Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone

Research output: Contribution to journalJournal articleResearchpeer-review

  • Ana Zutinic
  • Hanno Pijl
  • Bart E Ballieux
  • Ferdinand Roelfsema
  • Westendorp, Rudi GJ
  • Gerard J Blauw
  • Diana van Heemst

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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number7
Pages (from-to)e2572–e2580
Number of pages9
Publication statusPublished - 1 Jul 2020

Bibliographical note

© Endocrine Society 2020.

    Research areas

  • Aged, Case-Control Studies, Female, Humans, Longevity/genetics, Male, Middle Aged, Recombinant Proteins/pharmacology, Thyroid Gland/drug effects, Thyrotropin/blood, Thyroxine/blood, Triiodothyronine/blood

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