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Higher Muscle Mass Implies Increased Free-Thyroxine to Free-Triiodothyronine Ratio in Subjects With Overweight and Obesity.
Zupo, R, Castellana, F, Sardone, R, Lampignano, L, Paradiso, S, Giagulli, VA, Triggiani, V, Di Lorenzo, L, Giannelli, G, De Pergola, G
Frontiers in endocrinology. 2020;:565065
Abstract
UNLABELLED Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT04327375.
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Trend of lipid and thyroid function tests in adults without overt thyroid diseases: A cohort from Tehran thyroid study.
Ahi, S, Amouzegar, A, Gharibzadeh, S, Delshad, H, Tohidi, M, Azizi, F
PloS one. 2019;(5):e0216389
Abstract
CONTEXT While the role of overt hypothyroidism in lipid disorders is clear, the association between dyslipidemia and subclinical thyroid diseases remains unclarified. OBJECTIVE To examine lipid trends based on thyroid function over a 10-year period. DESIGN This is a prospective population based cohort study. SETTING General community. PARTICIPANTS 2383 euthyroid participants, as well as those with subclinical thyroid diseases, in all residents of district 13 of Tehran were examined. Subjects who were on levothyroxine, anti-hyperthyroid drugs, and glucocorticoids, those with a history of thyroid surgery or RAI and pregnant women were excluded. MAIN OUTCOME MEASURES Lipid trends in Model 1 were adjusted for age and follow up duration, and in Model 2 gender-specific multivariate adjustments were performed for thyroid status, diabetes mellitus, smoking status, education, BMI, lipid lowering medications, age and follow up duration by using generalized estimating equations. RESULTS In every four years of assessments, there were significant decreases in levels of all lipid parameters (all Ps <0.001) except for HDL-C, in which a decrescendo-crescendo trend was observed. The results did not change after adjusting for thyroid status, consumption of lipid lowering drugs during the follow-up period, or other variables. There were significant decreases in the prevalence of hypercholesterolemia and hypertriglyceridemia (all Ps <0.001) during the follow-up period. CONCLUSION During a 10 year follow-up, decrescendo trends were observed in levels of total cholesterol, triglycerides, which were not be accounted for by the consumption of lipid lowering drugs and thyroid status.
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Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes.
Haddow, JE, Craig, WY, Neveux, LM, Palomaki, GE, Lambert-Messerlian, G, Malone, FD, D'Alton, ME, ,
PloS one. 2016;(2):e0149065
Abstract
Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI 1.37-3.09] (unadjusted); and 1.89 [95% CI 1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related low fT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.
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Association between Hyperhomocysteinemia and Thyroid Hormones in Euthyroid Diabetic Subjects.
Zhang, Y, Wang, Q, Li, Q, Lu, P
BioMed research international. 2015;:196379
Abstract
OBJECTIVES The concept now emerging is that higher thyroid-stimulating hormone (TSH) and lower thyroid hormone levels within the euthyroid range may adversely affect atherosclerosis. The present study aimed to investigate the potential associations between thyroid parameters and hyperhomocysteinaemia in a cohort of euthyroid diabetic subjects. MATERIAL AND METHODS Two hundred and seventy-three euthyroid diabetic subjects (167 males and 106 females) were consecutively recruited in this cross-sectional study. Clinical and biomedical data was collected. RESULTS TSH level was higher in females than males. Compared to normal-homocysteine group, hyperhomocysteinaemia group was more likely to be elderly, males, with longer diabetes history, and with lower diastolic blood pressure. Free thyroxine (FT4) level was lower in hyperhomocysteinaemia group than in normal-homocysteine group; however, it was not statistically significant. Adjusted for age, sex, body mass index, duration of diabetes, blood pressure, fasting glucose, total cholesterol, and triglyceride in logistic regression analyses, hyperhomocysteinaemia was significantly correlated with FT4 (P = 0.021). No significant association was found with TSH or free triiodothyronine. When analyzed in subjects with TSH < 2.5 uIU/mL separately, we got similar results. CONCLUSIONS In conclusion, we identified a relation between hyperhomocysteinemia and FT4 in a group of euthyroid diabetic patients.
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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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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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The dynamic pituitary response to escalating-dose TRH stimulation test in hypothyroid patients treated with liothyronine or levothyroxine replacement therapy.
Yavuz, S, Linderman, JD, Smith, S, Zhao, X, Pucino, F, Celi, FS
The Journal of clinical endocrinology and metabolism. 2013;(5):E862-6
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CONTEXT A recent trial showed that 1:3 μg:μg liothyronine (L-T3) substitution for levothyroxine (L-T4) achieving near-identical TSH levels resulted in a significant decrease in weight and cholesterol levels with no appreciable changes in cardiovascular parameters, suggesting a differential peripheral response to the therapy. OBJECTIVE We characterized the pituitary-thyroid axis in hypothyroid patients receiving equivalent doses of L-T3 or L-T4 by escalating-dose TRH stimulation test. DESIGN A secondary analysis of a L-T3 vs L-T4 therapy trial was performed. SETTING The study was conducted at the National Institutes of Health. PATIENTS Thirteen patients were studied. INTERVENTIONS Escalating-dose (5, 15, and 200 μg) TRH stimulation test on both treatment arms. MAIN OUTCOME MEASURES Study outcomes were peak serum TSH concentration (Cmax), time to peak TSH concentration (Tmax), area under the curve from 0 to 60 minutes (AUC₀₋₆₀) after TRH injection. RESULTS Thirteen patients aged 51.2 ± 8.29 years completed escalating-dose TRH stimulation test. No significant difference between L-T3 and L-T4 treatments was observed in TSH Cmax or area under the curve. L-T4 resulted in a small but significantly shorter Tmax compared to L-T3 (3.5 ± 0.73 min on 200 μg TRH dose, P < .03). In addition, 5 μg TRH dose compared to 200 μg resulted in a shorter Tmax on both treatment arms (6.9 ± 0.59 min L-T3, 4 ± 0.3 min L-T4; P = .0002). CONCLUSIONS The assessment of the dynamic pituitary response to escalating doses of TRH confirms that substitution of L-T3 for L-T4 on a 1:3 ratio achieves a near-identical degree of pituitary euthyroidism. Furthermore, the data suggest that lower doses of TRH might provide clinically relevant information of thyrotroph function, particularly when investigating partial pituitary insufficiency states.
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Serum resistin and high sensitive CRP levels in patients with subclinical hypothyroidism before and after L-thyroxine therapy.
Aksoy, DY, Cinar, N, Harmanci, A, Karakaya, J, Yildiz, BO, Usman, A, Bayraktar, M
Medical science monitor : international medical journal of experimental and clinical research. 2013;:210-5
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BACKGROUND Subclinical hypothyroidism (SH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels. Resistin is secreted from adipose tissue and is reported to be associated with insulin resistance and/or inflammation. High sensitive CRP (hs-CRP) is a reliable marker of inflammation. Data related to levels of resistin and hs-CRP in SH and the effect of L-thyroxine treatment on those is limited. We aimed to determine the levels of resistin and hs-CRP in women with SH, and potential effects of L-thyroxine therapy on those levels. MATERIAL AND METHODS Thirty-six patients with SH and 27 age- and BMI-matched healthy control women were included. Waist circumference (Wc), waist-to-hip ratio (WHR), resting energy expenditure (REE), fat mass (FM) and lean mass (LM), TSH, free T4 (fT4), free T3 (fT3), total cholesterol (TC), triglycerides (TG), and HDL- and LDL-cholesterol were determined in all participants. Patients received L-thyroxine treatment for 6 months, after which all measurements were repeated. Resistin and hs-CRP levels were studied from frozen samples after the completion of the study. RESULTS The 2 groups had similar values for Wc, WHR, FM, LM, TC, TG, HDL-C, LDL-C, resistin, and hs-CRP at the beginning. fT4 were higher, whereas TSH was lower in the control group. Resistin and hs-CRP levels did not change after treatment. hs-CRP correlated with BMI and FM before and after treatment. CONCLUSIONS Our results suggest that achievement of euthyroid status by replacement therapy did not change resistin or hs-CRP levels in women with SH. hs-CRP correlated with parameters of obesity, which emphasizes the role of body weight in inflammation.
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Effects of selenomethionine supplementation on selenium status and thyroid hormone concentrations in healthy adults.
Combs, GF, Midthune, DN, Patterson, KY, Canfield, WK, Hill, AD, Levander, OA, Taylor, PR, Moler, JE, Patterson, BH
The American journal of clinical nutrition. 2009;(6):1808-14
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BACKGROUND Selenium, a potential cancer prevention agent currently being tested against prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), plays an integral role in thyroid metabolism. The effects of long-term selenium supplementation on thyroid hormone concentrations are unknown. OBJECTIVE The objective was to investigate the effects of long-term selenium supplementation on thyroid hormone concentrations. DESIGN Twenty-eight healthy adults took 200 microg selenomethionine/d for 28 mo. The thyroid hormones triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) were measured in plasma for 4 mo before supplementation and quarterly during supplementation. The assay methods were changed midstudy; the results of the 2 methods were not comparable. Therefore, one analysis was conducted based on the results of the first method, and a second analysis was based on all of the data, adjusted for the change. Serial data collection permitted a test for trends rather than simply a difference between initial and final values. RESULTS By 9 mo, mean (+/-SEM) plasma selenium concentrations had increased from 1.78 +/- 0.07 micromol/L at baseline to 2.85 +/- 0.11 micromol/L for men and from 1.64 +/- 0.04 to 3.32 +/- 0.1.2 micromol/L for women. T3 concentrations in men increased 5% per year (P = 0.01). T4 and TSH concentrations were unchanged. CONCLUSIONS Selenium supplementation produced no clinically significant changes in thyroid hormone concentrations. A small but statistically significant increase in T3 concentrations was noted in men, with no corresponding decreases in TSH. A subset of SELECT subjects might be monitored periodically for changes during long-term selenium supplementation.
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Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis.
Centanni, M, Gargano, L, Canettieri, G, Viceconti, N, Franchi, A, Delle Fave, G, Annibale, B
The New England journal of medicine. 2006;(17):1787-95
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BACKGROUND Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. We determined whether there is an increased need for thyroxine in patients with euthyroid multinodular goiter and impaired secretion of gastric acid. METHODS We assessed the dose of thyroxine required to obtain a low level of thyrotropin (0.05 to 0.20 mU per liter) in 248 patients with multinodular goiter. Of these 248 patients, 53 also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goiter and no gastric disorders. In addition, variation in the level of serum thyrotropin was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. RESULTS The daily requirement of thyroxine was higher (by 22 to 34 percent) in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions than in the reference group. In prospective studies, the occurrence of H. pylori infection in the 11 patients treated with thyroxine led to an increase in the level of serum thyrotropin (P=0.002), an effect that was nearly reversed on eradication of H. pylori infection. In a similar way, omeprazole treatment was associated with an increase in the level of serum thyrotropin in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37 percent. CONCLUSIONS Patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyroxine.
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Lack of a relation between human neonatal thyroxine and pediatric neurobehavioral disorders.
Soldin, OP, Lai, S, Lamm, SH, Mosee, S
Thyroid : official journal of the American Thyroid Association. 2003;(2):193-8
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The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. It has been hypothesized that neurobehavioral disabilities of childhood, such as attention deficit hyperactivity disorder (ADHD), learning disorders, and autism can be attributed to fetal thyroidal endocrine disruption in utero. To determine whether there is an association between neonatal thyroid status and a subsequent diagnosis of a neurobehavioral disability, neonatal thyroxine (T(4)) levels have been used as the indicator of the presence of intrauterine thyroidal dysfunction. Neonatal T(4) levels were obtained from the neonatal hypothyroidism screening program. All cases were diagnosed at medical school diagnostic clinics, the diagnostic categories being ADHD, autism spectrum disorder, behavioral disorder, cognitive disorder, developmental delay, emotional disorder, learning disability, and speech/language disorder. Conditional logistic regression analysis was performed for each clinical condition. Odds ratios for the conditions ranged from 0.92 to 1.13 with p values ranging between 0.19 and 0.84. No significant differences were detected between neonatal T(4) values of the cases and the controls for any of the neurobehavioral conditions. All neonatal T(4) values were within normal ranges. The data provide no evidence to suggest that intrauterine thyroid status as reflected by the neonatal T(4) values had an impact on the neurologic disorders diagnosed in childhood.