MODULE SUPPLEMENT: ENDOCRINE SYSTEM Hypothalamic-Pituitary-Thyroid Axis
The thyroid is important in multiple metabolic processes and, because basal metabolism declines with age, the thyroid use to be implicated in the aging process.
Consider the case mentioned earlier. Mr. Jones is a 72 year old African-American gentleman who came to clinic complaining of fatigue and difficulty concentrating, saying that he first noted this about six months ago but that it has gotten progressively worse. His workup reveals that he is hypothyroid.
Hypothalamic TRH stimulates the release of TSH (Thyroid Stimulating Hormone) from the pituitary while somatostatin can inhibit its release. TSH increases all known activities of the thyroid glandular cells. Thyroxine (T4) and triiodothyronine (T3) are both produced by the thyroid although the former is the major product with most of T3 arising from conversion of T4 to T3 in extrathyroidal tissues.
Not much is known about changes in TRH with age, and data on TSH tends to be somewhat conflicting. As compared to younger adults, reports have identified TSH to be slightly elevated, the same, or decreased in older adults, with a blunting of its circadian periodicity (Hassani & Hershman, 1999; Timiras, 2003). TSH may decline specifically in very elderly individuals (Hassani & Hershman, 1999; Magri, Muzzoni, et al., 2002).
Thyroxine (T4) is noted to stay within the normal range, with a decrease in both its secretion and clearance. Data on triiodothyronine (T3) are less clear with reports that it declines, especially in older men. A reduction in the peripheral conversion of T4 to T3 may be a factor in this decline (Timiras, 2003). However, although both hypo- and hyper- thyroidism are more common in older adults, which indicates a loss of reserve, normal healthy elderly individuals are able to maintain a euthyroid state.
Changes currently attributed to aging in the hypothalamic-pituitary-thyroid axis are conflicting but again suggest decreased reserve and also the potential effect of other concurrent problems on the findings from any study:
Measured TSH levels and its response to TRH: Increased, decreased,
and no significant change
Diurnal variation in TSH: Decreased
T4 production and removal: Decreased
Serum T4 levels: No significant change
Serum T3 levels: Possibly decreased or no change
Reverse T3: No significant change
It is important to realize that many non-thyroidal illnesses influence thyroid tests and that signs and symptoms of both hypo and hyper thyroidism are often much more subtle in older persons. For example, atrial fibrillation is a classic cardiac manifestation of hyperthyroidism that occurs almost exclusively in older persons. Congestive heart failure occurs in more than 50% of older persons with hyperthyroidism while exopthalmos is much less common. The incidence of apathetic hyperthyroidism is also more common. On the other hand, in hypothyroidism, about 2/3 of the cases have been noted to present with only debilitation and apathy, or be asymptomatic, or present again with congestive heart failure. Thus, it's very important to have a high index of suspicion regarding altered thyroid function and most older adults should be screened.
There are many functional reasons for being concerned about thyroid function, and cognition is one of them. Hypothyroidism is known to be associated with cognitive changes. However, some data also suggest that low normal levels of T4 are associated with lower levels of cognitive function in both men and women (Prinz, et al., 1999; Volpato, et al., 2002). The clinical implications of these findings need further study, but it suggests that monitoring thyroid function is an important aspect of the care for older adults.
