Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism

Nutr Metab Cardiovasc Dis. 2017 Oct;27(10):896-901. doi: 10.1016/j.numecd.2017.07.002. Epub 2017 Jul 11.

Abstract

Background and aim: Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F (8-iso-PGF) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy.

Methods and results: Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 μU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 μU/mL, p < 0.0001), sCD40L (from 6.11 ± 2.41 to 2.43 ± 2.00 ng/mL, p < 0.0001) and 8-iso-PGF (from 45.33 ± 6.94 to 40.36 ± 6.20, p < 0.0001) significantly decreased. Changes in circulating levels of sCD40L and 8-iso-PGF were directly correlated with each other (r = 0.349 p = 0.028) and with changes in TSH levels (r = 0.367 p = 0.020 and r = 0.339 p = 0.032, respectively).

Conclusion: Our study suggests an influential role of TSH on proatherogenic activation of platelets, probably through enhanced lipid peroxidation. These findings could partially explain the increased susceptibility of patients with subclinical hypothyroidism to develop atherosclerotic disease.

Keywords: Isoprostanes; Platelet activation; Thyroid hormones; sCD40 ligand.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Asymptomatic Diseases
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • CD40 Ligand / blood
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Female
  • Hormone Replacement Therapy*
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / diagnosis
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / etiology
  • Lipid Peroxidation / drug effects
  • Male
  • Middle Aged
  • Platelet Activation / drug effects*
  • Thyroidectomy / adverse effects*
  • Thyrotropin / blood
  • Thyroxine / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • CD40 Ligand
  • 8-epi-prostaglandin F2alpha
  • Thyrotropin
  • Dinoprost
  • Thyroxine