TSH Suppression – Review of the Literature

Evron JM, Hummel SL, Reyes-Gastelum D, Haymart MR, Banerjee M, Papaleontiou M. Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans. JAMA Netw Open. 2022 May 2;5(5):e2211863. doi: 10.1001/jamanetworkopen.2022.11863. PMID: 35552725; PMCID: PMC9099430.

  • Population retrospective cohort study from 2004-2017
  • 705 000 patients , > 18 yrs of age using data from Veterans Health. 88% were male
    • Patients with thyroid cancer were excluded
  • Study gathered at least 2 TSH readings from time of medication initiation until death or end of study
  • Patients with exogenous hyperthyroidism (overmedicated) had an increased risk of cardiovascular mortality compared to those who were euthyroid (TSH 0.5 – 5.5 mU/L)
    • TSH < 0.1 mU/L = Hazard Ratio of 1.39
    • TSH 0.1 – 0.5 mU/L = Hazard Ratio of 1.13
  • Patients with elevated FT4 levels also had a increased risk
    • FT4 levels > 1.9ng/dL (> 24.45 pmol/L) = Hazard Ratio of 1.29

Clinical Takeaways
– TSH suppression below 0.5 mU/L can increase risk of cardiovascular mortality.
– The risk increases significantly if the TSH is suppressed <0.1 mU/L
– The risk is also increased in aging populations and those with prior history of cardiovascular disease
– Important to note that the HRs for the under treatment of HYPOthyroidism (TSH > 5.5 mU/L) were far greater than over treatment (see forest plot above)
– The conclusions of this large scale study echo the ones presented below and that appeared in our TSH suppression lecture

Other Supporting Research 

Maria Papaleontiou, Deborah A Levine, David Reyes-Gastelum, Sarah T Hawley, Mousumi Banerjee, Megan R Haymart, Thyroid Hormone Therapy and Incident Stroke, The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 10, October 2021, Pages e3890–e3900, https://doi.org/10.1210/clinem/dgab444

Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L. Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study. Thyroid. 2018 May;28(5):566-574. doi: 10.1089/thy.2017.0517. Epub 2018 Apr 26. PMID: 29631518.

Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L. Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk. Eur J Endocrinol. 2019 Jun 1;180(6):407-416. doi: 10.1530/EJE-19-0006. PMID: 31035256.

Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010 Jan;95(1):186-93. doi: 10.1210/jc.2009-1625. Epub 2009 Nov 11. PMID: 19906785.

Thayakaran R, Adderley NJ, Sainsbury C, Torlinska B, Boelaert K, Šumilo D, Price M, Thomas GN, Toulis KA, Nirantharakumar K. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ. 2019 Sep 3;366:l4892. doi: 10.1136/bmj.l4892. PMID: 31481394; PMCID: PMC6719286.