Hello again. I want you to appreciate the fact that so far, I have stuck to my goal of at least one entry a week! In my last entry, I discussed diagnosis and treatment of hypothyroidism in children and adolescents, without focusing on specific disorders. I took that seemingly bizarre approach because, in most instances, it is more important to make the basic diagnosis than to know the why. But, I should at least touch on the differential diagnosis of hypothyroidism.
First, I want to emphasize the fact that hypothyroidism is by far the most common cause of thyroid dysfunction in children and adolescents. For convenience, I will first discuss congenital hypothyroidism, and then “acquired” hypothyroidism. This is not meant to be an encyclopedic discussion, but rather, a very focused presentation of what I think are key points. Some of you are probably very sophisticated about management of thyroid disorders, I apologize to you for my simplistic approach.
I would argue that congenital hypothyroidism might be the single most important cause of hypothyroidism because it is one of the most common preventable causes of mental retardation. There is a strong inverse relationship between the age of diagnosis and initiation of treatment and IQ. The condition occurs in 1/1500-1/5000 newborns. The wide range in incidence might reflect differences in diagnostic cut-offs and recent inclusion of mild cases picked up because of the widespread use of newborn screening programs around the world, but no one knows for sure. I won’t dwell on the details of newborn screening except to say that screening methods differ, depending on the country, but all involve filter paper collection of blood from newborns and assays of T4 and/or TSH. I prefer screening that includes both T4 and TSH, because a normal TSH value alone will not detect central hypothyroidism. We have learned quite a bit from the screening programs, first introduced in the 1970s. Perhaps, the most important thing we have learned is that most patients with congenital hypothyroidism have absolutely no signs or symptoms suggesting the diagnosis. Most cases are sporadic, but there are some genetic causes, such as the inborn errors in thyroid hormone synthesis (most of these patients have goiters, unlike the sporadic cases). Most sporadic cases are caused by thyroid dysgenesis, including ectopic thyroid (e.g., lingual thyroid). About twice as many females are diagnosed than males (especially ectopic thyroid). Congenital hypothyroidism can be primary or central. In rare cases it can be caused by resistance to TSH or to thyroid hormone, large hepatic hemangiomas, and other very rare conditions, which I won’t discuss. It can even be transient; some cases in this category are related to maternal iodine deficiency or iodine excess, maternal drugs or maternal anti-thyroid antibodies. Regardless of etiology, the important thing is to be certain every infant is tested for hypothyroidism and if diagnosed with the condition, treated promptly.
Again, acquired hypothyroidism can be primary or central. By far the most common cause of acquired hypothyroidism is autoimmune thyroiditis, also known as Hashimoto’s thyroiditis or chronic lymphocytic hypothyroidism (CLT). Most patients with CLT are asymptomatic and have enlarged thyroid glands, classically described as nodular or “lumpy bumpy.” Patients often have a small lymph node, called a Delphian node, just above the isthmus on the left (the patient’s left), and in my experience it is absolutely diagnostic of CLT. The node is the size of a small pea and slightly elongated. It is painless and easily movable. I find it interesting that it is almost impossible to find any mention of this physical examination finding in current textbooks and medical articles. CLT is found in up to 10% of adolescents, mostly females, and according to some studies, in 25% or more of women over age 40 years. For pediatricians, it is important to remember that CLT is very common in patients with the following conditions: Turner’s syndrome, celiac disease, type 1 diabetes mellitus or Down’s syndrome. The diagnosis is usually pretty simple: enlarged thyroid gland, normal or low free T4 (if the free T 4 is low, the TSH should be very high), normal or elevated TSH, and positive anti-peroxidase antibodies (TPO Abs). Patients may also have positive anti-thyroglobulin antibodies (TgAbs).
Other causes of acquired hypothyroidism include the following (not an all-inclusive list): iodine deficiency or excess; anti-thyroid medications; some anticonvulsant drugs; craniospinal radiation; late-onset congenital hypothyroidism (especially inborn errors of metabolism and ectopic thyroid); and thyroid hormone resistance syndrome.
That’s about it. When in doubt, always go back to how things work in people who do not have thyroid disorders (e.g., the fabulous negative feedback system), always consider thyroid disorders in all newborns, in any child who is not growing well, and in any child with a medical condition that is known to be associated with CLT. Finally, don’t be afraid to contact an endocrinologist if your patient’s thyroid test results just don’t make any sense.