Dr. G. E. Wilkins (biography and disclosures)
In the past 15 years there has been a rapid expansion of information about thyroid dysfunction in pregnancy. In 2007 an international task force published guidelines for management (1).
Overt hypothyroidism is seen in 0.3 to 0.5% of the general population and subclinical hypothyroidism (high TSH and normal free T4) is seen in 2-3%. Thyroid antibodies are identified in 5-15% of women.
1. What changes occur in the maternal thyroid during pregnancy?
Pregnancy increases the metabolism and clearance of thyroxin. In normal subjects thyroid production from the gland increases to maintain normal values. Patients with hypothyroidism cannot increase thyroid production and the dosage of thyroxin must be monitored and increased. The increased dosage requirement is seen as early as six weeks gestation and continues to rise until 18-20 weeks. It may increase by 30 to 50% over the non-pregnant dosage. It is then stable for the rest of the pregnancy. In pregnancy the full replacement dose is 2.0-2.4 ug/kg bw.d (per kg of body weight per day).
2. Does thyroid hormone cross the placenta to the fetus?
Maternal thyroid hormone does cross the placenta and is the only source of thyroxin for the fetus until fetal thyroxin is produced at 18-20 weeks.
3. Is maternal thyroid hormone important for fetal development?
In the first 18 weeks of pregnancy maternal thyroxin is essential for normal brain development. Maternal hypothyroidism does result in impaired mental function in the child and this is reported even in mild hypothyroidism (2).
4. Does the normal range for thyroid function tests change during pregnancy?
In normal subjects TSH declines in the first trimester. This is caused by the thyrotropic activity of HCG. The normal range is 0.03 to 2.5 mIU/l. In the second trimester the upper normal for TSH increases to 3.5mIU/l. The free T4 increases to the upper limit of the normal range in the first trimester.
5. How do we monitor the hypothyroid patient on thyroid supplement?
In hypothyroid women the dose of replacement should be monitored before a planned pregnancy to ensure a TSH of 0.3 to 2.5 mU/l. There are two options for therapy in pregnancy. One can educate the patient to increase the pre-pregnant dose by two pills per week when the pregnancy test is positive or alternately monitor the TSH at 4-6 weeks gestation and adjust the dose accordingly (3). The TSH should be monitored every 4 weeks until 20 weeks and then every 8 weeks. The goal of therapy is to maintain a TSH at less than 2.5 mIU/l
The diagnosis of hypothyroidism in pregnancy calls for immediate and aggressive replacement. After delivery the mother reverts to pre-pregnancy dosage.
6. Should all pregnant women have a TSH test?
There is controversy about doing a TSH as a screening test. The endocrine and obstetrical literature is divided between case finding and screening. It is documented that case finding alone will miss about 20% of patients with hypothyroidism. In my opinion a TSH is justified as a routine test in the first trimester. Maternal and fetal health are at risk and I think it is an appropriate screen.
7. Are thyroid antibodies of any significance?
The presence of maternal antibodies (anti-thyroid peroxidase) is often associated with hypothyroidism. The risk of post-partum thyroid disease is also dramatically increased in subjects with thyroid antibodies and in some studies is as high as 50%. Once again there is no consensus about this test as a screen I think it is justified as a onetime test in the first trimester. Many pregnant women have positive antibody titers but are euthyroid. They should be monitored during pregnancy because they are at increased risk of thyroid failure.
There is an increased risk of pregnancy complications in subjects with positive titers even when hypothyroidism is not evident (4).
8. What are the risks of maternal hypothyroidism for the pregnancy?
The risk of pregnancy complications is markedly increased in patients with untreated overt hypothyroidism. Spontaneous first trimester loss, perinatal death, abruption, eclampsia, prematurity and impaired intellectual development are all increased in maternal hypothyroidism. Subjects with subclinical hypothyroidism in the first 20 weeks of pregnancy are also at risk for pregnancy complications (5,6). These risks are dramatically reduced by proper management.
Over the past 15 years there have been major advances in our understanding of the deleterious effects of thyroid dysfunction on pregnancy. The stakes for mother and babe are high and demand appropriate monitoring and therapy.
References: (Note: Article requests might require a login ID with the BC College of Physicians website or UBC)
1. Abalovich M et al. Management of thyroid dysfunction during pregnancy and post-partum: an Endocrine Society clinical practice guideline., The Journal of Clinical Endocrinology and Metabolism 92: (suppl): S1-47, 2007. (View article with CPSBC or UBC)
2. Haddow JE et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child, New England Journal of Medicine 341: 549-555, 1999. (View article with CPSBC or UBC)
3.Yassa l et al. Thyroid hormone early adjustment in pregnancy (The Therapy Trial), Journal of Clinical Endocrinology and Metabolism 95:3234-3241, 2010. (View article with CPSBC or UBC)
4. Stagnaro-Green A. CLINICAL REVIEW: Maternal thyroid disease and pre-term delivery, Journal of Clinical Endocrinology and Metabolism 94:21-25, 2009. (View article with CPSBC or UBC)
5. Casey B et al. Subclinical hypothyroidism and pregnancy outcomes, Obstet Gynecol 105:239-245, 2005. (View article with CPSBC or UBC)
6. Smallridge RC and Ladenson P.W. Hypothyroidism in pregnancy: Consequences to neonatal health, Journal of Clinical Endocrinology and Metabolism 86:2349-53, 2001. (View article with CPSBC or UBC)
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I usually recheck my patient’s TSH 6-8 weeks after dose changes and readjust dosing accordingly. With pregnant patients, the recommendation to check TSH every 4-8 weeks makes it difficult to monitor and administer proper dose changes.
I’ll add TSH to screening tests in ER
very helpful. I noticed in the section about how to increase medications, it states to increase medication by two pills per week post-pregnancy. Is this based on a pill being 12.5mcg or are we attempting to increase dose by 1.5 times?
I will add anti-TPO to P/Nblood work.
Very informative and helpful article.
useful
very useful
great reminder of not forgetting such basic prenatal concerns as TSH.
I will now tend to screen whereas previously I was not doing so.
iliac to have more specific details of the treatment and the possible side effects that we have to watch out for.
Very helpful guideline in managing hypothyroidism in pregnancy.I will consider adding TSH as a screening test in the prenatal workup
I was ordering TSH with every prenatal blood work until recently had an abnormal low TSH ( hyperthyroid range) .I discussed this with perinatalogist who discouraged me from regular TSH checking in pregnancy unless pt was already diagnosed with thyroid abnormality prior to getting pregnant .Please advise with relevant links to support .
Thanks
Neetu
I was screening but not as frequently as suggested. I will definitely increase the number of times I screen throughout the pregnancy.
I check TSH b/4 pregnaancy in all planned pregnanacies and in known hypothyroid patient along with other first prenatal lab tests.
I have not been routinely doing TSh as part of PN work up but may consider it. I do in patients having more than 1 miscarriage. The hint on ruotinely increasing dose by 2 polls per week is helpfull.