eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 14
Clinical research

High-normal thyroid-stimulating hormone in euthyroid subjects is associated with risk of mortality and composite disease endpoint only in women

Servet Altay, Altan Onat, Günay Can, Eyyup Tusun, Barış Şimşek, Adnan Kaya

Arch Med Sci 2018; 14, 6: 1394–1403
Online publish date: 2016/10/26
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
The aim of the study was to evaluate whether serum thyroid-stimulating hormone (TSH) within the normal range in euthyroid subjects (having normal free triiodothyronine (fT3) and thyroxine (fT4)) is related to the risk of overall mortality or a composite endpoint of death and nonfatal events.

Material and methods
In 614 middle-aged adult hospital screenees, free of uncontrolled diabetes at baseline, the association of sex-specific TSH tertiles with death was prospectively assessed using Cox regression, with the composite endpoint assessed using logistic regression in adjusted analyses, stratified by gender.

In total, 64 deaths and additional incident nonfatal events in 141 cases were recorded at a mean 7.55 years’ follow-up. Multivariable linear regression revealed TSH to be significantly associated among men with age (p = 0.006), but in women inversely with fT3 and fT4 (p < 0.001, and p = 0.024 respectively). In logistic regression analysis, adjusted for age, fT3, fT4, systolic blood pressure and serum total cholesterol, sex-specific baseline TSH tertiles were associated in men neither with the risk of death nor with composite endpoint. In contrast, in women, the highest compared with the bottom TSH tertile predicted the risk of composite endpoint (relative risk: 2.02, 95% CI: 1.07–3.82) and, much more strongly, the mortality risk, independently of fT4 increments.

The significant association of higher range of normal serum TSH in euthyroid middle-aged adults with the risk of death and nonfatal adverse outcomes in women alone cannot be accounted for by the action of thyroid hormone and is consistent with involvement of TSH in the pro-inflammatory state.


cardiovascular events, euthyroid status, mortality, pro-inflammatory state, thyroid hormones, thyroid-stimulating hormone

Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in the elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001; 358: 861-65.
Åsvold BO, Bjøro T, Nilsen TI, Gunnell D, Vatten LJ. Thyrotropin levels and risk of fatal coronary heart disease. Arch Intern Med 2008; 168: 855-60.
Onat A, Hergenç G. Low-grade inflammation and dysfunction of high-density lipoprotein and its apolipoproteins as a major driver of cardiometabolic risk. Metabolism 2011; 60: 499-512.
Onat A, Hergenç G, Bulur S, Uğur M, Küçükdurmaz Z, Can G. The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks. Int J Cardiol 2010; 142: 72-9.
Onat A, Can G, Murat S, Çiçek G, Örnek E, Yüksel H. Aggregation of lipoprotein(a) to apolipoprotein A-I underlying HDL dysfunction as a major coronary risk factor. Anadolu Kardiyol Derg 2013; 13: 543-51.
Onat A, Çoban N, Can G, et al. Low “quotient” Lp(a) concentration mediating autoimmune activation predicts cardiometabolic risk. Exp Clin Endocr Diabetes 2014; 122: 11-8.
Onat A, Can G, Ademoğlu E, Çelik E, Karagöz A, Örnek E. Coronary disease risk curve of serum creatinine is linear in Turkish men, U-shaped in women. J Investig Med 2013; 61: 27-33.
Onat A, Yüksel H, Can G, Köroğlu B, Kaya A, Altay S. Serum creatinine is associated with coronary disease risk even in the absence of metabolic disorders. Scand J Clin Lab Inv 2013; 73: 569-75.
Altay S, Onat A, Özpamuk-Karadeniz F, Karadeniz Y, Kemaloğlu-Öz T, Can G. Renal “hyperfiltrators” are at elevated risk of death and chronic diseases. BMC Nephrol 2014; 15: 160.
Onat A, Köroğlu B, Can G, Karagöz A, Çelik E, Aydın M. Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. Anadolu Kardiyol Derg 2014; 14: 26-33.
Onat A, Can G. Enhanced pro-inflammatory state and autoimmune activation: a breakthrough to understanding chronic diseases. Curr Pharm Design 2014; 20: 575-84.
Onat A, Aydın M, Can G, et al. Normal thyroid-stimulating hormone levels, autoimmune activation, and coronary heart disease risk. Endocrine 2014; 48: 218-26.
Pereg D, Tirosh A, Elis A, et al. Mortality and coronary heart disease in euthyroid patients. Am J Med 2012; 125: 826e7-13.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012; 35 (Suppl 1): S64-71.
Laclaustra M, Hurtado-Roca Y, Sendin M, et al. Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on Spanish men. Nutr Metab Cardiovasc Dis 2015; 25: 1095-103.
Zhang Y, Chang Y, Ryu S, et al. Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung Health Study. J Clin Endocrinol Metab 2014; 99: 2467-76.
Rhee CM, Kim S, Gillen DL, et al. Association of thyroid functional disease. J Clin Endocrinol Metab 2015; 100: 1386-95.
Van de Ven AC, Netea-Maier RT, de Vegt F, et al. Associations between thyroid function and age. Eur J Endocrinol 2014; 171: 183-91.
Åsvold BO, Bjøro T, Platou C, Vatten LJ. Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT study in Norway. Clin Endocrinol 2012; 77: 911-7.
Ittermann T, Haring R, Sauer S, et al. Decreased serum TSH levels are not associated with mortality in the adult northeast German population. Eur J Endocrinol 2010; 162: 579-85.
Westerink J, van der Graaf Y, Faber DL, et al. Relation between thyroid-stimulating hormone and the occurrence of cardiovascular events and mortality in patients with manifest vascular diseases. Eur J Prev Cardiol 2012; 19: 864-73.
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 2014; 9: 51-7.
Ndrepepa G, Braun S, Mayer K, et al. Prognostic value of thyroid-stimulating hormone within reference range in patients with coronary artery disease. Metabolism 2015; 64: 1308-15.
Leader A, Ayzenfeld RH, Lishner M, et al. Thyroteopin levels within the lower normal range are associated with an increased risk of hip fractures in euthyroid women, but not men, over the age of 65 years. J Clin Endocrinol Metab 2014; 99: 2665-72.
Dodani S, Dong L, Guirgis FW, Reddy ST. Carotid intima media thickness and low high-density lipoprotein (HDL) in South Asian immigrants: could dysfunctional HDL be the missing link? Arch Med Sci 2014; 10: 870-9.
Jung CH, Rhee EJ, Shin HS, et al. Higher serum free thyroxine levels are associated with coronary artery disease. Endocrine J 2008; 55: 819-26.
Lee JJ, Pedley A, Marqusee E, et al. Thyroid function and cardiovascular disease risk factors in euthyroid adults: a cross-sectional and longitudinal study. Clin Endocrinol (Oxf) 2016 Jun 3. doi: 10.1111/cen.13124.
Cappola AR, Arnold AM, Wulczyn K, et al. Thyroid function in the euthyroid range and adverse outcomes in older adults. J Clin Endocrinol Metab 2015; 100: 1088-96.
Türemen EE, Çetinarslan B, Şahin T, et al. Endothelial dysfunction and low-grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocrine J 2011; 58: 349-54.
Onat A, Karadeniz Y, Tusun E, Kaya A. Advances in understanding gender difference in cardiometabolic disease risk. Expert Rev Cardiovasc Ther 2016; 14: 513-23.
Özcan KS, Osmonov D, Toprak E, et al. Sick euthyroid syndrome is associated with ST segment elevation myocardial infarction undergoing primary percutaneous intervention. Cardiology J 2014; 21: 238-44.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe