Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone
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Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone. / Zutinic, Ana; Pijl, Hanno; Ballieux, Bart E; Roelfsema, Ferdinand; Westendorp, Rudi G J; Blauw, Gerard J; van Heemst, Diana.
In: The Journal of clinical endocrinology and metabolism, Vol. 105, No. 7, 01.07.2020, p. e2572–e2580.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone
AU - Zutinic, Ana
AU - Pijl, Hanno
AU - Ballieux, Bart E
AU - Roelfsema, Ferdinand
AU - Westendorp, Rudi G J
AU - Blauw, Gerard J
AU - van Heemst, Diana
N1 - © Endocrine Society 2020.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - CONTEXT: Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown.OBJECTIVE: We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels.METHODS: We performed a case-control intervention study with a single intramuscular (gluteal) injection with 0.1 mg recombinant human TSH in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations.RESULTS: The AUC free T4/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean [95% confidence interval] 1.6 [1.2-1.9] and 2.2 [1.9-2.6], respectively, P = 0.01). The AUC thyroglobulin/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median [interquartile range] 2.1 [1.4-3.6] and 3.2 [2.7-7.4], respectively, P = 0.04). We observed the same trend with the AUC free T3/AUC TSH ratio, although the difference was not statistically significant (estimated mean [95% confidence interval] 0.6 [0.4-0.7] and 0.7 [0.6-0.8], respectively, P = 0.07).CONCLUSIONS: The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared with their partners.
AB - CONTEXT: Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown.OBJECTIVE: We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels.METHODS: We performed a case-control intervention study with a single intramuscular (gluteal) injection with 0.1 mg recombinant human TSH in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations.RESULTS: The AUC free T4/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean [95% confidence interval] 1.6 [1.2-1.9] and 2.2 [1.9-2.6], respectively, P = 0.01). The AUC thyroglobulin/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median [interquartile range] 2.1 [1.4-3.6] and 3.2 [2.7-7.4], respectively, P = 0.04). We observed the same trend with the AUC free T3/AUC TSH ratio, although the difference was not statistically significant (estimated mean [95% confidence interval] 0.6 [0.4-0.7] and 0.7 [0.6-0.8], respectively, P = 0.07).CONCLUSIONS: The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared with their partners.
KW - Aged
KW - Case-Control Studies
KW - Female
KW - Humans
KW - Longevity/genetics
KW - Male
KW - Middle Aged
KW - Recombinant Proteins/pharmacology
KW - Thyroid Gland/drug effects
KW - Thyrotropin/blood
KW - Thyroxine/blood
KW - Triiodothyronine/blood
U2 - 10.1210/clinem/dgaa195
DO - 10.1210/clinem/dgaa195
M3 - Journal article
C2 - 32303766
VL - 105
SP - e2572–e2580
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -
ID: 258781153