Interview: In Young Children, Thyroid Disease Accompanied by Obesity is a Reason for Further Testing

Erica van den Akker (47) is a pediatrician and pediatric endocrinologist at Erasmus MC-Sophia children's hospital.

What are your areas of special interest within pediatric endocrinology?

At Erasmus MC-Sophia, we focus on three areas: growth, obesity and DSD. My specialty is obesity, but I also see children with other problems.

Which thyroid gland abnormalities do you see most often?

The most common abnormalities in children are congenital hypothyroidism, abnormal heel prick screenings and Hashimoto's thyroiditis. These affect a large group of children, and often these children are seen in general hospitals in the region. At our hospital, we only see referrals from specialists at other hospitals — children with very specific thyroid problems that a general pediatrician or a pediatric endocrinologist cannot treat in a peripheral hospital. Here, we see very diverse clinical pictures, ranging from pituitary abnormalities to children with Graves' disease who are difficult to stabilize or who do not react to medications at all. Children who have euthyroid goiter or a nodule in the thyroid gland also come to the university hospital for their treatments. And finally, we see many children with obesity and thyroid problems which are part of a specific syndrome.

Is it easy for children to get a referral?

We have a good cooperative relationship with the general hospitals in our area. That means that the barriers continue to lower. We start with a short consultation on the telephone or by e-mail to see if it is a patient we must see. The process is continuing to get easier and quicker. Nodules in the thyroid gland are certainly signals that pediatricians are quick to react to. They are always treated in the university hospital.

So a child with a nodule gets to you quickly?

That depends on the history but, generally speaking, yes. There are emergency spots and emergency options for referrals. Although thyroid disorders are not a specific focal point within pediatric endocrinology at our hospital, it is for adults. We have a thyroid center here with an internist and an endocrinologist who see a great many patients with goiter and nodules. We sometimes see children jointly. Especially as these are problems that occur relatively frequently in adolescents. We do this in close collaboration. Sometimes we transfer our patients to them. We also have regular contact with our colleagues at the AMC in Amsterdam who have special expertise in thyroid gland disease.

How long do people with nodules wait before going to their general practitioners?

Often, it takes a long time before they come in. Probably because with a goiter or a nodule, there usually aren't that many complaints, and because they frequently grow quite slowly. When there are no symptoms, people often wait and see. At the first consultation, it often turns out that the goiter or nodule has been present for some time.

Do you see more children nowadays with a nodule or euthyroid goiter than you did in the past?

I have not investigated that. I have been working here for 15 years now, and I cannot substantiate it, nor can I say precisely what the reason for this is, but I do think that we see it somewhat more often than before. Right now, we do not have a separate pediatric protocol for euthyroid goiter but, to a great extent, we can take the information from the internists' guideline. It also contains sections about children. We mainly follow this.

Do general practitioners think of diagnoses like Hashimoto's thyroiditis or Graves' disease?

I notice that general practitioners check thyroid function, especially in girls around the age of puberty. When vague symptoms arise, they consider the thyroid gland as a potential cause. Perhaps this is also because general practitioners tend to think of thyroid problems in the case of obesity. The difficulty is that abnormalities or slight deviations in the biochemical results of thyroid hormone level tests occur more frequently in obese patients. For example, TSH can be elevated without an abnormality in the thyroid gland or in the levels of free T4. So, especially when children are obese, I notice that general practitioners tend to think of thyroid problems. But not as often for younger children and boys.

Do you also treat children with Hashimoto's thyroiditis?

It does happen, but it is the exception. Hashimoto's thyroiditis can be adequately treated in non-academic hospitals. What can happen with auto-immune diseases, like Hashimoto's, is that the adjustment of the medications is not optimal and that the thyroid values keep fluctuating. Or that the symptoms continue even though the medicines have resulted in baseline stabilization. These patients are then referred to us. But that rarely happens.

And what about Graves' disease?

That, we see more often. Children with Graves' disease are often difficult to stabilize and sometimes retain symptoms like chronic fatigue, concentration problems, and feeling generally unwell. These are symptoms that are difficult to interpret and for which a clear-cut cause cannot be found.

So, where do these symptoms come from?

That is the most difficult question to answer: where does this come from? We have no evidence that these 'cerebral' symptoms are a result of auto-immune processes in the brain. I think it is rather a matter of what is happening at the tissue level with your active thyroid hormone, T3, and how it is stabilized at the level of the tissues. But that is a terrifically difficult thing to ascertain because it is impossible to take measurements at that level. The fact that up until now there is little we can do for patients is, of course, very disappointing. So, in summary, you can look at persistent symptoms to see whether illnesses are involved which are related to Graves' disease or whether any additional illnesses are present. You can also investigate whether the patient is adequately stabilized or not. But, at this time, the testing of the activity of the active thyroid hormone at the tissue level is truly still in an experimental phase.

What results can be expected of Graves' disease treatment in children?

We know that some of the children with Graves' disease will go into remission, and the treatment may be stopped. It is difficult, though, to predict who will go into remission and who won't. There are factors that cannot be influenced, such as the age of onset of the Graves' disease, the elevation of the antibodies levels or the amount of free T4 (FT4) at the start of treatment. These factors determine how great the chance is that the illness will return. However, the duration of the treatment with Strumazol®, for example, is probably also an influencing factor. That is why we treat children with Strumazol® for a minimum of two years, and then first check whether the antibodies have disappeared before attempting to stop the treatment. Children are different than adults. We know, from a French follow-up study, that in children the illness can disappear (go into remission) after a long time, sometimes after four, five or even eight or nine years of treatment with medication. So, that is the reason that we often treat children for a very long time before we proceed to giving them radioactive iodine. In adults, we reach for definitive solutions, like liquid forms of radioactive iodine, more often.

To what extent does the thyroid gland play a role in the development of obesity?

Thyroid gland disorders are more common in people who suffer from obesity. However, that does not mean that if you treat the thyroid problems, usually hypothyroidism, you will also solve the obesity. If we look at what thyroid hormone treatment does to the weight of adults with thyroid problems, we see an average change of 2.7 kg in the total weight. We are talking about people who weigh 100 kilos or more. So, a change in weight of 2.7 kilos does not solve these obesity problems. Studies have also been done in which thyroid hormone is given as a medication against obesity, even to people who did not have a thyroid gland problem. This was done with the idea that the thyroid hormone boosts the metabolism and the energy combustion. But the results of these studies were not good. Therefore, if someone is obese and has a thyroid illness, you, as a doctor, must be realistic with the patient about the effect that can be expected. You must not give them the idea that the entire obesity problem will disappear as soon as the thyroid treatment starts, because the effect is, in fact, minimal.

Can abnormal thyroid values explain obesity?

There are cases where, during an examination by the general practitioner, the thyroid values by chance show a slightly abnormal, elevated TSH level whereas the free T4 and the active T3 are not reduced. You then have to ask yourself if this is the cause of the obesity. The answer is no. The obesity cannot be explained by this. So, treatment does not help in this case, and you have to be clear about that. Of course, you must provide treatment if, for example, there is a question of Hashimoto's thyroiditis, which occurs more commonly in obese people, otherwise this can have a long-term negative effect on weight. You must also pay careful attention to syndromes or congenital disorders which result in both thyroid problems and in obesity.

Which syndromes are those?

Those are rare syndromes, such as pseudohypoparathyroidism (php), where you have a genetic defect. That gene plays an important role in the recruitment of receptors which are involved in the signaling function of your thyroid gland, among other things, but also in the receptors involved in energy metabolism or in producing the feeling of satiation. This combination can result in a person having a thyroid hormone problem and severe obesity starting at a very young age.

How do you recognize this syndrome?

If the obesity and the thyroid problem arise at a very young age (less than five years). Certainly, if these problems are very clearly present in the first year of life. Generally speaking, congenital disorders and syndromes reveal themselves before the fifth year of life.
You must also be alert to this if you do not have another good explanation for the thyroid problem. For example, if you have a five-year-old child who has been obese since he was one and who also has hypothyroidism for which you actually do not have a clear cause. If you then find a highly elevated TSH level with negative antibodies while the heel prick was normal, then you have to keep searching. Together with below-average height and developmental delays, these are the alarm symptoms that tell you that something else is going on.

Do you have a fixed examination protocol?

Yes, in our Healthy Weight Center, we adhere to a fixed protocol when investigating whether the obesity is caused by a syndrome, by a genetic abnormality, or by another illness. We see patients from all over the country. They are referred by pediatricians and clinical geneticists with the specific question of whether or not there is an underlying disorder. The children and parents then come for three visits. During the first visit, they are examined extensively and asked many questions. We discuss the parents' expectations and what we may be able to do for them. The second visit consists of sample-taking for testing, such as blood, saliva, urine and DNA. For the third visit, they come back and all of the results are discussed one-by-one. They also receive these results on paper. We then make our conclusions and look together at what a possible treatment might consist of. It is possible, in this way, to arrive at a comprehensive whole in three visits.

So, the regular pediatrician must first recognize the symptoms?

Yes. The signals must be recognized by the pediatrician. The textbooks describe these alarm signals and when action must be taken. They describe specific frameworks for when you must think of underlying illnesses in cases of obesity. For example, in the early onset of obesity, certainly when there is an element of insatiability, reduced height, congenital thyroid disorders or developmental delays. These must serve as triggers for the pediatricians.

And do they?

There are pediatricians who are quick to recognize this and pediatricians for whom this is still a blind spot. Obesity is a relatively new problem for pediatricians. It will take years before the protocols are established and integrated into our educational system. But, in the meantime, at least, the syndromes have been included in the textbooks.