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

The Journal of Clinical Endocrinology & Metabolism, vol. 105, pp. e2572–e2580

Abstract

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.

Authors 7

1. Ana Zutinic corresponding Aachen Department of Internal Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Divis ion of Gerontology and Geriatrics, Leiden University Medical Centre, ZA, Leiden, The Netherlands

2. Hanno Pijl Aachen Department of Internal Medicine Division of Endocrinology and Metabolic Diseases

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, ZA, Leiden, The Netherlands

3. Bart E.P.B. Ballieux Aachen Department of Clinical Chemistry Laboratory Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, ZA, Leiden, The Netherlands

4. Ferdinand Roelfsema Aachen Department of Internal Medicine Division of Endocrinology and Metabolic Diseases

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, ZA, Leiden, The Netherlands

5. Rudi G. J. Westendorp

   University of Copenhagen

   Affiliation as printed

   Public Health and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark

6. Gerard J. Blauw Aachen Department of Internal Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Divis ion of Gerontology and Geriatrics, Leiden University Medical Centre, ZA, Leiden, The Netherlands

7. Diana van Heemst Aachen Department of Internal Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Divis ion of Gerontology and Geriatrics, Leiden University Medical Centre, ZA, Leiden, The Netherlands