A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

Taylor, Peter N.; Razvi, Salman; Pearce, Simon H.; Dayan, Colin M.

doi:10.1210/jc.2013-1315

Cited by 274Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

Taylor, Peter N., Razvi, Salman, Pearce, Simon H., Dayan, Colin M.·2013·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2013-1315

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Abstract

CONTEXT: Overt thyroid disease is associated with profound adverse health outcomes; however, data are conflicting for studies of borderline/subclinical thyroid dysfunction. Many studies of subclinical thyroid disease have had low power and were prone to selection bias. In contrast, large datasets are available from community studies in healthy individuals. Studies of the effects of variation of thyroid function across the reference range on health outcomes in these populations may provide useful information regarding thresholds for treatment of abnormal thyroid function. EVIDENCE ACQUISITION: MEDLINE and the Cochrane Database of Systematic Reviews and Controlled Trials Register were searched for articles studying the effect of variation in thyroid hormone parameters within the reference range on cardiovascular, bone, metabolic, pregnancy, neurological, and psychological outcomes. EVIDENCE SYNTHESIS: 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. The evidence base was good for cardiovascular, metabolic, bone, and pregnancy outcomes; however, high-quality data remained lacking for neurological and psychological outcomes. CONCLUSIONS: Common variation in persons with thyroid function in the normal range are associated with adverse health outcomes. These data suggest, by extrapolation, that carefully monitored treatment of even modest elevations of TSH may have substantial health benefits. Appropriately powered large-scale clinical trials analyzing the risks vs benefits of treating subclinical thyroid disease are required to determine whether these benefits can be achieved with levothyroxine therapy.

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There is increasing evidence that variation in thyroid status within the reference range is a risk factor for disease burden.
“There is increasing evidence that variation in thyroid status within the reference range is a risk factor for disease burden.[115][116][117][118]”
From Hypothyroidism (2024) · cites this paper as [116]
A 2013 meta-analysis of observational studies revealed that even within the population reference range, variations in thyroid hormone levels were associated with a range of adverse cardiovascular, metabolic, and bone outcomes.
“A 2013 meta-analysis of observational studies revealed that even within the population reference range, variations in thyroid hormone levels were associated with a range of adverse cardiovascular, metabolic, and bone outcomes [10].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [10]
High-normal TSH was associated with adverse cardiovascular and metabolic outcomes, whereas low-normal TSH was associated with adverse bone outcomes.
“In essence, high-normal TSH, was associated with adverse cardiovascular and metabolic outcomes whereas low-normal TSH was associated with adverse bone outcomes.”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [10]
Within the normal TSH reference range, TSH generally shows an inverse relationship with fracture risk, so low-normal TSH is associated with modestly increased fracture risk and decreased BMD.
“Variation in thyrotropin (TSH) levels within the normal reference range generally shows an inverse relationship with fracture risk so that low-normal TSH values are associated with modest increases in the risk of fractures.(13)(14)(15) and with decreases in BMD.(13,16)”
From The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis (2015) · cites this paper as [15]

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TSH concentration within the normal range is associated with cognitive function and ADHD symptoms in healthy preschoolers
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Pathogenesis of osteoporosis
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Influences of Thyroid Stimulating Hormone on Cognitive Functioning in Very Old Age
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Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass
Roef, G., Lapauw, B., Goemaere, S., Zmierczak, H., Fiers, T., Kaufman, J.-M., & Taes, Y. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-1113 · Cited by 54 · see citing works
Serum thyroid-stimulating-hormone concentration as an index of severity of major depression
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Antenatal Thyroid Screening and Childhood Cognitive Function
Eugster, E. A. (2012) · Yearbook of Endocrinology · doi:10.1016/j.yend.2012.03.006 · Cited by 47 · see citing works
Are thyroid hormone concentrations at birth associated with subsequent autism diagnosis?
Hoshiko, S., Grether, J. K., Windham, G. C., Smıth, D. J., & Fessel, K. D. (2011) · Autism Research · doi:10.1002/aur.219 · Cited by 44 · see citing works
ORIGINAL ARTICLE: The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men
Kim, B., Lee, S. H., Bae, S. J., Kim, H. K., Choe, J. W., Kim, H. Y., Koh, J., & Kim, G. S. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2010.03818.x · Cited by 43 · see citing works
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 · see citing works
Self-citation
Association Between Low Serum Free Thyroxine Concentrations and Coronary Artery Calcification in Healthy Euthyroid Subjects
Kim, E. S., Shin, J. A., Shin, J. Y., Lim, D. J., Moon, S. D., Son, H., & Han, J. H. (2012) · Thyroid · doi:10.1089/thy.2011.0366 · Cited by 41 · see citing works
Universal Screening Versus Case Finding for Detection and Treatment of Thyroid Hormonal Dysfunction During Pregnancy
Negro, R., Schwartz, A., Gismondi, R., Tinelli, A., Mangieri, T., & Stagnaro‐Green, A. (2010) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0b013e3181f0789b · Cited by 36 · see citing works
Basal Thyrotropin and Major Depression: Relation to Clinical Variables and Treatment Outcome
Joffe, R. T., & LEVITT, A. J. (2008) · The Canadian Journal of Psychiatry · doi:10.1177/070674370805301209 · Cited by 28 · see citing works
L-thyroxin treatment and post-menopausal osteoporosis: relevance of the risk profile present in clinical history.
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Relative Hypoadiponectinemia, Insulin Resistance, and Increased Visceral Fat in Euthyroid Prepubertal Girls With Low‐Normal Serum Free Thyroxine
Prats‐Puig, A., Sitjar, C., Ribot, R., Calvo, M., Clausell‐Pomés, N., Soler‐Roca, M., Soriano‐Rodríguez, P., Osiniri, I., Ros‐Miquel, M., Bassols, J., et al. (2011) · Obesity · doi:10.1038/oby.2011.206 · Cited by 24 · see citing works
Low serum free triiodothyronine levels are associated with the presence and severity of coronary artery disease in the euthyroid patients: an observational study
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Thyroid hormone within the normal range is associated with left ventricular mass in patients with hypertension
Iida, M., 山本, 充., Ishiguro, Y., Yamazaki, M., Honjo, H., & Kamiya, K. (2012) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2012.04.002 · Cited by 20 · see citing works
Associations of Thyroid-Stimulating Hormone and Free Thyroxine Concentrations with Health and Life Satisfaction in Elderly Adults
Eskelinen, S. I., Vahlberg, T. J., Isoaho, R. E., Löppönen, M. K., Kivelä, S., & Irjala, K. M. A. (2007) · Endocrine Practice · doi:10.4158/ep.13.5.451 · Cited by 15 · see citing works
Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractures in Patients on Long-Term Thyroxine Therapy
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The role of vasopressin in the impaired water excretion of myxedema
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Management of Subclinical Hypothyroidism: The Thyroidologists’ View
Pearce, S. H. S., Vaisman, M., & Wémeau, J.-L. (2012) · European Thyroid Journal · doi:10.1159/000335964 · Cited by 7 · see citing works
Self-citation
Pathogenesis of Osteoporosis
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Association between low serum free thyroxine concentrations and coronary artery calcification in healthy euthyroid subjects
Kim, E. S., Shin, J. A., Moon, S., Shin, J. Y., Han, J. H., & Son, H. (2012) · Thyroid · doi:10.1089/thy.2011-0366 · Cited by 2 · see citing works

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Global epidemiology of hyperthyroidism and hypothyroidism
Taylor, P. N., Albrecht, D., Scholz, A., Gutierrez-Buey, G., Lazarus, J. H., Dayan, C. M., & Okosieme, O. E. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2018.18 · Cited by 1,552 · see citing works
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Metabolism disrupting chemicals and metabolic disorders
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., Nadal, A., Palanza, P., Panzica, G., Sargis, R., et al. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.10.001 · Cited by 1,101 · see citing works
Role of Thyroid Hormones in Skeletal Development and Bone Maintenance
Bassett, J. H. D., & Williams, G. R. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1106 · Cited by 540 · see citing works
Falling Threshold for Treatment of Borderline Elevated Thyrotropin Levels—Balancing Benefits and Risks: Evidence From a Large Community-Based Study
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Self-citation
Subclinical and Overt Thyroid Dysfunction and Risk of All-Cause Mortality and Cardiovascular Events: A Large Population Study
Selmer, C., Olesen, J. B., Hansen, M. L., von Kappelgaard, L. M., Madsen, J. C., Hansen, P. R., Pedersen, O. D., Faber, J., Torp-Pedersen, C., & Gislason, G. H. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4184 · Cited by 288 · see citing works
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease
Santini, F., Marzullo, P., Rotondi, M., Ceccarini, G., Pagano, L., Ippolito, S., Chiovato, L., & Biondi, B. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0067 · Cited by 240 · see citing works
Hashimoto thyroiditis: an evidence-based guide: etiology, diagnosis and treatment
Kłubo-Gwieździńska, J., & Wartofsky, L. (2022) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.16222 · Cited by 230 · see citing works
Thyroid Function in the Euthyroid Range and Adverse Outcomes in Older Adults
Cappola, A. R., Arnold, A. M., Wulczyn, K., Carlson, M., Robbins, J., & Psaty, B. M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3586 · Cited by 201 · see citing works
Systematic Review of Toxicity Removal by Advanced Wastewater Treatment Technologies via Ozonation and Activated Carbon
Völker, J., Stapf, M., Miehe, U., & Wagner, M. (2019) · Environmental Science & Technology · doi:10.1021/acs.est.9b00570 · Cited by 201 · see citing works
Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis
Kim, D., Kim, W., Joo, S. K., Bae, J. M., Kim, J. H., & Ahmed, A. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.08.014 · Cited by 191 · see citing works
Circadian and Circannual Rhythms in Thyroid Hormones: Determining the TSH and Free T4 Reference Intervals Based Upon Time of Day, Age, and Sex
Ehrenkranz, J., Bach, P. R., Snow, G. L., Schneider, A., Lee, J. L., Ilstrup, S., Bennett, S. T., & Benvenga, S. (2015) · Thyroid · doi:10.1089/thy.2014.0589 · Cited by 190 · see citing works
Subclinical hypothyroidism, lipid metabolism and cardiovascular disease
Delitala, A., Fanciulli, G., Maioli, M., & Delitala, G. (2016) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2016.12.015 · Cited by 165 · see citing works
Associations between urinary diphenyl phosphate and thyroid function
Preston, E. V., McClean, M. D., Henn, B. C., Stapleton, H. M., Braverman, L. E., Pearce, E. N., Makey, C. M., & Webster, T. F. (2017) · Environment International · doi:10.1016/j.envint.2017.01.020 · Cited by 153 · see citing works
Hypertension in Thyroid Disorders
Berta, E., Lengyel, I. M., Halmi, S., Zrínyi, M., Erdei, A., Harangi, M., Páll, D., Nagy, E. V., & Bodor, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00482 · Cited by 153 · see citing works
Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis
Loh, H. H., Lim, L., Yee, A. H. A., & Loh, H. S. (2019) · BMC Psychiatry · doi:10.1186/s12888-018-2006-2 · Cited by 167 · see citing works
Thyroid hormones in diabetes, cancer, and aging
Gauthier, B. R., Sola‐García, A., Cáliz‐Molina, M. Á., Lorenzo, P. I., Cobo‐Vuilleumier, N., Capilla‐González, V., & Martín‐Montalvo, A. (2020) · Aging Cell · doi:10.1111/acel.13260 · Cited by 147 · see citing works
Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00177 · Cited by 143 · see citing works
Thyroid Function in Human Obesity: Underlying Mechanisms
Fontenelle, L. F., Feitosa, M. F., Severo, J. S., Freitas, T., Morais, J. B. S., Torres‐Leal, F. L., Henriques, G. S., & Marreiro, D. D. N. (2016) · Hormone and Metabolic Research · doi:10.1055/s-0042-121421 · Cited by 138 · see citing works
GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Zhou, W., Brumpton, B., Kabil, O., Gudmundsson, J., Thorleifsson, G., Weinstock, J., Zawistowski, M., Nielsen, J. B., Chaker, L., Medici, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17718-z · Cited by 129 · see citing works
Self-citation
Hypothyroidism
Taylor, P. N., Medici, M. M., Hubalewska-Dydejczyk, A., & Boelaert, K. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01614-3 · Cited by 128 · see citing works
Self-citation
Thyroid function and the risk of dementia
Chaker, L., Wolters, F. J., Bos, D., Korevaar, T. I. M., Albert Hofman, D., van der Lugt, A., Koudstaal, P. J., Franco, O. H., Dehghan, A., Vernooij, M. W., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003227 · Cited by 115 · see citing works
Thyroid hormone receptor-β analogues for the treatment of metabolic dysfunction-associated steatohepatitis (MASH)
Ratziu, V., Scanlan, T. S., & Bruinstroop, E. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.10.018 · Cited by 117 · see citing works
Whole-genome sequence-based analysis of thyroid function
Taylor, P. N., Porcu, E., Chew, S., Campbell, P. J., Traglia, M., Brown, S. J., Mullin, B. H., Shihab, H. A., Min, J., Walter, K., et al. (2015) · Nature Communications · doi:10.1038/ncomms6681 · Cited by 104 · see citing works
Self-citation
Prevalence of endocrine disorders in obese patients: systematic review and meta-analysis
van Hulsteijn, L. T., Pasquali, R., Casanueva, F., Haluzik, M., Ledoux, S., Monteiro, M. P., Salvador, J., Santini, F., Toplak, H., & Dekkers, O. M. (2020) · European Journal of Endocrinology · doi:10.1530/eje-19-0666 · Cited by 103 · see citing works
Maternal Early-Pregnancy Thyroid Function Is Associated With Subsequent Hypertensive Disorders of Pregnancy: The Generation R Study
Medici, M., Korevaar, T. I. M., Schalekamp–Timmermans, S., Gaillard, R., de Rijke, Y. B., Visser, W. E., Visser, W. E., Keizer‐Schrama, S. M. P. F. D. M., Albert Hofman, D., Hooijkaas, H., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1505 · Cited by 101 · see citing works
Reference intervals in the diagnosis of thyroid dysfunction: treating patients not numbers
Jonklaas, J., & Razvi, S. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30371-1 · Cited by 100 · see citing works
Self-citation
Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study
Chaker, L., Heeringa, J., Dehghan, A., Medici, M., Visser, W. E., Baumgartner, C., Albert Hofman, D., Rodondi, N., Peeters, R. P., & Franco, O. H. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2480 · Cited by 100 · see citing works
Impaired Sensitivity to Thyroid Hormones Is Associated with Hyperuricemia, Obesity, and Cardiovascular Disease Risk in Subjects with Subclinical Hypothyroidism
Sun, Y. J., Teng, D., Zhao, L., Shi, X., Li, Y., Shan, Z., Teng, W., & the Thyroid Disorders, I. S. A. D. E. S. G. (. (2022) · Thyroid · doi:10.1089/thy.2021.0500 · Cited by 100 · see citing works
The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis
Abrahamsen, B., Jørgensen, H. L., Laulund, A. S., Nybo, M., Bauer, D. C., Brix, T. H., & Hegedüs, L. (2015) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2416 · Cited by 98 · see citing works
No Effect of the Thr92Ala Polymorphism of Deiodinase-2 on Thyroid Hormone Parameters, Health-Related Quality of Life, and Cognitive Functioning in a Large Population-Based Cohort Study
Wouters, H. J. C. M., van Loon, H. C. M., van der Klauw, M. M., Elderson, M. F., Slagter, S. N., Kobold, A. M., Kema, I. P., Links, T. P., van Vliet-Ostaptchouk, J. V., & Wolffenbuttel, B. H. R. (2017) · Thyroid® · doi:10.1089/thy.2016.0199 · Cited by 97 · see citing works
Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus
Ying, H., Tang, Y., Bao, Y., Su, X., Cai, X., Li, Y., & Wang, D. (2016) · Endocrine · doi:10.1007/s12020-016-1022-6 · Cited by 97 · see citing works
Thyroid Hormone Action and Energy Expenditure
Yavuz, S., Prado, S. R. S. N. D., & Celi, F. S. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2018-00423 · Cited by 103 · see citing works
Thyroid hormone therapy and risk of thyrotoxicosis in community-resident older adults: findings from the Baltimore Longitudinal Study of Aging.
Mammen, J. S., McGready, J., Oxman, R., Chia, C. W., Ladenson, P. W., & Simonsick, E. M. (2015) · Thyroid · doi:10.1089/thy.2015.0180 · Cited by 94 · see citing works
Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis
Chaker, L., Baumgartner, C., den Elzen, W. P. J., Collet, T.-H., Ikram, M. A., Blum, M. R., Dehghan, A., Drechsler, C., Luben, R. N., Portegies, M. L. P., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2255 · Cited by 92 · see citing works
Self-citation
Genetic determination of the hypothalamic–pituitary–thyroid axis: where do we stand?
Medici, M., Visser, W. E., Visser, T. J., & Peeters, R. P. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1081 · Cited by 92 · see citing works
Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study
Pearce, S. H. S., Razvi, S., Yadegarfar, M. E., Martin-Ruiz, C., Kingston, A., Collerton, J., Visser, T. J., Kirkwood, T. B., & Jagger, C. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1935 · Cited by 91 · see citing works
Self-citation
Optimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89 · see citing works
The Normal TSH Reference Range: What Has Changed in the Last Decade?
Biondi, B. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2760 · Cited by 87 · see citing works
Clinical Parameters Are More Likely to Be Associated with Thyroid Hormone Levels than with Thyrotropin Levels: A Systematic Review and Meta-Analysis
Fitzgerald, S. P., Bean, N. G., Falhammar, H., & Tuke, J. (2020) · Thyroid® · doi:10.1089/thy.2019.0535 · Cited by 86 · see citing works
Subclinical Thyroid Dysfunction and the Risk for Fractures: A Systematic Review and Meta-analysis
Wirth, C. D., Blum, M. R., da Costa, B. R., Baumgartner, C., Collet, T.-H., Medici, M., Peeters, R. P., Aujesky, D., Bauer, D. C., & Rodondi, N. (2014) · Annals of Internal Medicine · doi:10.7326/m14-0125 · Cited by 85 · see citing works
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.
Sterenborg, R. B. T. M., Steinbrenner, I., Li, Y., Bujnis, M. N., Naito, T., Marouli, E., Galesloot, T. E., Babajide, O., Andreasen, L., Astrup, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44701-9 · Cited by 79 · see citing works
Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease
Åsvold, B. O., VATTEN, L. J., Bjøro, T., Bauer, D. C., Bremner, A., Cappola, A. R., Ceresini, G., den Elzen, W. P. J., Ferrucci, L., Franco, O. H., et al. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.0930 · Cited by 77 · see citing works
Self-citation
Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters
Knight, B., Shields, B. M., Hattersley, A. T., & Vaidya, B. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-0866 · Cited by 77 · see citing works
Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality
Kim, D., Vazquez‐Montesino, L. M., Escober, J. A., Fernandes, C. T., Cholankeril, G. T., Loomba, R. S., Harrison, S. A., Younossi, Z. M., & Ahmed, A. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000654 · Cited by 78 · see citing works
Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism
Chen, Y., Wu, X., Wu, R., Sun, X., Yang, B., Wang, Y., & Xu, Y. (2016) · Scientific Reports · doi:10.1038/srep26174 · Cited by 78 · see citing works
Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice
Taylor, P. N., Lansdown, A., Witczak, J., Khan, R., Rees, A., Dayan, C. M., & Okosieme, O. (2023) · Thyroid Research · doi:10.1186/s13044-023-00149-5 · Cited by 72 · see citing works
“There is increasing evidence that thyroid status within the reference range is a risk factor for disease burden [9, 10] and that over 95% of rigorously screened individuals without thyroid disease or autoantibodies have TSH concentrations below 2.”
BackgroundInfluentialSelf-citation
Thyroxine replacement: a clinical endocrinologist’s viewpoint
Eligar, V, Taylor, P., Okosieme, O., Leese, G., & Dayan, C. (2016) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/0004563216642255 · Cited by 72 · see citing works
Self-citation
High-Throughput Screening and Quantitative Chemical Ranking for Sodium-Iodide Symporter Inhibitors in ToxCast Phase I Chemical Library
Wang, J., Hallinger, D. R., Murr, A. S., Buckalew, A. R., Simmons, S. O., Laws, S. C., & Stoker, T. E. (2018) · Environmental Science & Technology · doi:10.1021/acs.est.7b06145 · Cited by 70 · see citing works
Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (<scp>TEARS</scp>)
A. Irving, S., Vadiveloo, T., & Leese, G. P. (2015) · Clinical Endocrinology · doi:10.1111/cen.12559 · Cited by 69 · see citing works
Exposure to Polybrominated Diphenyl Ethers (PBDEs) and Hypothyroidism in Canadian Women
Oulhote, Y., Chevrier, J., & Bouchard, M. F. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2659 · Cited by 68 · see citing works
Low–normal thyroid function and the pathogenesis of common cardio‐metabolic disorders
van Tienhoven‐Wind, L. J. N., & Dullaart, R. P. F. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12423 · Cited by 64 · see citing works
Lower TSH and higher free thyroxine predict incidence of prostate but not breast, colorectal or lung cancer
Chan, Y. X., Knuiman, M. W., Divitini, M., Brown, S. J., Walsh, J. P., & Yeap, B. B. (2017) · European Journal of Endocrinology · doi:10.1530/eje-17-0197 · Cited by 64 · see citing works
Within-Person Variation in Serum Thyrotropin Concentrations: Main Sources, Potential Underlying Biological Mechanisms, and Clinical Implications
van der Spoel, E., Roelfsema, F., & van Heemst, D. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.619568 · Cited by 62 · see citing works
Evaluation of potential sodium-iodide symporter (NIS) inhibitors using a secondary Fischer rat thyroid follicular cell (FRTL-5) radioactive iodide uptake (RAIU) assay
Buckalew, A. R., Wang, J., Murr, A. S., Deisenroth, C., Stewart, W. M., Stoker, T. E., & Laws, S. C. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02664-y · Cited by 59 · see citing works
Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark: Following Guidelines or Following Trends?
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Self-citation

Authors: Taylor, P. N., Razvi, S., Pearce, S. H., & Dayan, C. M.
Affiliations: Cardiff University (GB)
Gateshead Health NHS Foundation Trust (GB)
Royal Victoria Infirmary (GB)
Corresponding author: Dayan, Colin M.
ORCID: Taylor, Peter N.
Razvi, Salman
Pearce, Simon H.
Dayan, Colin M.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2013-09
Volume: 98
Issue: 9
Pages: 3562-3571
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2013-1315
OpenAlex: W2136343353
Cited by: 274
References: 101
Citations by year: 2026: 9 · 2025: 14 · 2024: 18 · 2023: 19 · 2022: 25 · 2021: 24 · 2020: 17 · 2019: 29 · 2018: 18 · 2017: 20 · 2016: 33 · 2015: 26 · 2014: 17 · 2013: 5
FWCI: 3.97
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Cardiff University
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: subclinical thyroid dysfunction, thyroid-stimulating hormone, thyroid hormones, cardiovascular risk, bone mineral density, fracture risk, pregnancy outcomes, metabolic outcomes, levothyroxine therapy, treatment thresholds, healthy individuals
MeSH terms: Cardiovascular Diseases, Female, Humans, Male, Pregnancy, Pregnancy Outcome, Reference Values, Risk Factors, Thyroid Diseases, Thyroid Gland, Thyroid Hormones

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A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

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