Flame-retardant exposure increases thyroid disease risk in women


High blood levels of polybrominated diphenyl ethers, or PBDEs, a common type of flame retardant, may increase the risk for thyroid problems in women, with the effect more pronounced after menopause, according to study findings published in Environmental Health.

Joseph G. Allen, MPH, DSc, assistant professor of exposure assessment science at Harvard T.H. Chan School of Public Health, and colleagues evaluated data from women participating in the National Health and Nutrition Examination Survey 2003-2004 cycle to determine the link between thyroid disease and PBDE exposures, particularly to BDE 47 (n = 1,396), BDE 99 (n = 1,378), BDE 100 (n = 1,413) and BDE 153 (n = 1,413). During the survey, participants were asked to indicate whether a doctor or health care professional had said the participant had a thyroid disease and whether the participant still had a thyroid problem.

Postmenopausal participants were twice as likely to report ever having a thyroid problem (P < .05) and to currently having a thyroid problem (P < .1) compared with premenopausal participants. Compared with participants in the lowest quartiles of serum concentrations, participants in the highest quartile of serum concentrations for BDE 47 (OR = 1.48; 95% CI, 1.05-2.09), BDE 99 (OR = 1.78; 95% CI, 1.16-2.75) and BDE 100 (OR = 1.5; 95% CI, 0.97-2.31) had greater odds of currently having a thyroid problem.

When the analysis was restricted to postmenopausal participants, the ORs for participants in the highest exposure category were greater for all PBDE congeners except BDE 153.

“Perhaps the most striking and unique finding in this study is that the odds of having a current thyroid problem associated with PBDEs are so much higher in postmenopausal women,” the researchers wrote. “One hypothesis is that this is related to the change in hormone concentrations in postmenopausal women and the affinity of PBDEs to binding sites for both estrogen and thyroid hormones.” – by Amber Cox

Thyroid screening may benefit women with fertility problems


Screening for thyroid disease should be considered in women with fertility problems and recurrent early pregnancy loss, according to a review published in The Obstetrician & Gynaecologist.

“Abnormalities in thyroid function can have an adverse effect on reproductive health and result in reduced rates of conception, increased miscarriage risk and adverse pregnancy and neonatal outcomes,” Amanda Jefferys, BMBS, BMedSci, MRCOG, of the Bristol Center for Reproductive Medicine at Southmead Hospital in the United Kingdom, said in a press release. “However, with appropriate screening and prompt management, these risks can be significantly reduced.”

Jefferys and colleagues conducted the review to gather information on the effect of thyroid disorders on reproductive health. The researchers also sought to gather information on how to optimize thyroid function in order to improve reproductive outcomes.

There can be adverse effects on reproductive health, decreased conception rates, increased early pregnancy loss, and adverse pregnancy and neonatal outcomes with abnormalities in thyroid function, including hyperthyroidism and hypothyroidism.

Compared with 1.5% of women in the general population, 2.3% with fertility problems have hyperthyroidism. Menstrual irregularity has been linked to hyperthyroidism. Preterm delivery, preeclampsia, growth restriction, heart failure and stillbirth are all possible adverse outcomes of pregnancy in women with hyperthyroidism.

Less than 1% of women of reproductive age have hypothyroidism, which can cause a delay in reaching sexual maturity during childhood and adolescence as well as menstrual problems in adulthood.

Currently, national guidelines do not recommend screening for asymptomatic women with problems conceiving.

“Thyroid disease can have significant effects on reproduction from conception to birth; however, with appropriate screening, a high index of suspicion and prompt management, risks can be significantly reduced if not ameliorated,” the researchers wrote. “The benefits of [levothyroxine] replacement in euthyroid women and with [autoimmune thyroid disease] both preconceptually and during pregnancy remain a grey area and further research is needed to confirm benefit.”

EFFECT OF THYROID DISORDERS ON REPRODUCTIVE HEALTH


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Thyroid disease can have significant effects on a woman’s reproductive health and screening for women presenting with fertility problems and recurrent early pregnancy loss should be considered, suggests a new review published today (23 January) inThe Obstetrician & Gynaecologist (TOG).

The review examines the effect of thyroid disorders on reproductive health and reviews the current evidence on how to optimise thyroid function to improve reproductive outcomes.

Thyroid hormones control the metabolism via the production of two hormones triiodothyronine and thyroxine. These hormones also have key roles in growth and development, particularly brain development. Changes in thyroid function can impact greatly on reproductive function before, during and after conception.

Thyroid disease is divided into hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid), and the causes of the diseases are numerous.

The review highlights that hyperthyroidism is found in approximately 2.3% of women presenting with fertility problems, compared with 1.5% of women in the general population. The condition is linked with menstrual irregularity. Hypothyroidism affects around 0.5% of women of reproductive age. Hypothyroidism in childhood and adolescence is associated with a delay in reaching sexual maturity, and in adulthood is associated with menstrual problems and in some cases a lack of ovulation, state the authors.

The authors note that thyroid disease has long been associated with fertility problems, however, national guidance does not currently recommend routine measurement of thyroid function in asymptomatic women presenting with problems conceiving.

Additionally, the authors of the review note that miscarriage is common, affecting approximately one in five pregnancies and recurrent miscarriage, defined as three consecutive miscarriages, affects 1% of couples. Given that thyroid hormone plays an important part in embryonic development, thyroid disease has long been associated with an increased risk of miscarriage.

Thyroid disease, in particular hyperthyroidism, can also have a significant effect on pregnancy, the authors of the review state. Adverse outcomes can include preterm delivery, pre-eclampsia, growth restriction, heart failure and stillbirth.

The authors conclude that screening for thyroid disease should be considered in women presenting with fertility problems and recurrent pregnancy loss. Additionally, the authors highlight that there is evidence to suggest that routine screening of the general population for thyroid dysfunction at the start of pregnancy may be beneficial.

Furthermore, women diagnosed with thyroid disease should continue on anti-thyroid medication throughout pregnancy and receive close monitoring, emphasise the authors.

Amanda Jefferys, from the Bristol Centre for Reproductive Medicine, Southmead Hospital, Bristol, and co-author of the study said:

“Abnormalities in thyroid function can have an adverse effect on reproductive health and result in reduced rates of conception, increased miscarriage risk and adverse pregnancy and neonatal outcomes.

“However, with appropriate screening and prompt management, these risks can be significantly reduced.”

Jason Waugh, TOG Editor-in-chief, added:

“Thyroid disease is common in the reproductive medicine setting, in fact, it is the most common endocrine condition affecting women of reproductive age.

“This paper highlights how thyroid disorders can affect fertility and pregnancy and makes a case for universal screening.”

Nonenhanced neck CT may detect diffuse thyroid disease


Nonenhanced CT images are effective for differentiating diffuse thyroid disease from normal thyroid, according to recent findings published in the International Journal of Endocrinology.

Myung Ho Rho, MD, of the Inje University College of Medicine in Korea, andDong Wook Kim, MD, of the Sungkyunkwan University School of Medicine in Korea, evaluated 209 patients (170 women; aged 22-75 years) who received preoperative neck CT and subsequent thyroid surgery to determine the diagnostic accuracy of individual CT features, as well as cutoff criteria for detecting diffuse thyroid disease (DTD).

Papillary thyroid carcinoma was the most common histopathology of the main surgical thyroid lesion (n=186), followed by nodular hyperplasia (n=14), follicular adenoma (n=7) and follicular thyroid carcinoma (n=2). Thyroidectomy was the most common thyroid surgery (n=106), followed by hemithyroidectomy (n=87) and subtotal thyroidectomy (n=16). Normal thyroid was the most common histopathologic diagnosis (n=157), followed by non-Hashimoto’s lymphocytic thyroiditis (n=34), Hashimoto’s thyroiditis (n=17) and diffuse hyperplasia (n=1).

A significant difference between normal thyroid and DTD was found between the degree and pattern of parenchymal attenuation, glandular margin and pattern of parenchymal enhancement with frequencies of individual CT features. However, there was no difference found for glandular size.

Compared with other conditions, nonenhanced CT was most effective in diagnosing DTD using a cutoff value of <100 Hounsfield units in the thyroid parenchyma. However, no significant difference in cutoff value was found for the degree of parenchymal enhancement between normal thyroid and DTD.

Low attenuation, inhomogeneous attenuation, increased glandular size, lobulated margin and inhomogeneous enhancement were CT features suggestive of DTD. Isoattenuation, homogenous attenuation, anteroposterior diameter of 1 cm to 2 cm, smooth margin and homogenous enhancement were CT features that suggested normal thyroid.

Number of abnormal CT features were categorized as one or more (n=98), two or more (n=50), three or more (n=31), four or more (n=15) and five (n=5). DTD diagnosis accuracy was highest when the three or more classification was used.

“In conclusion, the study results showed that CT features suggestive of DTD included low attenuation, inhomogeneous attenuation, increased glandular size, lobulated margin and inhomogeneous enhancement and that CT diagnosis of DTD using the ‘3 or more’ CT classification was superior,” the researchers wrote. “In addition, most of [the] useful CT features for differentiating DTD from normal thyroid were detected in nonenhanced CT images.”

Thyroid disease diagnosis leads to work absence, disability in first year


Once diagnosed with thyroid disease, patients are more likely to be absent from work in the year following diagnosis than subsequent years, according to research published in The Journal of Clinical Endocrinology & Metabolism.

The results of a longitudinal register study by M. A. Nexo, a PhD student in Health Sciences at Copenhagen University, Denmark, and colleagues, also showed patients with Graves’ orbitopathy (GO) have the highest risk of work disability.

Using data from Danish national registers of social benefits, health and work characteristics from 1994 to 2011, the researchers compared 862 outpatients with nontoxic goiter, hyperthyroidism, GO, autoimmune hypothyroidism or other thyroid diseases and 7,043 matched controls.

Transitions between work, long-term sickness absence, unemployment and disability pension were measured through Cox regression analyses. Adjusted hazard ratios (HRs) were estimated for the first year after diagnosis and subsequent years.

Significant differences were seen between patients with thyroid disease and the general population for sickness absence, disability pension, return from sickness absence and unemployment.

In the year following diagnosis, higher risks for sickness absence were seen for patients diagnosed with GO (HR=6.94) and hyperthyroidism (HR=2.08); the same patients were less likely to return from sickness absence (HR=0.62) and more likely to have disability pension (HR=4.15). The probability that patients with autoimmune hypothyroidism would return from sickness absence was also lower (HR=0.62) in the first year.

In subsequent years, GO patients were at significantly higher risk for sickness absence (HR=2.08) and less likely to return from sickness absence (HR=0.51); these patients were also at greater risk for unemployment (HR=0.52) and to have disability pension (HR 4.40). Patients diagnosed with hyperthyroidism also demonstrated difficulties returning from sickness absence (HR=0.71).

When Thyroid Disease Masks as a Mental Health Disorder .


Most people experience periodic bouts of depression, forget where they’ve placed their car keys or snap at their spouse because they left the cap off the toothpaste again. These are usually symptoms of enduring a traumatic event or simply having a bad day – things that pass. But if chronic depression, flashes of rage or a significant loss in cognitive function tend to stick around, you may want to get your thyroid checked before filling that prescription for a psychotropic medication.

depressionthyroid

According to a study that analyzed the medication usage of 2.5 million Americans (with insurance, it should be noted), the use of antidepressants, antianxiety medications and other psychotropic drugs increased 22% between 2001 and 2010, translating to one in five adults. Women between the ages of 45 and 65 swallowed the most pills, with 20% taking antidepressants and 11% taking antianxiety medications. Remarkably, the Centers for Disease Control and Prevention (CDC) reports that the majority of Americans receive these medications from their primary health care physician without any evaluation by a mental health professional whatsoever. For many of these folks, the problem isn’t in their head; it’s in their thyroid.

Portrait of a Thyroid Imbalance

The thyroid is a gland shaped like a butterfly that rests at the base of your neck, just above the collar bone. Specifically, it’s an endocrine gland charged with the task of producing hormones that cells use to perform a variety of functions from regulating body temperature to keeping your heart ticking. The primary thyroid hormone is thyroxine (T4), which, with the help of cortisol from the adrenal glands, cells pull from storage and convert to the active form, triiodothyronine (T3).

A vitamin deficiency, autoimmune disease or excessive exposure to radiation, among other things, can cause thyroid function to get out of whack. A hyperactive thyroid (hyperthyroidism) is characterized by weight loss and heart palpitations because the metabolism is running in high gear. An underactive or sluggish thyroid (hypothyroidism) typically results in steady weight gain and low energy. However, feelings of anxiety, depression, poor memory and difficulty concentrating often piggyback these symptoms. According to Dr. Christiane Northrup, this is because T3, the active form of thyroid hormone, is a neurotransmitter that regulates important “feel good” chemicals in the brain like serotonin and GABA (gamma aminobutyric acid).

Without proper screening and diagnosis, thyroid dysfunction remains undetected. Worse, if a physician has prescribed psychiatric drugs to treat symptoms without the benefit of an evaluation by a mental health professional, the cycle of improper medication and the associated side effects and risks that come with it continues.

Thyroid Testing Ahead, No Cheating

The thyroid is a marvelous yet complicated piece of equipment. There are also many complicating factors that can cause, mask or escalate symptoms or complicate test results. This is especially true in women because they experience hormonal fluctuations from pregnancy, peri-menopause and menopause at different stages of life. Cost may be a consideration depending on your insurance status, but in order to get a complete and accurate picture it’s important not to skimp on thyroid testing.

The most sensitive test for thyroid dysfunction measures thyroid-stimulating hormone, or TSH. Ideally, however, the most comprehensive screening will include testing levels of free T4, free T3, T3 and T4 uptake, as well as hyroglobulin antibody, thyroid peroxidase antibody and thyroid receptor antibody.

Remember what we said about the relationship between the thyroid and the adrenal glands? According to Dr. Kelly Brogan, a holistic psychiatrist who specializes in women’s health, testing for thyroid disease should include a check on hormone functioning, with particular attention to daily cortisol release and utilization in response to stress.

Working with Your Health Team

If it turns out that your thyroid is to blame for your mood swings and forgetfulness, it doesn’t necessarily mean you’re doomed to a lifetime of thyroid medications. Strategies to enhance thyroid function include a adhering to a low-sugar diet and following a supplement regimen that supports the immune system and adrenal glands. For instance, curcumin, vitamin C, B vitamins, zinc, selenium, N-acetylcysteine and adaptogenic herbs like Rhodiola or Astragalus that help the body cope with stress may be of benefit. In addition, lifestyle changes that promote stress management a sense of well-being can also help, such as meditation, gentle yoga or simply walking or journaling each day.

Don’t go it alone, though. In addition to consulting your doctor, consider bringing a nutritionist or holistic practitioner on board to help you develop an individual treatment and recovery plan that’s right for you.

References

New York Times: For Some, Psychiatric Trouble May Start in Thyroid

American Psychological Association: Inappropriate Prescribing

Medscape: America’s Use of Psychotropic Medications on the Rise

The Healthy Home Economist: Thyroid Disease as a Psychiatric Pretender; Dr. Kelly Brogan

Levothyroxine could suppress TSH in subclinical thyroid disease.


The common practice of prescribing levothyroxine sodium to improve thyroid function among patients with subclinical thyroid disease may increase the potential for overtreatment, according to data in a United Kingdom-based retrospective cohort study.

Peter N. Taylor, MSc, MRCP, of the Cardiff University School of Medicine, and colleagues used data from the United Kingdom Clinical Practice Research Datalink to assess the trends in thyroid-stimulating hormone levels at the beginning of levothyroxine therapy and the risk for developing TSH suppression after treatment. The dataset included more than 52,000 patients who were given a prescription for the drug between January 2001 and October 2009, according to data.

“Overall, 30% of people were treated for levels of thyroid hormone deficiency potentially below those recommended in national guidelines, equivalent to 190,000 people in the UK. In addition, when thyroid blood levels were rechecked after 5 years on treatment, more than 1 in 10 people on levothyroxine were being overtreated,” Taylor told Endocrine Today.

Median TSH levels at the beginning of levothyroxine treatment decreased from 8.7 mIU/L to 7.9 mIU/L from 2001 to 2009, according to data. Five years after levothyroxine was initiated, 5.8% of patients displayed a TSH level of <0.1 mIU/L.

In 2009, patients with TSH levels of ≤10 mIU/L were prescribed levothyroxine more frequently compared with those treated in 2001 (OR=1.30; 95% CI, 1.19-1.42), according to data.

Between 2001 and 2006, there was a 1.81-fold increase in the rate of index levothyroxine prescriptions, researchers wrote. After adjustments for age, data revealed that there was still a 1.79-fold increase in the rate of index levothyroxine prescriptions.

Furthermore, older patients and those with cardiovascular disease risk were more likely to undergo levothyroxine treatment with TSH levels ≤10 mIU/L, according to researchers.

Moreover, patients with depression or tiredness at baseline showed an increased likelihood for developing TSH-suppression, unlike patients with CVD risk factors (ie, atrial fibrillation, diabetes, hypertension and raised lipids), researchers wrote.

The American Thyroid Association guidelines currently recommend levothyroxine therapy at TSH levels ≤10 mIU/L, when there are clear symptoms of hypothyroidism, positive thyroid autoantibodies, or signs of atherosclerotic CVD or heart failure.

“Taken together, this indicates that not only has the number of people being tested and treated for low thyroid hormone levels increased, but the majority of people nowadays are starting thyroid hormone for minor levels of underactivity for which we have no clear evidence of benefit,” Taylor said. “Studies are urgently required to clarify the risk vs. the benefits of exposing such a large number of these people to long-term thyroid hormone therapy.” – by Samantha Costa

Soure: Endocrine Today

Subclinical thyroid disease: where is the evidence?


Subclinical thyroid disease is very common, particularly in elderly people. Recognition of this endocrine disorder is increasing, partly due to a large increase in thyroid function testing, especially in primary care. Many cross-sectional studies have investigated whether subclinical hyperthyroidism or subclinical hypothyroidism are associated with specific symptoms, signs, or comorbidities, and a smaller number of prospective studies have examined whether subclinical thyroid disease predicts specific adverse outcomes.1

What is the latest evidence driving the need, or otherwise, for therapeutic intervention in these common, and largely asymptomatic, biochemically defined disorders? A large and seemingly irrefutable body of evidence exists supporting the association of subclinical hyperthyroidism with atrial fibrillation risk, especially when thyroid-stimulating hormone (TSH) is at undetectable concentrations.23 Subclinical hyperthyroidism is also associated with other adverse cardiac outcomes, such as coronary heart disease events and mortality, and heart failure. Evidence linking cardiovascular disorders with tests of thyroid function within the reference range, including higher circulating free thyroxine concentrations,4 suggests that the cardiovascular system is particularly sensitive to subtle changes in thyroid status. Thus, the cardiovascular system is the most important physiological system for which to consider risk, and, in turn, with the potential to benefit from treatment.

If the evidence for risk association with cardiovascular endpoints is strong, why is there controversy about intervention? Several crucial reasons exist. First, association does not prove causation, and many studies have not fully considered potential confounders for comorbidities in conditions such as coronary heart disease and heart failure. Second, nearly all studies have been based on one or two TSH measurements in individual subjects, but low TSH is often transient, especially when only slightly low, and frequently reflects non-thyroidal illnesses or drugs, rather than underlying thyroid disease such as mild Graves’ disease or toxic nodular hyperthyroidism. Third, intervention for subclinical hyperthyroidism means radioiodine therapy or antithyroid drugs, neither of which is trivial. Radioiodine is generally considered the treatment of choice for toxic nodular disease (the most common underlying thyroid diagnosis, in view of the typical age when subclinical hyperthyroidism is diagnosed). Radioiodine treatment often results in hypothyroidism and the need for permanent thyroxine replacement. Since up to half of patients taking thyroxine have subclinical hyperthyroidism or hypothyroidism biochemically, subclinical hyperthyroidism can be perpetuated or replaced with subclinical hypothyroidism. Finally, there have been no randomised controlled trials of treatment of subclinical hyperthyroidism with meaningful clinical endpoints. Two trials were stopped because of low recruitment and a third has recruitment that is lower than planned, although it is continuing. These issues were described in a recent article about the problems encountered with such trials.4 Despite this absence of evidence, expert groups recommend that treatment should be strongly considered, especially in elderly patients;5 surveys of practice show this is occurring. It seems extraordinary that evidence that the benefit of treatment outweighs the risk does not exist in the 21st century for such a common disorder. We can only hope that evidence will accrue in the next few years.

The situation regarding subclinical hypothyroidism is probably more complex and controversial than that for subclinical hyperthyroidism. The most relevant physiological system is again cardiovascular; the largest meta-analysis performed so far reports an association with cardiovascular mortality in more severe cases (ie, serum TSH >10 mIU/L).6 Again, raised TSH is frequently transient, although a persistent increase is a more specific indicator of underlying thyroid disease. However, the upper limit of the TSH reference range rises with age,7 leading to controversy about the definition of disease, especially if TSH is in the 5—10 mIU/L range in elderly people. Randomised controlled trials of treatment (thyroxine replacement) have been done, but these are largely small, heterogeneous, and underpowered, and their findings are unsurprisingly negative or conflicting. A Cochrane review indicated insufficient evidence to recommend for, or against, treatment, including in those with a TSH greater than 10 mIU/L and in very elderly patients.8 However, new evidence9 exists for improved outcomes of coronary heart disease in younger, but not older, patients treated with thyroxine, and there are new data10 showing that thyroxine treatment helps to preserve renal function in people with subclinical hypothyroidism and chronic kidney disease. Fortunately, several clinically relevant trials are underway—including one EU-funded multicentre study of patients older than 80 years that will examine cardiovascular and quality-of-life outcomes—so the evidence base for subclinical hypothyroidism should increase and better guide us in our therapeutic approach.

References

1 Cooper DS, Biondi B. Subclinical thyroid disease. Lancet 2012; 379: 1142-1154. Summary | Full Text | PDF(416KB) |CrossRef | PubMed

2 Collet TH, Gussekloo J, Bauer DC, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.Arch Intern Med 2012; 172: 799-809. CrossRef | PubMed

3 Gammage MD, Parle JV, Holder RL, et al. Association between serum free thyroxine concentration and atrial fibrillation.Arch Intern Med 2007; 167: 928-934. CrossRef | PubMed

4 Goichot B, Pearce SH. Subclinical thyroid disease: time to enter the age of evidence-based medicine. Thyroid 2012; 22:765-768. CrossRef | PubMed

5 Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 2011; 17: 456-520.CrossRef | PubMed

6 Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality.JAMA 2010; 304: 1365-1374. CrossRef | PubMed

7 Waring AC, Arnold AM, Newman AB, Buzkova P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab 2012; 97: 3944-3950.CrossRef | PubMed

8 Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 2007; 3. CD003419

9 Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med 2012; 172: 811-817. CrossRef | PubMed

10 Shin DH, Lee MJ, Kim SJ, et al. Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism. J Clin Endocrinol Metab 2012; 97: 2732-2740. CrossRef | PubMed

Source: Lancet

Subclinical thyroid disease: where is the evidence?


Subclinical thyroid disease is very common, particularly in elderly people. Recognition of this endocrine disorder is increasing, partly due to a large increase in thyroid function testing, especially in primary care. Many cross-sectional studies have investigated whether subclinical hyperthyroidism or subclinical hypothyroidism are associated with specific symptoms, signs, or comorbidities, and a smaller number of prospective studies have examined whether subclinical thyroid disease predicts specific adverse outcomes.1

What is the latest evidence driving the need, or otherwise, for therapeutic intervention in these common, and largely asymptomatic, biochemically defined disorders? A large and seemingly irrefutable body of evidence exists supporting the association of subclinical hyperthyroidism with atrial fibrillation risk, especially when thyroid-stimulating hormone (TSH) is at undetectable concentrations.23 Subclinical hyperthyroidism is also associated with other adverse cardiac outcomes, such as coronary heart disease events and mortality, and heart failure. Evidence linking cardiovascular disorders with tests of thyroid function within the reference range, including higher circulating free thyroxine concentrations,4 suggests that the cardiovascular system is particularly sensitive to subtle changes in thyroid status. Thus, the cardiovascular system is the most important physiological system for which to consider risk, and, in turn, with the potential to benefit from treatment.

If the evidence for risk association with cardiovascular endpoints is strong, why is there controversy about intervention? Several crucial reasons exist. First, association does not prove causation, and many studies have not fully considered potential confounders for comorbidities in conditions such as coronary heart disease and heart failure. Second, nearly all studies have been based on one or two TSH measurements in individual subjects, but low TSH is often transient, especially when only slightly low, and frequently reflects non-thyroidal illnesses or drugs, rather than underlying thyroid disease such as mild Graves’ disease or toxic nodular hyperthyroidism. Third, intervention for subclinical hyperthyroidism means radioiodine therapy or antithyroid drugs, neither of which is trivial. Radioiodine is generally considered the treatment of choice for toxic nodular disease (the most common underlying thyroid diagnosis, in view of the typical age when subclinical hyperthyroidism is diagnosed). Radioiodine treatment often results in hypothyroidism and the need for permanent thyroxine replacement. Since up to half of patients taking thyroxine have subclinical hyperthyroidism or hypothyroidism biochemically, subclinical hyperthyroidism can be perpetuated or replaced with subclinical hypothyroidism. Finally, there have been no randomised controlled trials of treatment of subclinical hyperthyroidism with meaningful clinical endpoints. Two trials were stopped because of low recruitment and a third has recruitment that is lower than planned, although it is continuing. These issues were described in a recent article about the problems encountered with such trials.4 Despite this absence of evidence, expert groups recommend that treatment should be strongly considered, especially in elderly patients;5 surveys of practice show this is occurring. It seems extraordinary that evidence that the benefit of treatment outweighs the risk does not exist in the 21st century for such a common disorder. We can only hope that evidence will accrue in the next few years.

The situation regarding subclinical hypothyroidism is probably more complex and controversial than that for subclinical hyperthyroidism. The most relevant physiological system is again cardiovascular; the largest meta-analysis performed so far reports an association with cardiovascular mortality in more severe cases (ie, serum TSH >10 mIU/L).6 Again, raised TSH is frequently transient, although a persistent increase is a more specific indicator of underlying thyroid disease. However, the upper limit of the TSH reference range rises with age,7 leading to controversy about the definition of disease, especially if TSH is in the 5—10 mIU/L range in elderly people. Randomised controlled trials of treatment (thyroxine replacement) have been done, but these are largely small, heterogeneous, and underpowered, and their findings are unsurprisingly negative or conflicting. A Cochrane review indicated insufficient evidence to recommend for, or against, treatment, including in those with a TSH greater than 10 mIU/L and in very elderly patients.8 However, new evidence9 exists for improved outcomes of coronary heart disease in younger, but not older, patients treated with thyroxine, and there are new data10 showing that thyroxine treatment helps to preserve renal function in people with subclinical hypothyroidism and chronic kidney disease. Fortunately, several clinically relevant trials are underway—including one EU-funded multicentre study of patients older than 80 years that will examine cardiovascular and quality-of-life outcomes—so the evidence base for subclinical hypothyroidism should increase and better guide us in our therapeutic approach.

Source: Lancet

 

Case report links artificial sweeteners, Hashimoto’s thyroiditis.


Recent literature suggest sugar-sweetened beverages increase the likelihood of incident obesity and diabetes. However, data from a case report presented here suggest that patients who consume a large amount of artificial sweeteners, such as Splenda, are also more likely to develop Hashimoto’s thyroiditis.

“We know that in the 20th and 21st century there is an increasing consumption of sugar substitutes. If you look at the literature in animal studies, it suggests it may cause obesity and some tumors. I found that this sugar substitute increases insulin levels in consumers and high insulin levels may be associated with obesity,” Issac Sachmechi, MD, FACE, FACP, clinical associate professor of medicine at Icahn School of Medicine at Mount Sinai; and chief of endocrinology at Queens Hospital Center, said during a press conference.

According to abstract data, Sachmechi treated a woman aged 52 years with a history of high intake of artificial sweeteners and a diagnosis of Hashimoto’s hypothyroidism in 2008. The patient’s TSH measured 12.2 mIU/L, free T4was 0.5 ng/dL and antithyroid peroxidase antibodies (TPOAb) were 196 IU/mL.

Sachmechi treated the patient with levothyroxine 0.75 mg per day and normalized her TSH (between 1.23 mIU/L and 2.16 mIU/L) over 3 years of treatment. Subsequently, the patient stopped ingesting the sweeteners in February 2012 due to weight gain.

This resulted in a TSH level of 0.005 mIU/L, where it remained low despite a decrease of levothyroxine dose to 0.05 mg per day. Furthermore, a complete discontinuation of the drug was followed with normal TSH and anti-TPOAb <20 IU/mL, TSI of 113% and TBII <6%.

Sachmechi reported that the patient continued to be clinically euthyroid without further treatment during subsequent follow-up visits.

“We know there is an increased prevalence of Hashimoto’s hypothyroidism and differentiated thyroid cancer without currently known etiologies. “It is possible that the artificial sweetness may have a roll in this,” Sachmechi said.

“We plan to do a study looking at the use of artificial sweetness in large number patients with diagnosis of Hashimoto’s hypothyroidism and patients with well differentiated thyroid cancer to see if we find any coloration consumption of artificial sweetness and those thyroid diseases.”

These data indicate eliminating artificial sweeteners from the diet can benefit patients with thyroid disease. Sachmechi told Endocrine Today that a study is underway to confirm these findings in a larger cohort. – by Samantha Costa

Source: Endocrine Today