Levothyroxine Improves Abnormal Cardiac Bioenergetics in Subclinical Hypothyroidism: A Cardiac Magnetic Resonance Spectroscopic Study

Madathil, Asgar; Hollingsworth, Kieren G.; Blamire, Andrew M.; Razvi, Salman; Newton, Julia L.; Taylor, Roy; Weaver, Jolanta U.

doi:10.1210/jc.2014-2942

Cited by 25 publications

(14 citation statements)

References 16 publications

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“…Studies of euthyroid individuals found positive association between the TSH levels and coronary heart disease (CHD)-related mortality 29 . The TSH levels within the normal range are inversely associated with all-cause mortality 18,[30][31][32][33] . Adult Taiwanese subjects with SH were reported to have an increased risk of all-cause mortality and CVD death over a 10-year period 34 .…”

Section: Discussionmentioning

confidence: 99%

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The frequency of metabolic syndrome in patients with the subclinical hypothyroidism

et al. 2018

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Background/Aim. An increased cardiovascular risk of thyroid dysfunction is associated with the impairment of lipid and lipoprotein metabolism, endothelial dysfunction, metabolic, hormonal, hemodynamic changes and coagulation disorders. Subclinical hypothyroidism is characterized by supernormal thyroid-stimulating hormone (TSH) level along with normal values of thyroid hormones. The association of subclinical hypothyroidism with higher cardiovascular risk has not been fully clarified. The aim of the study was to determine the frequency of metabolic syndrome and the associated cardiovascular risk factors in patients with the subclinical hypothyroidism. Method. The study included 140 subjects aged from 18 to 65 years, out of which 105 subjects had subclinical hypothyroidism and 35 subjects were the euthyroid controls. The clinical trial program, completed in all subjects, included: detailed medical history and physical examination, waist circumference, and laboratory tests [fasting glycemia, lipid and lipoprotein status, free triiodothyronine (FT3) and free thyroxine (FT4) and TSH levels]. Results. Out of 105 patients with the subclinical hypothyroidism, mean age 44.15 ± 11.23 years, 77 (73.3%) patients had metabolic syndrome. In the control group consisting of 35 subjects, mean age 33.80 ± 10.60 years, only 3 (8.6%) subjects had metabolic syndrome. Mean values of the waist circumference, fasting glycemia, triglycerides, systolic and diastolic blood pressure were higher in subclinical hypothyroidism group in relation to the controls (p < 0.0001). Mean value of high-density lipoprotein (HDL) cholesterol was lower in subclinical hypothyroidism group as compared to the controls (p < 0.002). Conclusion. The frequency of metabolic syndrome was 9 times higher in subjects with the subclinical hypothyroidism in relation to subjects without any subclinical hypothyroidism.

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Section: Discussionmentioning

confidence: 99%

“…The authors presume that benefit from l-thyroxine treatment of these patients will reflect in reduction of CD related mortality 13,14,[17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

The frequency of metabolic syndrome in patients with the subclinical hypothyroidism

et al. 2018

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“…All of these results implied that TSH might play non-classical extrathyroidal roles in proinflammatory functions, platelet activation and the enhancement of oxidative stress through eicosanoids. These effects might be important mechanisms underlying the susceptibility of SH patients to atherosclerosis, coronary heart disease and other serious cardiovascular diseases [35] . It is generally accepted that SSH patients should be treated with LTR.…”

Section: Discussionmentioning

confidence: 99%

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients

Zhang

et al. 2016

Acta Pharmacol Sin

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Aim: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. Methods: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. Results: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. Conclusion: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

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“…Cardiovascular risks associated with hypothyroidism include impaired cardiac contractility and diastolic function, increased systemic vascular resistance, possibly caused by decreased endothelial-derived relaxation factor, and elevated levels of serum cholesterol, C-reactive protein and homocysteine [ 37 ]. Abnormal cardiac bioenergetics in hypothyroidism is improved by substitution with levothyroxine [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Second degree AV block and severely impaired contractility in cardiac myxedema: a case report

et al. 2015

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The heart is a major target organ for thyroid hormone action. Severe overt hypothyroidism can result in diastolic hypertension, lowered cardiac output, impaired left ventricular contractility and diastolic relaxation, pericardial effusion and bradycardia. However, the function of the atrial pacemaker is usually normal and the degree by which the heart rate slows down is often modest. Here we report the case of a 20 year old male Caucasian with severe overt hypothyroidism. He presented with syncopation due to second degree atrioventricular block type Mobitz 2 and heart failure with reduced ejection fraction (38 %). Laboratory testing revealed a severe overt hypothyroidism with markedly elevated TSH (>100 mIU/L) and reduced fT3 and fT4 levels. The condition was caused by hypothyroid Graves’ disease (Graves’ disease with Hashimoto component). Although magnetic resonance imaging of the heart demonstrated decreased cardiac contractility and pericardial effusion, suggesting peri-myocarditis, plasma levels for BNP and troponin I were low. A possible infectious cause was unlikely, since testing for cardiotropic viruses was negative. The patient was treated with intravenous levothyroxine and after peripheral euthyroidism had been achieved, left ventricular ejection fraction returned to normal and pericardial effusion dissolved. Additionally, bradycardiac episodes abated, although intermittent second degree AV block was still occasionally present during the night. In conclusion, overt hypothyroidism may be associated by cardiac myxedema affecting both electrophysiology and contractility, observations that underscore the necessity of thyroid testing in different phenotypes of heart failure.Electronic supplementary materialThe online version of this article (doi:10.1186/s13044-015-0018-2) contains supplementary material, which is available to authorized users.

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Levothyroxine Improves Abnormal Cardiac Bioenergetics in Subclinical Hypothyroidism: A Cardiac Magnetic Resonance Spectroscopic Study

Abstract: Our results demonstrate early cardiac bioenergetic impairment in SCH, which is reversible with levothyroxine therapy. This mechanistic insight provides justification for longitudinal trials to determine whether improvement in bioenergetic function improves cardiovascular outcome.

Cited by 25 publications

References 16 publications

The frequency of metabolic syndrome in patients with the subclinical hypothyroidism

The frequency of metabolic syndrome in patients with the subclinical hypothyroidism

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients

Second degree AV block and severely impaired contractility in cardiac myxedema: a case report

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