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A prospective, observational clinical trial on the impact of COVID-19-related national lockdown on thyroid hormone in young males.
Brigante, G, Spaggiari, G, Rossi, B, Granata, A, Simoni, M, Santi, D
Scientific reports. 2021;(1):7075
Abstract
Trying to manage the dramatic coronavirus disease 2019 (COVID-19) infection spread, many countries imposed national lockdown, radically changing the routinely life of humans worldwide. We hypothesized that both the pandemic per se and the consequent socio-psychological sequelae could constitute stressors for Italian population, potentially affecting the endocrine system. This study was designed to describe the effect of lockdown-related stress on the hypothalamic-pituitary-thyroid (HPT) axis in a cohort of young men. A prospective, observational clinical trial was carried out, including patients attending the male infertility outpatient clinic before and after the national lockdown for COVID-19 pandemic. The study provided a baseline visit performed before and a follow-up visit after the lockdown in 2020. During the follow-up visit, hormonal measurements, lifestyle habits and work management were recorded. Thirty-one male subjects were enrolled (mean age: 31.6 ± 6.0 years). TSH significantly decreased after lockdown (p = 0.015), whereas no significant changes were observed in the testosterone, luteinising hormone, follicle-stimulating hormone, estradiol and prolactin serum levels. No patient showed TSH serum levels above or below reference ranges, neither before nor after lockdown. Interestingly, TSH variation after lockdown was dependent on the working habit change during lockdown (p = 0.042). We described for the first time a TSH reduction after a stressful event in a prospective way, evaluating the HPT axis in the same population, before and after the national lockdown. This result reinforces the possible interconnection between psychological consequences of a stressful event and the endocrine regulation.
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2.
Metabolomic profile in hyperthyroid patients before and after antithyroid drug treatment: Correlation with thyroid hormone and TSH concentration.
Piras, C, Arisci, N, Poddighe, S, Liggi, S, Mariotti, S, Atzori, L
The international journal of biochemistry & cell biology. 2017;:119-128
Abstract
Hyperthyroidism (HT) is characterized by an intense metabolic impact which affects the lipid, carbohydrate and amino acids metabolism, with increased resting energy expenditure and thermogenesis. Metabolomics is a new comprehensive technique that allows to capture an instant metabolic picture of an organism, reflecting peculiar molecular and pathophysiological states. The aim of the present prospective study was to identify a distinct metabolomic profile in HT patients using 1H NMR spectroscopy before and after antithyroid drug treatment. This prospective study included 15 patients (10 female, 5 male) who were newly diagnosed hyperthyroidism. A nuclear magnetic resonance (1H NMR) based analysis was performed on plasma samples from the same patients at diagnosis (HypT0) and when they achieved euthyroidism (HypT1). The case groups were compared with a control group of 26 healthy volunteers (C). Multivariate statistical analysis was performed with Partial Least Squares-Discriminant Analysis (PLS-DA). PLS-DA identified a distinct metabolic profile between C and untreated hyperthyroid patients (R2X 0.638, R2Y 0.932, Q2 0.783). Interestingly, a significant difference was also found between C and euthyroid patients after treatment (R2X 0.510, R2Y 0.838, Q2 0.607), while similar cluster emerged comparing HypT0vs HypT1 patients. This study shows that metabolomic profile is deeply influenced by hyperthyroidism and this alteration persists after normalization of thyrotropin (TSH) and free thyroid hormone (FT3, FT4) concentration. This suggests that TSH, FT3 and FT4 assays may not be insufficient to detect long lasting peripheral effects of the thyroid hormones action. Further studies are needed to clarify whether and to what extent the evaluation of metabolomics profile may provide relevant information in the clinical management of hyperthyroidism.
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Intake of Phthalate-tainted Foods and Serum Thyroid Hormones in Taiwanese Children and Adolescents.
Tsai, HJ, Wu, CF, Tsai, YC, Huang, PC, Chen, ML, Wang, SL, Chen, BH, Chen, CC, Wu, WC, Hsu, PS, et al
Scientific reports. 2016;:30589
Abstract
On April-May, 2011, phthalates, mainly Di-(2-ethylhexyl) phthalate (DEHP), were deliberately added to a variety of foodstuff as a substitute emulsifier in Taiwan. This study investigated the relationship between DEHP-tainted foodstuffs exposure and thyroid function in possibly affected children and adolescents. Two hundred fifty participants <18 years possibly exposed to DEHP were enrolled in this study between August 2012 and January 2013. Questionnaires were used to collect details on their past exposure to DEHP-tainted food items. Blood and urine samples were collected for biochemical workups to measure current exposure derived from three urinary DEHP metabolites using a creatinine excretion-based model. More than half of 250 participants were estimated to be exposed to DEHP-tainted foods found to exceed the recommend tolerable daily intake of DEHP established by the European Food Safety Authority (<50 μg/kg/day). The median daily DEHP intake (DDI) among those 250 participants was 46.52 μg/kg/day after multiple imputation. This value was ~10-fold higher than the current median DEHP intake (4.46 μg/kg/day, n = 240). Neither past nor current DEHP exposure intensity was significantly associated with serum thyroid profiles. Future studies may want to follow the long-term health effects of this food scandal in affected children and adolescents.
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4.
The feasibility of low-dose oral lithium therapy and its effect on thyroidal radioiodine uptake, retention, and hormonal parameters in various subcategories of hyperthyroid patients: a pilot study.
Chouhan, A, Abhyankar, A, Basu, S
Nuclear medicine communications. 2016;(1):74-8
Abstract
BACKGROUND Radioactive iodine (I) (RAI) is used widely for the treatment of hyperthyroidism either as a first-line treatment or following relapse after antithyroid drug treatment. Intrathyroidal retention of RAI is considered an important determinant of its effectiveness, which is believed to be prolonged by lithium. AIMS AND OBJECTIVES To study the impact of low-dose oral lithium therapy on RAI uptake and retention parameters in different subgroups of hyperthyroidism patients, and thus explore its potential role in enhancing the therapeutic efficacy of RAI in these groups of patients. MATERIALS AND METHODS A total of 28 patients (age range=18-70 years) who were being considered for RAI therapy were included in this prospective pilot study. The patients were divided into two groups: (i) those who had not received any RAI therapy before were included in 'group I' (n=22), whereas (ii) 'group II' (n=6) included patients who were found to be persistently hyperthyroid on biochemical and clinical follow-up despite previous RAI therapy for hyperthyroidism. Patients in group I were further divided into four subgroups on the basis of the underlying etiopathology: (a) subgroup Ia - diffuse toxic goiter (n=15), (b) subgroup Ib - autonomous functioning module (n=2), (c) subgroup Ic - toxic multinodular goiter (n=4), and (d) subgroup Id - nontoxic multinodular goiter (n=1) on the basis of scintigraphic and clinical findings. All patients first underwent 25 μCi I uptake estimation at 2, 24, and 48 h and values thus obtained were considered the baseline for further evaluation. After biochemical assessment of normal renal and liver functions, patients received 900 mg lithium per day in three divided doses orally, and on the fourth day after starting tab lithium, the serum lithium level was estimated with continued lithium administration. On the fifth, sixth, and seventh day, patients underwent lithium-primed 25 μCi I uptake estimation at 2, 24, and 48 h. Retention index (RI) was calculated using the formula [RI=(48 h uptake-24 h uptake)/24 h uptake×100]. A day after completion of uptake study, that is, on the third day from diagnostic (25 μCi I) RAI administration, patients received a fixed 5 mCi therapeutic RAI dose after their suitability for the same was ascertained using clinical, biochemical, and scintigraphic findings as the criteria. Lithium administration was stopped 5 days after therapy. RESULTS Lithium priming resulted in a significantly reduced serum FT4 level in subgroup Ia (diffuse goiter) of group I. Similarly, lithium priming resulted in a statistically significant increase in the radioiodine RI in subgroup Ia. Lithium priming resulted in increased retention of radioiodine and reduced serum FT4 level in the rest of the study population also, but the difference was not statistically significant (likely because of fewer patients in these subgroups). The low-dose lithium priming regimen used in the present study was found to be feasible and safe. The mean serum lithium concentration was 0.6 mEq/l with the dose protocol administered and hence was considered safe. Only one patient had achieved a level of 1.5 mEq/l, without any obvious side effects, and it was clinically uneventful. One patient experienced headache necessitating dose reduction. CONCLUSION The results of this study, carried out in different groups of patients with hyperthyroidism, suggested that a short course of lithium is safe and could be beneficial for hyperthyroid patients considered for RAI therapy as it increased the RAI retention in thyroid, and thus had the potential to increase the effect of RAI therapy. Alternatively, it is proposed that lithium priming could help reduce the dose of RAI administered without compromising on therapeutic efficacy, with possible potential implications for cost reduction, radiation safety precautions, and lowered radiation dose to nontarget organs.
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Relationship of urinary phthalate metabolites with serum thyroid hormones in pregnant women and their newborns: a prospective birth cohort in Taiwan.
Kuo, FC, Su, SW, Wu, CF, Huang, MC, Shiea, J, Chen, BH, Chen, YL, Wu, MT
PloS one. 2015;(6):e0123884
Abstract
BACKGROUND The purpose of this study was to examine the relationship of phthalates exposure with thyroid function in pregnant women and their newborns. METHODS One hundred and forty-eight Taiwanese maternal and infant pairs were recruited from E-Da hospital in southern Taiwan between 2009 and 2010 for analysis. One-spot urine samples and blood samples in the third trimester of pregnant women and their cord blood samples at delivery were collected. Nine phthalate metabolites in urine were determined by triple quadrupole liquid chromatography tandem mass spectrometry, whereas serum from pregnant women and their cord blood were used to measure thyroid profiles (thyroid-stimulating hormone [TSH], thyroxine, free thyroxine, and triiodothyronine) by radioimmunoassay. RESULTS Median levels of urinary mono-n-butyl phthalate, mono-ethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate (μg/g creatinine) were the three highest phthalate metabolites, which were 37.81, 34.51, and 21.73, respectively. Using Bonferroni correction at a significance of < 0.006, we found that urinary mono-benzyl phthalate (MBzP) levels were significantly and negatively associated with serum TSH in cord blood (β = -2.644, p = 0.003). CONCLUSIONS Maternal urinary MBzP, of which the parental compound is butylbenzyl phthalate, may affect TSH activity in newborns. The alteration of thyroid homeostasis by certain phthalates in the early life, a critical period for neurodevelopment, is an urgent concern.
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Plasma Selenium Levels in First Trimester Pregnant Women with Hyperthyroidism and the Relationship with Thyroid Hormone Status.
Arikan, TA
Biological trace element research. 2015;(2):194-9
Abstract
The thyroid gland has the highest selenium (Se) concentration per unit weight among all tissues. The aims of the present study were to evaluate the Se levels in the plasma of hyperthyroidic pregnant women and to investigate the association between maternal plasma Se concentrations and thyroid hormone levels. The study population consisted of 107 pregnant women, 70 healthy pregnant women (group 1) and 37 pregnant women with hyperthyroidism (group 2). The plasma free triiodothyronine (fT3) and free thyroxine (fT4) levels were significantly higher, and the plasma thyroid-stimulating hormone (TSH) and Se levels were significantly lower in group 2 than in group 1 (p < 0.05). A correlation analysis showed a positive correlation between Se and fT4 in group 1 and with TSH in group 2 (p < 0.05). Decreased maternal serum antioxidant trace element Se in hyperthyroidic pregnant women compared with normal pregnant women supported the hypothesis that hyperthyroidism was associated with decreased antioxidant response.
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Thyroid function and metabolic risk factors in obese youth. Changes during follow-up: a preventive mechanism?
Bouglé, D, Morello, R, Brouard, J
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2014;(9):548-52
Abstract
OBJECTIVES High TSH levels often observed in overweight subjects are associated with metabolic risk. Thyroid hormones which are involved in fat and carbohydrates metabolism are more rarely studied; their blood levels were measured to more precisely explain the relationships between thyroid function and obesity, in healthy overweight youth. This correlation was studied at baseline and during follow-up of some patients. MATERIALS/METHODS Data collected were BMI and BMI z score, thyroid hormones (TSH, fT4, fT3), fasting blood glucose, HOMA-IR, lipids (triglycerides, HDL and LDL cholesterol), transaminase activity, fibrinogen, leptin, IGF-I; body composition (biphotonic absorptiometry). Data collected in a sample of the group after 6-18 months of medical intervention could also be studied. RESULTS At baseline, 13% of the 528 obese subjects (55% girls; 11.3±2.4 years, range 4.1-17.9; BMI z score: 5.4±2.4) had TSH>4mUI/l; fT3 levels were associated with age and transaminase activity; using multivariate regression analysis, with z-score and age as covariates, fT4 showed correlations with TSH, insulin, HOMA IR, blood lipids, and fibrinogen. No correlations were found with leptin, iodine excretion, IGF-I.In 79 patients followed for 52±15 wk (45% girls; age range 8-18.3 years), univariate regression showed a positive correlation between changes in TSH and HOMA-IR, and between changes in fT4 and HDL. Multivariate regression analysis with z score as covariate showed that baseline TSH was associated with negative changes in HOMA-IR. CONCLUSIONS Increased TSH may be predictive of a decrease in insulin resistance, it should be measured with thyroid hormones; fT4 was associated with a low metabolic risk. Changes in thyroid function could protect against the occurrence of obesity-associated metabolic diseases.
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Elevated serum polybrominated diphenyl ethers and alteration of thyroid hormones in children from Guiyu, China.
Xu, X, Liu, J, Zeng, X, Lu, F, Chen, A, Huo, X
PloS one. 2014;(11):e113699
Abstract
Informal electronic waste (e-waste) recycling results in serious environmental pollution of polybrominated diphenyl ethers (PBDEs) and heavy metals. This study explored whether there is an association between PBDEs, heavy metal and key growth- and development-related hormones in children from Guiyu, an e-waste area in southern China. We quantified eight PBDE congeners using gas chromatographic mass spectrometry, lead and cadmium utilizing graphite furnace atomic absorption spectrometry, three thyroids with radioimmunoassay and two types of growth hormones by an enzyme-linked immune-sorbent assay (ELISA) in 162 children, 4 to 6 years old, from Guiyu. In blood, median total PBDE was 189.99 ng/g lipid. Lead and cadmium concentrations in blood averaged 14.53±4.85 µg dL-1 and 0.77±0.35 µg L-1, respectively. Spearman partial correlation analysis illustrated that lead was positively correlated with BDE153 and BDE183. Thyroid-stimulating hormone (TSH) was positively correlated with almost all PBDE congeners and negatively correlated with insulin-like growth factor binding protein-3 (IGFBP-3), whereas free triiodothyronine (FT3) and free thyroxine (FT4) were negatively correlated with BDE154. However, no correlation between the hormones and blood lead or cadmium levels was found in this study. Adjusted multiple linear regression analysis showed that total PBDEs was negatively associated with FT3 and positively associated with TSH. Notably, FT4 was positively correlated with FT3, house functions as a workshop, and father's work involved in e-waste recycling and negatively correlated with vitamin consumptions. TSH was negatively related with FT4, paternal residence time in Guiyu, working hours of mother, and child bean products intake. IGFBP-3 was positively correlated with IGF-1 and house close to an e-waste dump. These results suggest that elevated PBDEs and heavy metals related to e-waste in Guiyu may be important risk factors for hormone alterations in children.
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Moderate weight loss is sufficient to affect thyroid hormone homeostasis and inhibit its peripheral conversion.
Agnihothri, RV, Courville, AB, Linderman, JD, Smith, S, Brychta, R, Remaley, A, Chen, KY, Simchowitz, L, Celi, FS
Thyroid : official journal of the American Thyroid Association. 2014;(1):19-26
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Abstract
BACKGROUND Thyroid hormones are important determinants of energy expenditure, and in rodents, adipose tissue affects thyroid hormone homeostasis via leptin signaling. The relationship between thyroid hormones and nutritional status in humans has been assessed primarily in drastic dietary or bariatric surgery interventions, while limited information is available on serial assessment of this axis during moderate, prolonged dietary restriction. METHODS To evaluate the effects of moderate dietary restriction on thyroid hormone homeostasis, 47 subjects with a body mass index (BMI) of 25-45 kg/m(2) were enrolled in a longitudinal intervention study; 30 nonoverweight volunteers were also enrolled as controls. Overweight and obese subjects underwent a 12-month individualized dietary intervention aimed at achieving a 5-10% weight loss. RESULTS The intervention resulted in a 6.3±0.9 kg (6.5±1.0%) weight loss. At baseline, thyrotropin (TSH) and T3 concentrations correlated significantly with fat mass (R=0.257, p=0.024 and R=0.318, p=0.005, respectively). After weight loss, T3 decreased significantly (from 112.7±3.1 to 101.8±2.6 ng/dL, p<0.001) in the absence of significant changes in TSH or free T4 (fT4). The decrease in serum T3 correlated with the decrease in weight (R=0.294, p<0.001). The T3:fT4 ratio decreased significantly (p=0.02) in individuals who lost >5% body weight. CONCLUSIONS T3 concentration closely correlates with individual nutritional status, and moderate weight loss results in a decrease in T3 with minimal changes in other thyroid hormone homeostasis parameters. The data suggest that a decrease in peripheral conversion of the prohormone T4 into its hormonally active metabolite T3 is at least in part responsible for the observed changes in thyroid hormone homeostasis.
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Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans.
Bonde, Y, Breuer, O, Lütjohann, D, Sjöberg, S, Angelin, B, Rudling, M
Journal of lipid research. 2014;(11):2408-15
Abstract
Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect.