Thyroid hormones and cardiovascular disease Jabbar, Avais; Pingitore, Alessandro; Pearce, Simon H S ...
Nature reviews cardiology,
01/2017, Volume:
14, Issue:
1
Journal Article
Peer reviewed
Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones ...in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome - adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.
Milk is widely fortified, but in the UK only infant formula milk and margarine have statutory vitamin D supplementation (1-2.5 μg (40-100 IU) per 100 kCal and 8 μg (320 IU) per 100 g, ...respectively). ...the typical UK diet, and that of many other countries, is profoundly lacking in vitamin D. A low dietary vitamin D intake, combined with the lack of skin synthesis for half of the year, is reflected in the disturbingly high prevalence of vitamin D insufficiency across the UK. 3 5 How can vitamin D deficiency and insufficiency be determined?
Full text
Available for:
BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract
Graves’ hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive ...thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves’ hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves’ patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves’ hyperthyroidism.
Graphical Abstract
Graphical Abstract
IMPORTANCE: Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis. ...OBJECTIVE: To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non–ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017. INTERVENTIONS: Levothyroxine treatment (n = 46) commencing at 25 µg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup n = 60), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. RESULTS: Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% 95% CI, −0.93% to 2.46%; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. CONCLUSIONS AND RELEVANCE: In this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction. TRIAL REGISTRATION: isrctn.org Identifier: http://www.isrctn.com/ISRCTN52505169
Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. ...Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.
We provide guidance on prevention of adrenal crisis during the global COVID-19 crisis, a time with frequently restricted access to the usual level of healthcare. Patients with adrenal insufficiency ...are at an increased risk of infection, which may be complicated by developing an adrenal crisis; however, there is currently no evidence that adrenal insufficiency patients are more likely to develop a severe course of disease. We highlight the need for education (sick day rules, stringent social distancing rules), equipment (sufficient glucocorticoid supplies, steroid emergency self-injection kit) and empowerment (steroid emergency card, COVID-19 guidelines) to prevent adrenal crises. In patients with adrenal insufficiency developing an acute COVID-19 infection, which frequently presents with continuous high fever, we suggest oral stress dose cover with 20 mg hydrocortisone every 6 h. We also comment on suggested dosing for patients who usually take modified release hydrocortisone or prednisolone. In patients with adrenal insufficiency showing clinical deterioration during an acute COVID-19 infection, we advise immediate (self-)injection of 100 mg hydrocortisone intramuscularly, followed by continuous i.v. infusion of 200 mg hydrocortisone per 24 h, or until this can be established, and administration of 50 mg hydrocortisone every 6 h. We also advise on doses for infants and children.
Adrenal insufficiency is characterised by inadequate glucocorticoid production owing to destruction of the adrenal cortex or lack of adrenocorticotropic hormone stimulation. In primary adrenal ...insufficiency, lack of mineralocorticoids is also a feature. Patients can present with an insidious onset of symptoms, or acutely in adrenal crisis, which requires prompt recognition and treatment. Chronic glucocorticoid therapy is the most common cause of adrenal insufficiency. The diagnosis of adrenal insufficiency is made by demonstrating low basal and/or stimulated serum cortisol and should be followed by appropriate investigations to establish the underlying aetiology. Maintenance glucocorticoid replacement is usually given as a twice or thrice daily hydrocortisone preparation. Patients with primary adrenal insufficiency also require mineralocorticoid. Regular monitoring for features of under- and over- replacement is essential during follow-up. Patient education is a key feature of management of this condition.
Full text
Available for:
GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Context:
Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood.
Objective:
This study sought to determine whether thyroid ...hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds.
Design:
A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years.
Setting and Participants:
Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom.
Main Outcomes:
All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT4, FT3, and rT3). Models were adjusted for age, sex, education, body mass index, smoking, and disease count.
Results:
After adjustment for age and sex, all-cause mortality was associated with baseline serum rT3 and FT3 (both P < .001), but not FT4 or TSH. After additional adjustment for potential confounders, only rT3 remained significantly associated with mortality (P = .001). Baseline serum TSH and rT3 predicted future disability trajectories in men and women, respectively.
Conclusions:
Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serum TSH levels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges.
In a cohort of 85 year olds, serum reverse T3 and FT3, but not TSH or FT4, predicted mortality over 9 years. TSH and reverse T3 predicted disability outcomes in men and women, respectively.
Context: Subclinical hypothyroidism (SCH) is a common condition that has been associated with ischemic heart disease (IHD) in some, but not all, studies. This may be due to differences in study ...design and the characteristics of participants.
Objective: Our objective was to investigate whether age and gender influence IHD prevalence, incidence, and mortality in people with SCH.
Data Sources: Computerized (PubMed, EMBASE, and Cochrane Library) and manual searches of the literature to May 2007, published in English, were performed.
Study Selection: Epidemiological studies that quantified thyroid status and IHD events in adults were performed.
Data Extraction: Two authors independently reviewed articles and abstracted data. Results were compared across two groups based on the minimum age of participants studied (younger than 65 yr and 65 yr or older).
Data Synthesis: There were 15 studies included for analysis with 2,531 SCH participants and 26,491 euthyroid individuals. IHD incidence and prevalence were higher in SCH subjects compared with euthyroid participants from studies including those younger than 65 yr, but not studies of subjects aged older than 65 yr odds ratio (95% confidence interval): 1.57 (1.19–2.06) vs. 1.01 (0.87–1.18) and 1.68 (1.27–2.23) vs. 1.02 (0.85–1.22), respectively. Cardiovascular/all-cause mortality was also elevated in participants from the younger than 65-yr studies, but not from the studies of older people: odds ratio 1.37 (1.04–1.79) vs. 0.85 (0.56–1.29). Prevalent IHD was higher in SCH participants of both genders, although this was statistically significant only in women.
Conclusions: SCH is associated with increased IHD (both prevalence and incidence) and cardiovascular mortality only in subjects from younger populations. These data suggest that increased vascular risk may only be present in younger individuals with SCH.
Context:
Several studies have reported an association between low serum TSH, or subclinical hyperthyroidism (SH), and dementia, but little emphasis has been placed on this field because not all ...studies have demonstrated the same association. We performed a detailed systematic review to assess the evidence available to support the association between these two conditions.
Methods:
We performed a systematic search through the PubMed, Embase (1996 to 2012 wk 4), Cochrane Library, and Medline (1996 to January wk 4, 2012) electronic databases using key search terms encompassing subclinical hyperthyroidism, TSH, dementia, and cognitive impairment.
Results:
This review examines the 23 studies that provide information about the association between SH or lower serum TSH within the reference range and cognition. Fourteen of these studies, including several well-designed and well-powered cross-sectional and longitudinal analyses, have shown a consistent finding of an association between SH with cognitive impairment or dementia.
Conclusion:
There is a substantial body of evidence to support the association between SH and cognitive impairment, but there is no clear mechanistic explanation for these associations. Nor is there an indication that antithyroid treatment might ameliorate dementia. Larger and more detailed prospective longitudinal or randomized controlled trials are required to inform these important questions.
PDF
