinated biphenyls (PCBs) are persistent organic chemicals that exert neurotoxic and endocrine disrupting effects. The aims of this study were to examine the effects of prenatal Aroclor 1254 (PCBs mixture) exposure on central nervous system tissues DNA and to evaluate the effects of curcumin. Methods Rat pups were assigned to three groups: [Group 1], Aroclor 1254 administrated group; [Group 2], Aroclor 1254 and curcumin administrated group; and [Group 3], control group. Plasma, cerebrum, cerebellum, pons and medulla oblongata tissue homogenates 8-hydroxy-2'-deoxyguanosine [8-(OH)DG] levels and plasma freeT4 levels were determined. Global DNA methylation and hydroxymethylation status were determined in cerebrum, cerebellum, pons and medulla oblongata. To this aim, DNA 5-hydroxymethylcytosine and 5-methylcytosine levels were measured, respectively. Results Mean cerebellum and cerebral cortex 5-hydroxymethylcytosine and 5-methylcytosine levels were higher in the control group than in the experimental groups. Mean plasma, cerebellum and cerebral cortex 8-(OH)DG concentrations were higher in Group 1 than the control group. No statistically significant difference was observed between Group 2 and the control group in terms of cerebellum and cerebral cortex 8-(OH)DG concentrations. Histopathological changes were also observed in the cerebral cortex and cerebellum of rat pups exposed to Aroclor 1254. PCBs exposure changes both DNA methylation and hypomethylation status and induces cerebellar and cerebral cortex DNA damage in the prenatal period. Exogenous curcumin may have protective effect on PCBs-induced DNA damage in cerebellum and cerebral cortex.

Prenatal Exposure to Polychlorinated Biphenyls and Mercury Are Associated with Insulin-Like Growth Factor 1 and Thyroid-Stimulating Hormone in Cord Plasma

Impact on maternal endocrine system during pregnancy may also affect growth and development of a fetus. Certain toxic elements and polychlorinated biphenyls (PCBs) are known to disturbe human endocrine system. In our previous study, we showed that birth weight were affected by prenatal PCBs and methylmercury exposure. In this study, we used the data from the Tohoku Study of Child Development in Japan. The objective of the study was to evaluate the effect of prenatal exposure to methylmercury, arsenic, cadmium, lead, and PCBs on insulin-like growth factor 1 (IGF-1) and thyroid related hormones (TSH, T3, freeT3, T4 and freeT4) in cord blood. Those factros are considered to be associated with fetal growth. Elements except for mercury were analyzed by an inductivity coupled plasma mass spectrometry. Mercury levels were measured using a cold vapor atomic absorption spectrometer. IGF-1 and insulin-like growth factor binding protein 1 (IGFBP1) were detemined by an enzyme-linked immunosorbent assay (ELISA). Thyroid related hormones were assessed by an electrochemiluminescence immunoassay. The data were examined by Pearson&amp;#8217;s correlation and multiple regression analyses. The IGF-1 in cord plasma was negatively associated with PCB concentrations in cord blood, especially with tri-, tetra-, penta-, hexa- and hepta-chlorobiphenyls. Cord plasma free T4 was negatively associated with mercury concentrations in cord blood. This study indicated PCBs and mercury could affect birth weight through altering the IGF1 and T4 mechanism. Further studies are necessary to investigate the effect of decrease in IGF-1 and thyroid hormones on birth weight.

Free Thyroxin T4 in Early Pregnancy and Risk of Gestational Diabetes Mellitus

Our study aims to evaluate the correlations between thyroid hormone levels in early pregnancy and the incidence of gestational diabetes mellitus (GDM). A total of 2112 pregnant women were recruited from our hospital, Guangzhou, China, from June 2016 to June 2017. Fasting plasma glucose (FPG), Thyrotropin (TSH), free T4 (FT4), and thyroid peroxydase antibody (TPO-Ab) were measured at 9-14 weeks’ gestation (first trimester) and 75-g OGTT (24-28 weeks’ gestation) were performed in each subject. Diagnosis of GDM was made by the IADPSG guideline (2010). All subjects had median age of 30 years (interquartile range:27-34 years). Two hundred and twenty four subjects (10.6%) were diagnosed as GDM. GDM women had older age and higher FPG(P&amp;lt;0.05). The level of free T4 (FT4) in GDM women was similar than that in non-GDM women (16.45±3.42pmol/L and 16.80±3.46 pmol/L, respectively, P=0.152). No difference was observed in the levels of TSH and TPO-Ab between GDM women and non-GDM women (all P&amp;gt;0.05). The prevalence of GDM in subjects among different quartiles of FT4 levels were 11.9%, 11.5%, 9.5% and 9.5% from the first to fourth quartile (P=0.429,χ2=2.766). By using logistic regression, FT4 in the first trimester odds ratios for GDM were not significant: OR 0.970 [95% CI 0.931-1.011] (unadjusted) and 0.960[95% CI 0.920-1.002] (adjusted for age, TSH, TPO-Ab). Our results indicated the level of FT4 in the first trimester may not have strong correlation with incidence of GDM. Disclosure P. Li: None. S. Lin: None. L. Li: None. L. Ouyang: None. J. Fan: None.

Norepinephrine and T4 Are Predictors of Fat Mass Gain in Humans With Cold-Induced Brown Adipose Tissue Activation.

In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16°C for 2 hours to quantify CIBA. CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry. Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = -0.65, P = 0.03; and r = -0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (β = -3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (β = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and β = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively). Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

Effect of Laparoscopic Ovarian Drilling on Anti-Müllerian Hormone Level among Women with Polycystic Ovary Syndrome : A Retrospective Study

Background: Thyroid dysfunction is associated with increased cardiovascular morbidity and mortality. Hyperthyroidism increases the susceptibility of the heart to ischemia reperfusion injury. Moreover, myocardial ischemia can be further worsened by increased cardiac workload and oxygen demand elicited by the excess thyroid hormones. Objectives: Investigating the cardiac dysfunction induced by ischemia-reperfusion (IR) in rats exposed to excess thyroid hormones and role of somatostatin analogue against ischemia/reperfusion injury in hyperthyroid rats. Patients and Methods: This study was performed on 24 adult male albino rats of a local strain weighing 140-200 g, allocated into three equal groups: Group I (Control IR group): Euthyroid control group exposed to ischemia-reperfusion. Hearts of this group were isolated and perfused in a Langendorff apparatus. Isolated hearts were subjected to 15 min of stabilization, 20 min of zero-flow global ischemia and 30 min of reperfusion. Group II (Hyperthyroid IR group) were subjected to the same protocol of ischemia reperfusion. Group III (Hyperthyroid IR-OCT group): Hyperthyroid rats were supplemented with the somatostatin analogue, octreotide (OCT), 35 µg/kg subcutaneously, 20 minutes before sacrifice, followed by in-vitro study of cardiac responses to ischemia reperfusion. Blood samples were collected for measurement of plasma free T3, T4 and TSH. Coronary efflux lactate dehydrogenase levels were measured. Also, cardiac tissue malondialdehyde (MDA) levels and tumor necrosis factor alpha (TNF-α) levels were estimated. Results: Hyperthyroid (IR) rats revealed significant elevation in plasma free T3 and T4 with concomitant decrease in TSH levels. A significant reduction in final BW and BW gain were observed with higher absolute weights of left ventricle (LV) and cardiac index compared to the euthyroid controls. Systolic blood pressure (SBP) and mean arterial pressure (MAP) significantly elevated in non-treated hyperthyroid rats with a significant increase in their baseline chronotropic and inotropic activity compared to euthyroid control rats. But after ischemia those rats exhibited significantly higher degree of bradycardia (∆HR) and % change in heart rate (HR) compared to control rats. Moreover, significantly deteriorated post-ischemic recovery of inotropic parameters and significantly higher ∆ changes of these parameters were observed compared to euthyroid controls. These changes were accompanied by significant elevation in coronary efflux LDH levels and both cardiac tissue MDA and TNFα. Meanwhile, octreotide administration to hyperthyroid rats showed improvement of their baseline chronotropic and inotropic parameters as evidenced by the significantly reduced degree of bradycardia as well as significantly lower ∆ change of PT and PT/LV parameters compared to non-treated hyperthyroid rats. Such findings could be ascribed partly to the reduction of oxidative and inflammatory responses to IR as determined by the significantly decreased cardiac tissue MDA and TNFα respectively. Conclusion: Hyperthyroid hearts are less tolerant to ischemia/reperfusion injury with higher susceptibility to oxidative stress as well as overproduction of pro-inflammatory mediators. Thus, pharmacological targets that defend oxidative challenge and confer anti-inflammatory properties, namely octreotide (somatotstatin analogue) are considered to have potential therapeutic effect and may protect against myocardial ischemic damage in hyperthyroidism.

Excess maternal and postnatal thyroxine alters chondrocyte numbers and the composition of the extracellular matrix of growth cartilage in rats

ABSTRACTPurpose/Aim: The aim of this study was to evaluate the effects of excess maternal and postnatal thyroxine on chondrocytes and the extracellular matrix (ECM) of growth cartilage. Materials and Methods: We used 16 adult female Wistar rats divided into two groups: thyroxine treatment and control. From weaning to 40 days of age, offspring of the treated group (n = 8) received L-thyroxine. Plasma free T4 was measured. Histomorphometric analysis was performed on thyroids and femurs of all offspring. Alcian blue histochemical staining and real-time reverse transcription polymerase chain reaction measurements of gene expression levels of Sox9, Runx2, Aggrecan, Col I, Col II, Alkaline phosphatase, Mmp2, Mmp9, and Bmp2 were performed. Data were analyzed for statistical significance by student’s t-test. Results: Excess maternal and postnatal thyroxine reduced the intensity of Alcian blue staining, altered the number of chondrocytes in proliferative and hypertrophic zones in growth cartilage, and reduced the gene expression of Sox9, Mmp2, Mmp9, Col II, and Bmp2 in the growth cartilage of all offspring. Additionally, excess thyroxine altered the gene expression of Runx2, Aggrecan and Col I, and this effect was dependent on age. Conclusions: Excess thyroxine in neonates suppresses chondrocyte proliferation, stimulates chondrocyte hypertrophy and changes the ECM composition by reducing the amount of proteoglycans and glycosaminoglycans (GAGs). Prolonged exposure to excess thyroxine suppresses chondrocyte activity in general, with a severe reduction in the proteoglycan content of cartilage and the expression of gene transcripts essential for endochondral growth and characteristics of the chondrocyte phenotype.

Insulin Plant (Costus pictus) Extract Restores Thyroid Hormone Levels in Experimental Hypothyroidism.

Background:The aim of the present study was to investigate the preventive effect of Costus pictus leaf extract in experimental hypothyroidism.Materials and Methods:Forty male Wistar rats were randomly divided into four groups with ten rats in each group: Control (C), hypothyroid (H), control+extract (C+E), and hypothyroid+extract (H+E). Rats in C group did not receive any intervention throughout the experimental period. The rats in the C+E and H+E groups received pretreatment with C. pictus leaf extract for 4 weeks. Subsequently, for the next 6 weeks, rats in the H group received 0.05% propylthiouracil in drinking water while C+E group received C. pictus leaf extract and H+E group received propyl thiouracil and C. pictus leaf extract.Results:Hypothyroid group rats exhibited dramatic increase in thyroid-stimulating hormone (TSH) levels with concomitant depletion in the levels of thyroid hormones. Treatment with the extract resulted in remarkable improvement in thyroid profile. Extract produced 10.59-fold increase in plasma free T3, 8.65-fold increase in free T4, and 3.59-fold decrease in TSH levels in H+E group in comparison with H group. Treatment with the extract ameliorated hypercholesterolemia, decreased levels of plasma C-reactive protein and tumor necrosis factor alpha, suppressed tissue oxidative stress and prevented hepatic and renal damage caused due to thyroid hormone depletion in the H+E group. Pentacyclic triterpenes alpha and beta amyrins were identified and quantified in the extract.Conclusions:This is the first study to reveal that C. pictus extract has therapeutic potential to restore thyroid hormone levels and prevent the biochemical complications due to thyroid hormone insufficiency in the animal model of experimental hypothyroidism.SUMMARY The preventive effect of Costus pictus leaf extract in experimental hypothyroidism was evaluated in the present study.Hypothyroidism was induced in the experimental animals by giving 0.05% propylthiouracil in drinking water.Hypothyroid rats exhibited dramatic increase in thyroid-stimulating hormone (TSH) levels with concomitant depletion in the levels of thyroid hormones.Treatment with Costus pictus leaf extract in hypothyroid rats significantly improved the thyroid profile. It also ameliorated hypercholesterolemia, decreased the levels of plasma inflammatory markers, suppressed tissue oxidative stress and prevented hepatic and renal damage caused due to thyroid hormone depletion.The possible active principles alpha and beta amyrins were identified and quantified in the extract through LC-MS. Abbreviations Used: APCI: Atmospheric pressure chemical ionization; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; C group: Control group; C+E group: Control+extract group; C. pictus: Costus pictus; CRP: C-reactive protein; DPPH: 2,2-diphenyl-1-picrylhydrazyl; FRAP: Ferric reducing antioxidant power; HDL: High-density lipoprotein; H group: Hypothyroid group; H+E group: Hypothyroid+extract group; LDL: Low-density lipoprotein; LC-MS: Liquid chromatography-mass spectrometry; MDA: Malondialdehyde; PTU: 6-Propyl-2-thiouracil; SRM: Single reaction monitoring; TSH: Thyroid-stimulating hormone; TPTZ: 2,4,6-tri-(2-pyridyl)-5-triazine; TBA: 2-Thiobarbituric acid; TG: Triglyceride; TNFα: Tumor necrosis factor alpha; TAS: Total antioxidant status

Neonatal Pituitary-Thyroid Axis Dysregulation with Combined Thyroid Hormone and Thyrotropin Resistance in Infant with Trisomy 21 and Maternal Subclinical Hypothyroidism

Trisomy 21 is commonly associated with thyroid problems. Although autoimmune hypothyroidism is the commonest thyroid problem in Trisomy 21, infants with this chromosomal disorder are also known to have dysregulated pituitary thyroid axis. This results in elevated thyrotropin (TSH) levels in absence of autoimmunity and structurally normal thyroid gland. The mechanism for this phenomenon is not clearly understood and it is possible that this may be due to genomic imbalance from trisomy of chromosome 21. Some authors have proposed that thyroid hormone resistance (RTH) might be a contributing factor to this. However, the genes coding for TSH receptor and the two proteins known to be implicated in TSH resistance are normal in patients with Trisomy 21. In newborns, transient hyperthyrotropinaemia is considered to be associated with maternal thyroperoxidase (TPO) antibody positivity. We describe a case of term infant with Trisomy 21, who was identified on newborn congenital hypothyroidism screening. The infant had high TSH and raised plasma free T4 (FT4) with clinical signs and symptoms of congenital hypothyroidism. We discuss the management of this case and possible mechanisms contributing to the uncommon presentation.

Excess Maternal Thyroxine Alters the Proliferative Activity and Angiogenic Profile of Growth Cartilage of Rats at Birth and Weaning.

Objective The aim of this study was to unravel the mechanisms by which thyroxine affects skeletal growth by evaluating proliferative activity and angiogenic profile of growth cartilage of neonatal and weanling rats. Methods Sixteen adult Wistar rats were equally divided into 2 groups: control and treated with thyroxine during pregnancy and lactation. The weight, measurement of plasma free T4 and thyroids, femurs' histomorphometric analysis, and proliferative activity and angiogenic profile by immunohistochemical or real-time reverse transcriptase-polymerase chain reaction in growth cartilage was performed. Data were analyzed using Student's t test. Results The free T4 was significantly higher in the treated rats. However, the height of the follicular epithelium of the thyroid in newborns was significantly lower in the treated group. The excess maternal thyroxine significantly reduced the body weight and length of the femur in the offspring but significantly increased the thickness of trabecular bone and changed the height of the zones of the growth plate. Furthermore, excess maternal thyroxine reduced cell proliferation and vascular endothelial growth factor (VEGF) expression in the growth cartilage of newborn and 20-day-old rats ( P < 0.05). There was also a reduction in the immunohistochemical expression of Tie2 in the cartilaginous epiphysis of the newborns and FLK-1 in the articular cartilage of 20-day-old rats. No significant difference was observed in Ang2 expression. Conclusions The excess maternal thyroxine during pregnancy and lactation reduced endochondral bone growth in the progeny and reduced the proliferation rate and VEGF, Flk-1, and Tie2 expression in the cartilage of growing rats without altering the mRNA expression of Ang1 and Ang2.

Hypothalamic-Pituitary Axis Dysfunction in Survivors of Childhood CNS Tumors: Importance of Systematic Follow-Up and Early Endocrine Consultation.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. An 11-year-old male with a history of metastatic tectal plate low-grade glioma who was diagnosed at age 2.8 years transferred his care to the long-term follow-up clinic. He completed treatment with multiagent chemotherapy-carboplatin, vincristine, temozolomide, procarbazine, lomustine, and thioguanine-at age 4.5 years and did not require radiotherapy. At primary diagnosis, he presented with hydrocephalus that required ventriculoperitoneal shunt placement, with a subsequent shunt revision at age 6 years. Residual metastatic tumors in the third and fourth ventricles and in the suprasellar region remained stable for more than 5 years. The patient achieved normal developmental milestones and was not taking medications. He was offered screening for hypothalamic-pituitary axis (HPA) dysfunction because of his suprasellar lesion. His height was at the 25th percentile for chronological age, with decline from the 50th percentile noted during the preceding 18 months ( Fig 1 , point c). Pubertal stage was Tanner 4 for pubic hair and penile size, which contrasted with small testes (4.5 mL). Pubic hair and voice changes were noticed 2 to 3 years before this visit. Plasma testosterone level was consistent with Tanner 4 (255 ng/dL = 8.9 nmol/L). An x-ray of the left hand revealed a notably advanced bone age of 15.5 years. Plasma free T4, thyroid-stimulating hormone (TSH), and 8 am cortisol levels were normal. The patient was referred to the endocrinology clinic where he was diagnosed with growth hormone deficiency and was started on replacement therapy. He reached his final adult height of 144.1 cm at age 13.3 years ( Fig 1 , point d).

Inhaling Benzene, Toluene, Nitrogen Dioxide, and Sulfur Dioxide, Disrupts Thyroid Function in Captive American Kestrels (Falco sparverius).

Research investigating the effects of air contaminants on biota has been limited to date. Captive adult female American kestrels (Falco sparverius) were exposed to a mixture of benzene (0.6 ppm), toluene (1 ppm), nitrogen dioxide (NO2; 2 ppm) and sulfur dioxide (SO2; 5.6 ppm), in a whole-body inhalation chamber. Thyroid axis responses to meet metabolic demands were examined through thyroid histology, plasma thyroxine (T4), and triiodothyronine (T3), and hepatic outer ring deiodination (T4-ORD). Plasma free (F) T3 and T4 were measured at baseline, and at 9 days and 18 days of exposure, whereas total (T) T3 and TT4, thyroid histology and hepatic T4-ORD were determined at the final 18 day exposure. Inhalation of these contaminants significantly suppressed plasma FT4 and TT4, and depleted follicular colloid and increased epithelial cell height at 18 days, and significantly altered the temporal pattern of plasma FT4. Significant histological changes in the follicular colloid:epithelial cell height ratio indicated sustained T4 production and release by the thyroid glands. There was no effect on plasma FT3, TT3, or hepatic T4-ORD. We hypothesize that contaminant-related activation of the hypothalamus-pituitary-thyroid axis in the kestrels increased elimination of plasma T4 through Phase II enzymes. Further research is required to test this hypothesis in wild birds.

Toxic effects of copper sulfate and copper nanoparticles on minerals, enzymes, thyroid hormones and protein fractions of plasma and histopathology in common carp Cyprinus carpio

Differences in toxicological effects of dissolved copper and copper nanoparticles were studied in common carp, Cyprinus carpio. The fish were exposed to 0.25mgL−1 copper as copper sulfate (0.25Cu), 0.25mgL−1 copper as copper oxide nanoparticles (0.25NCu) and 25mgL−1 copper as copper oxide nanoparticles (25NCu) over 14days. Plasma biochemical, enzymatic and hormonal characteristics, and liver and kidney histopathology were examined at the end of the experiment. The results showed that both forms of copper had no significant effects on plasma calcium levels, however, significantly increased plasma phosphorous levels, compared to control group (no added copper). Plasma alanine transaminase (ALT) activity increased in 0.25Cu and 25NCu treatments compared to the control and 0.25NCu treatments. Nanoparticle copper exposure significantly decreased plasma alkaline phosphatase (ALP) activity compared to the control and 0.25Cu treatments. Only copper sulfate exposure caused plasma aspartate transaminase (AST) elevation. Both copper forms increased plasma T4 and free T4 (FT4); however, copper sulfate effect was higher than nanoparticle copper. Copper sulfate exposure increased plasma albumin fraction, whereas, 25mgL−1 copper nanoparticle exposure increased plasma α2-globulin fraction compared to the control. Both copper forms damaged the fish liver and kidney, however, copper sulfate caused more severe damages compared to nanoparticle copper. Overall, except for plasma ALP and α2-globulin fraction, dissolved copper seems to be more toxic than nanoparticle copper in common carp.