Josine van der Heyden (38) is a pediatrician and pediatric endocrinologist at the Sint Franciscus Gasthuis in Rotterdam.

Which thyroid disorders do see most often?

Mostly, I see autoimmune-related thyroid disorders, such as Hashimoto's thyroiditis and Graves' diseases. I see around ten patients with each.

Have these children had symptoms for long by the time they see you?

That varies. It depends on the symptoms that the patient presents with, and these symptoms can be quite vague. For example, fatigue is a difficult complaint, especially when it involves an adolescent. I can imagine that when they are presented with this symptom, both the parents and the general practitioner wait a little while before ordering a thyroid function test.

What tests are carried out?

The first thing some general practitioners think of is infectious mononucleosis. Others check for thyroid problems while checking for anemia. When checking the thyroid, they test the blood for TSH but not so often for free T4. If the patients have elevated TSH levels, then they come here to the outpatient clinic.

What do you do if they come to you with suspected Hashimoto's thyroiditis, for example?

First and foremost, I repeat the blood tests; because once you make a diagnosis, you often begin on a lifelong treatment trajectory. If there is a clear indication of hypothyroidism, then I test the blood for the antibodies against the thyroid gland (anti-TPO antibodies) and perform an ultrasound. After that, I check to see whether everything fits the diagnosis of Hashimoto's thyroiditis or whether there are any loose ends. With an elevated TSH, a reduced free T4, a clearly elevated anti-TPO, preferably accompanied by an enlarged thyroid gland (goiter), and an ultrasound that shows the enlarged thyroid gland that is in keeping with Hashimoto's thyroiditis, I consider the diagnosis complete, and I start treatment.

How do you monitor children with Hashimoto's thyroiditis?

With check-ups and, mainly, with blood tests. I like to see the patients more often in the beginning. This lets the patient see the clinical picture, and we discuss what is expected of me and of them. Depending on how long they have been familiar with their diagnoses, I then perform more blood tests every three to six months. One week after taking the blood sample, we have an appointment by telephone to discuss the results. From that point on, I see them once per year for a check-up.

Is this treatment for Hashimoto's thyroiditis successful in most cases?

The result of the laboratory tests is often good, but some of the children still retain symptoms like fatigue or feeling generally unwell.

Do people start to doubt the diagnosis or treatment if the symptoms do not go away?

In cases when the symptoms do not abate, I always reconsider whether the diagnosis is actually correct. If it is, the problem may lie in the baseline stabilization. One person may feel fine with a T4 level of 12, while another needs a T4 level of 18 to feel just as good. For example, if someone with a reasonably good value of 12 still does not feel well, you can consider adjusting the dosage and going to a value of 18, which may make the patient feel better. I often use the term "set point" for the value at which a patient feels good.

Do you talk about these types of numbers with the patients, too?

I try to include them in the discussion. I try to explain to them that one person may feel fine at a certain value while another person might not feel so good at that same value.

Do you ever refer patients to other specialists?

I'm the only pediatric endocrinologist at this hospital. Therefore if I am presented with an atypical course of symptoms, it can be good to confer with a pediatric endocrinologist from a university hospital. Sometimes it also helps if a patient hears from two specialists that complaints of fatigue accompanying Hashimoto's thyroiditis can sometimes remain in spite of good blood values. If I think that further academic care is needed, for example, because several specialties should be involved, then the path to the university is short, and we consult about how the patient can make his or her way to the university as easily as possible.

What can you say about arriving at the diagnosis of Graves' disease?

Children with hyperthyroidism do not always come to our hospital with a clear-cut story, like an increased heart rate. More often, they have generalized complaints, such as tiredness or not feeling well. Their free T4 levels (high with hyperthyroidism), TSH levels (low with hyperthyroidism) and anti-TSH antibodies are also tested. Usually, these antibodies are positive; that means they are present. If not, then I reconsider if this really is Graves' disease (the cause of hyperthyroidism in children in 95% of cases). When in doubt, I order a thyroid scan or consult with the university.

How intensively do you monitor children with Graves' disease?

Just as I do with Hashimoto's thyroiditis, but in the beginning I see them somewhat more frequently. Four weeks after the diagnosis, I schedule a half hour appointment. Following that, I see them three months after the diagnosis. And, after that, I see them every three or six months, depending on what feels best for the patient and the parents. I explain that Graves' disease involves an autoimmune process that, in principle, should react well to treatment. I also tell them about the different types of therapies (medicinal, radioactive iodine, surgery) and the possible side effects of these treatments.
These parents and children need more information than those dealing with Hashimoto's thyroiditis, because there are several treatment options, and the medicinal therapy is somewhat more complicated in these cases.

What is block and replace?

With block and replace, we first completely shut down the thyroid gland with the medicine thiamazole (Strumazol®), the 'block' element of the treatment. Doing so allows the thyroid to rest and is an attempt to bring the autoimmune process to a standstill. Since the thyroid gland becomes completely deactivated, we then also administer levothyroxine (such as Thyrax® or Euthyrox®), the 'replace' element of the treatment. This way, the child once again has thyroid hormone circulating in the blood. We continue this medicinal treatment for at least two years, and then we stop it and check to see if the illness returns. At first, there is a significant chance that it will return. Studies, including a large French study from 2012, show that the chance of recidivism ('chance of recurrence') is approximately 80% after the first stop attempt. After ten years, though, during which time the medication was stopped every two years, the disease was no longer active 18 months after stopping the medication in approximately one half of the cases.

Do children with Graves' disease and their parents have that patience to wait that long?

There are two other treatment options: administration of radioactive iodine or surgery. I always allow the parents and, if possible, the child to make the decision together with me. For a twelve-year-old girl, for example, it is difficult to fully take stock of such an important decision, and therefore it is great if we can gain some time by continuing the medicinal treatment. So, I am always honest about the fact that there are other options, but that I will only start them after the first attempt to stop the medicine has failed. After all, some of the patients do become symptom-free with the medication alone. Besides that, I also notice that younger patients are not very enthusiastic about the treatment with radioactive iodine. They think it is a bit scary, since it is radioactive.

Are there risks associated with the treatment with radioactive iodine?

Children under five years of age may have a somewhat greater risk of developing cancer in the long term, although very little research into this has been done. At a later age, we do not think that the treatment increases the risk. Sometimes one treatment with radioactive iodine is not enough, and a second or sometimes even a third treatment is necessary. The intention of the treatment with radioactive iodine is to return to a normally functioning thyroid gland; we call this euthyroidism. But that does not always work. The risk of a thyroid gland that no longer functions (hypothyroidism) is quite significant. To treat that, you only need to take one medicine, levothyroxine, but you must take it for the rest of your life.

Are there risks associated with surgical treatment?

With a thyroidectomy (removal of the thyroid gland), you will have a scar on your throat. There is also a minor risk that the parathyroid glands will also be removed or become damaged. This will result in low calcium blood levels. Then, in addition to levothyroxine, you will also have to take active vitamin D for the rest of your life. Another (minor) risk is damage to the nerves of the vocal cord.

Are there side effects associated with the treatment with Strumazol®?

Recently, I encountered this for the first time in one of my patients. It is described more often in the literature, but in practice, I don't see it that often. The side effects can be quite varied; for example, joint complaints and low white blood cell count (which increases your risk of bacterial infection) but also jaundice and skin abnormalities. They mostly occur in the first three months of the treatment.

What happens if the thyroid values from a heel prick are abnormal?

In principle, the general practitioner calls me up and we discuss it. We evaluate the child and repeat the blood tests, in particular those for free T4 and TSH. If the results clearly indicate congenital primary hypothyroidism, so not hypothyroidism of a central (pituitary) origin, then I also test the thyroglobulin and we wait for those results. If the results are abnormal, I schedule an ultrasound of the thyroid gland and a scan with which you can see where the thyroid is located, whether the thyroid gland is present, and how it is functioning. For an infant, I usually order these two tests to be done in the university hospital in my region.
Often, the results are not abnormal in the end. Nonetheless, I repeat the blood tests very soon thereafter, except if the values were very good. After all, you want to know for certain for the patient's sake. I also always want to confer with the university hospital in the case of ambiguous results and interpret the blood results together with them. I visit the university in my region once every two weeks to discuss my work but, if necessary, we can discuss matters more frequently by telephone. We have a very accommodating arrangement in this regard.

How often do you see children with a nodule in the thyroid gland?

I don't see them here too often. Recently, we performed an ultrasound on a child with a goiter and found two nodules by accident. Then, I asked for a second opinion from a pediatric radiologist at the university; something I always do in the case of a nodule. Further testing, like a needle biopsy, can then be done, if necessary. But first, I consider for myself what the diagnosis could be, so that I go the consultation with a clear-cut presentation of the question at hand.

And do you sometimes see disorders which originate in the pituitary?

We do find them sometimes, but they are very rare. We encounter this if the heel prick screening shows low free T4 and low or low-normal TSH levels. Or if someone comes to us with a symptom that stems from the failure of another function of the pituitary, such as the reproductive hormones or growth hormone.

Are you then extra alert when you have these findings?

Yes, indeed we are. For example, a gene defect, the IGSF1 gene mutation, has recently been described in association with a central hypothyroidism in which the onset of puberty is delayed and where the boys have remarkably large testicles. A boy that I saw had had central hypothyroidism for years, had late-onset of puberty (based on male-pattern hair growth and penis size) but already had relatively large testicles (another feature of puberty). At the time, I ordered genetic testing together with the university, and then this genetic defect was found. So, it is important always to take another critical look at the results and the clinical findings. Because in someone with a low free T4 or low-normal TSH, the levels may be at a set point — at these values this person feels fine; in fact, there appears to be nothing wrong. But if you find, in addition to these values, an enlarged testicular volume, for example, and a boy with these symptoms this starts his puberty late, then a hereditary problem like this may be at issue. So, it is important to continue to look at every patient afresh with all that new information and to ask yourself whether there isn't something else going on.