Reference Ranges for Thyroid-Stimulating Hormone and Free Thyroxine in Older Men: Results From the Health In Men Study

Background In older adults, thyroid-stimulating hormone (TSH) concentrations are raised and higher free thyroxine (FT4) is associated with poorer health outcomes. As use of nonage-appropriate reference ranges could lead to suboptimal management, we aimed to define reference intervals for TSH and FT4 in older men. Methods We conducted the study on community-dwelling men aged 70-89 years. Baseline TSH and FT4 levels were assayed (Elecsys 2010, Roche Diagnostics). Conventional reference intervals for TSH and FT4 were 0.4-4.0 mIU/L and 10-23 pmol/L, respectively. Incident deaths were ascertained using data linkage. Results Of the 3,885 men included in the analysis, the 2.5th and 97.5th centiles for TSH and FT4 were 0.64-5.9 mIU/L and 12.1-20.6 pmol/L (0.94-1.60ng/dL), respectively. Of the 411 very healthy men defined by excellent or very good self-rated health and absence of major medical comorbidities, 2.5th to 97.5th centiles for TSH and FT4 were 0.67-4.98 mIU/L and 12.1-20.5 pmol/L (0.94-1.59ng/dL), respectively. TSH was not associated with mortality, whereas higher FT4 was associated with increased mortality. Applying intervals based on very healthy older men to the cohort as a whole led to the reclassification of 310 men (8.0%). More men were classified as being hyperthyroid or hypothyroid, or having subclinical hyperthyroidism, and fewer as having subclinical hypothyroidism. Conclusions In older men, the reference interval for TSH in older men is shifted upward, whereas the reference interval for FT4 is compressed compared with the conventional reference ranges. Applying reference intervals based on healthy older men identifies a substantial number of older men as having overt thyroid disease or subclinical hyperthyroidism and reduces the number classified as having subclinical hypothyroidism.

[1]  L. Ferrucci,et al.  Free Thyroxine and Functional Mobility, Fitness, and Fatigue in Euthyroid Older Men and Women in the Baltimore Longitudinal Study of Aging. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[2]  T. Strandberg,et al.  Association of Self-Rated Health in Midlife With Mortality and Old Age Frailty: A 26-Year Follow-Up of Initially Healthy Men. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[3]  S. Benvenga,et al.  Circadian and Circannual Rhythms in Thyroid Hormones: Determining the TSH and Free T4 Reference Intervals Based Upon Time of Day, Age, and Sex. , 2015, Thyroid : official journal of the American Thyroid Association.

[4]  J. Hennessey,et al.  CLINICAL MANAGEMENT OF THE GERIATRIC PATIENT Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults : A Review of the Literature , 2015 .

[5]  A. Uitterlinden,et al.  Subclinical thyroid dysfunction and fracture risk: a meta-analysis. , 2015, JAMA.

[6]  O. Franco,et al.  Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis. , 2015, The Journal of clinical endocrinology and metabolism.

[7]  B. Psaty,et al.  Thyroid function in the euthyroid range and adverse outcomes in older adults. , 2015, The Journal of clinical endocrinology and metabolism.

[8]  R. Chou,et al.  Screening and Treatment of Thyroid Dysfunction: An Evidence Review for the U.S. Preventive Services Task Force , 2015, Annals of Internal Medicine.

[9]  M. Lishner,et al.  Thyrotropin 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. , 2014, The Journal of clinical endocrinology and metabolism.

[10]  J. Faix.  Principles and pitfalls of free hormone measurements. , 2013, Best practice & research. Clinical endocrinology & metabolism.

[11]  G. Hankey,et al.  Higher free thyroxine levels are associated with all-cause mortality in euthyroid older men: the Health In Men Study. , 2013, European journal of endocrinology.

[12]  G. Hankey,et al.  Higher free thyroxine levels predict increased incidence of dementia in older men: the Health in Men Study. , 2012, The Journal of clinical endocrinology and metabolism.

[13]  G. Hankey,et al.  Perception of worsening health predicts mortality in older men: the Health in Men Study (HIMS). , 2012, Archives of gerontology and geriatrics.

[14]  A. Newman,et al.  Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. , 2012, The Journal of clinical endocrinology and metabolism.

[15]  J. Franklyn,et al.  Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. , 2012, Archives of internal medicine.

[16]  G. Hankey,et al.  Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study , 2012, Clinical endocrinology.

[17]  A. Arnold,et al.  The natural history of subclinical hypothyroidism in the elderly: the cardiovascular health study. , 2012, The Journal of clinical endocrinology and metabolism.

[18]  J. Beilby,et al.  Age-related changes in thyroid function: a longitudinal study of a community-based cohort. , 2012, The Journal of clinical endocrinology and metabolism.

[19]  A. Arnold,et al.  Predictors of thyroid hormone initiation in older adults: results from the cardiovascular health study. , 2011, The journals of gerontology. Series A, Biological sciences and medical sciences.

[20]  M. Surks,et al.  An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. , 2011, Thyroid : official journal of the American Thyroid Association.

[21]  J. Franklyn,et al.  Subclinical hypothyroidism and the risk of coronary heart disease and mortality. , 2010, JAMA.

[22]  M. Beekman,et al.  Low serum free triiodothyronine levels mark familial longevity: the Leiden Longevity Study. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[23]  Leon Flicker,et al.  Cohort Profile: The Health In Men Study (HIMS). , 2009, International journal of epidemiology.

[24]  A. J. Bass,et al.  A decade of data linkage in Western Australia: strategic design, applications and benefits of the WA data linkage system. , 2008, Australian health review : a publication of the Australian Hospital Association.

[25]  M. Surks,et al.  Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. , 2007, The Journal of clinical endocrinology and metabolism.

[26]  G. Hankey,et al.  Association of cardiovascular risk factors and disease with depression in later life. , 2007, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[27]  Harvey J. Motulsky,et al.  Detecting outliers when fitting data with nonlinear regression – a new method based on robust nonlinear regression and the false discovery rate , 2006, BMC Bioinformatics.

[28]  K. Byth,et al.  Are Australian children iodine deficient? Results of the Australian National Iodine Nutrition Study , 2006, The Medical journal of Australia.

[29]  Joachim Thiery,et al.  New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. , 2005, Clinical chemistry.

[30]  H E Solberg,et al.  The theory of reference values Part 5. Statistical treatment of collected reference values. Determination of reference limits. , 1983, Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie.

[31]  J. Haerting,et al.  Thyroid analytes TSH, FT3 and FT4 in serum of healthy elderly subjects as measured by the Roche modular system: do we need age and gender dependent reference levels? , 2014, Clinical laboratory.

[32]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[33]  E. Gwinner,et al.  Circadian and circannual rhythms in birds , 1975 .