The current debate over treatment of subclinical hypothyroidism to prevent cardiovascular complications

Abstract

Background Subclinical hypothyroidism (SCH) is an asymptomatic condition associated with increased thyroid‐stimulating hormone (TSH) >4 mIU/L with normal thyroxine (T4) and triidothyronine (T3) levels. It is more common in older subjects and especially in women with an overall incidence of 10%. Objective Because the normal TSH levels increase with age up to 7.5 mIU/L in older people, several studies have reported either no benefits whereas others have reported the benefits of treatment. These studies have caused a great debate over the treatment of SCH, especially in older subjects. Therefore, the objective of this study was to review the current evidence over this debate by reviewing the recent literature on the subject to discern whether treatment of SCH is necessary and under what circumstances. Methods To get a better perspective on the current debate over treatment of SCH, a focused Medline search of the English language literature was conducted from 2012 to 2019 using the terms, hypothyroidism, subclinical, dyslipidaemia, cardiovascular disease, heart failure and 38 papers with pertinent information were selected. Results The analysis of results from these papers indicated that the normal levels of TSH are increasing with the advancement of age from 4 mIU/L up to 7.5 mIU/L for patients ≥75 years of age. Also, several of reviewed studies have shown no benefits of treatment whereas, others have shown definite benefits of treatment with levothyroxine supplementation on the clinical and metabolic effects of SBH with reductions in CVD, HF and mortality. The treatment is more effective in younger persons and less so in older persons. Conclusions Based on the overall evidence, treatment of SCH is indicated in younger persons with a TSH level >4.0 mIU/L. In older subjects, treatment should be individualised and based on the presence of symptoms, the level of TSH, and initiated at TSH levels ≥10 mIU/L and at low doses to avoid adverse cardiovascular effects from overtreatment.

Levothyroxine for the Treatment of Subclinical Hypothyroidism and Cardiovascular Disease

“…Increased blood pressure in SCH may be a result of reduced thyroid hormone-mediated endothelialdependent vasodilation (16). Specific to dyslipidemia, decreased activity of both lipoprotein lipase activity in adipose tissue and hepatic lipase activity in the liver are thought to contribute to increased serum triglyceride levels (17). A reduced number of lowdensity lipoprotein (LDL) receptors and decreased cholesterol breakdown may also explain the dyslipidemia seen in SCH (16).…”

“…In addition to increasing metabolic risk factors, SCH may negatively impact cardiac function itself, with studies demonstrating a possible role of liothyronine (T3) in mitochondrial function and repair/ damage (18) and the improvement of cardiac output and reduction of peripheral vascular resistance upon T3 administration (19). Other studies have found that SCH is also associated with decreased ejection fraction, decreased arterial compliance, and increased risk of heart failure, possibly through increased reninangiotensin-aldosterone axis activation, increased vasoconstriction, increased sympathetic activity, and reduced renal blood flow and glomerular filtration rates (16,17).…”

Association between Subclinical Hypothyroidism and Albuminuria in Patients with Type 2 Diabetes Mellitus: A Cross Sectional Study in Iran

“…Other studies have shown that subclinical hypothyroidism can increase creatinine levels and ultimately decrease GFR [23,24]. Another hypothesis about the association between subclinical hypothyroidism and albuminuria is decreased cardiac output and increased peripheral vascular resistance in these patients [25,26]. Recent studies have shown that patients with subclinical hypothyroidism develop disorders in vascular endothelial structure through reduced endothelium-related vasodilation and nitric oxide disorders, leading to an increase in albuminuria and impaired renal function in these patients [27].…”

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“…Graves' hyperthyroidism is frequently manifested by systemic symptoms such as dermopathy, ophthalmopathy, and acropathy with high affinity to recurrence even after different therapeutic options [4]. More importantly, the likelihood of cardiovascular morbidity and mortality can also rise due to hyperthyroidism flare [5,6].…”