Endocrine Abstracts

Subclinical thyroid diseases are common, affecting around 5% of the general population, and rising in prevalence with advancing age. While some people have a congenital abnormality of the hypothalamic–pituitary–thyroid axis set point, for instance due to germline mutations that cause loss of TSH-receptor function, this does not appear to account for the majority of cases of subclinical thyroid disease. There is a change in the reference range for TSH (which is the defining parameter for subclinical thyroid diseases), such that the reference intervals are wider in advanced age. This has several implications.

Firstly, that age-specific reference ranges should be used when defining subclinical thyroid disease. Secondly, that there is a physiological ageing of the HPT axis, which leads to the widening of the reference intervals. Lastly, that we should be particularly cautious about treating subclinical thyroid diseases in the elderly, in the absence of any evidence for benefit.

To return to the second point, that there is physiological ageing of the HPT axis, and to apply this to the state of subclinical hyperthyroidism. There is a well documented drop in the lower limit of the reference range for TSH in advanced age, such that the median TSH values in centenarians is around 1.0 mU/l. Thus a substantial proportion of individuals of this age have a TSH value suggesting subclinical hyperthyroidism. This is likely due to a decrease in peripheral disposal of thyroid hormones and possibly changes in hypothalamo–pituitary sensitivity to thyroid hormones, both leading to decreased flux of thyroid hormone through the system and a lower axis ‘tone’. Both are also likely to be biological markers of advanced age. While it is known that individuals with subclinical hyperthyroidism have an adverse prognosis, with an excess in atrial fibrillation, vascular disease, dementia and osteoporosis, it remains unclear whether these morbidities are wholly due to the adverse effects of thyroid hormone on the heart and bone (i.e. there is true endogenous hyperthyroidism causing end organ damage). An alternative interpretation is that these degenerative disorders may simply be a consequence of advanced biological age, associated with the physiological decline in HPT axis. This latter possibility adds a layer of complexity to the management of elderly individuals with a low or suppressed TSH, but one which bears serious consideration in the clinical context of the oldest old.