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Authors: Alan L. Rubin

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Finding the right dose of hormone

A question that keeps coming up among doctors who treat hypothyroidism is

‘What is the correct dose of thyroid medication?’ Depending on the particular laboratory doing the test, the normal range for TSH is usually 0.3 to 4.5 µU/ml 20_031727 ch14.qxp 9/6/06 10:47 PM Page 160

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(microunits per millilitre). Some physicians believe that lowering a patient’s level of thyroid-stimulating hormone (TSH) to under 5 is sufficient to eliminate signs and symptoms of low thyroid function, but many people still have symptoms at that level. In a study published in the
Medical Journal of Australia
in February 2001, the authors show that lowering the TSH to between 0.3 and 2.0 µU/ml is beneficial.

Against this research, however, is a paper published in the journal
Neurology,
in 2004. Scientists measured the level of TSH in 178 people with Alzheimer’s disease and compared their results with 291 people with normal thyroid function. They found that people with Alzheimer’s disease have significantly lower levels of TSH and conclude that having a lowered TSH within the normal range is a risk factor of Alzheimer’s disease, even when a number of other factors such as smoking are taken into account.

Determining the prevalence

of hypothyroidism

How common is thyroid disease in the population? A group in Norway studied this question and published their answer in the
European Journal of
Endocrinology,
in November 2000. The group looked at the TSH levels of people who supposedly had no thyroid disease and found that their levels were between 0.49 and 5.7 µU/ml (microunits per millilitre) for females and 0.56 and 4.6 µU/ml for males. By then excluding the people who tested positive for thyroid autoantibodies, which indicates that they are prone to thyroid disease, the range of ‘normal’ TSH numbers dropped to between 0.49

and 1.9 µU/ml in women. The study did not report the range for the men.

The conclusion these researchers arrive at is that despite a huge number of recognised cases of thyroid disease in the population, a significant number of cases are not recognised.

This study offers further proof that the correct normal range for TSH (a range that excludes any person with thyroid disease) is lower than the one quoted by most laboratories.

Linking heart disease and hypothyroidism

A study in
Thyroid
in 1999, pointed out that homocysteine, a substance found in the blood, is an independent risk factor (like high blood pressure, smoking, and high cholesterol) for hardening and furring up of the arteries (athero-sclerosis). Because heart disease is commonly found in people with hypothyroidism, the authors of the study measured homocysteine levels in people 20_031727 ch14.qxp 9/6/06 10:47 PM Page 161

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with clinical hypothyroidism. They found that homocysteine levels were abnormally high, and that these levels fell when the hypothyroidism was treated with thyroid hormone replacement. The authors suggest that the combination of abnormal fats (especially cholesterol) and high levels of homocysteine is the reason that people with clinical hypothyroidism have an increased risk for heart attacks.

A study published in
Endocrine Research
in 2004, found that people with subclinical hypothyroidism have homocysteine levels within the normal range, although when compared with a healthy control group, the difference between them is significant. This discovery suggests that as hypothyroidism worsens, so does the ability to process homocysteine properly.

Recent evidence shows that homocysteine levels are lowered when taking a combination of B-group vitamins, which are involved in processing homocysteine in the body.

A study published in the
Journal of Internal Medicine
in 2003, investigated the relationship between homocysteine levels, B-vitamins, and smoking in 112 people with Graves’ disease, both before and after antithyroid therapy.

The study found that, in people with hyperthyroidism, homocysteine levels were low, and levels of folate, vitamin B12, and B2 were high. Following antithyroid treatment, homocysteine levels increased while the concentration of B-vitamins decreased significantly. And, for those who smoked, levels of folate and B2 fell significantly lower than for non-smokers. This study also confirms that homocysteine levels increase as levels of B-vitamins decrease.

The authors conclude that homocysteine levels change according to thyroid function and are partly attributable to altered blood levels of B-vitamins, particularly in smokers.

If you have hypothyroidism, ask your doctor to measure your homocysteine levels, although this test is not yet routinely available in hospitals. Private laboratories offer the service and you can buy kits to send off a blood sample to measure your homocysteine levels from many pharmacies. Taking a supplement providing folic acid (the synthetic form of folate), B12, B6, and B2

is also a good idea.

Dealing with Hyperthyroidism

Despite the availability of several treatments for hyperthyroidism (see Chapter 6), specialists are not satisfied with any of them. Each treatment is associated with either frequent failure or undesirable side effects like hypothyroidism. The search for better therapy continues.

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Measuring calcium levels

A study published in January 2001, emphasises the importance of measuring calcium levels in people with thyroid conditions, especially hyperthyroidism.

This German study shows that after thyroid surgery, hypoparathyroidism –

the loss of parathyroid function (refer to Chapter 13) – frequently occurs and leads to low calcium levels. In this study, excess parathyroid function was also relatively common in association with thyroid disease, leading to a high calcium level.

Both decreased and increased parathyroid function is found at a higher rate in patients with hyperthyroidism than in people who don’t have thyroid disease.

If you have hyperthyroidism, ask your doctor to check your calcium levels.

Controlling weight gain

Many people with hyperthyroidism are concerned about getting treatment as they fear they’ll gain weight when their thyroid function decreases.

In a study from Edinburgh, Scotland, published in the journal
Thyroid
in December 2000, the authors compare the weight at diagnosis of hyperthyroidism with their weight after normal thyroid function was restored in 43

people given antithyroid drugs, 56 people undergoing thyroid surgery, and 131 people with Graves’ disease. The study shows that people who start taking T4 thyroid hormone replacement immediately after their treatment (because they quickly became hypothyroid) gain much less weight than those who did not start taking hormone replacement because their TSH

levels were normal.

Harry, the hyperthyroid horse

Hyperthyroidism is managed in a variety of ways.

(refer to Chapter 6), including fever, nervousness,

However, for a horse named Harry, surgery and weight loss. His thyroid was prominent, was the only consideration. Harry’s case was

especially on the right side. Harry was treated

reported in the Journal of the American Veteri-

with surgery to remove the overactive lobe and

nary Medical Association in October 2000. He

responded very well.

suffered from all the symptoms that people show

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The authors conclude that defining hypothyroidism using the usual range of TSH after treatment of hyperthyroidism leads to many people not getting the treatment they need. Well-known studies indicate that TSH levels tend to lag behind (remain low) as a person resumes normal thyroid function or even becomes hypothyroid after treatment of hyperthyroidism. In this situation, clinical symptoms and a reduced free T4 level are better indicators of the need for treatment than the TSH level.

Revolutionising thyroid surgery

A new type of thyroid surgery using tiny scopes instead of a large open incision in the neck is suitable for removing thyroid nodules, thyroid lobes and, in some cases, for removing the whole thyroid gland. Some procedures use the gas, carbon dioxide, to raise the skin and gain access to the thyroid gland, via a small incision, while others use a video-assisted, gasless technique. At present, these techniques are suitable for people with small thyroid nodules (less than 35mm) or a small thyroid gland (less than 30ml volume), who have not undergone previous neck surgery. If cancer is found in a nodule, the operation is usually converted into a traditional open-neck surgery for more extensive dissection of lymph nodes. Endoscopic thyroid surgery is rapidly developing and is likely to prove suitable for a wider range of thyroid problems in the near future.

Gathering clues to hyperthyroid

eye disease

Just exactly why hyperthyroid eye disease occurs is not clear, but researchers generally believe that the cause is an autoimmune disorder (refer to Chapter 4 for a discussion of thyroid autoantibodies). One suggestion is that thyroglobulin enters the muscles of the eyes, and antibodies react against it. A study from Italy in the journal
Thyroid
in 2001, shows that thyroglobulin is, indeed, found in the muscle tissue of the eyes. The study demonstrates that the thyroglobulin originated in the thyroid gland. This confirms that the autoimmune reaction that takes place in the thyroid is similar to the autoimmune reaction that takes place in the eyes.

Research published in
Thyroid
in 2005, suggests that an antibody named anti-Gal plays a role in the development of eye problems in Graves’ disease.

Those people without clinical ophthalmopathy (thyroid eye disease) tended to have lower anti-Gal antibody levels than those with ophthalmopathy. This trend is under further study.

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Treating Goitres and Nodules

Goitres and nodules are a common problem in thyroid medicine. Newer studies are changing how doctors manage people with these conditions.

Performing surgery after ethanol injections

One of the newer techniques for eliminating nodules in the thyroid is the injection of ethanol (alcohol) directly into the nodules (refer to Chapter 7).

When brand-new, this technique raised the question of whether surgeons would face complications if they had to operate on people receiving ethanol injections. For example, a surgeon might need to operate if the ethanol failed to eliminate a nodule, if a doctor suspected that a nodule was malignant, or if a nodule were compressing a person’s trachea.

A study published in
Thyroid
in 2000, reports that surgeons did not encounter any special surgical problems when operating on the thyroids of 13 people who had previously received ethanol injections.

Shrinking goitres

Thyroid hormone is often used to treat goitres in the hope of shrinking the thyroid swelling. Most recent studies show that goitres respond little, if at all, to thyroid hormone.

In a study published in 2001, in the
Journal of Clinical Endocrinology and
Metabolism
from the Netherlands, the authors compare thyroid hormone to radioactive iodine in the treatment of goitre.

Using ultrasound to measure the goitre, the study found that people who receive radioactive iodine have, on average, a 44 per cent reduction in goitre size, while those taking thyroid hormone have a reduction of just 1 per cent.

Only 1 of 29 patients didn’t respond to radioactive iodine, while 16 of 28 had no response to thyroid hormone. Almost half of those receiving radioactive iodine developed hypothyroidism, while 10 of 28 taking thyroid hormone had symptoms of hyperthyroidism. In addition, those on thyroid hormone developed increased bone turnover and a loss of bone mineral density. The conclusion of this study is that radioactive iodine is more effective and better tolerated than thyroid hormone in the treatment of goitres.

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Developing New Approaches

in Thyroid Cancer

Not surprisingly, much of the research concerning advances in thyroid disease centres around thyroid cancer. The following sections provide you with some of the more provocative and important studies of the last few years.

Undoubtedly, many more studies are in the pipeline.

Understanding the impact

of radioiodine exposure

More than 15 years after the nuclear disaster in Chernobyl, researchers still follow the children exposed to excessive radioactive iodine. In the
World
Journal of Surgery
in 2000, a group of Russian scientists published the results of surgery on 330 children with thyroid cancer after Chernobyl. These cancers tend to develop rapidly after exposure, are more aggressive than typical thyroid cancers, and spread early to distant sites in the body. The children affected are treated with total thyroidectomy (removal of the entire thyroid) then radioactive iodine treatment and suppression of TSH. The authors of the study emphasise that many more cases of thyroid cancer are expected among the children of Chernobyl, and monitoring continues long-term.

Are any environmental factors protective in the situation of radioactive iodine exposure? A study in
Environmental Health
in 2000, looked at people exposed to radioactive iodine in Germany. The study confirms that drinking coffee and eating cruciferous vegetables, such as broccoli, reduces the risk of developing cancer. Broccoli contains substances that help to protect against a number of cancers, but may reduce thyroid function in people lacking in iodine, due to its goitrogen content (see Chapter 12). If a person has a goitre prior to the exposure, or if that person consumes decaffeinated coffee instead of caffeinated, their risk for malignant or benign tumours increases.

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