Cited by 753Thyroid Disorders and TreatmentsRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

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Small Differences in Thyroid Function May Be Important for Body Mass Index and the Occurrence of Obesity in the Population

Knudsen, Nils, Laurberg, Peter, Rasmussen, Lone B., Bülow, Inge, Perrild, Hans, Ovesen, Lars, Jørgensen, Torben·2005·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2004-2225

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Abstract

CONTEXT: Increasing prevalence of overweight in the population is a major concern globally; and in the United States, nearly one third of adults were classified as obese at the end of the 20th century. Few data have been presented regarding an association between variations in thyroid function seen in the general population and body weight. OBJECTIVE: The aim of this study was to investigate the association between thyroid function and body mass index (BMI) or obesity in a normal population. DESIGN: A cross-sectional population study (The DanThyr Study) was conducted. PARTICIPANTS: In all, 4649 participants were investigated, and 4082 were eligible for these analyses after exclusion of subjects with previous or present overt thyroid dysfunction. MAIN OUTCOME MEASURES: The study examined the association between category of serum TSH or serum thyroid hormones and BMI or obesity in multivariate models, adjusting for possible confounding. RESULTS: We found a positive association between BMI and category of serum TSH (P < 0.001) and a negative association between BMI and category of serum free T(4) (P < 0.001). No association was found between BMI and serum free T(3) levels. The difference in BMI between the groups with the highest and lowest serum TSH levels was 1.9 kg/m(2), corresponding to a difference in body weight of 5.5 kg among women. Similarly, the category of serum TSH correlated positively with weight gain during 5 yr (P = 0.04), but no statistically significant association was found with weight gain during 6 months (P = 0.17). There was an association between obesity (BMI > 30 kg/m(2)) and serum TSH levels (P = 0.001). CONCLUSIONS: Our results suggest that thyroid function (also within the normal range) could be one of several factors acting in concert to determine body weight in a population. Even slightly elevated serum TSH levels are associated with an increase in the occurrence of obesity.

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BackgroundInfluential
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BackgroundSelf-citation
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Background
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Background
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Result
Low-Normal or High-Normal Thyrotropin Target Levels During Treatment of Hypothyroidism: A Prospective, Comparative Study
Boeving, A., Paz-Filho, G., Radominski, R. B., Graf, H., & de Carvalho, G. A. (2011) · Thyroid · doi:10.1089/thy.2010.0315 · Cited by 58
“Two recently published reports corroborate the theory that there is a direct correlation between TSH levels and BMI (29), even with TSH levels in normal reference range (30).”
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“Based on data from the National Health and Nutrition Examination Survey, Kitahara et al found a positive association between TSH and BMI among euthyroid adults (16), which was similar to the findings from another Danish study (17).”
Result
Subclinical Hypothyroidism and Cardiovascular Disease
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“Similarly, differences in thyroid function, within what is considered the normal range, are associated with differences in BMI, caused by longstanding minor alterations in energy expenditure.(13) What is more, obesity is associated with insulin resistance and increased production of insulin and insulin-like growth fac…”
Background
Serum 25-hydoxyvitamin D concentrations in relation to Hashimoto’s thyroiditis: a systematic review, meta-analysis and meta-regression of observational studies
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Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study
Mahdavi, M., Amouzegar, A., Mehran, L., Madreseh, E., Tohidi, M., & Azizi, F. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00743-4 · Cited by 65
“2005 Denmark [21] n: 4082, aged 18–65 years Average follow-up: 5 years -Positive association between TSH and BMI -Positive association between FT4 and BMI”
Background
A Locus on Chromosome 1p36 Is Associated with Thyrotropin and Thyroid Function as Identified by Genome-wide Association Study
Panicker, V., Wilson, S. G., Walsh, J. P., Richards, J. B., Brown, S. J., Beilby, J. P., Bremner, A., Surdulescu, G. L., Qweitin, E., Gillham‐Nasenya, I., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.08.005 · Cited by 55
Di-(2-Ethylhexyl) Phthalate Metabolites in Urine Show Age-Related Changes and Associations with Adiposity and Parameters of Insulin Sensitivity in Childhood
Smerieri, A., Testa, C., Lazzeroni, P., Nuti, F., Grossi, E., Cesari, S., Montanini, L., Latini, G., Bernasconi, S., Papini, A. M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117831 · Cited by 56
“High MEHP and high 6-OH-MEHP concentrations were associated with a high BMISDS with a moderate-high link strength.”
BackgroundInfluential
State of the art: surgery for endemic goiter—a plea for individualizing the extent of resection instead of heading for routine total thyroidectomy
Dralle, H., Lorenz, K., & Machens, A. (2011) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-011-0809-4 · Cited by 54
“Although thyroid hormone replacement therapy, by and large, does not affect quality of life, some patients reported alterations in psychological well-being [43] as well as increases in body weight secondary to increased lipogenesis [28, 38].”
Background
Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis
Posadas‐Romero, C., Galarza, E. J., Posadas‐Sánchez, R., Acuña-Valerio, J., Juárez-Rojas, J. G., Kimura‐Hayama, E., Medina-Urrutia, A. X., & Cardoso-Saldaña, G. C. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0150 · Cited by 55
Central hypothyroidism and its replacement have a significant influence on cardiovascular risk factors in adult hypopituitary patients
Klose, M., Marina, D., Hartoft-Nielsen, M.-L., Klefter, O., Gavan, V., Hilsted, L., Rasmussen, Å. K., & Feldt-Rasmussen, U. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1610 · Cited by 53
Body Mass Index as a Determinant of Brown Adipose Tissue Function in Healthy Children
Robinson, L., Ojha, S., Symonds, M. E., & Budge, H. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.10.005 · Cited by 59
Anthropometric factors at age 20 years and risk of thyroid cancer
Suzuki, T., Matsuo, K., Hasegawa, Y., Hiraki, A., Kawase, T., Tanaka, H., & Tajima, K. (2008) · Cancer Causes & Control · doi:10.1007/s10552-008-9194-x · Cited by 54
“One study reported an association between serum TSH level and weight and BMI in a normal population [16], and showed that an elevated serum TSH level which was induced by depressed thyroid hormone was associated with excessive weight.”
Background
Association Between Thyroid Hormones, Thyroid Antibodies, and Cardiometabolic Factors in Non-Obese Individuals With Normal Thyroid Function
Liu, J., Duan, Y., Fu, J. H., & Wang, G. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00130 · Cited by 54
The difficult patient: drug interaction and the influence of concomitant diseases on the treatment of hypothyroidism
Ward, L. S. (2010) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302010000500002 · Cited by 53
“The second hypothesis suggests that low thyroid function may lead to obesity, probably reducing basal metabolic rate (13).”
Background
Assay of Thyroid Hormones and Related Substances
Spencer, C. A. (2013) · Europe PMC (PubMed Central) · Cited by 53
Low-Normal Thyroid Function and Novel Cardiometabolic Biomarkers
van Tienhoven‐Wind, L. J. N., & Dullaart, R. P. F. (2015) · Nutrients · doi:10.3390/nu7021352 · Cited by 54
“Nonetheless, small differences in thyroid function even within the normal range are likely to be relevant for obesity, as judged by a positive association of BMI with the TSH level and an inverse association with FT4, as well as by a higher prevalence of obesity in a community-dwelling study among adults from Denmark…”
BackgroundInfluential
A review of species differences in the control of, and response to, chemical-induced thyroid hormone perturbations leading to thyroid cancer
Foster, J. R., Tinwell, H., & Melching‐Kollmuss, S. (2021) · Archives of Toxicology · doi:10.1007/s00204-020-02961-6 · Cited by 54
Thyroid hormonal status among children with obesity
Ghergherehchi, R., & Hazhir, N. (2015) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018815571892 · Cited by 51
Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study
Kuś, A., Marouli, E., Fabiola Del Greco, M., Chaker, L., Bednarczuk, T., Peeters, R. P., Teumer, A., Medici, M., & Deloukas, P. (2020) · Thyroid · doi:10.1089/thy.2020.0393 · Cited by 53
“Multiple observational studies showed that there is a positive association between BMI and TSH levels, even within the normal range (76).”
Reference values for TSH may be inadequate to define hypothyroidism in persons with morbid obesity: Di@bet.es study
Valdés, S., Maldonado‐Araque, C., Lago‐Sampedro, A., Lillo‐Muñoz, J. A., Garcia‐Fuentes, E., Perez‐Valero, V., Gutiérrez‐Repiso, C., Garcia‐Escobar, E., Goday, A., Urrutia, I., et al. (2017) · Obesity · doi:10.1002/oby.21796 · Cited by 50
“TSH, FT4, FT3, and FT3/FT4 ratios according to BMI A positive relation between BMI and TSH levels was seen in the unadjusted model (P for trend 5 0.006) and also in the linear models adjusted for age and sex (P 0.001) and multivariate (P 0.001).”
BackgroundResultInfluential
Prenatal Exposures to Perfluoroalkyl Acids and Associations with Markers of Adiposity and Plasma Lipids in Infancy: An Odense Child Cohort Study
Jensen, R. C., Andersen, M., Larsen, P. V., Glintborg, D., Dalgård, C., Timmermann, C. A. G., Nielsen, F., Sandberg, M. B., Andersen, H. R., Christesen, H. T., et al. (2020) · Environmental Health Perspectives · doi:10.1289/ehp5184 · Cited by 50
“A rodent study (Yu et al. 2009) indicated that both prenatal exposure and postnatal PFOS exposure were associated with decreased thyroxine levels (T4) in o ﬀ spring, which is linked to decreased basal metabolic rate and increased BMI in humans (Knudsen et al. 2005).”
Overweight increases risk of first trimester hypothyroxinaemia in iodine‐deficient pregnant women
Gowachirapant, S., Melse‐Boonstra, A., Winichagoon, P., & Zimmermann, M. B. (2013) · Maternal and Child Nutrition · doi:10.1111/mcn.12040 · Cited by 52
The pattern of TSH and fT4 levels across different BMI ranges in a large cohort of euthyroid patients with obesity
Mele, C., Mai, S., Cena, T., Pagano, L., Scacchi, M., Biondi, B., Aimaretti, G., & Marzullo, P. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1029376 · Cited by 56
Subclinical hypothyroidism and the risk of metabolic syndrome: A meta-analysis of observational studies
Yang, L., Lv, X., Yue, F., Wei, D., Liu, W., & Zhang, T. (2016) · Endocrine Research · doi:10.3109/07435800.2015.1108332 · Cited by 49
“The components of MetS have been reported to be closely related to hypothyroidism or SCH (5,6).”
Background
Paradoxical Relationship Between Body Mass Index and Thyroid Hormone Levels: A Study Using Mendelian Randomization
Taylor, P. N., Richmond, R., Davies, N., Sayers, A., Stevenson, K., Woltersdorf, W., Taylor, A., Groom, A., Northstone, K., Ring, S., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3505 · Cited by 48
Bisphenol S increases the obesogenic effects of a high-glucose diet through regulating lipid metabolism in Caenorhabditis elegans
Xiao, X., Zhang, X., Bai, J., Li, J., Zhang, C., Zhao, Y., Zhu, Y. G., Zhang, J., & Zhou, X. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.127813 · Cited by 48
Prevalence of hypothyroidism in patients with metabolic syndrome
Kota, S., Meher, L. K., Raveendranathan, S. K., Sarangi, J., & Jali, S. N. (2013) · Thyroid Research and Practice · doi:10.4103/0973-0354.110583 · Cited by 48
Metformin and Thyroid: An Update
Παππά, Θ., & Alevizaki, M. (2013) · European Thyroid Journal · doi:10.1159/000346248 · Cited by 51
Sex Differences in the Associations of Obesity With Hypothyroidism and Thyroid Autoimmunity Among Chinese Adults
Wang, B., Song, R., He, W., Yao, Q., Li, Q., Jia, X., & Zhang, J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01397 · Cited by 48
“Finally, most published studies on the associations of obesity with hypothyroidism and TAI in adults uniformly used a generic reference range of TSH for adults with different ages, sex and BMI (Table 7), which followed current clinical guidelines to define hypothyroidism and SCH (Knudsen et al., 2005; Asvold et al., 2…”
Background
Subclinical Hypothyroidism Is Associated with Increased Risk for Cancer Mortality in Adult Taiwanese—A 10 Years Population-Based Cohort
Tseng, F., Lin, W., Li, C.-I., Li, T., Lin, C., & Huang, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122955 · Cited by 46
Thyroid Antagonists (Perchlorate, Thiocyanate, and Nitrate) and Childhood Growth in a Longitudinal Study of U.S. Girls
Mervish, N. A., Pajak, A., Teitelbaum, S. L., Pinney, S. M., Windham, G. C., Kushi, L. H., Biro, F. M., Valentín-Blasini, L., Blount, B. C., Wolff, M. S., et al. (2015) · Environmental Health Perspectives · doi:10.1289/ehp.1409309 · Cited by 47
“Studies show elevated thyroid hormone levels [TSH, T4, and triiodothyronine (T3)] in obese children and adults compared with normal weight persons (Chomard et al. 1985; Gussekloo et al. 2004; Knudsen et al. 2005; Matzen et al. 1989; Reinehr and Andler 2002; Shalitin et al. 2009).”
Background
Risk of Coronary Heart Disease and Mortality for Adults With Subclinical Hypothyroidism
Rotondi, M., Magri, F., & Chiovato, L. (2010) · JAMA · doi:10.1001/jama.2010.1786 · Cited by 48
“The elevated serum TSH found in obese (and particularly in morbidly obese) patients may be a mere consequence of the excess body weight rather than a condition of primary thyroid failure.(2-4) This concept would imply that obese patients with a moderate elevation in serum TSH would not experience increased systemic va…”
Background
Is autoimmune thyroiditis a risk factor for early atherosclerosis in premenopausal women even if in euthyroid status?
Topaloğlu, O., Gökay, F., Küçükler, K., BURNİK, F. S., Mete, T., Yavuz, H. C., Berker, D. S., & Güler, S. (2012) · Endocrine · doi:10.1007/s12020-012-9842-5 · Cited by 46
“Previous studies reported a positive correlation between TSH and BMI in euthyroid subjects [9, 13, 14].”
Background
Effect of weight loss after gastric bypass surgery on thyroid function in euthyroid people with morbid obesity
MacCuish, A. C., Razvi, S., & Syed, A. A. (2012) · Clinical Obesity · doi:10.1111/j.1758-8111.2012.00036.x · Cited by 43
“Clear associations between thyroid function and obesity have been observed in the euthyroid general population, with serum thyrotropin (TSH) correlated to weight gain (1,2).”
Background
Thyroid hormones and breast cancer association according to menopausal status and body mass index
Ortega-Olvera, C., Ulloa‐Aguirre, A., Ángeles-Llerenas, A., Mainero‐Ratchelous, F., González-Acevedo, C. E., Hernández-Blanco, M., Ziv, E., Avilés-Santa, L. M., Pérez‐Rodríguez, E., & Torres-Mejı́a, G. (2018) · Breast Cancer Research · doi:10.1186/s13058-018-1017-8 · Cited by 45
A cross sectional study of urinary phthalates, phenols and perchlorate on thyroid hormones in US adults using structural equation models (NHANES 2007–2008)
Przybyla, J., Geldhof, G. J., Smit, E., & Kile, M. L. (2018) · Environmental Research · doi:10.1016/j.envres.2018.01.039 · Cited by 44
“Since BMI is related to both thyroid hormones and EDCs, BMI was allowed to correlate with THs and all the individual EDCs (except perchlorate) (Carwile and Michels, 2011; Elobeid et al., 2010; Hatch et al., 2008; Knudsen et al., 2005; Milionis and Milionis, 2013).”
Background
Mechanisms of action, chemical characteristics, and model systems of obesogens
Griffin, M. D., Pereira, S. R., DeBari, M. K., & Abbott, R. D. (2020) · BMC Biomedical Engineering · doi:10.1186/s42490-020-00040-6 · Cited by 48
A Manual for Encoding Probability Distributions.
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Insulin Resistance in Nodular Thyroid Disease
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“Previous studies have shown that low-normal free thyroid hormone levels and/or elevated TSH were associated with metabolic syndrome and insulin resistance (14,15).”
Background
Serum Thyrotropin Is Positively Correlated with the Metabolic Syndrome Components of Obesity and Dyslipidemia in Chinese Adolescents
Zhang, J., Jiang, R., Li, L., Li, P., Li, X., Wang, Z., Li, L., & Teng, W. (2014) · International Journal of Endocrinology · doi:10.1155/2014/289503 · Cited by 43
The Prevalence of Thyroid Nodules and Their Association with Metabolic Syndrome Risk Factors in a Moderate Iodine Intake Area
Feng, S., Zhang, Z., Xu, S., Mao, X., Feng, Y. Y., Zhu, Y. N., & Liu, C. (2016) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2016.0077 · Cited by 43
“Previous studies assessing thyroid functional changes in obesity found that the serum level of thyroid-stimulating hormone (TSH) was higher in patients with MetS than in controls.(15,16) WC was significantly positively associated with the TSH level, which may be explained by some humoral or hormonal mediators from adi…”
Thyroid functions and serum lipid profile in metabolic syndrome
Gutch, M., Rungta, S., Kumar, S., Agarwal, A., Bhattacharya, A., & Razi, S. M. (2017) · Biomedical Journal · doi:10.1016/j.bj.2016.12.006 · Cited by 43
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Association Between Exposure to Ambient Air Pollution and Thyroid Function in Korean Adults
Kim, H., Kwon, H., Yun, J. M., Cho, B., & Park, J. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa338 · Cited by 43
Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats
Ferguson, D. C., Caffall, Z. F., & Hoenig, M. E. (2007) · Journal of Endocrinology · doi:10.1677/joe-07-0064 · Cited by 43
“It should be noted that non-dialysis techniques were used to estimate FT4 concentration (Knudsen et al. 2005).”
BackgroundMethod
A meta-analysis of the associations between common variation in the PDE8B gene and thyroid hormone parameters, including assessment of longitudinal stability of associations over time and effect of thyroid hormone replacement
Taylor, P. N., Panicker, V., Sayers, A., Shields, B., Iqbal, A., Bremner, A. P., Beilby, J. P., Leedman, P. J., Hattersley, A. T., Vaidya, B., et al. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-0938 · Cited by 41

Authors: Knudsen, N., Laurberg, P., Rasmussen, L. B., Bülow, I., Perrild, H., Ovesen, L., & Jørgensen, T.
Affiliations: Bispebjerg Hospital (DK)
Aalborg University Hospital (DK)
Corresponding author: Knudsen, Nils
ORCID: Knudsen, Nils
Rasmussen, Lone B.
Jørgensen, Torben
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2005-07
Volume: 90
Issue: 7
Pages: 4019-4024
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2004-2225
OpenAlex: W2133682334
Semantic Scholar: 20e3a19b8599c2b8587d25dfab6ed083b7ff3e0f
Cited by: 753
References: 39
Citations by year: 2026: 15 · 2025: 28 · 2024: 35 · 2023: 33 · 2022: 41 · 2021: 38 · 2020: 50 · 2019: 49 · 2018: 38 · 2017: 43 · 2016: 46 · 2015: 47 · 2014: 56 · 2013: 47 · 2012: 41
FWCI: 10.82
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: thyroid function, body mass index, obesity, serum TSH, free thyroxine, free triiodothyronine, weight gain, subclinical thyroid dysfunction, healthy population
MeSH terms: Adolescent, Adult, Aged, Cross-Sectional Studies, Humans, Middle Aged, Obesity, Thyroid Hormones, Thyrotropin, Body Mass Index

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Small Differences in Thyroid Function May Be Important for Body Mass Index and the Occurrence of Obesity in the Population

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