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Authors: Alan L. Rubin

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The researchers also found that tomato consumption was a risk factor for malignant disease. They suggest that off-season tomatoes coming from areas where the farmers are careless about the use of chemicals may promote the development of thyroid cancer. This news is disappointing since tomatoes are a rich source of the antioxidant carotenoid, lycopene, found in other studies to protect against cancer. Perhaps the message here is to select organically grown produce, especially tomatoes.

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Blocking oestrogen slows tumour growth

A source of bewilderment about thyroid cancer is that it occurs around three times more often in women than men. One study suggests the reason may lie with the fact that women make oestrogens as their primary sex hormone, and oestrogen may stimulate thyroid tumour cell growth. One early study published in 1991, found that around 4 per cent of the well-differentiated thyroid cancer biopsies they studied contained oestrogen receptors.

In a more recent study published in the
Journal of Clinical Endocrinology and
Metabolism
during 2001, researchers confirmed the presence of oestrogen receptors in cells derived from human goitre nodules and thyroid cancers, but found no difference between the presence of these receptors in males and females. When cells are exposed to an oestrogen, however, the expression rates increase significantly as oestrogen activates a metabolic pathway that leads to much greater growth activity in both malignant and benign thyroid cells. Exposing the cells to a drug that blocks oestrogen action, meant the tumour cells were no longer stimulated.

Women have significantly higher oestrogen levels than males, which may explain why women are more likely to develop these thyroid problems than males.

Predicting thyroid cancer

Can doctors predict the future occurrence of thyroid cancer? In a study from Iceland, the authors present an analysis of blood taken many years before the diagnosis of thyroid cancer in 164 patients. Their study is published in
Acta
Oncologica
(2000).

The authors report that levels of thyroglobulin, the chemical that resides in the thyroid, and which is monitored when following people with thyroid cancer, was found in much elevated levels up to 15 years before the diagnosis of thyroid cancer was made. In contrast, no difference was found in the blood levels of TSH or thyroid hormone in those going on to develop thyroid cancer compared to those who do not.

Detecting residual thyroid cancer

Another important recent advance is in the ability to detect thyroid cancer that remains after surgery. Thyroglobulin plays a major role in detecting 20_031727 ch14.qxp 9/6/06 10:47 PM Page 167

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remaining cancer. Another important tool that is often used is the whole body radioactive iodine scan, which can locate active thyroid tissue. The limitation of the scan is that it can’t locate thyroid tissue that isn’t making thyroid hormone. Sometimes a thyroglobulin level is high, indicating that active thyroid tissue is present, but the body scan is negative.

A newer type of scan called a PET scan is able to localise thyroid tissue that is not functioning well as thyroid tissue but which is still metabolically active.

A study in
Advances in Internal Medicine
in 2001 reviews the successful use of the PET scan for this purpose.

The study points out that the need still exists for new agents that attack these tumour tissues when they are discovered as they don’t concentrate radioactive iodine.

If you have thyroid cancer and discover a new growth that does not concentrate radioactive iodine on a thyroid scan, ask your doctor about the possibility of having a PET scan.

Following up thyroid cancer treatment

Do people with treated thyroid cancer need follow-up for life, or does a point arise at which they’re considered cured of the disease? The authors of a study in
Annales Chirurgiae et Gynecologica
in 2000, attempt to answer this question.

The researchers followed people for seven months after they have had thyroid surgery then divided them into four groups:

ߜ
Group I:
Patients with microcancers

ߜ
Group II:
Patients with no lymph node involvement or metastases, and normal thyroglobulin

II-A:
Younger than age 45

II-B:
Age 45 or older

ߜ
Group III:
Patients with cancer with lymph node involvement but a normal thyroglobulin

ߜ
Group IV:
Patients who have extension of the cancer beyond local lymph nodes or an elevated thyroglobulin

The survival rates for these groups are shown in Table 14-1.

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Table 14-1

Survival Rates for Thyroid Cancer Patients

Study Group

Length of Time after Surgery

10 Years

15 Years

Group I

100 per cent

100 per cent

Group II-A

100 per cent

100 per cent

Group II-B

96 per cent

92 per cent

Group III

100 per cent

100 per cent

Group IV

86 per cent

73 per cent

The latest time a recurrence was found in Groups I and II-A was at 12 years.

For Groups II-B, III, and IV, tumours were discovered as late as 16 years after treatment. The study emphasises the importance of carrying out thyroglobulin tests and whole body scanning every 5 years.

Results suggest that people in Groups I and II-A need follow-up for up to 15 years, while other patients need following for 20 years before saying with certainty that the disease is eliminated. If a recurrence occurs, then the patient needs follow-up for another 10 years after treatment, before declaring that he or she is cancer-free.

Knowing what to expect from

medullary thyroid cancer

Medullary thyroid cancer
(MTC) is different from thyroid cell cancers like follicular or papillary cancer (refer to Chapter 8). MTC arises from the C-cells in the thyroid and is not detectable with radioactive iodine. Cases are divided into hereditary (inherited) MTC and sporadic (not inherited) MTC.

A study from Finland in the
Annales Chiarurgiae et Gynecologica
in 2000, found that sporadic MTC is a more aggressive disease than familial MTC. The debate continues, but it seems that more important predictors of survival are involvement of lymph nodes, distant metastases, and local spread of the cancer in the neck.

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Using recombinant TSH

to treat thyroid cancer

Scientists can now make TSH in the laboratory by inserting the gene that codes for human TSH into a bacterial culture. The product is known as recombinant TSH and is identical to the TSH normally produced by the pituitary gland. Recombinant TSH is a valuable tool both for the detection and treatment of residual thyroid cancer. Before the development of recombinant TSH, people undergoing testing for residual cancer with a total body scan, were taken off thyroid replacement hormone for four weeks or longer to allow their tissues to become hypothyroid. Going off hormone replacement greatly enhances the uptake of radioactive iodine, allowing for a more accurate scan of thyroid tissue.

This action is of concern as the time off thyroid hormone may allow cancer cells to grow more rapidly. In contrast, recombinant TSH can stimulate uptake and identify cancer recurrences without needing to stop thyroid hormone replacement.

A group in Massachusetts, writing in the
Journal of Clinical Endocrinology and
Metabolism
in 2001, explored the dose of recombinant TSH required for optimal effect. They found that a dose of 0.3 milligrams of recombinant TSH produces the maximal increase in thyroglobulin and radioactive iodine uptake.

Going higher than 0.3 milligrams doesn’t increase the effect of treatment.

Another group from New York shows that using recombinant TSH is just as good as taking people off thyroid medication in stimulating thyroglobulin secretion and radioactive iodine uptake. They conclude that preparing people for a scan with recombinant TSH is equivalent to taking them off thyroid hormone, in terms of diagnostic accuracy. Their work is found in the
European Journal of Endocrinology
, 2001.

Finally, recombinant TSH is useful to stimulate thyroid cancer uptake of radioactive iodine in order to destroy it. In a study published in 2001, in the
European Journal of Endocrinology
, scientists note that the recombinant TSH

produces excellent results when used in this way, and was free of side effects other than mild nausea. The thyroid cancer treatment was as effective as with patients who were taken off thyroid hormone therapy prior to treatment. Using recombinant TSH meant patients avoid the discomfort of going without thyroid hormone for weeks.

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Testing calcium levels after cancer surgery

During removal of the thyroid gland for thyroid cancer, patients inevitably experience some trauma to the parathyroid glands that lie on the back of the thyroid lobes. Most of the time, these glands recover, but sometimes the trauma results in permanent hypoparathyroidism, which leads to low calcium levels.

In a study published in the
Journal of the European Society of Surgery and
Oncology
in 2000, researchers looked at how long it takes people undergoing surgery for thyroid cancer to recover their normal calcium levels, as well as to determine how often treatment is necessary.

The study shows that if a person has just one lobe of the thyroid removed, even though two of the parathyroid glands were not touched, a 10 per cent drop in their calcium level occurred. Just over a third of people undergoing this type of surgery require some calcium treatment because the level falls too low. Their calcium levels returned to normal within one week after surgery and remained normal.

When both sides of the thyroid are operated on, as expected, the greater effect is on the parathyroids and the calcium. Calcium levels decreased by an average of 15 per cent and some people experienced severely low levels early in their recovery. The calcium decline was greater if fewer parathyroid glands were preserved. In 15 per cent of cases, calcium treatment was needed for 2

to 7 days, in 26 per cent for 8 to 180 days, and in 9 per cent for longer than a year. Only 1 patient out of 82 required permanent treatment for low calcium after a single thyroid surgery on both sides, while one of four who had several thyroid surgeries needed permanent calcium treatment.

Tackling Iodine Deficiency Disease

The number of people affected by iodine deficiency disease is high (refer to Chapter 12) and lots of research is going on in this area. This section describes the more important recent studies on iodine deficiency disease.

Recognising the importance of selenium

Selenium is a trace element that plays a role in thyroid hormone production, as it forms part of a seleno-enzyme responsible for converting T4 into T3.

Until recently, researchers believed that selenium deficiency alone does not 20_031727 ch14.qxp 9/6/06 10:47 PM Page 171

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171

cause hypothyroidism and that selenium deficiency only contributes to the disease when iodine deficiency exists. However, a study from the journal
Biological Trace Element Research
in 2000, describes three girls with hypothyroidism due to lack of selenium alone. When given replacement selenium, all returned to normal thyroid function. This study is the first description of hypothyroidism due to lack of selenium alone.

Using iodised oil for goitres

Iodised oil injection is commonly used to treat iodine deficiency and prevent goitre formation in areas of the world where iodine deficiency persists (refer to Chapter 12). The authors of a study in
Medicine
in 2001, looked at potential problems associated with Lipiodol – a type of iodised oil. The study found that, when Lipiodol is given to someone who already has a multinodular goitre, the person sometimes becomes hyperthyroid. The hyperthyroidism tends to be mild and doesn’t last long, however. If given to a pregnant woman, the iodine sometimes entered the bloodstream of the foetus but did not cause a problem there.

The study confirms that using iodised oil for the replacement of iodine is a safe, cheap, and effective way to treat this deficiency.

Increasing the intelligence of babies

born to hypothyroid mothers

Babies born to hypothyroid mothers tend to have reduced intelligence. A study from Taiwan, published in the
Journal of the Formosan Medical Association
in 2001, looked at the level of intelligence of 62 babies of hypothyroid mothers and sought an early screening to avoid disability. They found that the level of T4 at the time of diagnosis was a good predictor of the future intelligence of the baby. By measuring T4 at birth and giving replacement thyroid hormone, they significantly improved the outlook for these babies in terms of their intelligence.

As you can see, just about every aspect of thyroid disease is being studied, with articles in every medical journal. If you have a particular problem that concerns you or a loved one, don’t hesitate to use the enormous, free resources at your disposal. Go to the Pub Med Web page, www.ncbi.nlm.

nih.gov/PubMed, or check out your local bookstore and library. And be sure to utilise the references you find in Appendix B of this book.

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