Year : 2013 | Volume
: 10 | Issue : 4 | Page : 3--4
TSH and longevity
Subhankar Chowdhury, Partha P Chakraborty
Department of Endocrinology & Metabolism; IPGME&R/SSKM Hospital, Kolkata, India
Professor & Head, Department of Endocrinology & Metabolism, Ronald Ross Building; 4th Floor, IPGME&R/SSKM Hospital, 244, A. J. C Bose Road, Kolkata - 20
The process of normal aging affects the hypothalamic-pituitary-thyroid axis in a number of ways, resetting of the set point being the most important of them. Contrary to the earlier belief, longevity has been reported to be associated with high serum TSH. Most recent studies have demonstrated an age dependent decline in serum free T3 levels, whereas FT4 levels remains relatively unchanged and TSH & rT3 levels increase with age. Two recent meta-analyses have shown increased risk of adverse cardiovascular outcomes in patients younger than 65 years of age, but not in those more than 65 year old. There is a good number of evidence documenting increased mortality in elderly individual with sub- clinical hyperthyroidism, which should be kept in mind while treating mildly elevated TSH in these patients. It is also important to remember that thyroid functions in the elderly closely mimics that found in sick euthyroid syndrome.
|How to cite this article:|
Chowdhury S, Chakraborty PP. TSH and longevity.Thyroid Res Pract 2013;10:3-4
|How to cite this URL:|
Chowdhury S, Chakraborty PP. TSH and longevity. Thyroid Res Pract [serial online] 2013 [cited 2020 Aug 9 ];10:3-4
Available from: http://www.thetrp.net/text.asp?2013/10/4/3/106801
In parallel with the other organ systems of the body, the human endocrine system is also affected by the ageing process. With regard to thyroid function, the age related alterations are not well defined. The process of ageing affects both the prevalence and clinical presentation of hypo and hyperthyroidism. It was shown previously that serum thyroid stimulating hormone (TSH) is suppressed in elderly individuals,  the decreased thyroid hormone levels observed in ageing are due to lower TSH concentration. The pituitary set point was also said to be modified resulting in lesser serum TSH elevation in response to low circulatory thyroid hormones in older subjects.  Centenarians were found to exhibit significantly lower TSH levels together with slightly higher reverse T3 (rT3) levels than controls. However, in contrast to several previous documentations on the association between low TSH level and senescence, heritable longevity has been reported to be associated with high serum TSH and low free T4 (FT4) levels.  Thus, though the relation between the level of TSH and lifespan seems conflicting, most recent studies have demonstrated an age dependent decline in serum free T3 (FT3) levels, whereas FT4 levels remain relatively unchanged and TSH and rT3 levels increase with age. It should also be stressed that during ageing, gender specific alterations in TSH and FT4 levels were observed. With increasing age in males FT4 decreases much more than alteration in TSH concentrations, whereas in females, the FT4 levels remain somewhat unchanged but TSH levels increase in an age-dependent manner.
The relation between lower family mortality history score of the parents of the nonagenarian siblings and higher TSH coupled with lower T4 levels in the nonagenarian siblings may indicate that lower activity of the pituitary-thyroid axis is a heritable phenotype that contributes to exceptional longevity in some families. The study by Atzmon et al.  also demonstrated that the offspring of people with exceptional longevity have somewhat higher serum TSH levels than age matched controls without familial longevity. The association between exceptional longevity and raised serum TSH has been well documented in a number of studies. ,
The gradual elevation in serum TSH concentration and distribution with increasing age,  probably suggests either a decline in thyroid function or a reset in the TSH set point with ageing. This increase could be partly due to an increase in prevalence of acquired autoimmune thyroid disease as there are ample evidences showing increased prevalence of anti-thyroid antibody with age.  Autoimmune thyroid disease, while probably present in some of the elderly population can not be solely responsible for this type of population shifts observed. The other possible explanations for this continuum of progressive increase in TSH with ageing, are increased prevalence of chronic systemic illness, effects of different medications, age related alterations in TSH glycosylation, atrophic non autoimmune changes in the thyroid or hypothyroidism. As an individual age, there could be changes in TSH bioactivity, thyroidal TSH responsiveness, thyroid hormone uptake and metabolism in peripheral tissues, thyroid hormone receptors, and cofactors that modulate the T3-responsiveness of a given gene in a given cell.
Alterations in thyroid physiology in chronic systemic illness, popularly known as sick euthyroid syndrome is associated with low levels of T3 and high levels of rT3, and, depending on the duration and the severity of the illness, low FT4 and subnormal to supranormal TSH. Some of these alterations closely mimic the changes in thyroid hormone levels observed in the elderly population. Therefore, distinguishing between changes related to "normal" ageing per se and changes that are disease related, is a major challenge to the treating physician while managing this particular group of patients.
Despite extensive research, the clinical implications of higher serum TSH observed with aging remain unclear, and it remains uncertain whether the raised serum TSH adversely affects health, has no clinical importance, or is a factor that simply contributes to healthy aging. , A lower activity of thyroid hormone, and thus a lower basal metabolic rate, could possibly serve as an adaptive mechanism to prevent excessive catabolism in the elderly. Furthermore, lowering oxidative metabolism will reduce DNA damage by reactive oxygen species. Considering the well established fact that centenarians have higher serum TSH concentration, this increase in serum TSH is supposed to play a favorable role in their healthy aging process regardless of the underlying mechanism. In this regard, it is worth mentioning that hypothyroidism is associated with extreme longevity in certain animal models. 
Subclinical hypothyroidism is said to be present when serum TSH concentration is above the upper reference limit and FT4 remains within the reference range. The prevalence increases with aging and ranges from 3-16% in individuals aged 60 years and older. This particular clinical entity being dependent on isolated raised serum TSH, accurate and age-specific reference ranges are of utmost clinical importance. A recent reanalysis of the NHANES III data, using age, sex and ethnicity specific TSH reference limits, the 97.5 percentile for TSH values in whites between 70 to 79 years old was 5.6 mU/L, and for those over age 80 it was 6.6 mU/L. The current recommendation of professional societies, albeit controversial, is to treat patients of subclinical hypothyroidism with levothyroxine. , Data concerning adverse health consequences in untreated subclinical hypothyroidism are conflicting. Numerous studies on cardiovascular outcomes in subclinical hypothyroidism and even several meta-analyses have come to opposite conclusions.  However, two recent meta-analyses suggest that increased risk for adverse cardiovascular outcomes occurs in patients younger than 65 years of age, but not in those more than 65 year old. There is evidence that a low activity of thyroid hormone might be beneficial in the elderly, whereas sub clinical hyperthyroidism is a predictor of mortality. Until these issues are settled by further research, it seems prudent not to treat routinely elderly patients with levothyroxine because they are found to have a minimal increase in serum TSH.
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