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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BackgroundSelf-citation
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Background
Patients Treated for Hyperthyroidism Are at Increased Risk of Becoming Obese: Findings from a Large Prospective Secondary Care Cohort
Torlińska, B., Nichols, L., Mohammed, M. A., McCabe, C., & Boelaert, K. (2019) · Thyroid · doi:10.1089/thy.2018.0731 · Cited by 36
“Patients’ and background population’s BMI was compared as categorical and continuous measurements.”
Influential
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Background
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“High TSH has been associated with elevated BMI in non-pregnant subjects (22, 28, 29), and there are several suggested mechanisms that may lead to increased TSH levels in obesity.”
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BackgroundInfluential
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Result
Iodine Treatment in Children with Subclinical Hypothyroidism Due to Chronic Iodine Deficiency Decreases Thyrotropin and C-Peptide Concentrations and Improves the Lipid Profile
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“Age-and sex-speciﬁc criteria from the World Health Organization (35) were used to calculate BMI Z-scores.”
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“In several previous population-based studies, the TSH level was found to be associated with BMI (3, 5, 6, 11, 19-21); yet, four of the six studies reported a lack of association between the serum TSH level and waist circumference (15, 22-24).”
Background
Thyroid-Stimulating Hormone, Degree of Obesity, and Metabolic Risk Markers in a Cohort of Swedish Children with Obesity
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“Hypothyroidism may be a risk factor for obesity, because metabolic rates tend to be decreased (1).”
Physiology of the Hypothalamic-Pituitary-Thyroid Axis
Mariotti, S., & Beck‐Peccoz, P. (2016) · Cited by 35
Maternal thyroid function, prepregnancy obesity and gestational weight gain—The Generation R Study: A prospective cohort study
Collares, F. M., Korevaar, T. I. M., Albert Hofman, D., Steegers, E. A. P., Peeters, R. P., Jaddoe, V. W. V., & Gaillard, R. (2017) · Clinical Endocrinology · doi:10.1111/cen.13412 · Cited by 34
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Association between Thyroid Hormone Levels and Diabetic Kidney Disease in Euthyroid Patients with Type 2 Diabetes
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Craniosynostosis and risk factors related to thyroid dysfunction
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“Many risk factors for thyroid disease have been identified, such as older maternal age, white or Hispanic race-ethnicity, and higher body mass index [Hollowell et al., 2002; Knudsen et al., 2005].”
Background
Evaluation of body composition changes, epicardial adipose tissue, and serum omentin-1 levels in overt hypothyroidism
Cerit, E. T., Aktürk, M., Altınova, A. E., Tavıl, Y., Özkan, Ç., Yayla, Ç., Altay, M., Demirtas, C., & Çakır, N. (2014) · Endocrine · doi:10.1007/s12020-014-0460-2 · Cited by 31
“T G (m g /d L ) 1 5 0 [5 5 – 4 1 1 ] 1 1 8 [4 3 – 3 1 8 ] 0 .”
Background
Raised serum TSH in morbid-obese and non-obese patients: effect on the circulating lipid profile
Rotondi, M., Leporati, P., Rizza, M. I., Clerici, A., Groppelli, G., Pallavicini, C., Manna, A. L., Fonte, R., Magri, F., Biondi, B., et al. (2013) · Endocrine · doi:10.1007/s12020-013-9928-8 · Cited by 32
“In favour of this hypothesis, several investigations, mostly cross-sectional population studies [10], demonstrated a positive association between serum levels of TSH and BMI, suggesting that even a slightly elevated serum TSH might be important in determining an excess of body weight [10, 11].”
BackgroundResult
Ft3 is Higher in Males than in Females and Decreases Over the Lifespan
Strich, D., Karavani, G., Edri, S., Chay, C., & Gillis, D. (2017) · Endocrine Practice · doi:10.4158/ep171776.or · Cited by 32
Impact of Obesity on Serum Levels of Thyroid Hormones among Euthyroid Saudi Adults
Al-Musa, H. M. (2017) · Journal of Thyroid Research · doi:10.1155/2017/5739806 · Cited by 32
Thyroid-Stimulating Hormone Levels Are Positively Associated with Insulin Resistance
Zhu, P., Liu, X., & Mao, X. (2018) · Medical Science Monitor · doi:10.12659/msm.905774 · Cited by 32
Thyroid Functions and Trace Elements in Pediatric Patients with Exogenous Obesity
Çayır, A., Döneray, H., Kurt, N., Orbak, Z., Kaya, A., Turan, M. İ., & Yıldırım, A. (2014) · Biological Trace Element Research · doi:10.1007/s12011-013-9880-8 · Cited by 31
“In contrast, there are studies reporting that although thyroid functions are generally normal in obese individuals, BMI and TSH are positively correlated, that TSH levels increase slightly in obese individuals compared to those of normal weight subjects, and that T4 values are normal and T3 values are normal or slight…”
Background
Genetic variation in thyroid hormone transporters
van der Deure, W. M., Peeters, R. P., & Visser, T. J. (2007) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2007.03.006 · Cited by 31
Thyroid Function in Obese Children and Adolescents and Its Association with Anthropometric and Metabolic Parameters
Rumińska, M., Witkowska–Sędek, E., Majcher, A., & Pyrżak, B. (2016) · Advances in experimental medicine and biology · doi:10.1007/5584_2016_232 · Cited by 30
Association between Lower Normal Free Thyroxine Concentrations and Obesity Phenotype in Healthy Euthyroid Subjects
Shin, J. A., Mo, E. Y., Kim, E. S., Moon, S. D., & Han, J. H. (2014) · International Journal of Endocrinology · doi:10.1155/2014/104318 · Cited by 30
“This is further supported by another study, which found that slightly decreased thyroid function within the normal range was correlated with weight gain during a 5-year follow-up in 4082 subjects [24].”
Incidence of thyroid disease following exposure to polybrominated biphenyls and polychlorinated biphenyls, Michigan, 1974–2006
Yard, E. E., Terrell, M. L., Hunt, D. R., Cameron, L. L., Small, C. M., McGeehin, M. A., & Marcus, M. (2011) · Chemosphere · doi:10.1016/j.chemosphere.2011.06.020 · Cited by 30
The effect of bariatric surgery on hypothyroidism: Sleeve gastrectomy versus gastric bypass
Rudnicki, Y., Slavin, M., Keidar, A., Kent, I., Berkovich, L., Tiomkin, V., Inbar, R., & Avital, S. (2018) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2018.06.008 · Cited by 30
Impact of Adjusting for the Reciprocal Relationship Between Maternal Weight and Free Thyroxine During Early Pregnancy
Haddow, J. E., Craig, W. Y., Palomaki, G. E., Neveux, L. M., Lambert-Messerlian, G. M., Canick, J. A., Malone, F. D., & Tr, M. E. D. F. T. F. A. S. (2012) · Thyroid · doi:10.1089/thy.2012.0440 · Cited by 29
“This differs from the positive relationship previously reported for nonpregnant adults in two studies (11,12), but not in a third (13).”
Result
Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene–diet interactions
Fernández‐Real, J. M., Corella, D., Goumidi, L., Mercader, J. M., Valdés, S., Rojo‐Martínez, G., Ortega, F. J., Martinez-Larrad, M.-T., Gómez‐Zumaquero, J. M., Salas‐Salvadó, J., et al. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.11 · Cited by 28
Relation between thyroid-stimulating hormone and the occurrence of cardiovascular events and mortality in patients with manifest vascular diseases
Westerink, J., van der Graaf, Y., Faber, D. R., Spiering, W., & Visseren, F. L. J. (2011) · European Journal of Preventive Cardiology · doi:10.1177/1741826711416045 · Cited by 29
“There is a strong relation between higher TSH levels within the normal range and increased bodyweight and BMI, pointing to the possibility that changes in thyroid function might influence adiposity or vice versa.(16,17) We recently showed in a similar study population of patients with manifest vascular disease that TS…”
Association of Thyroid-stimulating Hormone and Cardiovascular Risk Factors
Sun, X., Sun, Y., Li, W., Chen, C.-Y., Chiu, Y.-H., Chien, H.-Y., & Wang, Y. (2015) · Internal Medicine · doi:10.2169/internalmedicine.54.4514 · Cited by 29
“Indeed, it was reported that a higher TSH level was associated with an increased risk of metabolic syndrome in euthyroid postmenopausal women (20), while other studies demonstrated that the circulating TSH level was positively correlated with the BMI (84, 87, 88) and HbA1c (27).”
Background
Sex-Specific Associations Between Thyrotropin and Serum Lipid Profiles
Meisinger, C., Ittermann, T., Tiller, D., Agger, C., Nauck, M. A., Schipf, S., Wallaschofski, H., Jørgensen, T., Linneberg, A. R., Thiery, J., et al. (2013) · Thyroid · doi:10.1089/thy.2013.0259 · Cited by 28
“Additionally, prior studies found an association between thyroid hormone levels and endothelial (7,8) and cardiac function, atherosclerosis (9,10), and a positive association between thyrotropin (TSH) and body mass index or waist circumference (11,12).”
Self-citation
Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure, leptin and thyrotropin levels in obese non-morbid premenopausal women
Arrizabalaga, M., Larrarte, E., Margareto, J., Maldonado‐Martín, S., Barrenechea, L., & Labayen, I. (2013) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0300-5 · Cited by 27
“Previous studies showed that small increases in TSH levels are associated with body weight and adiposity gain and altered REE even in euthyroid individuals [1, 20, 36].”
Obesity with and without metabolic syndrome: Do vitamin D and thyroid autoimmunity have a role?
Ağbaht, K., Mercan, Y., Kutlu, S., Alpdemir, M. F., & Sezgin, T. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.08.001 · Cited by 29
“correlation between weight gain over a 5-year period and a progressive increase in serum TSH [34], and elevated TSH levels in obesity are normalized after substantial weight loss and not related to serum lipids [35].”
Background
The debate on treating subclinical hypothyroidism
Tan, E. (2016) · Singapore Medical Journal · doi:10.11622/smedj.2016165 · Cited by 29
“(16) Lastly, obesity may be a confounder in TSH measurement, although observational studies were inconsistent in this area.(17-20) Hence, the reference intervals for TSH based on age, gender, ethnicity, body mass index (BMI) and pregnancy status may need to be established before SCH can be clearly defined.”
Background
Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches
Silvestri, E., Lombardi, A., de Lange, P., Glinni, D., Senese, R., Cioffi, F., Lanni, A., Goglia, F., & Moreno, M. (2010) · BioMed Research International · doi:10.1155/2011/810242 · Cited by 29
“However, in terms of protein composition they are “hybrid” organelles resulting from the coordinated expression of the nuclear and their own genome.”
Background
Morbid Obesity in Women is Associated to a Lower Prevalence of Thyroid Nodules
Cappelli, C., Pirola, I., Mittempergher, F., MARTINO, E. D., Casella, C., Agosti, B., Nascimbeni, R., Formenti, A., Rosei, E. A., & Castellano, M. (2011) · Obesity Surgery · doi:10.1007/s11695-011-0410-5 · Cited by 27
“Few studies have investigated functional and morphological changes of the thyroid gland in relation to obesity and/or metabolic syndrome [16, 19–23].”
Background
Body Weight Changes in A Large Cohort of Patients Subjected to Thyroidectomy for A Wide Spectrum of Thyroid Diseases
Rotondi, M., Croce, L., Pallavicini, C., Manna, L. L., Accornero, S., Fonte, R., Magri, F., & Chiovato, L. (2014) · Endocrine Practice · doi:10.4158/ep14125.or · Cited by 26
Effects of thyroid hormones and cold acclimation on the energy metabolism of the striped hamster (Cricetulus barabensis)
Wen, J., Qiao, Q.-G., Zhao, Z., Wang, D., Zheng, W., Wang, Z.-X., & Liu, J.-S. (2019) · Journal of Comparative Physiology B · doi:10.1007/s00360-018-1197-7 · Cited by 26
Free triiodothyronine is associated with smoking habit, independently of obesity, body fat distribution, insulin, and metabolic parameters
Pergola, G. D., Ciampolillo, A., Alò, D., Sciaraffia, M., & Guida, P. (2010) · Journal of Endocrinological Investigation · doi:10.1007/bf03350348 · Cited by 25
Association Between Thyrotropin Levels and Insulin Sensitivity in Euthyroid Obese Adolescents
Javed, A., Balagopal, P., Vella, A. V., Fischer, P. R., Piccinini, F., Man, C. D., Cobelli, C., Giesler, P. D., Laugen, J. M., & Kumar, S. (2015) · Thyroid · doi:10.1089/thy.2015.0005 · Cited by 26
“model, persisted even after adjusting for BMI, thereby suggesting that this association is not solely attributable to obesity (31–33).”
Chemically or Surgically Induced Thyroid Dysfunction Altered Gut Microbiota in Rat Models
Shin, N. R., Bose, S., Wang, J., Nam, Y., Song, E., Lim, D., Kim, H., Lim, Y., Choi, H. S., & Kim, H. (2019) · The FASEB Journal · doi:10.1096/fj.201903091rr · Cited by 27
Direct and rapid effects of 3,5-diiodo-L-thyronine (T2)
Moreno, M., Giacco, A., Di Munno, C., & Goglia, F. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.02.012 · Cited by 25
Urinary bisphenol A and thyroid function by BMI in the Korean National Environmental Health Survey (KoNEHS) 2012–2014
Kwon, J. A., Shin, B., & Kim, B. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.124918 · Cited by 25
Sex differences in subclinical hypothyroidism and associations with metabolic risk factors: a health examination-based study in mainland China
Jiang, L., Du, J., Wu, W., Fang, J., Wang, J., & Ding, J. (2020) · BMC Endocrine Disorders · doi:10.1186/s12902-020-00586-5 · Cited by 29
Central Ghrelin Affects Pituitary-Thyroid Axis: Histomorphological and Hormonal Study in Rats
Šošić‐Jurjević, B., Stevanović, D., Milošević, V., Sekulić, M., & Starcevic, V. P. (2008) · Neuroendocrinology · doi:10.1159/000188603 · Cited by 24
Association between measurements of thyroid function and the acrylamide metabolite N-Acetyl-S-(propionamide)-cysteine in adolescents and young adults
Lin, C., Lin, L., Chen, Y.-C., Wen, L., Chien, K., Sung, F., Chen, P., & Su, T. (2014) · Environmental Research · doi:10.1016/j.envres.2014.08.043 · Cited by 25
“Hypothyroidism and hyperthyroidism can affect blood pressure (Luboshitzky et al., 2002; Prisant et al., 2006), and thyroid function may influence BMI and glucose homeostasis (Knudsen et al., 2005).”
Background
The Philippine Thyroid Diseases Study (PhilTiDeS 1): Prevalence of Thyroid Disorders Among Adults in the Philippines
Carlos-Raboca, J., Jimeno, C., Kho, S., Andag‐Silva, A., Jasul, G., Nicodemus, N. A., Cunanan, E. C., & Duante, C. A. (2012) · Journal of the ASEAN Federation of Endocrine Societies · doi:10.15605/jafes.027.01.04 · Cited by 25
Subclinical hypothyroidism: Controversies to consensus
Raza, S., & Mahmood, N. (2013) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.123555 · Cited by 25
“Subclinical hypothyroidism and neuropsychiatric issues There are several reports linking SCH with neuropsychiatric diseases,[62-65] while there are many including a large study of primary care patients in England do not support this observation.[15,66-68] Link between SCH and some of the neuropsychiatric disorders are…”
Result
Changes in Body Weight after Treatment of Primary Hypothyroidism with Levothyroxine
Lee, S. Y., Braverman, L. E., & Pearce, E. N. (2014) · Endocrine Practice · doi:10.4158/ep14072.or · Cited by 25
Indices of adiposity and thyroid hormones in euthyroid postmenopausal women
Lambrinoudaki, I. V., Armeni, E., Rizos, D., Georgiopoulos, G. A., Athanasouli, F., Triantafyllou, N. I., Panoulis, K. P. C., Augoulea, A., Creatsa, M. G., Alexandrou, A. P., et al. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0141 · Cited by 25
Serum vaspin levels in hypothyroid patients
Çınar, N., Gülçelik, N. E., Aydın, K., Akın, Ş., Usman, A., & Gürlek, A. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0180 · Cited by 25
OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions
Alligier, M., Barrès, R., Blaak, E. E., Boirie‌, Y., Bouwman, J., Brunault, P., Campbell, K., Clément, K., Farooqi, I. S., Farpour‐Lambert, N. J., et al. (2020) · Obesity Facts · doi:10.1159/000505342 · Cited by 30
Triiodothyronine level predicts visceral obesity and atherosclerosis in euthyroid, overweight and obese subjects: T3 and visceral obesity
Nam, J. S., Cho, M., Park, J. S., Ahn, C. W., Soo, B., Lee, E. J., Lim, S. K., Kim, K. R., & Lee, H. C. (2010) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2010.08.003 · Cited by 25
The relation between thyroid-stimulating hormone and measures of adiposity in patients with manifest vascular disease
Westerink, J., van der Graaf, Y., Faber, D. R., Visseren, F. L. J., & on behalf of the SMART study group (2010) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02391.x · Cited by 24
Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement
Guastamacchia, E., Triggiani, V., Aglialoro, A., Aiello, A., Ianni, L., Maccario, M., Zini, M., Giorda, C. B., Guglielmi, R., Betterle, C., et al. (2014) · Endocrine · doi:10.1007/s12020-014-0474-9 · Cited by 24
Circulating adiponectin concentrations were related to free thyroxine levels in thyroid cancer patients after thyroid hormone withdrawal
Lin, S., Huang, S.-C., & Sheu, W. H. (2009) · Metabolism · doi:10.1016/j.metabol.2009.06.032 · Cited by 24
Effect of Roux-en-Y gastric bypass on thyroid function in euthyroid patients with obesity and type 2 diabetes
Liu, F., Di, J., Yu, H., Han, J., Bao, Y., & Jia, W. (2017) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2017.06.001 · Cited by 23
Differences in DBA/1J and DBA/2J reveal lipid QTL genes
Stylianou, I. M., Langley, S. R., Walsh, K., Chen, Y., Revenu, C., & Paigen, B. J. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800244-jlr200 · Cited by 24
Thyroid function tests in metabolic syndrome
Chugh, K., Goyal, S., Shankar, V., & Chugh, S. N. (2012) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.102999 · Cited by 24
“increased thyroid hormone levels,[6] increased TSH with no effect on T3 and T4, [7-9] or increase in TSH and T3 with no effect on T4 [10-12]; on the other hand, subclinical hypothyroidism as a result of slow metabolism can lead to the obesity.”
BackgroundInfluential

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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