Hypothyroidism and Risk of Cardiovascular Disease.

Thyroid hormones (TH) have a significant impact on cellular oxidative metabolism. Besides that, they maintain vascular homeostasis by positive effects on endothelial and vascular smooth muscle cells. Subclinical (SCH) and clinical (CH) hypothyroidism influences target organs by changing their morphology and function and impaired blood and oxygen supply induced by accelerated atherosclerosis. The increased risk of acceleration and extension of atherosclerosis in patients with SCH and CH could be explained by dyslipidemia, diastolic hypertension, increased arterial stiffness, endothelial dysfunction, and altered blood coagulation. Instability of atherosclerotic plaque in hypothyroidism could cause excessive activity of the elements of innate immunity, which are characterized by the significant presence of macrophages in atherosclerotic plaques, increased nuclear factor kappa B (NFkB) expression, and elevated levels of tumor necrosis factor α (TNF-α) and matrix metalloproteinase (MMP) 9, with reduced interstitial collagen; all of them together creates inflammation milieu, resulting in plaque rupture. Optimal substitution by levothyroxine (LT4) restores biochemical euthyroidism. In postmenopausal women and elderly patients with hypothyroidism and associated vascular comorbidity, excessive LT4 substitution could lead to atrial rhythm disorders and osteoporosis. Therefore, it is of interest to maintain thyroid-stimulating hormone (TSH) levels in the reference range, thus eliminating the deleterious effects of lower or higher TSH levels on the cardiovascular system. This review summarizes the recent literature on subclinical and clinical hypothyroidism and atherosclerotic cardiovascular disease and discusses the effects of LT4 replacement therapy on restoring biochemical euthyroidism and atherosclerosis processes.

Regulation of nitric oxide production in hypothyroidism.

Hypothyroidism is a common endocrine disorder that predominantly occurs in females. It is associated with an increased risk of cardiovascular diseases (CVD), but the molecular mechanism is not known. Disturbance in lipid metabolism, the regulation of oxidative stress, and inflammation characterize the progression of subclinical hypothyroidism. The initiation and progression of endothelial dysfunction also exhibit these changes, which is the initial step in developing CVD. Animal and human studies highlight the critical role of nitric oxide (NO) as a reliable biomarker for cardiovascular risk in subclinical and clinical hypothyroidism. In this review, we summarize the recent literature findings associated with NO production by the thyroid hormones in both physiological and pathophysiological conditions. We also discuss the levothyroxine treatment effect on serum NO levels in hypothyroid patients.

Serum nitric oxide levels correlate with quality of life questionnaires scores of hypothyroid females.

Primary hypothyroidism can affect lipid metabolism, cardiovascular (CV) function, and overall patients' quality of life (QoL). Decrease in serum nitric oxide (NO) levels could promote the atherosclerosis acceleration in hypothyroid patients. Our hypothesis is that serum NO level is altered in hypothyroidism; more specifically, we hypothesize that the early vascular changes that can be observed in hypothyroidism could be due to these alterations and that serum NO levels are associated with lipid levels in female patients diagnosed with subclinical hypothyroidism (SCH) or clinical hypothyroidism (CH). Furthermore, since serum NO level is an early marker of atherosclerosis and related CV disorders, which are commonly present and follow hypothyreosis and greatly contribute to overall QoL, we further hypothesized that NO level would correlate with Thyroid Symptom Questionnaire (TSQ) and General Health Questionnaire 12 (GHQ12) scores in hypothyroid patients. A collaterally of our hypothesis was that levothyroxine (LT4) treatment would affect serum NO levels as well as TSQ and GHQ12 scores. Therefore, we have analyzed lipid profile, the level of NO and QoL scores in female patients diagnosed with SCH and CH in order to determine the correlation between NO and generic and thyroid disease symptoms in treatment naïve SCH and CH patients and after LT4 treatment and laboratory euthyroidism achievement. As a consequence of our hypothesis is that measurement of serum NO level in SCH and CH patients may be an innovative way to improve LT4 treatment efficacy. This assumption could have a practical significance for future investigations regarding the management of hypothyroidism treatment protocols in current guidelines.

Hypothesis regarding the effects of gonadotropins on the level of free fatty acids and phospholipids in serum and follicular fluid during controlled ovarian stimulation.

Controlled ovarian stimulation (COS) is used to augment the number of retrieved oocytes in in vitro fertilization (IVF). Follicular fluid (FF) contributes significantly to oocyte quality. Since the FF is composed of follicular secretions and plasma exudation, it reflects alterations in granulosa and thecal cells secretion as well as changes in the level of plasma constituents. Phospholipids (PL) and free fatty acids (FFA) are important constituents of both, FF and serum. Our hypothesis is that COS affects the level of PL and FFA in serum. Furthermore, since the level of PL and FFA in FF partially depends on their levels in serum, as a collaterally of our hypothesis is that the existing level of PL and FFA in serum correlates with the levels of PL and FFA in FF, and that the dose of applied gonadotropins during COS will correlate with the levels of PL and FFA in serum and FF. In addition, we assume that the level of PL and FFA in serum and in FF after COS will correlate with the retrieved number of GQ oocytes, one of the most important outcomes of COS. .