Category Archives: TSH


Another Update on Subclinical Hypothyroidism in Pregnancy

Thyroid DiseaseWe have blogged previously about the ongoing debate regarding the treatment of subclinical hypothyroidism in pregnancy (here and here).  In brief, there was a study published in 1999 that demonstrated that 7-9 year old children, from women with abnormal thyroid measurements during pregnancy, performed slightly less well than the control children on 15 IQ tests. Of the 62 women with thyroid disease who were not treated for their hypothyroidism 48 had children who had significantly lower IQ scores than the control children. This report led to a number of follow-up studies to support or refute this study.

Another one of the follow-up studies was recently published in the New England Journal of Medicine.  The authors screened women <20 weeks gestation for: subclinical hypothyroidism TSH ≥4 IU/L with normal fT4 (n=677); and women with hypothyroxinemia normal TSH with fT4 <0.86 ng/dL (n=526). Women in those two groups were then randomly assigned to receive levothyroxine or placebo. The dosage was adjusted each month to maintain normal TSH or normal fT4 (depending on which arm of the study they were in). The children were then followed for 5 years. The authors found that in the subclinical hypothyroidism group, the median IQ in the treated group was 97 and 94 in the untreated group.  In the hypothyroxinemia group, the median IQ was 94 in the treated group and 91 in the untreated group. There were no significant differences between groups in either arm of the study suggesting that there was no benefit to treating.

This study is consistent with the findings in the CATS trial which we have discussed previously. However, as discussed in an editorial about this article, both this study and the CATS trial are limited by the late initiation of treatment (17 weeks in this study). This is important because the fetal thyroid becomes active at 16-20 weeks of gestation, therefore the fetus relies on maternal T4 prior to that time.

The authors of the editorial concluded that because early intervention is feasible and may be beneficial, they still endorse the American Thyroid Association recommendations that suggest screening of certain high risk women and early treatment as indicated.  I suspect we will be blogging about this topic again in the future.

hCG and the thyroid gland

Thyroid tests First things first. The main job of human chorionic gonadotropin (hCG) hormone is to increase the synthesis of progesterone in early pregnancy. Without steadily increasing concentrations of progesterone, an early pregnancy will fail. hCG usually has nothing to do with the thyroid gland.

As a reminder, the thyroid gland, located in the neck in close proximity to the larynx (voice box), is basically responsible for controlling our body's metabolism. It is regulated by a different hormone: thyroid stimulating hormone or TSH.

So hCG maintains pregnancy and TSH regulates the thyroid gland. Sometimes, however, hCG can act like TSH and crank up the function of the thyroid gland. When the thyroid gland is in an over-active state the condition is called hyperthyroidism. Symptoms of hyperthyroidism include weight loss, increased appetite, heat intolerance, hair loss, weakness and fatigue, irritability, and sweating. In extreme cases, hear palpitations, and shortness of breath can occur. How can hCG cause hyperthyroidism? The answer lies in the molecular structure of these two hormones.

As it turns out, hCG and TSH are rather similar to each other. Both are composed of two different protein subunits. One of those protein subunits is called "alpha" and the other "beta." The alpha subunits of hCG and TSH are identical but the beta subunits are a different; but not by much. The beta subunits of hCG and TSH are about 40 percent identical. When present a very high concentrations, hCG can actually stimulate the thyroid gland sending it a message to go into over-drive. In other words, hCG can sometimes act like TSH. Fortunately, this doesn't happen unless the amount of hCG in the blood gets to be very, very elevated.

How elevated? Well, that has been the subject of some recent investigations. Conventional wisdom was that hyperthyroidism could occur in women with an hCG concentration that was greater than 50,000 IU/L. While this hCG concentration may seem very elevated, it's actually quite normal in pregnant women who are in their first trimester. Because the vast majority of pregnant women in early pregnancy do not have symptoms of hyperthyroidism, the 50,000 IU/L threshold didn't seem accurate.

In one study (disclaimer: I participated in that study), an hCG threshold of 400,ooo IU/L was identified as the concentration above which actual symptoms of hyperthyroidism could occur. The lower hCG concentration of 200,000 IU/L was identified as the threshold above which a majority of women demonstrated biochemical signs of hyperthyroidism (i.e. decreased TSH) but they did not have actual symptoms of hyperthyroidism until the hCG increased to twice that amount.

Another study reported that women developed suppressed TSH and/or symptoms of hyperthyroidism only when the hCG concentration was greater than 100,000 IU/L.

A normal, singleton, intrauterine pregnancy doesn't usually produce such sustained elevations of hCG. This means that the vast majority of pregnant women will never have symptoms of hCG-induced hyperthyroidism. However, extreme elevations of hCG can be produced in women with gestational trophoblastic disease (GTD). These are a family of diseases that arise from an abnormal fertilization event so hCG is produced even in the absence of a viable fetus.

The bottom line is that extremely high hCG concentrations can cause biochemial and physical signs of hyperthyroidism but these are rarely the result of the hCG concentrations found in normal pregnancy.