Hanneke van Santen (41) is a pediatric endocrinologist at UMC Utrecht, Wilhelmina Children's Hospital. She spends much of her time working on thyroid cancer.

What does your position entail?

As a pediatric endocrinologist, I treat hormonal disorders in childhood. One of my focus areas is cancer in the endocrine, or hormonal, organs and the side effects of treatments for other cancers on those endocrine organs. And the thyroid gland is one of those organs.

How frequently does thyroid cancer occur in children in the Netherlands?

It is very rare during childhood. We more frequently see children with a lump in the throat or in the lymph glands of the throat, but, thankfully, these do not turn out to be cancer very often. First, we feel the lump, then we perform an ultrasound and take a needle biopsy to see what types of cells it contains. Often, the lump is benign, but very occasionally it will be malignant. Luckily, that does not happen very often. In the Netherlands, there are ten to fifteen new cases of children with thyroid cancer per year. There are two different types of thyroid cancer in childhood: differentiated thyroid cancer, which arises in the cells that produce thyroid hormone, and medullary cancer. Medullary thyroid cancer is the rarest type. It occurs only in families who suffer from certain syndromes. Therefore, we won't discuss it any more here. Differentiated thyroid cancer can occur of its own accord, but it can also occur after prior radiation of the throat.

Can you tell whether a lump is benign or not just by feeling it?

It is difficult to feel this difference. Cysts (a fluid-filled cavity) can also form in the thyroid gland. These cysts can empty out and swell up again. If a lump fluctuates like that, it is always benign. If it grows and does not go away, it can be bad, but you can't tell for sure by feeling it from the outside. Further examination is then necessary. For example, using ultrasound.

What happens with an ultrasound?

An ultrasound is used to see how large the lump is, whether it is actually in the thyroid gland, and if it moves when the patient swallows. If the lump is larger than 1 cm, then we will perform a needle biopsy. If it is smaller than that, then you can wait, unless it is a small nodule with suspicious features like calcium specks. We also look to see if the lymph nodes in the throat are enlarged. In addition, we test the blood to check the thyroid gland function. Some nodules produce a large amount of thyroid hormone. However, in the case of thyroid cancer in particular, there is usually nothing wrong with the thyroid function values.

What happens with a needle biopsy?

With this test, a bit of anesthetic cream is applied to the throat, and then the radiologist uses the ultrasound image to guide the needle into the lump to retrieve some cells. The radiologist checks immediately to be sure that he or she has collected enough cells. The results usually take about ten days to come back. In most cases, a thyroid nodule is benign. In that case, we wait three months and perform another ultrasound to see if the nodule has remained stable, gotten smaller, or has continued to grow. Usually, it has remained stable. Should the lump start to grow, then we sometimes perform a second needle biopsy; the results may change. Sometimes the results are not conclusive, and then we remove half of the thyroid gland in order to study the cells under a microscope.

Can you live a healthy life without half of your thyroid gland?

You can live a fine life with only half of your thyroid gland. Some people have several benign nodules in the thyroid gland. This is called multinodular goiter. Even if they are larger than 1 cm and the biopsy has shown that the cells are benign, you usually won't have to remove them surgically. Sometimes, a nodule is so large that the patient is bothered by it, or a biopsy returns an uncertain result, in those cases we advise removing the affected half of the thyroid gland. If the other half also has many nodules, it is possible that the thyroid will not produce enough hormone. In this case, the patient will need to receive additional thyroid hormone. But that is an exception.

And if the result is not benign?

Then the entire thyroid gland must be removed. Usually, the cancer is only on one side of the gland. If the ultrasound shows suspicious lymph glands in the throat, then they are also removed. After the removal of the thyroid gland, you will nearly always receive additional treatment with radioactive iodine. Often, the surgeon is not able to actually remove all of the thyroid tissue; a few thyroid gland cells are always left behind. There is a chance that these cells may be cancerous, although they may also be healthy thyroid cells. Radioactive iodine is taken up by thyroid gland cells, so we can use it to treat all thyroid cells. To see if a child has recovered from thyroid cancer, we check for the presence of certain tumor markers (the thyroglobulin protein) in the blood. This protein is produced by healthy and by malignant thyroid cells. We also perform a body scan, because you can see whether or not cells have metastasized to the lungs and the liver. The body scan can show this directly. If there is metastasis, then it is treated immediately with radioactive iodine.

Does thyroid gland cancer metastasize easily?

It can, especially to the lymph glands in the throat, the lungs and the liver. Usually, first to the lymph glands and then to the lungs. My experience is that we usually catch it early enough, although it metastasizes more often in children than it does in adults. Still, the prognosis is just as positive. Adults present more frequently with a lump in the thyroid gland, and children more often have a lump in the throat by the lymph glands. This is because thyroid cancer in children can be small, so you don't feel it, yet it has already grown into a lymph gland.

At what age does thyroid carcinoma usually occur?

Usually during the teenage years.

Is it easy to catch it in time?

Yes. The throat is a spot that is clearly visible. Parents notice it, or the children see it themselves. If you then look back at old photos, you can see that it has been there for several weeks already. But sometimes, it is found by chance. There was a young boy who had a motorbike accident that left him with neck pain. So, he underwent a CT scan of the neck and throat area, and a nodule was found in the thyroid gland. It turned out to be cancer. There was no sign of that nodule in his throat. It was found by accident.

Is the removal of a thyroid gland a difficult operation?

No, it is not, but it must be performed by an experienced surgeon. Complications may arise. The parathyroid glands, which are located right next to the thyroid gland, look a lot like fat cells, and the difference can be difficult for the surgeon to see. If they are removed along with the thyroid gland, the calcium levels in your blood will become way too low. This can be serious, because you will have to remain in the hospital longer, and you can suffer from muscle cramps. Usually, the situation stabilizes, but sometimes the problem remains, and you must take calcium supplements twice a day for the rest of your life.
The vocal cords may also be damaged, and then your voice becomes hoarse. People find it very unpleasant if their voices change. In severe cases, you can even end up with respiratory problems. This can also happen in children.

If there are no complications, and you have completed the follow-up treatment, is there anything else that has to happen?

Yes. Once you have lost your thyroid gland, you must take thyroid hormone (thyroxine) medication for the rest of your life. This maintains the metabolism in the cells and safeguards your longitudinal growth (height or length). Taking thyroid hormone does not present any problems. For example, there are children born without thyroid glands who take this medication daily from their second week of life without issues. In principle, you can reach your ninetieth birthday using bottled thyroid hormone. We usually do not start administering thyroid hormone immediately after the operation, because we want the thyroid-stimulating hormone levels as high as possible during the radioactive scan. They rise when the thyroid hormone level in your blood is low. So, we only start the thyroid hormone treatment after the radioactive iodine treatment. And then you have to visit the outpatient clinic regularly to make sure that you are properly stabilized. In the beginning, your baseline stabilization is very high in order to suppress the thyroid-stimulating hormone. This is to prevent the cancer from coming back.

How many times does a patient make return visits after that?

In the beginning, this depends in particular on the blood calcium levels. If they are good, the child can usually go home again three days after the operation. After a week, I see them again in the outpatient clinic. Then, we start to administer thyroid hormone after the treatment with radioactive iodine (usually after 4-6 weeks). After that, I usually see the children once every two months for a blood test. And following that, once every three months. After six months, we stop the thyroid hormone (thyroxine) temporarily to check that everything is gone. We perform an ultrasound of the throat to determine whether any thyroid gland tissue remains, and we measure the tumor marker. If we do find thyroid gland cells, a second radioactive iodine treatment will be needed. If we cannot detect any more thyroid gland cells, we repeat the ultrasound once every twelve months until five years after the diagnosis. We also measure the tumor marker every year, but we do not temporarily stop the Thyrax anymore as doing so makes the child so terribly tired. If the cancer cells have not returned after five years, the child is considered to have made a full recovery.

After the treatment, are these children different than other children?

No. Although they have gone through a lot and have been very tired along the way. Not so much due to the cancer, but due to the treatment. The fact that I give them thyroxine and then sometimes stop the medication for a time and then they are jabbed again, well, this has quite an impact. In theory, children that are treated for thyroid cancer can do everything other children can, and they continue going to their regular schools. Top-level sport is the only thing that must be stopped temporarily while the child is not receiving thyroid hormone. This is because a lack of thyroid hormone in your body may affect your heart, so you should not do anything that requires too much exertion. This is no problem, though, when you are taking thyroxine.

The entire treatment requires thorough explanation. Do you spend a lot of time on that?

I try to explain a lot, but not all at once. I tell them that it is cancer during the first consultation. I acknowledge that this is very unfortunate but that the prognosis is good. I also tell them that we will operate and give radiation treatment, but nothing more. After that, many, many questions come up. I try to discuss it in small steps and often explain things several times.

How do the children react?

Emotionally. But also protective towards their parents. If they see that their parents are having a difficult time, the children become tougher. They easily accept the operation and return home again shortly afterwards. Taking thyroxine is never a problem. For small children, swallowing the calcium tablets can be a problem because they have an unpleasant taste. This can be a battle with toddlers.
I find that the children, generally speaking, handle it quite well, as tired as they are. I know a little boy that went swimming with a thyroid hormone level that would have left me asleep in bed! Children are so strong, and it takes quite a bit to make them feel lousy. Actually, they handle it very well.

Is research being done that specifically targets thyroid carcinoma?

Yes. I myself look mostly at children who have had radiation to the throat and neck and have developed cancer because of that. A large, national research study, which we and other academic centers are participating in, is being carried out in Groningen (under the direction of Professor T. Links) into the delayed effects of childhood thyroid carcinoma. This study looks at all children who have been treated for this illness in the past thirty years in the Netherlands. We are expecting the results in the autumn of 2015.
One of the questions that the study is addressing is what the delayed effects of childhood thyroid cancer are. For example, we treat children with quite high thyroxine dosages. This treatment may have an effect on bone density and the heart or may result is symptoms of fatigue. The occurrence of these complaints is also being investigated in the study. As is fertility.

Is there an effect on fertility?

I expect that people who have had thyroid cancer are just as fertile as those who have not. There is a link between radioactive iodine and fertility, but hard evidence for this link has not yet been found. It is important, though, to be consistent about taking your thyroid hormone, because if your baseline thyroid function is unstable, that can play a role in fertility.

Can you also get thyroid cancer after receiving radiation in the throat?

Since your thyroid gland is so sensitive to radiation, you can develop thyroid cancer due to radiation. Years ago, children were treated with radiation on the throat and neck for birthmarks or problems in the ENT area. Back then, this treatment had just been discovered. We are now working on making international guidelines for children who are being treated for Hodgkin's lymphoma and leukemia, for example. The question is whether we should now screen all of these patients using ultrasound. Although we do not want to worry people unnecessarily, there are indications that it would be wise to do so. We are now figuring that out.