Levothyroxine Treatment May Not Benefit Pregnant Women With Subclinical Hypothyroidism

Highlights:

• Thyroid hormones play a critical role during pregnancy in maintaining the health of the baby as well as the mother.
• Two separate trials were conducted in pregnant women, those with subclinical hypothyroidism and those with hypothyroxinemia.
• The results suggest that administering levothyroxine did not improve the IQs of their babies or reduce preterm births or other negative outcomes.

Two separate trials were conducted on pregnant women who had two different clinical conditions, subclinical hypothyroidism and hypothyroxinemia. The drug called levothyroxine was tested to see if it improved the cognitive abilities of the babies born, or reduced preterm births or reduced other negative outcomes. The results were published in The New England Journal of Medicine (NEJM). Subclinical hypothyroidism and hypothyroxinemia are conditions that arise due to fluctuations in the blood levels of thyroid hormones.

Hypothalamus-Pituitary Gland-Thyroid Gland Loop

Thyroid hormones primarily regulate the body’s metabolism and are responsible for the proper development and differentiation of every cell in the human body.

The first step in the cascade of events of thyroid hormone or thyroxine release starts with the release of the thyrotropin-releasing hormone or TRH from the brain’s hypothalamus. The release of TRH stimulates the release of the thyroid-stimulating hormone or thyrotropin or TSH from the pituitary gland.

This pituitary hormone, thyrotropin then stimulates the production of thyroxine (T₄) followed by triiodothyronine (T₃) which then speed up cell metabolism.

Thyroid homeostasis is maintained via a feedback loop that involves the hypothalamus, pituitary gland and the thyroid gland. Low levels of T₃ and T₄ in the blood cause the hypothalamus to release more TRH that in turn, stimulates the release of more TSH to help to restore the levels of the hormones. Similarly, high levels of blood thyroid hormones can exert a negative feedback temporarily pausing the release of TRH and in turn TSH.

In certain circumstances and conditions, there could be fluctuations in the thyroid hormone levels that can be caused by a disruption or defect in any part of the process. While too much of the hormone in the blood could lead to hyperthyroidism causing body functions to speed up, too little of it can cause hypothyroidism which slows down many body functions.

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Hypothyroidism

Hypothyroidism, also known as underactive thyroid or low thyroid is a condition characterized by low thyroid hormone or thyroxine levels in the blood. The symptoms are tiredness, depression and weight gain. Untreated hypothyroidism during pregnancy can affect the growth and intellectual development in the baby, usually known as cretinism.

Hypothyroidism can result due to

• Poor functioning of the gland - Primary hypothyroidism
• Poor stimulation of TSH from the pituitary gland - Secondary hypothyroidism
• Poor release ofTRH from the brain’shypothalamus - Tertiary hypothyroidism

Primary hypothyroidism is the most common form of hypothyroidism and is caused mainly by iodine deficiency.

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Subclinical hypothyroidism (SCH) is a mild thyroid failure that occurs when the levels of thyroid-stimulating hormone (TSH) are normal but the thyroxine (T4) levels are in the low range.

Hypothyroxinemia occurs when the levels of thyroid-stimulating hormone (TSH) are normal but the thyroxine (T4) levels are in the low range.

Both these conditions occur in pregnancy and is more predominant in South Asia. They could be associated with adverse fetal neurologic effects including a lower-than-normal IQ in offspring.

Levothyroxine

Also known as L-thyroxine, levothyroxine is a synthetic form of the body’s thyroid hormone, T₄ and is used to typically treat hypothyroidism. It is taken as an oral pill or through intravenous injection and is the treatment of choice for people requiring lifelong thyroid hormone treatment. It is also used to treat subclinical hypothyroidism. It is safe to use during pregnancy.

Treatment of subclinical hypothyroidism or hypothyroxinemia with levothyroxine to improve cognitive function in children is a subject of ongoing debate and research.

Study

Two separate trials were conducted to see if treatment of pregnant women with subclinical hypothyroidism or hypothyroxinemia with levothyroxine improved the IQ of the baby or reduced preterm births or other negative outcomes. The results were published in The New England Journal of Medicine (NEJM).

Subclinical hypothyroidism was defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T₄) level (0.86 to 1.90 nanograms per deciliter [11 to 24 pmol per liter]). Hypothyroxinemia was defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T₄ level (<0.86 nanograms per deciliter).

The study included 677 pregnant women with subclinical hypothyroidism who underwent randomization at a mean of 16.7 weeks of gestation, and 526 pregnant women with hypothyroxinemia who underwent randomization at a mean of 17.8 weeks of gestation. The study participants were randomly assigned to receive levothyroxine or placebo in separate trials.

The research team checked the thyroid function on a monthly basis and the dosage of levothyroxine was titrated to attain a normal thyrotropin or free thyroxine levels (depending on the trial). The primary outcome gauged was the IQ levels of the children which were checked at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years.

Results

• Subclinical hypothyroidism group: The median IQ score of the children was reported to be 97 (in the levothyroxine group and 94 in the placebo group..
• Hypothyroxinemia group: The median IQ score was reported to be 94 in the levothyroxine group and 91in the placebo group.
• The IQ levels and other neurocognitive or pregnancy outcomes were not significantly different between the children of women given levothyroxine and children of those who received a placebo.

Conclusion

The study results suggest that there is no benefit in treating women with subclinical hypothyroidism or hypothyroxinemia during their pregnancies as it did not show any significantly better cognitive outcomes in children.

References:

1. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy - (http://www.nejm.org/doi/full/10.1056/NEJMoa1606205?query=featured_home)
2. Thyroid Disease and Pregnancy - (http://www.thyroid.org/thyroid-disease-pregnancy/)

Source-Medindia