Early in 2017, the American Thyroid Association (ATA) issued new guidelines for the diagnosis and management of thyroid diseases during pregnancy and the postpartum.   This 74 page document covers everything from thyroid function testing during pregnancy, to thyroid autoantibodies and pregnancy complications and thyroid disease and lactation. It is a comprehensive and well written document that is a must-read for anyone interested in thyroid function and laboratory testing during pregnancy.  There is no way I can summarize the whole document here, but I did want to highlight what I think are some important take-home points for laboratorians.

 Normal Reference Intervals for TSH During Pregnancy

In 2011 the ATA guidelines suggested the upper reference limit for serum TSH be set at 2.5 mU/L during the first trimester and 3.0 mU/L in the second and third trimesters. The 2017 guidelines point out that there are now studies demonstrating substantial variation between populations.  The ATA recommended that when possible, population-based trimester-specific reference intervals for serum TSH should be defined and utilized. This is excellent advice, but very difficult for laboratories to establish. When local assessments are not available, the panel now recommends that in the first trimester the non-pregnant reference interval be lowered by 0.4 mU/L at the low end and 0.5 mU/L at the high end (which equates to an upper reference limit of around 4.0 mU/L). This is a significant change from their previous recommendation.

T4 Assessment During Pregnancy

There have been publications which raise uncertainty about free T4 (fT4) measurements using immunoassays in pregnancy. The ATA again recommends that when possible, population-based trimester-specific reference intervals for fT4 should be defined and utilized. Again, such intervals are very difficult for laboratories to establish. When this is not possible, in lieu of measuring fT4, total T4 measurement can be used with the upper reference interval increased by 50% to account for the increased thyroid binding globulin present during pregnancy. They also indicate that free thyroid hormones can be assessed using equilibrium dialysis LC/MS/MS. This method is considered the gold standard, but it is more expensive. They also suggest use of the fT4 index, but I personally think that whenever possible, fT4 by equilibrium LC/MS/MS or total T4 should be used whenever possible rather than this antiquated method. I recently wrote an opinion piece about on this topic. fT4 index should not be used as a substitute for trimester-specific reference intervals. The guideline suggests that isolated hypothyroxinemia (low fT4 with normal TSH), should not be treated.

Iodine Assessment During Pregnancy

There is substantial day-to-day variation in urinary iodine intake and excretion. As such, urinary iodine concentrations cannot be used to identify patients with iodine deficiency. They suggest that all pregnant women should ingest ~250 ug of iodine daily and that excessive doses of iodine should be avoided.

Patients with Thyroid Autoantibodies     

There are increasing data indicating that there appears to be a greater risk for adverse events such as preterm delivery in pregnant women with thyroid autoantibodies compared to those who are thyroid antibody negative. The guidelines suggest that euthyroid pregnant women who are TPOAb or TgAb positive have TSH measured at the time of pregnancy confirmation and every 4 weeks throughout pregnancy in order to monitor them for the development of hypothyroidism.

Hypothyroidism During Pregnancy

Overt hypothyroidism during pregnancy is well known to be associated with adverse pregnancy complications (such as premature birth, low birth weight and pregnancy loss) and detrimental effects on fetal neurocognitive development (such as low IQ). For this reason, treatment of overt hypothyroidism is recommended during pregnancy. However, as we blogged about recently,  screening for and treatment of subclinical hypothyroidism is still being debated. Because of the averse outcomes associated with elevated TPO antibodies (mentioned above) the panel does have specific recommendations with regard to the screening and approach to subclinical hypothyroidism.  First, pregnant women with TSH concentrations >2.5 mU/L should be evaluated for TPO status. Second, subclinical hypothyroidism should be approached as follows:

T4 therapy is recommended for:

  • TPO positive and TSH greater than pregnancy specific reference interval
  • TPO negative and TSH greater than 10 mU/L

T4 therapy is considered for:

  • TPO positive and TSH greater than 2.5 mU/L and less than upper limit of pregnancy specific reference interval
  • TPO negative and TSH greater than pregnancy specific reference interval but less than 10 mU/L

T4 therapy is NOT recommended for:

  • TPO negative and TSH within pregnancy specific reference intervals

The panel suggests that thyroid hormone replacement therapy should target a treatment goal of maternal TSH concentrations below 2.5 mU/L.

About The Author

Professor of Pathology & Immunology, and Obstetrics & Gynecology, Washington University School of Medicine

Dr. Gronowski is a Professor of Pathology & Immunology, and Obstetrics & Gynecology at Washington University School of Medicine (St. Louis Missouri). She is Associate Medical Director of the Clinical Chemistry and Serology & Immunology laboratories at Barnes-Jewish Hospital. Dr. Gronowski received her Ph.D. in Endocrinology- Reproductive Physiology from University of Wisconsin, and is a diplomate of the American Board of Clinical Chemistry. Dr. Gronowski is past president of the American Board of Clinical Chemistry and the American Association for Clinical Chemistry. Her research focuses primarily on the laboratory diagnostics of endocrinology and reproductive physiology with a particular emphasis on maternal fetal medicine. She edited the book entitled “Handbook of Clinical Laboratory Testing During Pregnancy”.