Updated guidelines for managing thyroid disease during pregnancy and postpartum just issued by the American Thyroid Association,1 in collaboration with researchers from Boston University School of Medicine and Brigham and Women's Hospital include more than 100 clinical recommendations, to provide clearer guidance to clinicians. An estimated 300,000 pregnancies annually in the U.S. are impacted by thyroid disease.
The 162-page document, with recommendations and data backed up by more than 600 references, includes some substantial changes, Elizabeth Pearce, MD, MSc, associate professor of medicine, Boston University School of Medicine, told EndocrineWeb. Dr. Pearce co-chaired the committee developing the guidelines and is the corresponding author. The new recommendations were published online, in the January 2017 issue of Thyroid.
Dr. Pearce discussed 4 areas with EndocrineWeb that she said are worth highlighting for clinicians.
A major and substantial change in the new guidelines includes raising the upper limit in the normal thyroid function tests. For thyroid stimulating hormone (TSH), the upper limit was 2.5 in the 2011 guidelines; now, it is 4.0.
The experts addressed the question of what the normal reference range for serum TSH concentrations should be in women who are pregnant. The downward shift of the TSH reference range during pregnancy is seen in both the lower and upper limits of maternal TSH relative to the typical non-pregnant reference range, according to the new guidelines. The largest decline in serum TSH is seen during the first trimester, due to rising levels of serum hCG stimulating the TSH receptor and increasing thyroid hormone production. This downward shift varies greatly among different racial and ethnic groups. Initially, studies of pregnant women in the U.S. and Europe led to the earlier recommendation for a TSH upper reference limit of 2.5 mU/L in the first trimester, then 3.0 in trimesters 2 and 3.
However, recent studies have looked at women in Asia, India and the Netherlands, finding only a modest reduction in upper reference limits. Looking at the body of evidence, the upper reference limit should be set at 4.0 for the typical patient in early pregnancy, with a gradual return to nonpregnant levels later.
The recommendation is first to look at population specific information, Dr. Pearce said, then to use the 4.0 upper limit if none is available. The recommendation reads: "When possible, population-based, trimester-specific reference ranges for serum TSH should be defined through assessment of local population data representative of a healthcare provider’s practice.''
"This has been hugely controversial in pregnant women," said Dr. Pearce of whether to treat women with mildly elevated maternal TSH concentrations. “As the guidelines state, this is especially true in TPOAb [thyroperoxidase antibody] positive women.”
Much research has looked at subclinical hypothyroidism and pregnancy outcome, finding an increased risk of pregnancy complications, especially in TPOAb positive women, per the guidelines.1 However, Dr. Pearce said, there are few studies that have investigated whether treatment with levothyroxine (LT4) can make a difference.
After looking at the research, the experts concluded that treatment may reduce miscarriage in TPOAb positive women; so treatment may potentially benefit select subgroups of women during pregnancy. The recommendation is: women with TSH concentrations above 2.5 mU/L be evaluated for TPO antibody status.
Treatment with LT4 is strongly recommended for antibody positive women with TSH greater than the pregnancy specific references, and for antibody negative women with TSH levels higher than 10. The therapy may also be considered for others, depending on TSH levels.
In the last guidelines, the experts recommended switching women with hyperthyroidism on methimazole (MMI) to propylthiouracil (PTU) during the first trimester, Dr. Pearce explained.
"Now we are saying we don't know if that is the right approach," she said. Studies have found that PTU is also linked with birth defects, although apparently less severe than MMI-related defects.
In the new guidelines, several options are suggested. When pregnancy is diagnosed in a woman on antithyroid therapy who appears to be in remission, one option is to withdraw the medication and monitor her closely. Other options would be preconception surgery or radioiodine ablation.
"What's new is the recognition that both antithyroid drugs can cause birth defects and the risk is higher than we thought," Dr. Pearce said. In one Danish study, up to 3% of children exposed to PTU developed birth defects. Typically they involved cysts of the face and neck or, in boys, urinary tract abnormalities.
The new evidence, she concedes, ''doesn’t lead to a simple answer." The risk of relapse after medication withdrawal should be weighed, the guidelines suggest; if that risk is high, PTU is the drug of choice.
The guidelines also reflect the reality that the answers for some questions are still evolving despite the fact that research has grown substanitially in the last few years, according to Dr. Pearce.
The experts conclude there is ''basically not enough evidence'' to recommend universal screening of thyroid function for all pregnant women, Dr. Pearce said. Professional organizations have disparate recommendations with conflicting advice.
"In the U.S., we know practice is mixed," she said. "Some doctors do universal screening; others don't."
The 2017 guidelines for managing thyroid disease during pregnancy seem to highlight more information than in the past, said Melissa D. Katz, MD, assistant professor of medicine in endocrinology at Weill Cornell Medicine, who reviewed them for EndocrineWeb.
She believes one of the most important points in the guidelines is to individualize treatment. "That's not necessarily a change," she said. "I think it's always been critical."
One of the standard tests in her own practice is the antibody test.
"I find it useful," she said. "It tells you what the underlying condition is. It also gives you insight as to the thyroid health status." Depending on the results, she said, it may alert her that the woman needs thyroid hormone.
Another critical point highlighted in the updated guidelines, she said, is that the optimal level of thyroid hormones is very different for pregnant versus non-pregnant women.
The best advice for clinicians? "I feel the guidelines are there for a reason," Dr. Katz said. "You individualize them for your patients based on your clinical judgment."
1. Alexander EK, Pearce EN, Brent GA, et al. 2016 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum. Thyroid. Published online January 6, 2017. Available at: http://online.liebertpub.com/doi/abs/10.1089/thy.2016.0457.