Thyroid Function Associated With Atherosclerotic Cardiovascular Morbidity and Mortality

MedicalResearch.com Interview with:
Arjola Bano, MD, DSc

PhD candidate
Departments of Internal Medicine and Epidemiology
Erasmus Medical Center, Rotterdam, The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Atherosclerosis is a chronic condition, characterized by the accumulation of lipids and fibrous elements in the arterial walls. It can progress insidiously from an asymptomatic narrowing of the arterial lumen (subclinical phase) to the clinical onset of vascular events (as coronary heart disease or stroke) and death. Despite advances in prevention and treatment, atherosclerotic diseases remain a leading cause of mortality worldwide. Therefore, identifying additional modifiable risk factors for atherosclerosis is of major importance.

So far, the role of thyroid hormone on atherosclerosis remains unclear. Moreover, a comprehensive investigation exploring the link of thyroid function with the wide spectrum of atherosclerosis, including subclinical atherosclerosis, clinical atherosclerosis and atherosclerotic mortality, within the same population is lacking.

Therefore, in a prospective study of 9231 middle-aged and elderly people, we explored the association of thyroid function with subclinical atherosclerosis (coronary artery calcification), atherosclerotic events (fatal and nonfatal coronary heart disease or stroke) and atherosclerotic mortality (death from coronary heart disease, cerebrovascular or other atherosclerotic disease). Higher free thyroxine (FT4) levels were associated with higher risk of subclinical atherosclerosis, atherosclerotic events and atherosclerotic mortality, independently of cardiovascular risk factors.

The risk of atherosclerotic mortality increased with higher FT4 levels (HR; CI: 2.35; 1.61-3.41 per 1 ng/dl) and lower thyroid-stimulating hormone (TSH) levels (HR; CI: 0.92; 0.84-1.00 per 1 logTSH), with stronger estimates among participants with a history of atherosclerotic disease (HR; CI: 5.76; 2.79-11.89 for FT4 and 0.81; 0.69-0.95 for TSH).

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Thyroid Hormone Medication Should Not Be Taken With Cow’s Milk

MedicalResearch.com Interview with:
Deborah Chon MD
Endocrinology fellow
UCLA David Geffen School of Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our study shows that drinking cow’s milk concurrently with oral levothyroxine significantly reduces the absorption of the medication.

Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. It is the mostly commonly prescribed medication in the United States as of 2014. Frequent dose adjustments of levothyroxine have been shown to be a costly burden to the national healthcare system.

Previous studies have shown that certain foods and medication, such as calcium supplements, can interfere with levothyroxine absorption. However, this is the first study to demonstrate that ingesting cow?s milk, a common breakfast staple, affects oral levothyroxine absorption.

To determine the possible effect of cow’s milk ingestion, we measured levothyroxine absorption in humans with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and normal thyroid hormone function at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 ?g of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits.

Ten subjects (mean age 33.7?10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower when taking cow?s milk concurrently with levothyroxine compared levothyroxine alone (mean?SD: 67.26?12.13 vs. 73.48?16.96; p = 0.02). Also, peak serum TT4 concentrations were significantly lower in those who ingested levothyroxine concurrently with milk, compared to taking levothyroxine alone (p=0.04).
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Flame Retardant Chemicals In Homes May Be Raising Risk of Thyroid Cancer

MedicalResearch.com Interview with:

Julie Sosa, MD MA FACS Professor of Surgery and Medicine Chief, Section of Endocrine Surgery Director, Surgical Center for Outcomes Research (SCORES) Leader, Endocrine Neoplasia Diseases Group Duke Cancer Institute and Duke Clinical Research Institute Durham, NC 2771

Dr. Sosa

Julie Sosa, MD MA FACS
Professor of Surgery and Medicine
Chief, Section of Endocrine Surgery
Director, Surgical Center for Outcomes Research
Leader, Endocrine Neoplasia Diseases Group
Duke Cancer Institute and Duke Clinical Research Institute
Durham, NC 2771

MedicalResearch.com: What is the background for this study?

Response: The incidence of thyroid cancer has dramatically increased world-wide over the last several decades. In the United States, thyroid cancer is the fastest increasing cancer among women and men. This observation has been almost exclusively the result of an epidemic of papillary thyroid cancer, or PTC, which now comprises approximately 90% of new cases.

The use of flame retardant chemicals, or Flame Retardant Chemicals, also increased over the last several decades due to the implementation of mandatory and voluntary flammability standards for furniture, electronics, and construction materials. Over time, FRs come out of these products and accumulate in indoor environments where humans are exposed. Animal studies suggest that FRs can disrupt thyroid function, and many contribute to cancer risk. But many human health endpoints have not been investigated.

Our work was aimed at investigating whether exposure to Flame Retardant Chemicals could be associated with PTC. To address our research question, we recruited 140 adults, 70 with PTC and 70 who were healthy volunteers without evidence for thyroid cancer or thyroid disease. Then we visited participants’ homes and collected dust samples, a metric that we have previously shown is an indicator of long-term exposure to Flame Retardant Chemicals in the home.

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Study Fails To Support Routine Screening For Subclinical Hypothyroidism During Pregnancy

MedicalResearch.com Interview with:

Professor, Brian Casey, M.D. Gillette Professorship of Obstetrics and Gynecology UT Southwestern Medical Center

Dr. Casey

Professor Brian Casey, M.D.
Gillette Professorship of Obstetrics and Gynecology
UT Southwestern Medical Center 

MedicalResearch.com: What is the background for this study?
Response: For several decades now, subclinical thyroid disease, variously defined, has been associated with adverse pregnancy outcomes.  In 1999, two studies are responsible for increasing interest in subclinical thyroid disease during pregnancy because it was associated with impaired neuropsychological development in the fetus.  One study showed that children born to women with the highest TSH levels had lower IQ levels.  The other showed that children of women with isolated low free thyroid hormone levels performed worse on early psychomotor developmental tests. Together, these findings led several experts and professional organizations to recommend routine screening for and treatment of subclinical thyroid disease during pregnancy.

Our study was designed to determine whether screening for either of these two diagnoses and treatment with thyroid hormone replacement during pregnancy actually improved IQ in children at 5 years of age.

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Thyroid Hormone Disruptors Found In Household Cats and Dust

MedicalResearch.com Interview with:

Jana Weiss PhD Department of Environmental Science and Analytical Chemistry Stockholm University

Dr. Jana Weiss

Jana Weiss PhD
Department of Environmental Science and Analytical Chemistry
Stockholm University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In an earlier publication, we could see an association between elevated concentrations of brominated flame retardants (BFR) in the blood of cats with developed Feline hyperthyroidism, compared to healthy cats (Norrgran et al 2015, ES&T 49:5107-5014). To establish the exposure pathway we now took paired samples from healthy cats and dust from their households. We also analysed the cats food to include another major exposure pathway. In total 17 families participated. They lived in houses in the countryside or in apartments in the city. All families had kids under 12 years of age living at home, thus representing a household with typical child products. The dust was sampled from the living room, the child’s room and from the adult’s bedrooms. We could not see any difference in the composition of compounds between the rooms, but we saw that levels were in general higher in the living room compared to the other two rooms. This was expected as many products being treated with BFRs can be found in the living room.

We could see that higher levels of some  brominated flame retardants in the dust were correlated to elevated levels in the cat’s blood. Therefore, this hypothesized exposure pathways is now statistically established. We could also confirm cat food to be the major exposure pathway for naturally brominated compounds coming from the marine food web, such as6-OH-BDE47, a known thyroid hormone disruptor. Continue reading

Thyroid Hormone Treatment In Pregnant Women With Subclinical Hypothyroidism

MedicalResearch.com Interview with:

Dr. Spyridoula Maraka Assistant professor of medicine Division of Endocrinology and Metabolism Center for Osteoporosis and Metabolic Bone Diseases University of Arkansas for Medical Sciences and the Central Arkansas Veterans Health Care System Little Rock Arkansas

Dr. Spyridoula Maraka

Dr. Spyridoula Maraka
Assistant professor of medicine
Division of Endocrinology and Metabolism
Center for Osteoporosis and Metabolic Bone Diseases
University of Arkansas for Medical Sciences and
Central Arkansas Veterans Health Care System
Little Rock Arkansas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Subclinical hypothyroidism, a mild thyroid dysfunction, has been associated in pregnancy with multiple adverse outcomes. Our aim was to estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism.

Using a large national US dataset, we identified 5,405 pregnant women diagnosed with subclinical hypothyroidism. Of these, 843 women, with an average pretreatment TSH concentration of 4.8 milli-international units per liter, were treated with thyroid hormone. The remaining 4,562, with an average pretreatment TSH concentration of 3.3 milli-international units per liter, were not treated.

Compared with the untreated group, treated women were 38 percent less likely to experience pregnancy loss. However, they were more likely to experience a preterm delivery, gestational diabetes or preeclampsia. Moreover, the benefit of thyroid hormone treatment on pregnancy loss was seen only among women with higher TSH levels (4.1 to 10 mIU/L) before treatment. We also found that for women with lower levels of TSH (2.5–4.0 mIU/L), the risk of gestational hypertension was significantly higher for treated women than for untreated women.

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Thyroid Care Collaborative Improves Adoption of Thyroid Cancer Clinical Guidelines

MedicalResearch.com Interview with:

Ilya Likhterov, MD Assistant Professor, Otolaryngology Icahn School of Medicine at Mount Sinai

Dr. Ilya Likhterov

Ilya Likhterov, MD
Assistant Professor, Otolaryngology
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: As our understanding of thyroid cancer improves, the way these patients are diagnosed and treated is changing. It is difficult for clinicians to incorporate every individual scientific study into their practice. These studies are numerous and the results can be conflicting.

To address this difficulty, organizations such as the American Thyroid Association (ATA) create summary recommendations that account for the latest research and translate it into a format that is easily usable for physicians. Such clinical practice guidelines are available not just for thyroid cancer care, but in many other fields. The difficulty however, is how to ensure that clinicians have access to the guidelines and incorporate the recommendations into their practice.

There are a number of barriers to actually using the guidelines in practice, and we attempt to identify strategies on how to overcome these.

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Even With Normal TSH, Some Patients Still Feel Hypothyroid

MedicalResearch.com Interview with:

Antonio C. Bianco, MD, PhD Rush University Medical Center

Dr. Antonio C. Bianco

Antonio C. Bianco, MD, PhD
Rush University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The standard of care for patients with hypothyroidism is treatment with levothyroxine. The dosage of levothyroxine is adjusted for each patient with the goal of normalizing blood levels of TSH. About 15% of the patients treated this way exhibit variable degrees of residual symptoms, despite having a normal TSH level. These symptoms include difficulty losing weight, low energy and depression. However, given the subjective nature of these complains and that the blood levels of TSH are normal, many times such symptoms are dismissed by physicians as non-thyroid related.

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High and High-Normal Thyroid Levels Linked To Increased Risk of Sudden Cardiac Death

MedicalResearch.com Interview with:

Layal Chaker, MD, MSc Research and Curriculum Fellow Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA

Dr. Layal Chaker

Layal Chaker, MD, MSc
PhD candidate
Department of Endocrinology and Epidemiology
Erasmus Medical Center
Rotterdam, The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The association of thyroid function with coronary heart disease is well–established but not much was known about the association of thyroid function with sudden cardiac death. We conducted the study with the hypothesis that thyroid hormone levels affect cardiovascular risk factors and therefore could also affect the risk of sudden cardiac death (SCD). We were surprised to see that when we control our analyses for these cardiovascular risk factors, the association of high and high-normal thyroid function with SCD remained similar, suggesting that other pathways could play a role. Thyroid hormone has different effects on the cardiovascular systems and future studies should identify which pathway could be responsible for the increased risk of sudden cardiac death with higher thyroid hormone levels. This could lead to better assessment of individual risk and identify possible prevention targets.

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Iron Levels Should Be Checked During Pregnancy

MedicalResearch.com Interview with:
Kris Poppe, MD, PhD
Co-Head Endocrine Unit
CHU St-Pierre UMC
Université libre de Bruxelles

MedicalResearch.com: What is the background for this study? 

Response: Pregnant women are often referred by gynecologists to my endocrine practice, for altered thyroid function. At that occasion, I often noticed that the women also had low iron/ferritin levels (ferritin is the iron reserve). Searching in literature did not reveal many publications on the association between iron (deficiency) and thyroid function during pregnancy and so that was the background/aim to perform this study.

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Clinical Risk Factors and a Prediction Model for Low Maternal Thyroid Function during Early Pregnancy Identified

MedicalResearch.com Interview with:

Dr. Tim IM Korevaar, MD Epidemiology, Internal Medicine (General Medicine) Erasmus University Rotterdam, Rotterdam

Dr. Tim Korevaar

Dr. Tim IM Korevaar, MD
Epidemiology, Internal Medicine (General Medicine)
Erasmus University Rotterdam, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Korevaar: In the medical literature on this topic, many studies have studied risk factors for abnormal thyroid dysfunction during pregnancy – and this is important because it allows clinicians to distinguish high from low risk individuals. However, most studies focused on identifying a single risk factor, for example maternal age or parity. However, this does not translate to clinical practice because a patient sitting in front of you always has multiple characteristics and the combination of these characteristics is likely to be more specific for risk assessment.

In almost 10,000 women, we investigated what clinical characteristics are risk factors for high TSH or low FT4 during pregnancy and subsequently, we investigated to what extent the combination of these risk factors is able to distinguish women with abnormal thyroid function. We found that BMI, ethnicity and non-smoking are risk factors for high TSH, but that overall, these risk factors very poorly predict the risk of high TSH (C-statistic of 0.60). Subsequent analysis showed that the poor predictive ability of risk factors for high TSH was due to the large proportion of TPO antibodies

(TPOAb) positivity in the group of women with high TSH.

For low FT4, maternal age, BMI, smoking, parity and gestational age at presentation were risk factors for low FT4. Overall, these risk factors discriminated women with low FT4 from normal FT4 with good overall discriminative ability (C-statistic 0.76).

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Korevaar: First of all, clinicians can use these risk factors for distinguishing high from low risk patients. The identification of these risk factors can help raise awareness amongst patients and hopefully allow for more timely presentation of women with a high risk in clinical practice.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Korevaar: Further research should focus on investigating optimal cut-offs for our risk score, and the consequences of its potential use for screening modalities. 

MedicalResearch.com: Is there anything else you would like to add?

Dr. Korevaar: We also provide an online calculator for the prediction model of FT4 at: http://www.erasmusmc.nl/formulieren/schildklier/?lang=en

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: Abstract presented at the 2016 ENDO meeting April 2016

Identification of Clinical Risk Factors and a Prediction Model for Low Maternal Thyroid Function during Early Pregnancy

Tim IM Korevaar*1, Daan Nieboer2, Peter H Bisschop3, Mariette Goddijn4, Marco Medici5, Layal Chaker1, Yolanda B. de Rijke6, Vincent Jaddoe2, Henning Tiemeier1, Theo J Visser7, Ewout Steyerberg2, Tanja Vrijkotte4 and Robin P. Peeters8
1Erasmus Medical Center, Rotterdam, 2Erasmus MC, 3Academic Medical Center, Netherlands, 4Amsterdam Medical Center, 5Erasmus medical center, Rotterdam, Netherlands, 6Erasmus MC, Rotterdam, Netherlands, 7Erasmus Univ Med Ctr, Rotterdam, Netherlands,8Erasmus Univ Rotterdam, Rotterdam, Netherlands

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

 

Dr. Tim IM Korevaar, MD (2016). Clinical Risk Factors and a Prediction Model for Low Maternal Thyroid Function during Early Pregnancy Identified MedicalResearch.com

 

Malignant Thyroid Nodules Less Common But More Aggressive With Age

Erik K. Alexander, MD FACP Chief, Thyroid Section, Division of Endocrinology Brigham & Women's Hospital Associate Professor of Medicine, Harvard Medical School

Dr. Erik Alexander

MedicalResearch.com Interview with:
Dr. Erik K. Alexander, MD FACP
Chief, Thyroid Section, Division of Endocrinology
Brigham & Women’s Hospital
Associate Professor of Medicine, Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Dr. Alexander: Thyroid nodular disease has become an increasingly common medical illness, with prevalence reported to range between 26-67% in the adult.  Though advancing age is known to influence the formation of thyroid nodules, their precise relationship remains unclear.  Furthermore, it is uncertain whether age influences the risk that any thyroid nodule may prove cancerous.  Thus we conducted a study to determine the impact of patient age on nodule formation, the number of thyroid nodules, and risk of thyroid malignancy.

Medical Research:  What are the main findings?

Dr. Alexander: Our study is a prospective cohort analysis of consecutive adults who presented for evaluation of nodular disease from 1995-2011 at Brigham and Women’s Hospital, Boston, MA.  6,391 patients underwent thyroid ultrasound and fine needle aspiration that resulted in 12,115 thyroid nodules ≥1 cm.  Patients were stratified into six age groups and compared using sonographic, cytologic, and histologic endpoints.
We found that the prevalence of thyroid nodular disease increases with advancing age.  The mean number of nodules at presentation increased from 1.5 in the youngest cohort (ages 20–30) to 2.2 in the oldest cohort (>70 years).  In contrast, the risk for malignancy in a newly identified nodule declined with advancing age.  Thyroid cancer incidence per patient was 22.9% in the youngest cohort, but 12.6% in the oldest cohort.  Despite a lower likelihood of malignancy, identified cancers in older patients demonstrated a more aggressive cancer subtype.  While nearly all malignancies in younger patients were well-differentiated, older patients were more likely to have higher risk papillary thyroid cancer variants, poorly differentiated cancer, or anaplastic carcinoma.

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