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Authors: Alan L. Rubin

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Scientists are also attempting to increase a tumour’s ability to provoke an immune response against it. To do this, scientists insert genes into the tumour that cause it to produce new antigens, which the body attacks as it recognises them as foreign. Tumours like malignant melanoma and colon cancer are the target of this type of therapy. A similar technique involves inserting a gene directly into a tumour that activates a cancer-killing agent, which is subsequently injected. These techniques have led to some decrease in tumour size but, so far, no cures. Interestingly, the use of gene therapy isn’t limited to tumours that are brought on by faulty genes but are directed at any tumour, genetic or not.

The ethics of germline gene therapy

As you can see, the range of techniques for using genetic engineering to cure disease is enormous. New methods of delivering healthy genes to replace disease-conferring genes are discovered almost every day. This approach is certainly the most simple and elegant way of treating diseases provoked by inheritance of a single dominant gene. However, this type of treatment can only cure a particular individual – it doesn’t affect the transmission of the disease to his or her offspring. To eliminate these diseases from future generations, genetic engineering has to take place in the sperm and/or the egg, the germline of the individual.

Germline gene therapy raises tremendous ethical questions. If we can eliminate a recessively inherited condition such as Pendred syndrome, with the replacement of a Pendred gene with a normal gene, scientists also, potentially, have the tools for changing skin colour, height, or any other body characteristic in future generations.

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Although germline gene therapy is successful in some animals, it has not yet been allowed on humans for several reasons:

ߜ The methods used so far are very imprecise, so the final product is uncertain, including the possible introduction of harmful genes.

ߜ Many people fear that germline gene therapy may lead to germline enhancement, an attempt to produce a ‘superior’ human being.

ߜ It’s uncertain that germline gene therapy is even needed, because a harmful recessive trait requires mating with another human with the same trait to express itself, while dominant traits are present in only half of a germline. It therefore makes more sense to identify the sperm or egg with the normal gene and use that in fertilization, rather than trying to modify the sperm or egg with the abnormal gene. Genetic testing of the germline is needed to eliminate these diseases.

An entire field of genetics concerns ELSI, the ethical, legal, and social implica-tions of genetic science.

Clearly, genetics is the current frontier in medical science. It promises to prevent or cure many of the diseases that plague humans, including hereditary thyroid disease and nonhereditary tumours, but the road to that cure is filled with cracks and bumps so expect a very uneven ride.

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Chapter 18

Controlling Thyroid Disease

during Pregnancy

In This Chapter

ᮣ Understanding normal thyroid function in pregnancy

ᮣ Dealing with hypothyroidism during pregnancy

ᮣ Managing hyperthyroidism in pregnancy

ᮣ Treating new thyroid nodules

Having a thyroid disorder doesn’t affect your ability to have a healthy, bouncing baby. As thyroid disease is so common among women, and as so many women have babies, thyroid disease and pregnancy often go hand in hand. Some women enter the world of pregnancy with a pre-existing thyroid condition, whether they know about it or not, while other women develop thyroid problems during, and possibly as a result of, their pregnancy.

As a developing foetus is totally dependent on its mum’s thyroid hormones during early pregnancy, picking up and properly treating any thyroid problems during this stage is vital. The British Thyroid Association advice doctors to check thyroid function in pregnant women during their first antenatal booking appointment if they are at risk of a thyroid problem. This means women with:

ߜ A personal history of thyroid disease

ߜ Type I diabetes (which is sometimes associated with autoimmune thyroid problems)

ߜ A family history of thyroid disease

ߜ Symptoms that are suggestive of thyroid disease

In short, if you’re pregnant and have any concerns about thyroid problems, ask your doctor for a blood test. It doesn’t hurt to check. (Well, having a blood test does hurt a little, but as you’re having blood taken for other routine pregnancy blood tests anyway, you won’t feel any additional discomfort. Honest.) 25_031727 ch18.qxp 9/6/06 10:44 PM Page 222

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Thinking ahead is also worth doing. If you have a known thyroid problem and are planning to try for a baby, ask your doctor to check your TSH levels first, before you conceive, so your treatment is adjusted if necessary. For example, you may need your dose of thyroxine hormone increased both before, as well as after, conceiving.

Looking at Normal Thyroid

during Pregnancy

Three important changes occur in a pregnant woman’s body that increase her need for iodine:

ߜ During early pregnancy, blood flow to the kidneys is increased, resulting in lots more visits to the bathroom, and lots more iodine recycled back to the local water board.

ߜ As the tiny foetus can’t make thyroid hormones at first, the placenta –

the tissue that connects the foetus to its mum – scoops up thyroid hormones from mum’s circulation, so she needs to make more.

ߜ And, even when the growing foetus does start making its own thyroid hormones, the foetus takes iodine from mum’s circulation in order to do so.

At the same time, because of the extra oestrogen hormone floating around, the mother makes much more thyroxine-binding globulin – a protein that transports thyroid hormone through the blood (refer to Chapter 3) – than she used to. And, as she makes a form of thyroxine-binding globulin that leaves the circulation much more slowly than normal, she needs to make more thyroxine to make up for the increased amount that is protein bound.

The bottom line is that a pregnant woman has to make more thyroid hormone than normal, so her need for iodine significantly increases.

Importantly, you need to understand all these changes if you have hypothyroidism and take thyroid hormone pills. To maintain normal thyroid function, your dose of thyroid hormone replacement usually needs to go up during early pregnancy, and the amount of adjustment needed is based on your level of thyroid-stimulating hormone (TSH). Usually, your dose of thyroxine needs to go up at least 50µg (micrograms) daily to maintain normal serum thyroid-stimulating hormone concentrations. Levels of TSH are usually assessed in every three months (trimester) of pregnancy.

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Chapter 18: Controlling Thyroid Disease during Pregnancy
223

While all these changes are happening, the placenta makes a lot of a special hormone called
human chorionic gonadotrophin
(HCG). This hormone maintains early pregnancy as it acts as a signal for menstrual periods to stop.

Some parts of HCG are very similar to parts of TSH, and when it reaches the mother’s thyroid it stimulates production of more thyroid hormone, just as TSH does. This action is rather clever of Mother Nature, as more thyroxine is exactly what is needed during early pregnancy and, as a result, the mother’s level of free T4 rises, causing a fall in the amount of TSH her body produces.

If she is having twins, her HCG level is especially high and can persist for weeks, causing a form of hyperthyroidism, which we discuss in the section

‘Hyperthyroidism in Pregnancy’ later in this chapter.

Pregnancy and Hypothyroidism

A miracle of nature takes place during pregnancy as amazingly the mother’s body does not reject the foetus as a foreign intruder – which is just what happens with any other foreign invasion. (Even a few foreign cells injected inside your body wouldn’t last long.)

The fact that the mother’s body doesn’t reject the foetus is evidence of a general decline in immunity that occurs during pregnancy. As a result, women who have autoimmune diseases prior to pregnancy often find their condition improves during pregnancy, although it usually returns to its original state again after delivery. This case is true for people with either hypothyroidism or hyperthyroidism that results from an autoimmune condition.

Decreased fertility

If a woman has untreated hypothyroidism, she can experience difficulty in conceiving as hypothyroidism decreases her fertility. In one study of infertile women in Finland, published in
Gynecological Endocrinology
in 2000, 5 per cent of women who experienced difficulty getting pregnant had previously undiagnosed hypothyroidism. In addition, if a woman with hypothyroidism does manage to achieve pregnancy, her risk of miscarriage is higher than if she didn’t have a thyroid condition. And, if you are hypothyroid and are not receiving treatment with thyroid hormone replacement, your risk of obstetric complications, such as high blood pressure, problems with the placental connection to the foetus, and problems with delivery, all increase. The good news, however, is that once diagnosed and treated properly, all these risks return to normal.

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Iodine deficiency

A mother with an iodine deficiency during pregnancy cannot make sufficient thyroid hormone for herself, let alone her foetus, who relies on her for thyroid hormone up until the 20th week of the pregnancy. As a result, the mother makes increasing amounts of TSH in an attempt to stimulate her thyroid, which is on a go-slow without sufficient iodine supplies. This results in the development of a goitre (refer to Chapter 9). Laboratory tests show that iodine-deficient pregnant women have:

ߜ Reduced T4 and, if severe, reduced T3 hormone levels ߜ Increased TSH

ߜ Increased ratios of T3 to T4, because the thyroid begins to prefer making T3

ߜ Increased thyroglobulin

The mother’s goitre may not fully shrink after delivery, when her iodine needs are reduced. This fact may partly explain the much greater incidence of thyroid enlargement in women compared with men.

Iodine deficiency also affects the foetus, which may develop a goitre and, sadly, may experience abnormal brain development (refer to Chapter 12).

Autoimmune hypothyroidism

In iodine-rich countries, most cases of hypothyroidism in pregnancy result from autoimmune thyroid disease.

Understanding the risks to the mother and foetus

If lab tests show that a woman has thyroid autoantibodies – even if she is not diagnosed as hypothyroid because her thyroid function tests are normal –

she has a higher risk of miscarriage. Doctors are not sure why, but one suggestion is that these women really have mild hypothyroidism despite the normal test results. Another is that the autoantibodies are a sign that another autoimmune disease is present, and that this condition is what’s responsible for the miscarriage.

Thyroid autoantibodies are transmitted to the foetus through the placenta, causing hypothyroidism in the foetus. Usually, if the mother is hypothyroid and is adequately treated with thyroid hormone, enough gets to the foetus to prevent this problem. If the baby is born with hypothyroidism, he or she is 25_031727 ch18.qxp 9/6/06 10:44 PM Page 225

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placed on thyroid hormone replacement until the autoantibodies are cleared from the baby’s circulation, usually within three or four months. The baby does not need treatment after that.

Knowing when to treat the mother

At what point is treatment needed for autoimmune hypothyroidism in pregnancy? Usually, if a mother’s TSH level is greater than 4 µU/ml (microunits per millilitre), she is treated. She then needs regular thyroid function tests throughout the pregnancy to confirm that she is receiving the right amount of thyroid medication.

If the mother’s TSH level is between 2 and 4 µU/ml (microunits per millilitre), and she tests positive for thyroid autoantibodies, her doctor may decide to start treatment, and the foetus is checked for goitre or other signs of thyroid abnormality. Fortunately, recent studies show that if the mother has very mild hypothyroidism in early pregnancy, the condition has no negative effect upon the newborn’s hearing or physical activity.

Although autoimmune hypothyroidism generally improves during pregnancy, the mother’s hypothyroidism often worsens after the baby is born, and her T4 level may decrease further. Therefore, checking her TSH every six to eight weeks after delivery is important.

If you have hypothyroidism during pregnancy, make sure your thyroid function is checked about two months after delivery to confirm you are taking the right dose of thyroid hormone.

Certain drugs that are commonly taken during pregnancy, such as sucralfate, and aluminium hydroxide (refer to Chapter 10), can block the absorption of thyroid hormone. These drugs should be taken several hours before or after the thyroid hormone is taken.

Hyperthyroidism in Pregnancy

Two main conditions are responsible for hyperthyroidism in pregnancy: Graves’ disease and a condition called gestational transient thyrotoxicosis.

Regardless of the cause, the symptoms of hyperthyroidism in pregnancy include rapid heart rate, sweating, trouble sleeping, anxiety, heat intolerance, and fatigue. These symptoms are all fairly common for any pregnant woman.

One way to determine whether the mother is hyperthyroid is that if she has Graves’ disease, she will not usually gain a great deal of weight during pregnancy; she may even lose weight.

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Graves’ disease

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