70+ recent studies documenting adverse health effects associated with TSH levels within the "normal" or "reference" range.
© 2021 - 2023 PFPC
Compiled by Wendy Small
- A higher TSH level within the normal range has been identified as an independent risk factor of non-alcoholic fatty liver disease (Tahara et al., 2019; Kim et al., 2020; Martínez-Escudé et al., 2021; Fan et al.;, 2022). The prevalence of NAFLD increases steadily with increasing TSH levels.
Adverse Pregnancy Outcome - Pregnancy Loss Rate/Pre-eclampsia/Pre-term Birth, etc.
- A higher TSH level within normal range is associated with preterm birth. In continuous analyses, each 1-SD higher maternal TSH concentration was associated with a higher risk of preterm birth (Korevaar et al., 2019)
- A higher maternal TSH level within normal range is associated with small for gestational age neonates at term (Monen et al., 2014).
- First Trimester TSH levels are an independent risk factor for Adverse Pregnancy Outcome (Barišić et al., 2019; Hernández et al., 2019; Arbib et al., 2017; Negro et al., 2010; Lee et al., 2021; Kianpour et al., 2019; Zhang et al., 2019).
- A higher TSH level within the normal range is associated with unexplained infertility (Orouji et al., 2018). [American Thyroid Association Thyroid and Pregnancy Guidelines recommend checking TSH in all women seeking evaluation for infertility (Alexander et al., 2017).]
- TSH levels within the reference range were linearly and positive correlated with coronary heart disease (CHD) mortality in Norwegian women, but not men (HUNT study; Asvold et al., 2008).
- Lower TSH level within the normal range may be independent predictors of incident coronary heart disease in men, but not women (Onat et al., 2015).
- A higher TSH level within the reference range has been associated with higher blood pressure and adverse serum lipids (Asvold et al., 2013; Boggio et al., 2014).
- A higher TSH level within the reference range has been associated with an increased risk for atherosclerosis (Boggio et al., 2014; Yang et al., 2019).
- TSH positively correlates with inflammation and atherosclerosis in the population (Yang et al., 2019)
- Higher TSH/lower thyroid hormone levels are associated with more cardiovascular risk factors and cardiovascular events and worse metabolic parameters and pregnancy outcomes, whereas lower TSH/higher thyroid hormone levels are associated with reduced bone mineral density and increased fracture risk (Taylor et al., 2013).
- Even subtle variations of serum TSH within the normal range may be potential risk factors for cardiovascular diseases (Chen et al., 2019).
- Serum lipid profiles rise with increasing TSH level within the normal range (Luxia et al., 2020; Chen et al., 2020).
- TSH concentration was found to be an independent predictor of venous thromboembolism (VTE) in addition to gender, D-dimer, C-reactive protein (CRP), and age, among patients with VTE (Kovářová et al., 2015).
- A higher TSH level within the normal range is associated with cardiovascular risk factors in overweight and obese adolescents (Souza et al., 2016).
- TSH levels within the normal range are positively related with Body Mass Index (BMI). TSH has been found to be correlated also with leptin adjusted for BMI (Iacobellis et al., 2005).
- TSH was an independent predictor of circulating irisin (Stratigou et al., 2018).
- A higher TSH level within the normal range is associated with risk of mortality and composite disease endpoint in women, but not men (Altay et al., 2018).
- A lower TSH within the reference range is associated with increased risk for all-cause mortality (Møllehave et al., 2020; Pereg et al., 2012).
- A higher TSH level within the normal range has been associated with the Metabolic Syndrome (Li et al., 2020; Ruhla et al., 2010; Boggio et al., 2014).
A higher TSH level, even within the normal range, has a negative correlation with eGFR in patients with metabolic syndrome (Keshkin et al., 2021).
- Increments of TSH and decrements of free T4 (FT4) concentration within normal ranges were adversely associated with neuropsychological outcomes in 4-year-olds (Alvarez-Pedrerol et al. 2007).
- A higher TSH concentration within the normal range is associated with cognitive function and ADHD symptoms in healthy preschoolers (Alvarez-Pedrerol et al., 2007).
- A higher TSH level within the normal range has been associated with a higher risk of ADHD in girls (Endendijk et al., 2017).
- A higher TSH level within the normal range is associated with a decrease in cognitive function in 10-year old boys (Pérez-Lobato et al., 2015).
- A low normal TSH level within the normal range is associated with Alzheimer's Disease in the elderly (Wang et al., 2016), and cognitive impairment (Moon et al., 2020).
- TSH level has been identified as an independent risk factor for loss of IQ (Wang et al., 2020).
A high normal thyroid stimulating hormone level is associated with diabetic peripheral neuropathy in type 2 diabetes patients (Zhao et al., 2016).
- Moderate-to-high normal levels of TSH is a risk factor for urinary incontinence (UI) and a worse quality of life in the older women (Cuevas-Romero et al., 2017).
- A higher TSH level within normal range is associated with eGFR. The mean eGFR significantly decreased with increased TSH levels (Tanaka et al. 2018).
- Elevated TSH (anything above 2.0 uIU/L) is associated with elevated cortisol in healthy young men and women (Walter et al., 2012).
- A higher TSH level within normal range is associated with thyroid cancer (Zirilli et al., 2019; Polyzos et al., 2008; Ye et al., 2013; Kim et al., 2013; Boi et al., 2013; McLeod et al., 2012; Gómez-Izquierdo et al., 2020). (Boi = > 1.0 and young age 10-29)
Colorectal Cancer and other cancers:
TSH >3.5 mIU/L.
Research indicates that the effects of thyroid hormones are age-dependent (Gómez-Izquierdo et al., 2020; Boursi et al., 2015).
Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S - "2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum" Thyroid 27(3):315-389 (2017)
Altay S, Onat A, Can G, Tusun E, Şimşek B, Kaya A - "High-normal thyroid-stimulating hormone in euthyroid subjects is associated with risk of mortality and composite disease endpoint only in women" Arch Med Sci 14(6):1394-1403 (2018)
Alvarez-Pedrerol M, Ribas-Fitó N, Torrent M, Julvez J, Ferrer C, Sunyer J - "TSH concentration within the normal range is associated with cognitive function and ADHD symptoms in healthy preschoolers" Clin Endocrinol (Oxf). 66(6):890-8 (2007) doi: 10.1111/j.1365-2265.2007.02871.x. PMID: 17535399
"Statistically significant differences were observed in the highest quartiles of TSH, suggesting a need for re-evaluation of the upper limit of the normal TSH range."
Arbib N, Hadar E, Sneh-Arbib O, Chen R, Wiznitzer A, Gabbay-Benziv R - "First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome" J Matern Fetal Neonatal Med 30(18):2174-2178 (2017)
Asvold BO, Bjøro T, Nilsen TI, Gunnell D, Vatten LJ - "Thyrotropin levels and risk of fatal coronary heart disease: the HUNT study" Arch Intern Med 168(8):855-60 (2008)
"The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD."
Asvold BO, Bjøro T, Vatten LJ - "Associations of TSH levels within the reference range with future blood pressure and lipid concentrations: 11-year follow-up of the HUNT study" Eur J Endocrinol Jun 169(1):73-82 (2013)
Åsvold BO, Vatten LJ, Midthjell K, Bjøro T - "Serum TSH within the reference range as a predictor of future hypothyroidism and hyperthyroidism: 11-year follow-up of the HUNT Study in Norway" J Clin Endocrinol Metab 97(1):93-9 (2012)
Barišić T, Mandić V, Vasilj A, Tiric D - "Higher levels of thyrotropin in pregnancy and adverse pregnancy outcomes"J Matern Fetal Neonatal Med 32(17):2883-2888 (2019)
Bebeshko VG, Bruslova KM, Boyarska OY, Lyashenko LO, Tsvyetkova NM, Gonchar LO, Chernysh TO, Trychlib IV, Pismenniy VD, Yaroshenko ZS, Vasylenko VV - "Endocrine regulation of erythroid lineage of hematopoisis in children living under a low-dose radiation exposure after the Chornobyl NPP accident" Probl Radiac Med Radiobiol 25:374-389 (2020) doi: 10.33145/2304-8336-2020-25-374-389
"There was a direct correlation between theserum TSH level (over 3 μIU/ml) and micrognathia (brachygnathia) (r = 0.62) indicating the impact of thyroid disease on dentofacial development. The TSH at a level of upper limit of the reference range values may contribute toa decreased RBC count in peripheral blood, increased average volume and hemoglobin content in erythrocyte beingassociated with the initial manifestations of thyroid dysfunction."
Boggio A, Muzio F, Fiscella M, Sommariva D, Branchi A - "Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?" Intern Emerg Med 9(1):51-7 (2014)
Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, Borghero A, Mariotti S - "Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules" J Endocrinol Invest 36(5):313-20 (2013)
Boursi B, Haynes K, Mamtani R, Yang YX - "Thyroid dysfunction, thyroid hormone replacement and colorectal cancer risk" J Natl Cancer Inst. 107(6):djv084 (2015)
https://academic.oup.com/jnci/article/1 ... 084/871991
Chang YC, Hua SC, Chang CH, Kao WY, Lee HL, Chuang LM, Huang YT, Lai MS - "High TSH Level within Normal Range Is Associated with Obesity, Dyslipidemia, Hypertension, Inflammation, Hypercoagulability, and the Metabolic Syndrome: A Novel Cardiometabolic Marker" J Clin Med 8(6):817 (2019)
Chen Y, Chen Y, Wang N, et al. - "Thyroid Stimulating Hormone Within the Reference Range is Associated with Visceral Adiposity Index and Lipid Accumulation Product: A Population-Based Study of SPECT-China" Horm Metab Res 50(1):29-36 (2018) doi:10.1055/s-0043-122235
"Age, female to male ratio, BMI, systolic pressure, and HOMA-IR increased along with the increasing levels of TSH (p<0.01). Analysis of lipid profile showed significantly higher serum triglycerides and LDL cholesterol levels in the higher TSH quartile (p<0.001 and p=0.028, respectively). The levels of VAI and LAP were all increased along with increasing TSH level (all p<0.001)."
Chuang MH, Liao KM, Hung YM, Chou YC, Chou P - "Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease" PLoS One 12(1):e0168611 (2017)
Cuevas-Romero E, Sánchez-Cardiel A, Zamora-Gallegos AM, Cruz-Lumbreras R, Corona-Quintanilla DL, Castelán F, Martínez-Gómez M - "Moderate-to-high normal levels of thyrotropin is a risk factor for urinary incontinence and an unsuitable quality of life in women over 65 years" Clin Exp Pharmacol Physiol 44 Suppl 1:86-92 (2017)
Dagre AG, Lekakis JP, Papaioannou TG, Papamichael CM, Koutras DA, Stamatelopoulos SF, Alevizaki M - "Arterial stiffness is increased in subjects with hypothyroidism" Int J Cardiol 103(1):1-6 (2005) doi: 10.1016/j.ijcard.2004.05.068. PMID: 16061115
(Mild changes of arterial stiffness were observed even in subjects with TSH range 2.01-4.0 muU/ml suggesting that this group may have an early stage of mild thyroid failure. "Serum TSH values were positively correlated with central systolic blood pressure, central pulse pressure, augmentation pressure and negatively with reflection time index (RTI), which indicates the pressure wave velocity."
Diniz MFHS, Beleigoli AMR, Benseñor IM, Lotufo PA, Goulart AC, Barreto SM - "Association between TSH levels within the reference range and adiposity markers at the baseline of the ELSA-Brasil study" PLoS One 15(2):e0228801 (2020)
Endendijk JJ, Wijnen HAA, Pop VJM, van Baar AL - "Maternal thyroid hormone trajectories during pregnancy and child behavioral problems" Horm Behav 94:84-92 (2017) doi: 10.1016/j.yhbeh.2017.06.007. Epub 2017 Jul 11. PMID: 28668344.
"Increases in maternal TSH in early pregnancy showed weak but significant association with girls' ADHD symptoms."
Fan H, Liu Z, Zhang X, Wu S, Shi T, Zhang P, Xu Y, Chen X, Zhang T - "Thyroid stimulating hormone levels are associated with genetically predicted nonalcoholic fatty liver disease" J Clin Endocrinol Metab dgac393 (2022) doi: 10.1210/clinem/dgac393
https://academic.oup.com/jcem/advance-a ... 93/6619196
Freire C, Ramos R, Amaya E, Fernández MF, Santiago-Fernández P, Lopez-Espinosa MJ, Arrebola JP, Olea N - "Newborn TSH concentration and its association with cognitive development in healthy boys" Eur J Endocrinol 163(6):901-9 (2010)
Gómez-Izquierdo J, Filion KB, Boivin JF, Azoulay L, Pollak M, Yu OHY - "Subclinical hypothyroidism and the risk of cancer incidence and cancer mortality: a systematic review" BMC Endocr Disord 20(1):83 (2020) doi: 10.1186/s12902-020-00566-9
https://bmcendocrdisord.biomedcentral.c ... 20-00566-9
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O'Heir CE, Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, Klein RZ - "Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child" N Engl J Med 341(8):549-55 (1999)
Hernández M, López C, Soldevila B, Cecenarro L, Martínez-Barahona M, Palomera E, Rius F, Lecube A, Pelegay MJ, García J, Mauricio D, Puig Domingo M - "Impact of TSH during the first trimester of pregnancy on obstetric and foetal complications: Usefulness of 2.5 mIU/L cut-off value" Clin Endocrinol (Oxf) 88(5):728-734 (2018)
Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F - " Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women" Clin Endocrinol (Oxf) 62(4):487-91 (2005)
Ittermann T, Wittfeld K, Nauck M, Bülow R, Hosten N, Völzke H, Grabe HJ - "High Thyrotropin Is Associated with Reduced Hippocampal Volume in a Population-Based Study from Germany" Thyroid 28(11):1434-1442 (2018)
(NOTE: Cut off at 3.29 mIU/L!)
Ittermann T, Dörr M, Völzke H, Tost F, Lehmphul I, Köhrle J, Jürgens C - "High serum thyrotropin levels are associated with retinal arteriolar narrowing in the general population" Thyroid 24(10):1473-8 (2014) doi: 10.1089/thy.2014.0190
(Cut off at 3 mIU/L)
Jung G, Oh SB, Lee WY, Kim HR, Nam HK, Kim JH, Rhie YJ, Lee KH - "Thyroid function in girls with central precocious puberty" Ann Pediatr Endocrinol Metab. 24(2):124-128 (2019)
Kovářová M, Koller T, Štvrtinová V, Payer J - "Thyroid-stimulating hormone concentration as an independent risk factor of venous thromboembolism regardless of thyroid function" Endokrynol Pol 66(6):474-9 (2015) doi: 10.5603/EP.2015.0058
Keskin H, Cadirci K, Gungor K, Karaaslan T, Usta T, Ozkeskin A, Musayeva A, Yesildal F, Isman F, Zengin HY - "Association between TSH Values and GFR Levels in Euthyroid Cases with Metabolic Syndrome" Int J Endocrinol 2021:8891972 (2021)
"Increased TSH even in the normal range was associated with eGFR after adjusting for age and body mass index (BMI), especially in females. The high age (b = -0.160, p=0.005), high BMI (b = -0.134, p=0.020), high TSH (b = -0.380, p < 0.01), and high uric acid (b = -0.348, p < 0.01) were found as significant predictors of the eGFR in MetS patients."
Kianpour M, Aminorroaya A, Amini M, Feizi A, Aminorroaya Yamini S, Janghorbani M - "Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: A prospective population-based cohort study" Clin Endocrinol (Oxf) 91(1):163-169 (2019)
"Women with TSH levels > 2.5 mIU/L had an increased risk of SA, compared to women with TSH levels of 0.1-2.5 mIU/L (relative risk [RR] 3.719, 95% confidence interval [CI]:1.713-8.074). The risk of SA was increased in women with TSH levels > 4.6 mIU/L (RR 5.939, 95% CI: 1.711-20.620). The rate of SA was increased by 78% for every unit increase in standard deviation of TSH concentration (RR 1.35, 95% CI: 1.09-1.70)."
Kim D, Vazquez-Montesino LM, Escober JA, Fernandes CT, Cholankeril G, Loomba R, Harrison SA, Younossi ZM, Ahmed A - "Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality" Am J Gastroenterol (2020)
Kim HK, Yoon JH, Kim SJ, Cho JS, Kweon SS, Kang HC - "Higher TSH level is a risk factor for differentiated thyroid cancer" Clin Endocrinol (Oxf) 78(3):472-7 (2013)
Kiran Z, Sheikh A, Malik S, Meraj A, Masood M, Ismail S, Rashid MO, Shaikh Q, Majeed N, Sheikh L, Islam N - "Maternal characteristics and outcomes affected by hypothyroidism during pregnancy (maternal hypothyroidism on pregnancy outcomes, MHPO-1)" BMC Pregnancy Childbirth 19(1):476 (2019)
"A significant association existed between cesarean section and preconception thyrotropin levels > 2.5 mIU/L, whereas postpartum hemorrhage was significantly associated with thyrotropin levels > 2.5 mIU/L in the preconception and third trimester...Successful live births in our patients were complicated by maternal postpartum hemorrhage and a frequent number of emergency cesarean section."
Kitahara CM, Platz EA, Ladenson PW, Mondul AM, Menke A, Berrington de González A - "Body fatness and markers of thyroid function among U.S. men and women" PLoS One 7(4):e34979 (2012)
Korevaar TIM, Derakhshan A, Taylor PN, Meima M, Chen L, Bliddal S, Carty DM, Meems M, Vaidya B, Shields B, Ghafoor F, Popova PV, Mosso L, Oken E, Suvanto E, Hisada A, Yoshinaga J, Brown SJ, Bassols J, Auvinen J, Bramer WM, López-Bermejo A, Dayan C, Boucai L, Vafeiadi M, Grineva EN, Tkachuck AS, Pop VJM, Vrijkotte TG, Guxens M, Chatzi L, Sunyer J, Jiménez-Zabala A, Riaño I, Murcia M, Lu X, Mukhtar S, Delles C, Feldt-Rasmussen U, Nelson SM, Alexander EK, Chaker L, Männistö T, Walsh JP, Pearce EN, Steegers EAP, Peeters RP - Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth - "Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis" JAMA 322(7):632-641 (2019)
Kovářová M, Koller T, Štvrtinová V, Payer J - "Thyroid-stimulating hormone concentration as an independent risk factor of venous thromboembolism regardless of thyroid function" Endokrynol Pol 66(6):474-9 (2015)
Le TN, Celi FS, Wickham EP 3rd - "Thyrotropin Levels Are Associated with Cardiometabolic Risk Factors in Euthyroid Adolescents" Thyroid 26(10):1441-1449 (2016)
Lee SY, Pearce EN - "Testing, Monitoring, and Treatment of Thyroid Dysfunction in Pregnancy" J Clin Endocrinol Metab 106(3):883-892 (2021)
https://academic.oup.com/jcem/article-a ... m=fulltext
Li M, Zhang X, Zhou X, Han X, Zhang R, Fu Z, Wang L, Gao Y, Li Y, Ji L - "The Association Between Serum Thyrotropin Within the Reference Range and Metabolic Syndrome in a Community-Based Chinese Population" Diabetes Metab Syndr Obes 13:2001-2011 (2020)
https://www.ncbi.nlm.nih.gov/pmc/articl ... /32606859/
Luxia L, Jingfang L, Songbo F, Xulei T, Lihua M, Weiming S, Ying N, Gaojing J, Qianglong N, Yujuan L, Dan W, Fang Y, Huiping G, Pei S. Correlation Between Serum TSH Levels Within Normal Range and Serum Lipid Profile" Horm Metab Res 53(1):32-40 (2021)
Magri F, Bellingeri C, De Maggio I, Croce L, Coperchini F, Rotondi M, Chiovato L, Spinillo A, Beneventi F - "A first-trimester serum TSH in the 4-10 mIU/L range is associated with obstetric complications in thyroid peroxidase antibody-negative women" J Endocrinol Invest (2022) Dec 23. doi: 10.1007/s40618-022-01996-z. Epub ahead of print. PMID: 36562959.
https://link.springer.com/article/10.10 ... 22-01996-z
"In TPOAb-negative pregnant women, a first-trimester serum TSH level ranging from 4 to 10 mIU/L is significantly and independently linked to an increased uterine artery pulsatility index as well as to negative pregnancy outcomes such as pre-eclampsia, SGA and gestational diabetes."
Martínez-Escudé A, Pera G, Costa-Garrido A, Rodríguez L, Arteaga I, Expósito-Martínez C, Torán-Monserrat P, Caballería L - "TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population" J Clin Med 10(13):2907 (2021)
"We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively, in subjects with TSH ≥ 2.5 μIU/mL compared with TSH < 2.5 μIU/mL (control group), independent of the presence of MetS."
McLeod DS, Watters KF, Carpenter AD, Ladenson PW, Cooper DS, Ding EL - "Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response meta-analysis" J Clin Endocrinol Metab 97(8):2682-92 (2012)
Medici M, de Rijke YB, Peeters RP, Visser W, de Muinck Keizer-Schrama SM, Jaddoe VV, Hofman A, Hooijkaas H, Steegers EA, Tiemeier H, Bongers-Schokking JJ, Visser TJ - "Maternal early pregnancy and newborn thyroid hormone parameters: the Generation R study" J Clin Endocrinol Metab 97(2):646-52 (2012)
Meisinger C, Ittermann T, Tiller D, Agger C, Nauck M, Schipf S, Wallaschofski H, Jørgensen T, Linneberg A, Thiery J, Kluttig A, Greiser KH, Werdan K, Burkhardt K, Völzke H - "Sex-specific associations between thyrotropin and serum lipid profiles" Thyroid 24(3):424-32 (2014)
"In both sexes, TSH levels within the reference range were significantly positively associated with triglyceride concentrations."
Michalopoulou G, Alevizaki M, Piperingos G, Mitsibounas D, Mantzos E, Adamopoulos P, Koutras DA - "High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?" Eur J Endocrinol 138(2):141-5 (1998)
Møllehave LT, Skaaby T, Linneberg A, Knudsen N, Jørgensen T, Thuesen BH - "The association of thyroid stimulation hormone levels with incident ischemic heart disease, incident stroke, and all-cause mortality" Endocrine 68(2):358-367 (2020)
"There was a statistically significant association between TSH of 2.5-5 mU/l and all-cause mortality."
Monen L, Kuppens SM, Hasaart TH, Oosterbaan HP, Oei SG, Wijnen H, Hutton EK, Vader HL, Pop VJ - "Maternal thyrotropin is independently related to small for gestational age neonates at term" Clin Endocrinol (Oxf) 82(2):254-9 (2014)
Moon JH, Park YJ, Kim TH, et al.- "Lower-but-normal serum TSH level is associated with the development or progression of cognitive impairment in elderly: Korean Longitudinal Study on Health and Aging (KLoSHA)" J Clin Endocrinol Metab 99(2):424-432 (2014) doi:10.1210/jc.2013-3385
Ndrepepa G, Braun S, Mayer K, Cassese S, Fusaro M, Byrne RA, Hoppmann P, Schunkert H, Laugwitz KL, Kastrati A - "Prognostic value of thyroid-stimulating hormone within reference range in patients with coronary artery disease" Metabolism 64(10):1308-15 (2015)
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A - "Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy" J Clin Endocrinol Metab 95(9):E44-8 (2010)
"The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter."
Nichols PH, Pan Y, May B, Pavlicova M, Rausch JC, Mencin AA, Thaker VV - "Effect of TSH on Non-Alcoholic Fatty Liver Disease (NAFLD) independent of obesity in children of predominantly Hispanic/Latino ancestry by causal mediation analysis" PLoS One 15(6):e0234985 (2020)
Onat A, Aydın M, Can G, Çelik E, Altay S, Karagöz A, Ademoğlu E - "Normal thyroid-stimulating hormone levels, autoimmune activation, and coronary heart disease risk" Endocrine 48(1):218-26 (2015)
https://link.springer.com/article/10.10 ... 014-0269-z
Orouji Jokar T, Fourman LT, Lee H, Mentzinger K, Fazeli PK - "Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility" J Clin Endocrinol Metab 103(2):632-639 (2018)
Pereg D, Tirosh A, Elis A, Neuman Y, Mosseri M, Segev D, Lishner M, Hermoni D - "Mortality and coronary heart disease in euthyroid patients" Am J Med 125(8):826.e7-12 (2012)
Pérez-Lobato R, Ramos R, Arrebola JP, et al. - "Thyroid status and its association with cognitive functioning in healthy boys at 10 years of age"Eur J Endocrinol 172(2):129-139 (2015)
"Higher TSH slightly but significantly increased the risk of a lower score in certain neuropsychological tests."
Polyzos SA, Kita M, Efstathiadou Z, Poulakos P, Slavakis A, Sofianou D, Flaris N, Leontsini M, Kourtis A, Avramidis A - "Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy in patients presenting with thyroid nodules" J Cancer Res Clin Oncol 134(9):953-60 (2008)
Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, Schöfl C, Pfeiffer AF, Möhlig M - "A high normal TSH is associated with the metabolic syndrome" Clin Endocrinol (Oxf) May;72(5):696-701 (2010)
Sakamaki K, Tsunekawa K, Ishiyama N, Kudo M, Ando K, Akuzawa M, Nakajima K, Shimomura Y, Araki O, Kimura T, Murakami M - "Association between high normal-range thyrotropin concentration and carotid intima-media thickness in euthyroid premenopausal, perimenopausal and postmenopausal women" Maturitas 144:29-36 (2021)
Santhanam P, Nath T, Lindquist MA, Cooper DS - "Relationship between TSH levels and cognition in the young adult: An analysis of the Human Connectome Project Data" J Clin Endocrinol Metab. 2022 Apr 7:dgac189. doi: 10.1210/clinem/dgac189
Souza LL, Guedes EP, Teixeira PF, Moreira RO, Godoy-Matos AF, Vaisman M - "Serum TSH levels are associated with cardiovascular risk factors in overweight and obese adolescents" J Pediatr (Rio J). 92(5):532-8 (2016)
Stratigou T, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Christodoulatos GS, Karampela I, Papavassiliou AG - "Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors" Endocrine 61(1):83-93 (2018)
"TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09)."
Szczuko M, Splinter J, Zapałowska-Chwyć M, Ziętek M, Maciejewska D - "Fluorine may intensify the mechanisms of polycystic ovary syndrome (PCOS) development via increased insulin resistance and disturbed thyroid-stimulating hormone (TSH) synthesis even at reference levels" Med Hypotheses 128:58-63 (2019)
Szlejf C, Suemoto CK, Santos IS, Lotufo PA, Haueisen Sander Diniz MF, Barreto SM, Benseñor IM - "Thyrotropin level and cognitive performance: Baseline results from the ELSA-Brasil Study" Psychoneuroendocrinology 87:152-158 (2018) doi: 10.1016/j.psyneuen.2017.10.017. Epub 2017 Oct 20. PMID: 29096222.
Tahara K, Akahane T, Namisaki T, Moriya K, Kawaratani H, Kaji K, Takaya H, Sawada Y, Shimozato N, Sato S, Saikawa S, Nakanishi K, Kubo T, Fujinaga Y, Furukawa M, Kitagawa K, Ozutsumi T, Tsuji Y, Kaya D, Ogawa H, Takagi H, Ishida K, Mitoro A, Yoshiji H - "Thyroid-stimulating hormone is an independent risk factor of non-alcoholic fatty liver disease" JGH Open 4(3):400-404 (2019) doi: 10.1002/jgh3.12264. PMID: 32514444; PMCID: PMC7273701
Tanaka Y, Furusyo N, Kato Y, Ueyama T, Yamasaki S, Ikezaki H, Murata M, Hayashi J - "Correlation between Thyroid Stimulating Hormone and Renal Function in Euthyroid Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS)" J Atheroscler Thromb 25(4):335-343 (2018)
"Our findings demonstrated a significant correlation between serum TSH levels and eGFR in high-normal TSH participants...The mean eGFR significantly decreased with increased TSH levels"
Taylor PN, Razvi S, Pearce SH, Dayan CM - "Clinical review: A review of the clinical consequences of variation in thyroid function within the reference range"J Clin Endocrinol Metab 98(9):3562-71 (2013)
van Osch LA, Hogervorst E, Combrinck M, Smith AD - "Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease" Neurology 62(11):1967-71 (2004)
van Tienhoven-Wind LJ, Dallinga-Thie GM, Dullaart RP - "Higher Plasma ApoE Levels are Associated with Low-Normal Thyroid Function: Studies in Diabetic and Nondiabetic Subjects" Horm Metab Res 48(7):462-7 (2016)
"In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele."
Wang M, Liu L, Li H, Li Y, Liu H, Hou C, Zeng Q, Li P, Zhao Q, Dong L, Zhou G, Yu X, Liu L, Guan Q, Zhang S, Wang A - "Thyroid function, intelligence, and low-moderate fluoride exposure among Chinese school-age children" Environ Int 134:105229 (2020)
"We detected a significant modification effect by TSH on the association between urinary fluoride and IQ scores, without mediation by THs."
Wang Y, Sheng Q, Hou X, Wang B, Zhao W, Yan S, Wang Y, Zhao S - "Thyrotropin and Alzheimer's Disease Risk in the Elderly: a Systematic Review and Meta-Analysis" Mol Neurobiol 53(2):1229-1236 (2016)
Wang JJ, Zhuang CQ, Wang WX, Wang K, Zhang XB, Meng JG, Gao J, Tian J, Zheng T, Huang CL Tang N - "Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study" Journal of Geriatric Cardiology (1):61-70 (2022)
Wysokiński A, Kłoszewska I - "Level of thyroid-stimulating hormone (TSH) in patients with acute schizophrenia, unipolar depression or bipolar disorder" Neurochem Res 39(7):1245-53. (2014) doi: 10.1007/s11064-014-1305-3. Epub 2014 Apr 11. PMID: 24723220; PMCID: PMC4103998.
Walter KN, Corwin EJ, Ulbrecht J, Demers LM, Bennett JM, Whetzel CA, Klein LC - "Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women" Thyroid Res 5(1):13 (2012) doi: 10.1186/1756-6614-5-13. PMID: 23111240; PMCID: PMC3520819
"...these preliminary results suggest that TSH levels > 2.0 uIU/L may be abnormal."
Wartofsky L, Dickey RA - "The evidence for a narrower thyrotropin reference range is compelling" J Clin Endocrinol Metab 90(9):5483-8 (2005)
Worku B, Tortolani AJ, Gulkarov I, Isom OW, Klein I - "Preoperative hypothyroidism is a risk factor for postoperative atrial fibrillation in cardiac surgical patients" J Card Surg 30(4):307-12 (2015)
Wysokiński A, Kłoszewska I - "Level of thyroid-stimulating hormone (TSH) in patients with acute schizophrenia, unipolar depression or bipolar disorder" Neurochem Res 39(7):1245-53. (2014)
Yan F, Wang Q, Lu M, Chen W, Song Y, Jing F, Guan Y, Wang L, Lin Y, Bo T, Zhang J, Wang T, Xin W, Yu C, Guan Q, Zhou X, Gao L, Xu C, Zhao J -"Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity" J Hepatol 61(6):1358-64 (2014) doi: 10.1016/j.jhep.2014.06.037
"The prevalence of NAFLD increases steadily with increasing thyrotropin (TSH) levels...TSH increased the hepatic triglyceride content, indicating an essential role for TSH in the pathogenesis of NAFLD."
Yang C, Lu M, Chen W, He Z, Hou X, Feng M, Zhang H, Bo T, Zhou X, Yu Y, Zhang H, Zhao M, Wang L, Yu C, Gao L, Jiang W, Zhang Q, Zhao J - "Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques" J Exp Med 216(5):1182-1198 (2019) doi: 10.1084/jem.20181473. Epub 2019 Apr 2. PMID: 30940720; PMCID: PMC6504213
Ye ZQ, Gu DN, Hu HY, Zhou YL, Hu XQ, Zhang XH - "Hashimoto's thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer" World J Surg Oncol. 11:56 (2013)
Zhang Y, Wang H, Pan X, Teng W, Shan Z - "Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis" PLoS One 12(4):e0175708 (2017)
Zhao W, Zeng H, Zhang X, Liu F, Pan J, Zhao J, Zhao J, Li L, Bao Y, Liu F, Jia W - "A high thyroid stimulating hormone level is associated with diabetic peripheral neuropathy in type 2 diabetes patients" Diabetes Res Clin Pract 115:122-9 (2016)
Zirilli G, Salzano G, Corica D, Pajno GB, Mignosa C, Pepe G, De Luca F, Crisafulli G - "Thyrotropin serum levels and coexistence with Hashimoto's thyroiditis as predictors of malignancy in children with thyroid nodules" Ital J Pediatr 45(1):96 (2019)
All adverse health effects of fluoride are related to thyroid hormone metabolism.
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