Thyroid-stimulating hormone

Thyroid disorders may increase mortality risk in peritoneal dialysis

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Patients undergoing peritoneal dialysis with hypothyroidism or hyperthyroidism may have a higher risk for mortality, study data show.

Connie M. Rhee, MD, MSc, of the Harold Simmons Center for Kidney Disease Research and Epidemiology, division of nephrology and hypertension at the University of California, Irvine Medical Center in Orange, California, and colleagues evaluated data from a large national dialysis organization on 1,484 adults undergoing peritoneal dialysis who underwent one or more thyroid-stimulating hormone measurements from 2007 to 2011.

Thyroid status was divided into five categories: overt-hyperthyroid (TSH, < 0.1 mIU/L), subclinical-hyperthyroid (TSH, 0.1 mIU/L to < 0.5 mIU/L), low-normal (TSH, 0.5 mIU/L to < 3 mIU/L), high-normal (TSF, 3 mIU/L to < 5 mIU/L), subclinical-hypothyroid (TSH, mIU/L 5 to < 10 mIU/L) and overt-hypothyroid (TSH, 10 mIU/L)

Seven percent of participants had hyperthyroidism, 18% had hypothyroidismand 75% were euthyroid as defined by baseline TSH levels.

Through a total of 1,953 person-years of follow-up, there were 258 deaths for a rate of 132 deaths per 1,000 person-years. A higher risk for death was associated with TSH levels less than 0.1 mIU/L and 5 mIU/L or more.

Compared with participants who were euthyroid, participants with hyperthyroidism (adjusted HR = 1.69; 95% CI, 1.09-2.62) and hypothyroidism (adjusted HR = 2.08; 95% CI, 1.56-2.78) had a higher risk for mortality.

“Our study found that both hypothyroidism and hyperthyroidism were independently associated with higher mortality in a national [peritoneal dialysis] cohort, consistent with data in the hemodialysis population,” the researchers wrote. “Given the high prevalence of thyroid functional disease and exceedingly high mortality of the dialysis population, further studies are needed to determine the underlying mechanisms by which thyroid functional disease impacts mortality, whether thyroid hormone modulating therapies ameliorates mortality risk, and the precise TSH targets associated with improved outcomes in the dialysis population.” – by Amber Cox

Pregnant women with subclinical hypothyroidism more likely to miscarry

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Among pregnant women at low risk for thyroid dysfunction, the existence of subclinical hypothyroidism, thyroid autoimmunity or both prior to 8 weeks’ gestation increases the likelihood of miscarriage, according to recent findings.

In the prospective cohort study, researchers evaluated 3,315 women seen at the gynecology/obstetrics clinics of 13 hospitals and six prenatal clinics in three Chinese cities. The women were enrolled in the study between January and September of 2012 at the clinics, all of which were located in areas of China deemed iodine sufficient. Women identified for analysis were between 4 and 8 weeks’ gestation, and had lived in the area for more than 5 years.

Study participants completed questionnaires pertaining to demographic and obstetric history (maternal age, gestational age, previous pregnancies/births, and previous miscarriage). The questionnaires also elicited information about education level, income, smoking status, alcohol consumption, family history of thyroid disorders, history of type 1 diabetes, autoimmune diseases and treatments involving head or neck irradiation.

At baseline, all women were imaged by ultrasound to confirm ongoing pregnancy. The study’s primary outcome was miscarriage, which was characterized as sudden pregnancy loss before 20 weeks’ gestation. Participants underwent monthly thyroid function tests and ultrasound imaging at the clinics. The thyroid tests measured thyroid stimulating hormone, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody and urinary iodine.

On the basis of the thyroid test results, women were classified into four groups: euthyroidism (ET), isolated subclinical hypothyroidism (SCH), isolated thyroid autoimmunity (TAI) and subclinical hypothyroidism with TAI (SCH and TAI). Patients in the SCH cohort were further divided into two subgroups SCH1 and SCH2, based on TSH levels; as a result, the SCH and TAI group was also further stratified into two groups (SCH+TAI1 and SCH+TAI2).

The researchers found that compared with ET women (2.2%), those with SCH had a significantly higher risk of miscarriage (7.1%; adjusted OR=3.40; 95% CI: 1.62-7.15). Additionally, women with TAI alone were also at significantly increased risk of miscarriage (5.7%) vs. ET patients (2.2%; adjusted OR=2.71; 95% CI, 1.43-5.12), as were women in the TAI+SCH1 groups (10%; adjusted OR=4.96; 95% CI: 2.76-8.90) and the TAI+SCH2 groups (15.2%; adjusted OR=95% CI, 3.76-24.28).

Among 110 women who miscarried, the gestational ages were lower among those with subclinical thyroid disorders (11.3 weeks) vs. ET women (9.33 weeks; P =.024). The subgroup analysis also determined that higher TSH levels were associated with lower gestational age at miscarriage, in women with or without TAI.

The researchers said these findings may support the need to monitor thyroid function in pregnant women.

“To some extent, these finding support universal screening of women of reproductive age for thyroid function and thyroid autoimmunity early during pregnancy or during the preconception period,” the researchers wrote.

TSH suppression after thyroidectomy increases osteoporosis risk in women.

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 Suppressing thyroid-stimulating hormone after thyroid cancer resection increases the risk for osteoporosis without decreasing recurrence, according to data presented at the American Thyroid Association meeting.

 “TSH suppression up to 0.4 mU/L increases the risk of osteoporosis without changing recurrence in thyroid cancer patients at low and intermediate risk of recurrence,” said Laura Y. Wang, MD, of the department of surgery at Memorial Sloan-Kettering. “Thus, future therapeutic efforts should focus on avoiding harm in indolent disease.”

Wang presented a retrospective study looking at patients who had a total thyroidectomy at Memorial Sloan-Kettering Cancer Center from 2000 to 2006 with a median follow-up of 6.5 years. The study criteria excluded patients with primary hyperparathyroidism, fewer than three postoperative TSH lab results, preoperative atrial fibrillation, preoperative osteoporosis, and considered high risk by the ATA; they also excluded men from the osteoporosis analysis. After these exclusions, the study looked at 771 total patients and 537 patients in the osteoporosis analysis.

Patients with median TSH ≤0.4 mU/L were considered TSH suppressed. TSH labs were analyzed up to original recurrence or last follow-up.

“TSH suppression was the most powerful independent predictor of osteoporosis, conferring a nearly fourfold risk of development of postoperative osteoporosis,” Wang said. “The impact on TSH on osteoporosis risk was even higher on univariate analysis, increasing the HR from almost 3.5 to 4.3. This suggests that there is possibly a synergistic effect between older age and TSH suppression.”

The disease-free survival analysis showed that 43 of 771 (5.6%) patients recurred (HR=1.02; 95% CI, 0.54-1.91). After multivariate adjustment for age, gender, ATA risk of recurrence and administration of radioactive iodine, TSH suppression did not prevent recurrence (HR=0.88; 95% CI, 0.46-1.66).

The survival estimate for osteoporosis in this group showed 29 of the 537 (5.4%) developed postoperative osteoporosis (HR=3.5, 95% CI, 1.2-10.2). After multivariate analysis, the HR increased to 4.32 (95% CI, 1.45-12.85).

“It appears that at a TSH level of around 0.9-1 [mU/L], the risk of osteoporosis disappears but the risk of tumor recurrence remains unchanged,” Wang said.

Soure: Endocrine Today

Levothyroxine could suppress TSH in subclinical thyroid disease.

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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

Is Hypothyroidism Overdiagnosed and Overtreated?

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Over the past decade, doctors have become increasingly aggressive at initiating treatment for borderline hypothyroidism, possibly raising the risk for thyroid suppression as an unintended consequence, a new study suggests.

The American Thyroid Association recommends considering levothyroxine therapy at thyroid-stimulating hormone (TSH; thyrotropin) levels of 10 mIU/L or lower if symptoms of hypothyroidism, positive thyroid autoantibodies, or evidence of atherosclerotic cardiovascular disease or heart failure are present. But starting levothyroxine at or below 10 mIU/L in those without symptoms may do more harm than good, it cautions.

Yet in this new 9-year survey of more than 52,000 individuals in the United Kingdom, the number of individuals who received levothyroxine for a thyrotropin level of less than 10 mIU/L increased by 30% over the course of the study.

“This practice may be harmful, given the high risk of developing a suppressed thyrotropin level after treatment,” say the researchers, led by Peter N. Taylor, MRCP, from the Thyroid Research Group at the Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, United Kingdom, and colleagues, whose findings are published online October 7 in JAMA Internal Medicine.

Asked to comment on the findings for Medscape Medical News, Leonard Wartofsky, MD, chair of the department of medicine, Washington Hospital Medical Center, Washington, DC, said the authors are “raising the red flag that there is potentially overdiagnosis and overtreatment that has some risks.”

Most healthy people have thyrotropin levels less than 2.5 mIU/L, he explained. “If you simply go by the numbers, it’s hard to reconcile a TSH level of 7.9 as being normal when the rest of the population has numbers of 2.5 or less.” However, he added, thyrotropin levels do rise with age, so higher levels are normal for people 70 years of age or more and do not necessarily indicate treatment is necessary.

“Part of the problem is that this is a mild abnormality, and in most published studies it’s been difficult to show a clear benefit of intervention, because the number of subjects participating has been small, the abnormalities are minor, and you can’t show a major clinical effect of intervention,” Dr. Wartofsky observed. “This is a controversial issue, and it’s still unsettled.”

Threshold Lowered After 2004

Using the General Practice Research Database (GPRD; now called the Clinical Practice Research Datalink), which contains the records of more than 5 million patients in 508 primary-care practices across the United Kingdom, Dr. Taylor and coauthors conducted a retrospective cohort study of 52,298 adults who initiated levothyroxine therapy between January 1, 2001, and October 30, 2009, at a median age of 59 years.

Excluded from the study were people with a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking medication that affected thyroid function or whose thyroid problems were related to pregnancy; and/or those whose thyrotropin had been measured more than 3 months prior to beginning treatment.

To gauge the effect of therapy on thyroid function, they also studied thyrotropin levels at 30 to 36 months and 54 to 60 months after treatment began. Female patients outnumbered males by almost 4 to 1.

Following multivariate adjustment, the odds ratio of a patient receiving a levothyroxine prescription for a presenting thyrotropin level of less than 10.0 mIU/L in 2009 compared with 2001 was 1.30 (P < .001), and the number of new levothyroxine prescriptions increased by 74% over the study period.

The median thyrotropin level for initiating treatment fell from 8.7 mIU/L in 2001 to 7.9 mIU/L in 2009.

Individuals prescribed levothyroxine with a thyrotropin level between 4.0 and 10.0 mIU/L instead of exceeding 10.0 mIU/L were more likely to be female, have cardiovascular risk factors, and be older than 70 years when prescribed levothyroxine after 2004, with trends also observed for tiredness and depression, the authors write.

They conclude that “large-scale, prospective studies are required to assess the risk/benefit ratio of current practice.”

Overtreatment Can Lead to Problems, but So Can Undertreatment

Dr. Wartofsky said the study was designed to address whether starting levothyroxine therapy too early may result in overtreatment

Follow-up data showed that the percentage of patients with thyrotropin levels less than 0.1 mIU/L increased from 2.7% to 5.8% and the percentage of those with levels between 0.1 and 0.5 mIU/L increased from 6.3% to 10.2%, suggesting the presence of thyroid suppression. This “could lead to cardiac problems, arrhythmias, and atrial fibrillation and over the long term could lead to loss of bone mineral, osteopenia, and osteoporosis,” he explained.

But, he added, “I’m not particularly overwhelmed by the fact that only 5.8% of the patients were so oversuppressed. I think that is not unusual, even in the hands of expert endocrinologists — sometimes you oversuppress inadvertently.”

And the study does not show what the benefits of earlier treatment might be, probably because it takes longer for them to become apparent, he said. “In my view, there are compelling data that treating these populations does have a salutary effect”: lower serum cholesterol, a lower risk of coronary artery disease, and general symptom relief, among other things.

Is Hypothyroidism Overdiagnosed and Overtreated?

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Over the past decade, doctors have become increasingly aggressive at initiating treatment for borderline hypothyroidism, possibly raising the risk for thyroid suppression as an unintended consequence, a new study suggests.

The American Thyroid Association recommends considering levothyroxine therapy at thyroid-stimulating hormone (TSH; thyrotropin) levels of 10 mIU/L or lower if symptoms of hypothyroidism, positive thyroid autoantibodies, or evidence of atherosclerotic cardiovascular disease or heart failure are present. But starting levothyroxine at or below 10 mIU/L in those without symptoms may do more harm than good, it cautions.

Yet in this new 9-year survey of more than 52,000 individuals in the United Kingdom, the number of individuals who received levothyroxine for a thyrotropin level of less than 10 mIU/L increased by 30% over the course of the study.

“This practice may be harmful, given the high risk of developing a suppressed thyrotropin level after treatment,” say the researchers, led by Peter N. Taylor, MRCP, from the Thyroid Research Group at the Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, United Kingdom, and colleagues, whose findings are published online October 7 in JAMA Internal Medicine.

Asked to comment on the findings for Medscape Medical News, Leonard Wartofsky, MD, chair of the department of medicine, Washington Hospital Medical Center, Washington, DC, said the authors are “raising the red flag that there is potentially overdiagnosis and overtreatment that has some risks.”

Most healthy people have thyrotropin levels less than 2.5 mIU/L, he explained. “If you simply go by the numbers, it’s hard to reconcile a TSH level of 7.9 as being normal when the rest of the population has numbers of 2.5 or less.” However, he added, thyrotropin levels do rise with age, so higher levels are normal for people 70 years of age or more and do not necessarily indicate treatment is necessary.

“Part of the problem is that this is a mild abnormality, and in most published studies it’s been difficult to show a clear benefit of intervention, because the number of subjects participating has been small, the abnormalities are minor, and you can’t show a major clinical effect of intervention,” Dr. Wartofsky observed. “This is a controversial issue, and it’s still unsettled.”

Threshold Lowered After 2004

Using the General Practice Research Database (GPRD; now called the Clinical Practice Research Datalink), which contains the records of more than 5 million patients in 508 primary-care practices across the United Kingdom, Dr. Taylor and coauthors conducted a retrospective cohort study of 52,298 adults who initiated levothyroxine therapy between January 1, 2001, and October 30, 2009, at a median age of 59 years.

Excluded from the study were people with a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking medication that affected thyroid function or whose thyroid problems were related to pregnancy; and/or those whose thyrotropin had been measured more than 3 months prior to beginning treatment.

To gauge the effect of therapy on thyroid function, they also studied thyrotropin levels at 30 to 36 months and 54 to 60 months after treatment began. Female patients outnumbered males by almost 4 to 1.

Following multivariate adjustment, the odds ratio of a patient receiving a levothyroxine prescription for a presenting thyrotropin level of less than 10.0 mIU/L in 2009 compared with 2001 was 1.30 (P < .001), and the number of new levothyroxine prescriptions increased by 74% over the study period.

The median thyrotropin level for initiating treatment fell from 8.7 mIU/L in 2001 to 7.9 mIU/L in 2009.

Individuals prescribed levothyroxine with a thyrotropin level between 4.0 and 10.0 mIU/L instead of exceeding 10.0 mIU/L were more likely to be female, have cardiovascular risk factors, and be older than 70 years when prescribed levothyroxine after 2004, with trends also observed for tiredness and depression, the authors write.

They conclude that “large-scale, prospective studies are required to assess the risk/benefit ratio of current practice.”

Overtreatment Can Lead to Problems, but So Can Undertreatment

Dr. Wartofsky said the study was designed to address whether starting levothyroxine therapy too early may result in overtreatment

Follow-up data showed that the percentage of patients with thyrotropin levels less than 0.1 mIU/L increased from 2.7% to 5.8% and the percentage of those with levels between 0.1 and 0.5 mIU/L increased from 6.3% to 10.2%, suggesting the presence of thyroid suppression. This “could lead to cardiac problems, arrhythmias, and atrial fibrillation and over the long term could lead to loss of bone mineral, osteopenia, and osteoporosis,” he explained.

But, he added, “I’m not particularly overwhelmed by the fact that only 5.8% of the patients were so oversuppressed. I think that is not unusual, even in the hands of expert endocrinologists — sometimes you oversuppress inadvertently.”

And the study does not show what the benefits of earlier treatment might be, probably because it takes longer for them to become apparent, he said. “In my view, there are compelling data that treating these populations does have a salutary effect”: lower serum cholesterol, a lower risk of coronary artery disease, and general symptom relief, among other things.

Source: JAMA

Fluoridated Water Is Causing Thyroid Health Problems.

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But aside from all the sordid history, the suppression of scientific concern, and the labeling of dissenters as off-balanced “fluorophobes,” what should a sensible person do? Here are three appropriate actions for regular daily life, especially if you are bothered by feeling fat, fuzzy, frazzled, fatigued, depressed, beset by intolerance to heat or cold, annoyed by problems with skin-hair-nails, or suffering with severe constipation, low libido, infertility, or uncomfortable menopause.
First, if you are not a thyroid patient, have your thyroid status carefully checked. Insist on more testing than the simple AMA panel of TSH and Free T4. Add a Free T3 and the Thyroid Antibody Panel. You may be one of the millions of people whose fluoride exposure over the years has finally made you low thyroid.

Second, if you are already a thyroid sufferer and treatment is not going as well as you would like, consider an enhanced fluoride avoidance program. Stop drinking and cooking with tap water if it is fluoridated. Well-chosen bottled water is preferable. Start buying non-fluoridated tooth paste. It’s available at the health food store if you really look closely. Decline the fluoride dental treatments and make sure it is not in your mouth wash. The various other food sources are probably not a significant factor.

Commentary on 2006 Research Findings

Third, start speaking out against the unhealthy practice of fluoridation. Don’t expect that the Public Health Service will ever willingly admit to the most colossal error ever in the history of government science. The change will instead occur as more and more local communities decide against fluoridating their city water. They will thereby join those whole countries that have rejected or banned the practice, such as Japan, India, Finland, Denmark, Sweden, and Holland. Be guided by the credo of health professionals, “Above all, do no harm.” If fluoridated water is now highly suspected of harm, then let’s put a moratorium on proceeding further with it.

Sources: oawhealth.com

 

Subclinical thyroid disease: where is the evidence?

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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.2, 3 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

Desiccated thyroid extract a safe alternative to levothyroxine in hypothyroidism.

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Desiccated thyroid extract could be a potential alternative treatment to standard therapy with levothyroxine in patients with hypothyroidism, Thanh D. Hoang, DO, staff endocrinologist of the Walter Reed National Military Medical Center in Bethesda, Md., told Endocrine Today here at ENDO 2013.

During a poster session, Hoang said that desiccated thyroid extract could be a viable treatment option for patients with symptoms of hypothyroidism, despite normal TSH measurements while taking levothyroxine alone. Further, the desiccated thyroid extract yielded superior weight loss compared with levothyroxine, he said.

“The current gold standard right now is synthetic levothyroxine, so we wanted to do this randomized, double blind, crossover study to look at the efficacy of both drugs,” Hoang told Endocrine Today.

He and colleagues included 70 patients aged 18 to 65 years with primary hypothyroidism who were prescribed levothyroxine for 6 months. Patients were randomly assigned to either desiccated thyroid extract (DTE) or levothyroxine for 16 weeks.

According to data, patients assigned to DTE lost 3 lb, compared with those assigned levothyroxine (172.9 lb vs. 175.7 lb, P<.001).

“We didn’t find any differences in the neurocognitive measurements between the two therapies, but at the end of the study we did ask our patients which regimen they preferred,” Hoang said.

At the end of the 16-week study, 34 patients (48.6%) preferred DTE therapy, whereas 13 (18.6%) preferred levothyroxine; 23 (32.9%) did not specify a preference, he said. Further analysis confirmed those who preferred DTE lost even more weight over a 4-month period.

“We now know that once-daily desiccated thyroid extract is a safe alternative treatment for patients with hypothyroidism who are not satisfied with levothyroxine treatment. It’s an option for them to try, and also desiccated can cause modest weight loss in these patients as well,” Hoang said. –bySamantha Costa

Source: Endocrine today

Subclinical thyroid disease: where is the evidence?

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0


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.2, 3 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