Title:Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients
Volume: 14
Issue: 3
Author(s): Milan Obradovic, Zoran Gluvic, Emina Sudar-Milovanovic, Anastasija Panic, Jovana Trebaljevac, Vladan Bajic, Milos Zarkovic and Esma R Isenovic
Affiliation:
Keywords:
Nitric oxide, subclinical hypothyroidism, lipids, thyroid-stimulating hormone, biomarkers, cardiovascular disease.
Abstract: Subclinical hypothyroidism (SH) is characterized by a mildly elevated concentration of
thyroid stimulating hormone (TSH) despite free thyroxine (FT4) and triiodothyronine (FT3) levels
within the reference range. Numerous studies revealed SH to be an independent risk factor for
cardiovascular disease (CVD), including atherosclerosis, congestive heart failure, coronary heart
disease, ischemic heart disease and the associated mortality. The relationship between SH and CVD is well documented,
but the molecular mechanism underlying this correlation remain unknown. Endothelial dysfunction has been recognized
as an initial step leading to CVD in patients with SH. Changes in lipid profile, inflammation and/or oxidative stress
contribute to the endothelial dysfunction in SH. Moreover, the progression of SH is characterized by significantly decreased
nitrite and nitrate levels. Recent animal and clinical studies discussed in this review suggest that nitric oxide (NO)
levels could be a reliable biomarker for cardiovascular risk in SH. Understanding the regulation of NO production by thyroid
hormone may provide novel and useful knowledge regarding how endothelial dysfunction in SH is linked with CVD
and help us to uncover new treatments for SH. We suggest that serum NO level may be an indicator for the introduction
and dosage of levothyroxine (LT4) replacement therapy in SH patients. Future studies should focus on understanding
the molecular mechanisms underlying the effects of NO in physiological as well as in pathophysiological conditions
such as hypothyroidism and their clinical relevance.
