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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Exposure to BPA Substitute, BPS, Multiplies Breast Cancer Cells

Sumi Dinda

Dr. Sumi Dinda

MedicalResearch.com Interview with:
Sumi Dinda, PhD, NRP, IC.

Associate Professor
Biomedical Diagnostic and Therapeutic Sciences,
School of Health Sciences and
Adjunct Associate Professor
Department of Biological Sciences
School of Health Sciences
Oakland University
Rochester, MI 48309.


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

Response: Bisphenol-S (BPS), a substitute for bisphenol-A (BPA), has been suggested to be an endocrine disrupting compound interfering with normal hormonal activity. This bisphenol analogue is found in plastic substitutes, paper currency, and most products marked “BPA free.” Endocrine disrupting compounds interfere with the normal hormonal activity in the body.

Bisphenols, specifically, disrupt the proper functioning of estrogen receptors, such as ERα causing interference with the normal activity of the hormone estrogen. Studies suggest BPS induces ERα pathways via its estrogen-mimicking properties in the body causing increased cell proliferation resulting in increased breast cancer risk. Despite the hope of a safer substitute, studies have shown that BPS exhibits similar estrogenic activity compared to its analogue BPA, due to their structural commonalities.

BRCA1 is a commonly mutated gene in breast cancer; therefore, it is also important to study the effects of BPS on the expression of this protein. The potency of the endocrine disrupting abilities of BPS compared to BPA could show whether BPS is a suitable alternative to BPA in many everyday products.

The results of this study may contribute to the understanding of the relationship between ERα, BRCA1 expression and Bisphenol-S in breast cancer treatment and prevention.

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Pyrethroid Pesticides Linked To Earlier Puberty in Boys

MedicalResearch.com Interview with:

Jing Liu, Ph.D. Associate Professor College of Environmental & Resource Sciences Zhejiang University Hangzhou, China

Dr. Jing Liu

Jing Liu, Ph.D.
Associate Professor
College of Environmental & Resource Sciences
Zhejiang University
Hangzhou, China

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

Response: In addition to consistent observations of earlier pubertal onset in female since late 19th century, acceleration in male pubertal development also has been reported in more recent studies. Improved nutrition, health and living conditions may contribute to the secular trend towards an earlier pubertal onset. However, the potential role of environmental agents, specifically endocrine-disrupting chemicals (EDCs), also has been emphasized.

Pyrethroids are among the currently used pesticide classes placed on the list of the US Environmental Protection Agency (EPA) as potential EDCs. Pyrethroids are one of the top 10 classes of pesticides and account for greater than 30% of global insecticide usage. Increased human exposure to pyrethroids is thought to occur mainly via residues in diets and indoor residential use. The metabolites of pyrethroids have been widely identified in urine samples of adults, children and adolescents worldwide and the detection rate is usually more than 60% in human populations.

Here, we recognize pyrethroids as a new environmental contributor to the observed secular trend toward earlier male sexual maturity. For the first time to our knowledge, this work reveal a significant and positive association between pyrethroids exposure and gonadotropins levels in 463 Chinese boys, in which a 10% increase in 3-PBA (a common urinary metabolite of pyrethroids) is associated with more than 2% increase in both LH and FSH. Boys with increased urinary levels of 3-PBA have a significantly increased risk of earlier pubertal development, in which the odds of being in an advanced testicular volume and genitalia stage are increase by 113% and 268%, respectively.

Because it is difficult to test the direct causality of environmental risk factors in humans, we further sought to identify in animals how pyrethroids alter the timing of puberty. Postnatal exposure to a widely used pyrethroid pesticide, cypermethrin, can accelerate pubertal timing and induce circulating levels of gonadotropins and testosterone in male mice. Our findings reveal the activation of voltage-gated calcium channels pathway in pituitary gonadotropes and testicular Leydig cells as a newly discovered mechanism of pyrethroid-induced early pubertal development in the male.

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PAP May Provide New Therapeutic Target For Bone Metastatic Prostate Cancer

MedicalResearch.com Interview with

Dr. Alice Levine MD Professor, Medicine, Endocrinology, Diabetes and Bone Disease Associate Professsor ,Oncological Sciences Icahn School of Medicine at Mount Sinai

Dr. Alice Levine

Dr. Alice Levine MD
Professor, Medicine, Endocrinology, Diabetes and Bone Disease
Associate Professsor ,Oncological Sciences
Icahn School of Medicine at Mount Sinai

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

Response: Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. This cancer is unique in its tendency to produce osteoblastic (OB) bone metastases, which affects 90% of men with PCa bone metastases, compared to others that produce osteolytic bone metastases. Currently, there are no existing therapies that specifically target the OB phase and no effective therapies for PCa bone metastases that prolong survival. We have identified a secretory protein that promotes the development PCa osteoblastic bone metastases, Prostatic acid phosphatase (PAP). Prostatic epithelial cells produce PAP. The physiologic function of PAP is unknown. It was the first human tumor marker ever described. Patients with PCa bone metastases demonstrated high levels of PAP. PAP is expressed by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization.

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Omega-3 Fatty Acid Supplementation Improves Luteal Function in Obese Women

MedicalResearch.com Interview with:

Alex J. Polotsky, MD Associate Professor of Obstetrics and Gynecology University of Colorado Denver Practice homepage

Dr. Polotsky

Alex J. Polotsky, MD
Associate Professor of Obstetrics and Gynecology
University of Colorado Denver
Practice homepage

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

Response: It has been well established that profound dietary changes occurred over the past 100 years. The type and amount of fat consumed has changed quite a bit over the course of 20th century. Intake of omega-3 polyunsaturated fatty acids (PUFAs), previously consumed in large quantities by humans from vegetable and fish sources, has dropped significantly. The typical Western diet (sometimes also called the typical American diet) provides an omega-6 to omega-3 fatty acid ratio of as high as 25:1, which is quite different from what it used to up until about the 19th century (believed to be about 1:1 ratio).

In animal studies, diets enriched with omega-3 PUFA enhance early embryonic development and boost progesterone secretion. Obesity is well known to be associated with decreased progesterone production in women (even if a obese woman ovulates). The reasons for this are not clear. Obesity is also a state of low-grade chronic inflammation. Omega-3 fatty acids are well known to have anti-inflammatory properties.

We sought to test whether dietary supplementation with omega-3 PUFA favorably affects reproductive hormones in women and whether this effect includes normalization of progesterone production in obesity.

All women in the study tolerated supplementation well, and had significantly decreased their omega-6 to omega-3 ratios (they were normalized much closer to a 1:1 ratio). Omega-3 supplementation resulted in a trend for increased progesterone in obese women, thus enhancing ovulatory function. A 16 to 22 percent increase was observed. Additionally, the supplementation resulted in reduced systemic inflammation.

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Study Finds Statin Use Not Associated With Breast Cancer Prognosis

MedicalResearch.com Interview with:

Amanda Leiter, MD MSCR Medical Resident, Internal Medicine Icahn School of Medicine at Mount Sinai

Dr. Leiter

Amanda Leiter, MD MSCR
Medical Resident, Internal Medicine
Icahn School of Medicine at Mount Sinai

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

Response: Black women are more likely than White women to have breast cancer with poor prognostic features, which cannot be completely explained by differences in screening, treatment and established risk factors for breast cancer mortality. Black women have higher rates of obesity, insulin resistance and dyslipidemia when compared to White women. Prior studies have shown a decreased risk of breast cancer recurrence and improved survival with statin use.

As statins have an association with decreased breast cancer recurrence and potentially improved survival, disparities in statin use between Black and White women with breast cancer are important to investigate. We aimed to elucidate whether or not statin use differs between Black and White women with breast cancer and if racial disparities in breast cancer can be partially explained by differences in statin use.
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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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Taking Testosterone Doesn’t Increase Prostate Cancer Risk

MedicalResearch.com Interview with:

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York

Dr. Stacy Loeb

Dr. Stacy Loeb MD Msc
Assistant Professor of Urology and Population Health
New York University Langone Medical Center

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

Response: The association between exposure to testosterone replacement therapy and prostate cancer risk is controversial.  The purpose of our study was to examine this issue using national registries from Sweden, with complete records on prescription medications and prostate cancer diagnoses.  Overall, we found no association between testosterone use and overall prostate cancer risk. There was an early increase in favorable cancers which is likely due to a detection bias, but long-term users actually had a significantly reduced risk of aggressive disease.

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Oral Dydrogesterone May Become Preferred Treatment Option for IVF

MedicalResearch.com Interview with:
Matthias Straub
Senior Director, Clinical Development
Abbott

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

Response: The Lotus I study provides clinical evidence that oral dydrogesterone is a treatment option for women who undergo in vitro fertilization (IVF) treatment. The current standard of care for IVF globally is micronized vaginal progesterone (MPV), which is administered vaginally.

The Lotus I study concludes that oral dydrogesterone is similarly well-tolerated and efficacious compared to MVP, while being easier to administer than MVP.

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Vitamin D During Fetal Life and Bone Health in Children at Age 6

MedicalResearch.com Interview with:
Audry H. Garcia PhD

Scientist Department of Epidemiology
Erasmus MC, University Medical Center Rotterdam
Rotterdam, the Netherlands 

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

Response: Fetal bone mineralisation requires an adequate transfer of calcium to the fetus by the end of the pregnancy. Considering that vitamin D is required to maintain normal blood concentrations of calcium, adequate 25-hydroxyvitamin D (25[OH]D) concentrations in pregnant women seem to be crucial for bone development of the offspring. Maternal vitamin D deficiency during pregnancy has been associated with abnormal early skeletal growth in offspring and might be a risk factor for decreased bone mass in later life. Several studies have linked vitamin D deficiency in fetal life to congenital rickets, craniotabes, wide skull sutures and osteomalacia. However, the evidence of long-lasting effects of maternal vitamin D deficiency during pregnancy on offspring’s skeletal development is scarce and inconsistent, and has led to contradictory recommendations on vitamin D supplementation during pregnancy.

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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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