Age-related modifications in the regulation of the hypothalamic-pituitary-thyroid axis

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 fT(3) and TSH, and higher fT(4) levels with respect to controls (fT(3): 4.4 +/- 0.2 vs. 5.2 +/- 0.2 pmol/l, p < 0.05; fT(4): 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/l, 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/l, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 +/- 0.64 mIU/l, p = 0.01; B: 5.02 +/- 0.58 mIU/l, p < 0.01). The maximal PRL response was also blunted (A: 25.7 +/- 2.6 mu g/l, B: 27.7 +/- 5.2 mu g/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.