Levothyroxine Substitution in Patients with Subclinical Hypothyroidism and the Risk of Myocardial Infarction and Mortality

Andersen, Murray N.; Olsen, Anne-Marie Schjerning; Madsen, Jesper; Faber, Jens; Torp‐Pedersen, Christian; Gislason, Gunnar; Selmer, Christian

doi:10.1371/journal.pone.0129793

Cited by 62 publications

(80 citation statements)

References 59 publications

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“…A few physiopathological processes can explain these finding. Firstly, a negative chronotropic and inotropic effect caused by bradycardia, with reduced myocardial contractility and reduced ventricular filling, can result in decreased cardiac output and as a consequence, activation of the reninangiotensin-aldosterone system and decline in plasmatic levels of atrial natriuretic factor [25][26][27]. Secondly, pre-glomerular vasoconstriction can occur as an adaptive response to filtrate overload due to a deficiency of reabsorption of sodium and water by the proximal tubules [3].…”

Section: Discussionmentioning

confidence: 99%

Influence of low free thyroxine on progression of chronic kidney disease

et al. 2020

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Background: Hypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism. Methods: We assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels.. Results: One thousand six hundred ten patients (64 ± 15 years, 46.8% men, 25.3% diabetic) were included. At beggnining of follow up eGFR was between 45 and 60, 30-45 and 15-30 ml/min/1.73m 2 in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria (19.6% with LFT vs. 15.4% without LFT, p = 0.032). Median follow-up time was of 21 months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was − 0.05(− 0.26, 0.23) ml/min/1.73m 2 , reaching 1.7(1.3, 2.4) ml/min/1.73m 2 by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT. Conclusions: We confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Influence of low free thyroxine on progression of chronic kidney disease

et al. 2020

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“…The lack of benefits of treatment has been demonstrated by several studies, mostly in older subjects 14,43‐46 . The findings from these studies are summarised in Table 2, and they will be briefly discussed here.…”

Section: Treatment Of Subclinical Hypothyroidismmentioning

confidence: 99%

“…This study suggests that, the oldest old subjects should be carefully followed without treatment and a wait‐and‐see strategy should be adapted. The study by Andersen et al, 45 is a retrospective cohort study to determine the effects of levothyroxine treatment on the incidence of MI. CV death, and all‐cause mortality in patients with SCH.…”

Section: Treatment Of Subclinical Hypothyroidismmentioning

confidence: 99%

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

Chrysant

2020

Int J Clin Pract

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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.

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“…In total, there were 22 eligible studies, including 19 randomized controlled trials (RCTs) and 3 cohort studies. In 14 RCTs (16 publications), nonpregnant adults who screened positive for hypothyroidism were randomized to receive either levothyroxine treatment or placebo, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and 5 RCTs 38-42 and 3 cohort studies [43][44][45] compared levothyroxine treatment to no treatment. The length of follow-up ranged from 3 to 36 months for the RCTs and between 5.0 and 7.6 years (median)…”

Section: Treatment Of Screen-detected Thyroid Dysfunctionmentioning

confidence: 99%

“…Very low-certainty evidence on adults aged 40-70 years and younger than 65 years from 2 cohort studies was used to inform outcomes for younger adults. 43,45 These 2 studies 43,45 reported a minimal reduction in all-cause mortality and equivocal results for cardiovascular outcomes (Appendix 3, Supplemental Table 1). Two cohort studies 43,44 reported no statistically significant differences in all-cause mortality or cardiovascular events for women or men between those treated and not treated with levothyroxine for screen-detected hypothyroidism.…”

Section: Mortality (All-cause and Cardiovascular) And Cardiovascular mentioning

confidence: 99%

Recommendation on screening adults for asymptomatic thyroid dysfunction in primary care

Birtwhistle

Morissette

Dickinson

et al. 2019

CMAJ

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his guideline from the Canadian Task Force on Preventive Health Care focuses on screening for thyroid dysfunction among asymptomatic nonpregnant adults in primary care beyond usual care and vigilance for signs and symptoms of thyroid dysfunction. Thyroid dysfunction is diagnosed based on abnormal levels of serum thyroid-stimulating hormone (TSH) and can be characterized as either hypo-or hyperthyroidism. Hypothyroidism results from impaired thyroid hormone production (i.e., thyroxine [T 4 ] or triiodothyronine [T 3 ]), leading to elevated levels of TSH. Hypothyroidism is often caused by autoimmune disorders (e.g., Hashimoto thyroiditis) or occurs as a sequela of hyperthyroidism treatment, which can render the thyroid gland nonfunctional. 1 Hyperthyroidism results from an overproduction of thyroid hormone, leading to the suppression of TSH. 1 Causes of hyperthyroidism include Graves disease, toxic multinodular goitre and toxic adenoma. 2 Signs and symptoms of thyroid dysfunction are variable between patients and often nonspecific. For hypothyroidism, symptoms may include tiredness, sensitivity to cold, dry skin, hair loss, weight gain and slowed movements and thoughts. 1,3-6 For hyperthyroidism, symptoms may include sinus tachycardia, atrial fibrillation, hyperactivity or irritability, intolerance to heat, tremor and weight loss. 1,2,7 Some people with thyroid dysfunction are asymptomatic. 8 If left untreated, hypothyroidism may increase the risk of cardiac dysfunction, hypertension, dyslipidemia, cognitive impairment and, in rare cases, myxedema coma. 3,9 Untreated hyperthyroidism may increase the risk of cardiac conditions (e.g., atrial fibrillation, heart failure) or bone fractures, and could lead to thyroid storm, an uncommon, life-threatening condition associated with tachycardia, extreme fatigue, fever and nausea. 2,10 Minor variations in thyroid function as measured by abnormal levels of TSH are often self-limiting. Observational studies have reported that levels of TSH appear to revert to normal without treatment in 37%-62% of patients with initially elevated levels and 51% with initially low levels, particularly for milder cases of thyroid dysfunction (mean follow-up 32-60 mo). 11,12 Screening is intended to detect thyroid dysfunction in asymptomatic patients in order to prevent adverse consequences of untreated thyroid dysfunction. 13 Screening is done by performing a blood test for TSH. Abnormal levels of TSH are followed up with additional diagnostic testing that often includes blood tests to measure thyroid hormone levels or other tests (e.g., ultrasound) as warranted. An estimated 10% of Canadians aged 45 years or older report that they have been diagnosed with thyroid dysfunction, and prevalence is higher in women (16%) than in men (4%). 14 Prevalence has also been reported to be higher in adults older than 85 years (16%), 14 GUIDELINE HEALTH SERVICES CPD

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Levothyroxine Substitution in Patients with Subclinical Hypothyroidism and the Risk of Myocardial Infarction and Mortality

Cited by 62 publications

References 59 publications

Influence of low free thyroxine on progression of chronic kidney disease

Influence of low free thyroxine on progression of chronic kidney disease

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

Recommendation on screening adults for asymptomatic thyroid dysfunction in primary care

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