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Context  Familial longevity is associated with higher circulating levels of thyrotropin (TSH), in the absence of differences in circulating thyroid hormones, and a lower thyroid responsivity to TSH, as previously observed in the Leiden Longevity Study (LLS). Further mechanisms underlying these observations remain unknown.    Objective  We hypothesized that members from long-lived families (offspring) have higher thyroid hormone turnover or less negative feedback effect on TSH secretion compared to controls.    Methods   In a case-control intervention study, 14 offspring and 13 similarly aged controls received 100 µg 3,5,3′-triiodothyronine (T3) orally. Their circulating T3, free T3 (fT3), and TSH levels were measured during 5 consecutive days. We compared profiles of circulating T3, fT3, and TSH between offspring and controls using general linear modeling (GLM) and calculated the percentage decline in TSH following T3 administration.    Results  Circulating T3 and fT3 levels increased to supraphysiologic values and normalized over the course of 5 days. There were no serious adverse events. T3 and fT3 concentration profiles over 5 days were similar between offspring and controls (T3 GLM  P  = .11, fT3 GLM  P  = .46). TSH levels decreased in a biphasic manner and started returning to baseline by day 5. The TSH concentration profile over 5 days was similar between offspring and controls (GLM  P  = .08), as was the relative TSH decline (%).    Conclusions  Members of long-lived families have neither higher T3 turnover nor diminished negative feedback of T3 on TSH secretion. The cause and biological role of elevated TSH levels in familial longevity remain to be elucidated.

Circulating Thyroid Hormone Profile in Response to a Triiodothyronine Challenge in Familial Longevity