Age-Related Modifications in the Regulation of the Hypothalamic-Pituitary-Thyroid Axis

Abstract

We studied the hypothalamic-pituitary-thyroid function in two groups of healthy elderly subjects: group A (n = 23, age range 65-80 years), and group B (n = 11 age range 81-92 years), and in 32 controls, aged 20-60. A TRH test for TSH and prolactin was performed in all subjects, while the TSH circadian modulation was evaluated in elderly subjects only. Group B showed significantly lower fT₃ and TSH, and higher fT₄ levels with respect to controls (fT₃: 4.4 ± 0.2 vs. 5.2 ± 0.2 pmol/l, p < 0.05; fT₄: 13.1 ± 0.9 vs. 11.4 ± 0.4 pmol/l, p < 0.05; TSH: 1.07 ± 0.21 vs. 1.46 ± 0.13 mIU/1, p < 0.05). Morning TSH showed an inverse correlation with age (r = -0.42; p < 0.02) among the 34 elderly subjects, but not among controls. Evidence for TSH circadian modulation was found only in group A (nighttime TSH: 1.60 ± 0.17, vs. daytime: 1.25 ± 0.13 mIU/1, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 ± 0.64 mIU/1, p = 0.01; B: 5.02 ± 0.58 mIU/1, p < 0.01). The maximal PRL response was also blunted (A: 25.7 ± 2.6 μg/l, B: 27.7 ± 5.2 μg/l, p < 0.0005). In conclusion, a resetting of the pituitary threshold of the TSH feedback suppression, along with complex alterations in peripheral thyroid hormone levels, may progressively develop in older people, becoming apparent only with extreme senescence. Moreover, the TSH nocturnal surge may be lost with increasing age, thus providing evidence also for hypothalamic dysfunction.

Is Subclinical Hypothyroidism a Cardiovascular Risk Factor in the Elderly?

“…Accordingly, older people have lower TSH responses to thyrotropinreleasing hormone stimulation than do young people. In the oldest olds, the nocturnal surge of TSH is partially or completely lost, whereas the inhibitory effect of corticosteroids is attenuated (23,31).…”

“…However, there exist conflicting results concerning age-related serum TSH variations between earlier studies (mainly case-control or crosssectional) and recent large naturalistic studies (3, 16, 17, 19 -23). Former studies showed either unchanged or reduced serum TSH values along with declining FT 3 concentrations in healthy elderly humans (especially the oldest old), with low serum T 3 associated with better physical performance and higher lean body mass (16,17,23,24). This condition has been interpreted as an adaptive mechanism to prevent excessive catabolism and should be distinguished from the so-called "nonthyroidal illness syndrome" (frequently observed in older people), in which serum FT 3 decreases while FT 4 (within the normal range of healthy adults) and rT 3 (above the normal range of healthy adults) increase (25).…”

Aging and Subclinical Thyroid Dysfunction

“…Hypothalamic TRH content is reduced in aged rats [32,35] and thyrotroph response to TRH is mostly reported as decreased, both in rats [29,32,36] and [37,38] in humans. Non-stimulated TSH concentration has also been reported as relatively diminished by aging in a large population of older persons without hyperthyroidism, and in aging patients with resistance to thyroid hormone (and their non-affected relatives) [27].…”

A unifying hypothesis of Alzheimer's disease. I. Ageing sets the stage

“…Indices of the hypothalamic±pituitary±thyroid axis function in ageing individuals indicate a high incidence of thyroid hormone de®ciencies with normal or increased serum TSH, decreased stimulated TSH secretion, decreased sensitivity of the thyroid gland to TSH, impaired feedback control of T3 on pituitary thyrotrophs, decreased productive or releasing capacities of the thyroid gland and decreasing serum levels of T3 in ageing man, monkey and rat (Hesch et al, 1976;Harman et al, 1984;Drinka and Nolten, 1988;Monzani et al, 1996). T4 and T3 production rates are decreased in older rats and did not increase during overfeeding as observed in young adult rats (Katze, 1990).…”