How should We Treat Patients with Low Serum Thyrotropin Concentrations?

Anna L. Mitchell; Simon H. S. Pearce


Clin Endocrinol. 2010;72(3):292-296. 

In This Article

Thyroid Function and Ageing – Can Low TSH be Physiological?

Complex changes in thyroid physiology occur with increasing age.[2] When healthy elderly individuals are studied and the common confounders of thyroid disease, nonthyroidal illness and medication-related thyroid abnormalities are excluded, alterations in thyroid function are apparent, suggesting that they may represent physiological rather than pathological changes. Several studies have demonstrated a fall in median serum TSH levels in extreme old age or centenarians,[3] however, in the seventh and eighth decades of life there may be a rise in the median TSH level.[4,5]

There are several possible explanations for the changes in thyroid function in aging. A conventional analysis is that TSH secretion by the pituitary gland is reduced with advancing age.[6] Lower amplitude of nocturnal TSH pulses has been observed in healthy elderly volunteers, which may be as a result of decreased hypothalamic TRH secretion. Indeed, a blunted response to the TRH test has been demonstrated in elderly subjects,[7,8] suggesting increased pituitary sensitivity to circulating thyroid hormone levels. However, in common with hepatic drug clearance, thyroid hormone clearance is also known to decrease with increasing age. In parallel, thyroxine secretion may also be reduced, resulting in unchanged total and FT4 concentrations.[9] In contrast to this, total and FT3 levels are seen to decrease in the elderly, which is proposed to be due to reduced peripheral conversion of T4 to T3. Thus, either a central change in sensitivity to thyroid hormone feedback, reduced pituitary sensitivity to TRH or reduced peripheral hormone clearance leading to reduced axis tone and less throughput of thyroid hormone (i.e., less production, less clearance), or a combination of these mechanisms, could lead to the changes observed in the HPT axis with ageing.