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01/08/2012 12:05 AM

Low Thyroid Levels not Uncommon in Pregnancy

Bettyg
 
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Low Thyroid Levels not Uncommon in Pregnancy

By Kurt Ullman, Contributing Writer, MedPage Today

Published: January 05, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and

Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Gestational hypothyroidism may be more common than thought, affecting nearly 500,000 women each year, researchers estimated.

Of 117,892 women from the ages of 18 to 40, 15% tested positive for gestational hypothyroidism, Jon M. Nakamoto, MD, PhD, and colleagues from Quest Diagnostics, reported online in the Journal of Clinical Endocrinology & Metabolism.

Based on this finding, the researchers estimated that as many as 483,000 pregnant women with gestational hypothyroidism may go undetected each year.

Asian women were almost five times more likely to test positive for gestational hypothyroidism than African-American women (19.3% compared with 6.7%) and slightly more likely than Caucasian and Hispanic women (16.4% and 15.2%, respectively).

Positivity rates differed significantly across ethnicities at P<0.001.

&#9632;Gestational hypothyroidism may be more common than thought, affecting nearly 500,000 women each years.

&#9632;Of the pregnant women in the study, Asian women had the highest testing rate of 28% and African-American woman had the lowest rate at just 19%.

The researchers accessed the Quest Diagnostics Informatics Data Warehouse, what they called the largest private clinical data warehouse in the United States.

Pregnancy was defined when a woman underwent testing normally associated with the first prenatal visit and a maternal serum screen result.

Testing rates and estimates of the prevalence of hypothyroidism during pregnancy and immediately postpartum were measured using reference intervals specific to the particular assay and the trimester.

Screening and positive rates for thyroperoxidase antibody (TPO Ab) and free T4 tests were also reported.

Gestational hypothyroidism has been linked to medical complications for both mothers and babies.

However, the appropriate diagnostic approach and management of the condition remains controversial. The researchers wanted to analyze the current status of testing for thyroid disease during pregnancy.

Of the pregnant women in the study, Asian women had the highest testing rate of 28% and African-American woman had the lowest rate at just 19%. Testing rates increased with maternal age.

Multiple regression analysis found that women 35 to 40 years of age were 2.2 times more likely to be tested when compared with those between 18 and 24 (OR 2.223, 95% CI 2.161 to 2.287).

Weight was also a factor as those over 275 pounds (125 kg) were 1.3 times more likely to be tested than those weighing between 100 and 124 pounds (OR 1.328, 95% CI 1.269 to 1.390).

Nearly a quarter (24%) of the women with thyroid stimulating hormone (TSH) within the normal range and 33% of those with elevated TSH were further tested for gestational hypothyroxinemia.

Of the first group, 0.3% had a TPO Ab test with 15% testing positive. In the second, 0.66% got the follow-up test with 65% testing positive.

Only 20.7% of women with low thyroid received additional screening within 6 months of giving birth. Of this cohort, 11.5% received a diagnosis of postpartum hypothyroidism.

Younger women were slightly underrepresented in the study population and older women were slightly overrepresented.

Given the higher rates of gestational hypothyroidism among older women, the authors suggested that the overall rate is slightly lower than what they report.

"Because national and international endocrine and obstetrical organizations may consider the implications of universal prenatal and antenatal screening, this study demonstrates that the proportion of women tested for gestational hypothyroidism is low," wrote the authors.

"(I)f outcomes are shown to improve with intervention, then this may have a significant impact on the health of a large number of women and their children."

All three authors are employed by Quest Diagnostics.

Dr. Nakamoto and Harvey Kaufman also have an equity interest in Quest Diagnostics.

Primary source: Journal of Clinical Endocrinology & Metabolism

Source reference:

Blatt AJ, et al "National status of testing for hypothyroidism during pregnancy and postpartum" J Clin Endocrinol Metab 2012; 97: DOI: 10.1210/jc.2011-2038.

http://www.medpagetoday.com/OBGYN/Pregnancy/30510? utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

Lin Memm - Jan 06, 2012

This is really an important study and I hope it has some impact.

I can look back and see my own hypothyroidism and my research has led me to information about being hypo as a possible cause for long labors and the inability to produce much milk, both of which happened to me. Plus, my babies were born jaundiced.

Perhaps women who have low iodine intact are being affected because the fetus is taking it from her.

Could this also be a cause for breast cancer in young moms?

There is an undeniable link to hypthyroidism and breast cancer and more and more doctors are encouraging women get more iodine.

I firmly believe that my thyroid problems is what led to me getting breast cancer. If this was taken seriously, we could improve the health of a lot of women and their babies.

© 2012 Everyday Health, Inc. All rights reserved.[b]

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02/10/2012 03:09 PM
Bettyg
 
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Mom's Thyroid Rx Has No Effect on Kid's IQ

By Todd Neale, Senior Staff Writer, MedPage Today

Published: February 08, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points

Maternal hypothyroidism in pregnancy has been associated with miscarriage, preterm delivery, and reduced cognitive function in offspring, but whether universal screening should be performed is not clear.

This study found that antenatal screening and maternal treatment for hypothyroidism did not result in improved cognitive function (as defined by mean IQ scores) in children at 3 years of age.

Screening pregnant women for low thyroid hormone levels in the first trimester -- and treating accordingly -- does not impact a child's IQ at age 3, a randomized trial showed.

The average IQ was 99.2 among children whose mothers were treated for low thyroid hormone levels and 100.0 for those whose mothers were not treated (P=0.40), according to John Lazarus, MD, of Cardiff University in Wales, and colleagues.

Similarly, there was no difference between the groups in the proportion of children who had an IQ of less than 85 (12.1% versus 14.1%, P=0.39), the researchers reported in the Feb. 9 issue of the New England Journal of Medicine.

Gregory Brent, MD, of the University of California Los Angeles, said that the findings likely will not settle the debate about the need for universal testing of thyroid function during pregnancy.

"However," he wrote in an accompanying editorial, "the findings provide support for the position of clinicians who have resisted the call for universal thyroid-function screening in pregnancy and are concordant with recent guidelines published by the American Thyroid Association and the Endocrine Society."

Those guidelines recommend testing thyroid function only in women who are at increased risk, he noted.

The idea that treating thyroid deficiency during pregnancy would improve the children's IQ during childhood came from observational studies that showed an association between low thyroid hormone levels in mothers and impaired cognitive function in their children.

Lazarus and colleagues tested the concept in a randomized trial that included 21,846 pregnant women who provided blood samples at less than 16 weeks' gestation. It was conducted at 10 centers in the U.K. and one in Italy.

Half of the women had thyroid function assessed immediately and were treated as necessary.

Those with a positive result -- defined as thyrotropin levels greater than the 97.5th percentile, free thyroxine (T4) levels below the 2.5th percentile, or both -- received a starting dose of 150 µg of levothyroxine per day.

It could be adjusted to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter.

The rest of the women had their serum stored until shortly after delivery, when thyroid function was assessed.

Overall, 390 women (4.6%) in the screening group and 404 (5%) in the control group tested positive for thyroid deficiency.

Women with a positive result in the screening group initiated levothyroxine treatment at a median gestational age of 13 weeks 3 days. Through 20 weeks' gestation, treatment was associated with an average decrease in thyrotropin level by a factor of 10 and an average increase in free T4 of about 35%.

The changes, however, were not associated with differences in their children's total IQ scores -- measured using the Wechsler Preschool and Primary Scale of Intelligence -- or the verbal or performance components of the scores at age 3.

Adjustment for the initial thyrotropin measurements did not change the results.

Lazarus and colleagues speculated about the reasons for the lack of benefit from screening for and treating thyroid deficiency.

One possibility is that the observational studies that suggested such a benefit may have been subject to confounding, which was largely avoided by randomization.

Another is that there could have been an effect on more specific cognitive function than was measured in the current study.

It also is possible, the authors wrote, that screening and treatment were started too late in pregnancy to have much of an effect on brain development, or that the cognitive assessment was performed too early.

"Additional randomized trials are needed to determine whether earlier antenatal screening or later childhood cognitive assessment could show a benefit of thyroxine replacement in pregnancy," they wrote, noting that a trial using blood samples taken earlier during pregnancy and cognitive assessments at age 5 is ongoing.

In his editorial, Brent said another possible explanation for the lack of benefit is that the women in the trial had milder hypothyroidism than those in the observational studies.

The study authors acknowledged that the trial was limited in that about one-quarter of the participants were lost to follow-up, either because they could not be contacted or they declined assessment.

The study was supported by the Wellcome Trust and Compagnia di San Paulo in Turin, Italy.

Lazarus reported receiving consulting fees from Abbott Diagnostics and lecture fees from Abbott Diagnostics and Merck (Darmstadt).

Brent reported the following:

"I don't believe that the following represents a conflict of interest or needs to be disclosed to readers, but am providing for review.

I am a long-standing member (all greater than 10 years) of the American Thyroid Association, the Endocrine Society, and the American Association of Clinical Endocrinologists, all of which have presented positions, and in some cases guidelines, on thyroid screening in pregnancy.

I am currently on the editorial board of Journal of Clinical Endocrinology & Metabolism (journal of The Endocrine Society) and Immediate Past President and on the board of the American Thyroid Association.

I have not received any compensation from any of these entities and am not an author on the recent pregnancy guidelines from either the Endocrine Society or the American Thyroid Association, although have referenced both in my editorial."

Primary source: New England Journal of Medicine

Source reference:

Lazarus J, et al "Antenatal thyroid screening and childhood cognitive function" N Engl J Med 2012; 366: 493-501.

Additional source: New England Journal of Medicine

Source reference:

Brent G "The debate over thyroid-function screening in pregnancy" N Engl J Med 2012; 366: 562-563.

http://www.medpagetoday.com/Endocrinology/Thyroid/31086? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source=

© 2012 Everyday Health, Inc. All rights reserved.


04/27/2012 04:42 PM
Bettyg
 
Posts: 32240
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Best to Get Early Clues to Thyroid Balance

By Kristina Fiore, Staff Writer, MedPage Today

Published: April 23, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Subclinical thyroid disease appears to be tied to cardiovascular effects including ischemic events and atrial fibrillation, according to two new studies.

Note that in one of the studies, treating subclinical hypothyroidism with levothyroxine (Synthroid) was associated with fewer ischemic heart disease events in younger patients.

Subclinical thyroid disease -- whether hyper- or hypothyroidism -- appears to be tied to cardiovascular effects, according to two studies in the Archives of Internal Medicine.

In a meta-analysis, endogenous subclinical hyperthyroidism was associated with higher risks of overall mortality, cardiovascular mortality, and atrial fibrillation, according to Nicolas Rodondi, MD, of the University of Bern in Switzerland, and colleagues.

As for hypothyroidism, treating subclinical disease with levothyroxine (Synthroid) was associated with fewer ischemic heart disease events in younger patients, according to results of a large cohort study conducted by Salman Razvi, MD, of Newcastle University in Newcastle upon Tyne, England, and colleagues.

Minisha Sood, MD, an endocrinologist at Lenox Hill Hospital in New York, who wasn't involved in either study, told MedPage Today that the findings help guide treatment of subclinical thyroid disease, which is "a common dilemma faced by endocrinologists today."

She cautioned that the Rodondi study doesn't help clarify whether treatment of subclinical hyperthyroidism can improve survival or reduce heart risks.

In addition, randomized, controlled trials must examine the use of levothyroxine therapy in subclinical hypothyroidism.

Rodondi and colleagues looked at data on 52,674 patients, median age 59, from a total of 10 cohorts in the Thyroid Studies Collaboration.

About 4.2% of the total population had subclinical hyperthyroidism, which was defined as thyrotropin (TSH) levels lower than 0.45 mIU/L with normal free thyroxine (FT4) levels.

During a median follow-up of 8.8 years, the authors found the condition was associated with an increased risk of:

Death overall: HR 1.24, 95% CI 1.06 to 1.46

Cardiovascular death: HR 1.29, 95% CI 1.02 to 1.62

Atrial fibrillation: HR 1.68, 95% CI 1.16 to 2.43

There was a trend toward an increased risk of heart disease events as well, but the confidence interval straddled zero, the researchers found.

The risk of stroke and cancer death, however, wasn't higher with subclinical hyperthyroidism.

In further analyses, they found that the risks of cardiovascular death and atrial fibrillation events were significantly higher with thyrotropin levels lower than 0.10 mIU/L, compared with levels between 0.10 and 0.44 mIU/L (P&#8804;0.03 for trend).

They said these increased risks could be tied to systemic effects of thyroid hormones, such as a change in cardiac function or cardiac arrhythmia.

The study was limited in its generalizability, as most cohorts were made up of white patients, with the exception of one involving Brazilians of Japanese descent.

Also, not all patients had data on T3 levels, which may have skewed the data given that diagnoses were only made by TSH and T4 levels, the researchers warned.

They concluded that the findings should be "interpreted with caution in clinical practice" because they were based on observational data, and noted that the study can't address whether cardiovascular risks would be lowered by treatment of subclinical hyperthyroidism.

In an accompanying editorial, Kenneth Burman, MD, of Georgetown University in Washington, D.C., said the study "provides important information regarding the importance of recognizing" the condition and its relationship to cardiovascular disease.

"The relationship between subclinical hyperthyroidism and increased mortality, [cardiovascular] mortality, and atrial fibrillation presently provides sufficient evidence to consider treatment of subclinical hyperthyroidism, especially in elderly patients with cardiac risks, hyperthyroid symptoms, or osteoporosis," he said, but cautioned that further prospective, long-term, controlled studies are still needed.

Subclinical hypothyroidism, defined as thyrotropin levels of 5 to 10 mIU/L with normal free thyroxine levels, has been associated with ischemic heart disease, especially in young to middle-age adults, but it's unclear whether treating the condition with levothyroxine reduces the risk of cardiovascular disease.

Razvi and colleagues looked at data from the United Kingdom General Practitioner Research Database on 3,093 younger patients (ages 40 to 70) and 1,642 older patients (ages 70 and up) who were diagnosed with subclinical hypothyroidism between 2001 and 2009.

Younger patients were followed for a median of 7.6 years, and older patients were followed for a median 5.2 years.

About 52.8% of younger patients and 49.9% of older patients were treated with levothyroxine (median dose 75 &#956;g/day).

Razvi and colleagues found that younger patients had fewer heart events if they were treated with the medication (4.2% versus 6.6%, multivariate adjusted HR 0.61, 95% CI 0.39 to 0.95).

They also had lower all-cause mortality than patients who weren't treated with levothyroxine (multivariate adjusted HR 0.36, 95% CI 0.19 to 0.66), mainly because of a reduction in circulatory and cancer-related deaths.

There were fewer cardiovascular events in older patients who didn't receive treatment, but the findings didn't differ significantly, the researchers wrote (10.7% versus 12.7%, HR 0.99, 95% CI 0.59 to 1.33).

Rates of all-cause death were also similar in both treated and untreated older patients, they found.

One potential explanation for the protective effects of levothyroxine in younger patients could be that the drug has been shown to reduce low-density lipoprotein (LDL) cholesterol levels and improve endothelial function, carotid intima-media thickness, and left ventricular diastolic function, the researchers said.

They cautioned that the study was limited by its retrospective nature and that further randomized trials are needed to determine the true effects of drug therapy on these events.

The study by Rodondi and colleagues was supported by grants from the Swiss National Science Foundation.

The researchers reported no conflicts of interest.

Burman reported relationships with Pfizer and Eisai.

The study by Razvi and colleagues was supported by a grant from the Medical Research Council.

A co-author reported relationships with Merck Serono.

Primary source: Archives of Internal Medicine

Source reference:

Collet TH, et al "Subclinical hyperthyroidism and the risk of coronary heart disease and mortality" Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.402.

Additional source: Archives of Internal Medicine

Source reference:

Razvi S, et al "Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality" Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.1159.

Additional source: Archives of Internal Medicine

Source reference:

Burman KD "What is the clinical importance of subclinical hyperthyroidism?" Arch Intern Med 2012; DOI10.1001/archinternmed.2012.1114.

http://www.medpagetoday.com/Cardiology/ AcuteCoronarySyndrome/32313?utm_content=&utm_medium=email& utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.


06/28/2012 10:34 AM
Bettyg
 
Posts: 32240
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Test May Help Exclude Benign Thyroid Lesions

By Charles Bankhead, Staff Writer, MedPage Today

Published: June 25, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Take Posttest

Action Points

Note that thyroid nodules are common and with ultrasound can be detected in up to half of adults.

Note also that this study provides evidence that a gene-expression classifier test can be used to identify low-risk thyroid nodules in patients with indeterminate cytology on fine-needle aspirates and may possibly be used to reduce unnecessary surgery.

HOUSTON -- A gene-expression test correctly identified more than 90% of suspicious thyroid nodules as malignant as confirmed by histopathologic confirmation, investigators reported.

Follow-up analysis showed that all but one false-positive result was associated with inadequate sampling by fine-needle aspiration.

The results suggest that many unnecessary diagnostic interventions can be avoided for patients with thyroid nodules of indeterminate status, as reported online in the New England Journal of Medicine.

"This study shows that a gene-expression classifier can be used to identify a subpopulation of patients with a low likelihood of cancer in a population of patients for whom diagnostic surgery is otherwise recommended," Erik K. Alexander, MD, of Harvard and Brigham and Women's Hospital in Boston, and co-authors wrote in conclusion.

"Though each clinical decision must be individualized, these data suggest consideration of a more conservative clinical approach for patients who have nodules with indeterminate cytologic features on fine-needle aspiration and a benign result on gene-expression classifier testing."

The study also was reported at ENDO 2012 in Houston.

As many as 15% of suspicious thyroid nodules prove to be malignant.

As a consequence, most nodules 1 cm and larger lead to a diagnostic evaluation. Fine-needle aspiration cytology remains the cornerstone of evaluation, but as many as 30% of procedures lead to indeterminate findings.

Indeterminate cytology for a thyroid nodule falls into one of three classifications:

Atypia of undetermined significance

Follicular neoplasm or suspected neoplasm

Suspicious for malignancy

Patients referred unnecessarily for diagnostic surgical evaluation face a 2% to 10% risk of serious complications, most of which would lead to lifelong levothyroxine replacement therapy, the authors noted.

Molecular analysis holds great promise as an adjunct to microscopic evaluation of thyroid tissue, as 60% to 70% of thyroid cancers have one or more known genetic mutations.

In one study, analysis of genetic markers with a high specificity for thyroid malignancy revealed mutations in 16% of cases (J Clin Endocrinol Metab 2011; 976: 3390-3397).

Recently, a gene-expression classifier showed promise for distinguishing benign thyroid nodules from malignant lesions.

A pilot study demonstrated sensitivity and negative predictive value exceeding 90% (J Clin Endocrinol Metab 2010; 95: 5296-5304).

Alexander and colleagues reported findings from a large, prospective, multicenter validation study of the gene-expression classifier in patients with indeterminate thyroid nodules.

Investigators at 49 sites evaluated 4,812 fine-needle aspirates of thyroid nodules 1 cm or larger in 3,789 patients.

Beginning with 577 cytologically indeterminate aspirates, they honed the number to 265, each of which had a corresponding histopathologic specimen from the same lesion.

The gene-expression classifier comprises 25 genes that filter out rare neoplasms and 142 genes that serve as the primary classifier.

Blinded histopathologic review identified 85 of 265 indeterminate aspirates as malignant. The gene-expression classifier identified 78 of 85 as suspicious, resulting in sensitivity of 92%.

The test correctly classified 93 of 180 benign lesions, resulting in a specificity of 52%.

The test achieved 90% or higher sensitivity for all categories of indeterminate thyroid lesions.

Used as an aid to clinical decision making, the gene-expression classifier might eliminate a third of the estimated 75,000 diagnostic surgeries performed each year for cytologically indeterminate thyroid lesions, the author of an accompanying editorial wrote.

The potential downside of the test is that 5% to 10% of nodules classified as benign might prove to be malignant, particularly lesions that are indeterminate but suggestive of cancer.

"Because this group is at high risk for cancer, it might be reasonable to repeat the fine-needle aspiration biopsy or perform a diagnostic hemithyroidectomy even when the gene-expression classifier indicates a benign profile," wrote J. Larry Jameson, MD, PhD, of the University of Pennsylvania in Philadelphia.

"In this era of focusing on high-quality outcomes at lower cost, this new gene-expression classifier test is a welcome addition to the tools available for informed decision making about the management of thyroid nodules," Jameson added.

The study was supported by Veracyte, developer of the gene-expression test, and co-authors included Veracyte employees.

Alexander and co-authors disclosed relationships with Veracyte, Asuragen, Genzyme, AstraZeneca, Eli Lilly, Bayer/Onyx, Eisai, Exelixis, Roche, Novo Nordisk, MLCI, Elsevier, Springer, Humana Press, Cytoscore, Milestone, Ventana, and BD Diagnostics.

Jameson disclosed relationships with Quest Diagnostics, Kinship Foundation, Cedars Sinai, and Massachusetts General Hospital.

Primary source: New England Journal of Medicine

Source reference:

Alexnder EK, et al "Preoperative diagnosis of benign thyroid nodules with indeterminate cytology" N Engl J Med 2012; DOI: 10.1056/NEJMoa1203208.

Additional source: New England Journal of Medicine

Source reference:

Jameson LK "Minimizing unnecessary surgery for thyroid nodules" N Engl J Med 2012; DOI: 10.1056/NEJMe1205893.

http://www.medpagetoday.com/MeetingCoverage/ENDO/33454? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines& utm_source

© 2012 Everyday Health, Inc. All rights reserved

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