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      Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile

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          Abstract

          Previous studies suggested that subclinical hypothyroidism has a detrimental effect on cardiovascular risk factors, and that its effective treatment may have a beneficial impact on overall health. The main purpose of this review and meta-analysis was to assess whether subclinical hypothyroidism treatment is of clinical relevance, based on cardiovascular risk parameters correction. A systemic research of the literature using MEDLINE tool was performed to identify the relevant studies. Only placebo-controlled randomized control trials were included. A quantitative analysis was also performed. This systematic review and meta-analysis of randomized placebo-controlled trials assess the different impact of levothyroxine vs placebo treatment. A significant decrease in serum thyroid-stimulating hormone and total and low-density lipoprotein cholesterol was obtained with levothyroxine therapy (66, 9 and 14%, respectively) and, although modest, this could be significant in terms of reduction of the incidence of coronary artery disease. Other significant results of lipid parameters were not obtained. This systematic review provides a strong evidence-based data in favour of specific changes and beneficial effects of levothyroxine treatment.

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          Most cited references35

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          The clinical significance of subclinical thyroid dysfunction.

          Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.
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            Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.

            Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based clinical guidelines for the clinical management of hypothyroidism in ambulatory patients. The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update. Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered. Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.
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              Thyroid disease and lipids.

              The composition and the transport of lipoproteins are seriously disturbed in thyroid diseases. Overt hypothyroidism is characterized by hypercholesterolaemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A) because of a decreased fractional clearance of LDL by a reduced number of LDL receptors in the liver. The high-density lipoprotein (HDL) levels are normal or even elevated in severe hypothyroidism because of decreased activity of cholesteryl-ester transfer protein (CETP) and hepatic lipase (HL), which are enzymes regulated by thyroid hormones. The low activity of CETP, and more specifically of HL, results in reduced transport of cholesteryl esters from HDL(2) to very low-density lipoproteins (VLDL) and intermediate low-density lipoprotein (IDL), and reduced transport of HDL(2) to HDL(3). Moreover, hypothyroidism increases the oxidation of plasma cholesterol mainly because of an altered pattern of binding and to the increased levels of cholesterol, which presents a substrate for the oxidative stress. Cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Hypothyroidism is often accompanied by diastolic hypertension that, in conjunction with the dyslipidemia, may promote atherosclerosis. However, thyroxine therapy, in a thyrotropin (TSH)-suppressive dose, usually leads to a considerable improvement of the lipid profile. The changes in lipoproteins are correlated with changes in free thyroxine (FT(4)) levels. Hyperthyroidism exhibits an enhanced excretion of cholesterol and an increased turnover of LDL resulting in a decrease of total and LDL cholesterol, whereas HDL are decreased or not affected. The action of thyroid hormone on Lp(a) lipoprotein is still debated, because both decrease or no changes have been reported. The discrepancies are mostly because of genetic polymorphism of apo(a) and to the differences between the various study groups. Subclinical hypothyroidism (SH) is associated with lipid disorders that are characterized by normal or slightly elevated total cholesterol levels, increased LDL, and lower HDL. Moreover, SH has been associated with endothelium dysfunction, aortic atherosclerosis, and myocardial infarction. Lipid disorders exhibit great individual variability. Nevertheless, they might be a link, although it has not been proved, between SH and atherosclerosis.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                February 2017
                01 March 2017
                : 6
                : 3
                : 188-199
                Affiliations
                [1 ]Faculty of Medicine University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal
                [2 ]Department of Endocrinology Diabetes and Metabolism, Centro Hospitalar S. João, Alameda Professor Hernâni Monteiro, Porto, Portugal
                [3 ]Instituto de Investigação e Inovação em Saúde Universidade do Porto, Porto, Portugal
                Author notes
                Correspondence should be addressed to I M Abreu; Email: isabelmrabreu1992@ 123456gmail.com
                Article
                EC170028
                10.1530/EC-17-0028
                5428911
                28249936
                a13eb6b1-3e62-4c76-a523-a67b1639b298
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License..

                History
                : 14 February 2017
                : 1 March 2017
                Categories
                Research

                subclinical,hypothyroidism,treatment,lipids
                subclinical, hypothyroidism, treatment, lipids

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