CONTEXT: Longevity is associated with changes in circulating levels of thyroid hormone (TH) and/or TSH in animals and humans, but underlying mechanisms remain elusive.

OBJECTIVE: We explored in 38 offspring of nonagenarian participants from the Leiden Longevity Study, who are enriched for longevity and in their partners, ultradian and circadian rhythmicity of TSH, temporal relationship, and feedback and forward interplay between TSH and TH.

METHODS: We collected blood samples every 10 minutes for 24 hours for TSH and TH profiles. We used a deconvolution analysis to estimate basal (nonpulsatile), pulsatile, and other secretion parameters to characterize ultradian rhythmicity and locally weighted polynomial regression of TSH to assess circadian rhythmicity. A cross-correlation analysis was used to investigate the temporal relationship between TSH and TH and cross-approximate entropy to assess feedback and forward interplay between TSH and TH.

RESULTS: Compared with partners, offspring displayed higher mean (95% confidence interval [CI]) basal TSH secretion (34.3 [95% CI 27.2-43.1] mU/L per 24 hours vs 18.5 [95% CI 14.4-23.7] mU/L per 24 hours, P = .001) but no differences in ultradian or circadian properties of TSH. The temporal relationship between TSH and free T3 at zero delay was higher in offspring (0.48 ± 0.2) compared with partners (0.26 ± 0.4) (P = .05), but the feedback and forward interplay between TSH and TH did not differ.

CONCLUSIONS: Familial longevity is associated with increased basal TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH and TH.