TY - JOUR

T1 - Circulating Thyroid Hormone Profile in Response to a Triiodothyronine Challenge in Familial Longevity

AU - Zutinic, Ana

AU - Blauw, Gerard J.

AU - Pijl, Hanno

AU - Ballieux, Bart E.

AU - Westendorp, Rudi G. J.

AU - Roelfsema, Ferdinand

AU - van Heemst, Diana

PY - 2020

Y1 - 2020

N2 - ContextFamilial 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.ObjectiveWe hypothesized that members from long-lived families (offspring) have higher thyroid hormone turnover or less negative feedback effect on TSH secretion compared to controls.MethodsIn 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.ResultsCirculating 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 (%).ConclusionsMembers 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.

AB - ContextFamilial 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.ObjectiveWe hypothesized that members from long-lived families (offspring) have higher thyroid hormone turnover or less negative feedback effect on TSH secretion compared to controls.MethodsIn 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.ResultsCirculating 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 (%).ConclusionsMembers 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.

KW - thyroid

KW - TSH

KW - 3,5,3 '-triiodothyronine

KW - longevity

KW - negative feedback

U2 - 10.1210/jendso/bvaa117

DO - 10.1210/jendso/bvaa117

M3 - Journal article

C2 - 32964174

VL - 4

JO - Endocrine Research Communications

JF - Endocrine Research Communications

SN - 0743-5800

IS - 10

M1 - bvaa117

ER -