Ep 164: A 25-Year-Old Pregnant Woman Asking About Her Thyroid

Today’s episode discusses thyroid testing and function in pregnancy.

Read more on this topic in Harrison's.

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi, everyone, welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to Harrison's Podclass. Today's episode is a 25-year-old pregnant woman asking about her thyroid. Cathy, today's patient is a 25-year-old woman who's thrilled to find out she's pregnant with her first child. She estimates that she's about nine weeks pregnant and is having significant morning sickness and vomiting. She's otherwise very healthy and has started taking prenatal vitamins. She works as an elementary school teacher and has no significant family history of autoimmune or clotting diseases. Her first OB appointment is next week. 

[Dr. Handy] So, all sounds fine. Sounds like she's doing the right things for now. Are there any questions? 

[Dr. Wiener] Yeah, she saw on a TikTok video that thyroid problems are a major worry during pregnancy. She's trying to stay calm and is coming to you for advice about if she needs screening or doing anything different. 

[Dr. Handy] That she's coming in and talking to us rather than relying just on Dr. TikTok. 

[Dr. Wiener] Okay. And so, let's get to the question. Our question asks, which of the following statements regarding thyroid function during pregnancy is true? Option A, all women should be screened for hypo or hyperthyroidism during pregnancy by measuring TSH. Option B, hyperemesis gravidum is a manifestation of hypothyroidism in pregnancy. Option C, subclinical hypothyroidism occurs in 20 to 25% of pregnant women. Option D, thyroid-stimulating hormone, or TSH, typically rises during the first trimester of pregnancy. And option E. is, total T3 and T4 levels are typically elevated during pregnancy. 

[Dr. Handy] This is a great topic, and let's start by reviewing some of the physiology. The thyroid axis is a classic example of an endocrine feedback loop. Hypothalamic thyroid-releasing hormone, or TRH, stimulates pituitary production of thyroid-stimulating hormone, or TSH. That, in turn, stimulates thyroid hormone synthesis and secretion. The thyroid gland then produces two related hormones: thyroxine, T4, and triiodothyronine, or T3, which are active throughout the body. T3 and T4 act via negative feedback to inhibit TRH and TSH production. The setpoint in the axis is established by TSH. 

[Dr. Wiener] So that's why we use TSH as a screen for either hypo or hyperthyroidism, but I thought most pituitary hormones are secreted in a pulsatile fashion. Doesn't that make it hard to interpret them? 

[Dr. Handy] Yes, TSH is released in a pulsatile manner and exhibits a diurnal rhythm. However, these TSH excursions are modest in comparison to those of other pituitary hormones, and TSH has a long half-life. So single measurements of TSH are adequate for assessing its circulating level. A low TSH can be used for the diagnosis of primary hyperthyroidism, or a high TSH indicating primary hypothyroidism. 

[Dr. Wiener] Okay, great, but things change during pregnancy. We know that. What happens then? 

[Dr. Handy] Five factors alter thyroid function in pregnancy. So one, the transient increase in hCG during the first trimester, which weakly stimulates the TSH receptor. Two, you have the estrogen-induced rise in thyroid-binding globulin during the first trimester, which is sustained during pregnancy. Three, you have alterations in the immune system, and that may lead to the onset of an autoimmune disorder or exacerbation or amelioration of an underlying autoimmune thyroid disease. Four, you have increased thyroid hormone metabolism by the placenta. And five, you have increased urinary iodine excretion, which can cause impaired thyroid hormone production in areas of marginal iodine sufficiency. 

[Dr. Wiener] So that's why women in parts of the world with precarious iodine intake are most at risk of developing a goiter during pregnancy or giving birth to an infant with a goiter and even hypothyroidism. 

[Dr. Handy] And why iodine is recommended to take in pregnancy. The World Health Organization recommends a daily iodine intake of about 250 micrograms during pregnancy and lactation. And prenatal vitamins should contain around 150 micrograms per tablet. 

[Dr. Wiener] So I'm getting to see why there are TikTok videos about this, but what else do we need to know? 

[Dr. Handy] The rise in circulating hCG levels during the first trimester is accompanied by a reciprocal fall in TSH that persists into the middle of pregnancy. This reflects a weak binding of hCG, which is present at very high levels to the TSH receptor. HCG-induced changes in thyroid function can result in transient gestational hyperthyroidism that may be associated with hyperemesis gravidum. However, this usually abases without treatment other than adequate hydration and does not require therapy. 

[Dr. Wiener] Okay. So option B. is false. Hyperemesis is not a manifestation of hypothyroidism. What's next? 

[Dr. Handy] Well, the true statement is E. Total T3 and T4 levels are typically elevated throughout pregnancy. 

[Dr. Wiener] Why is that? 

[Dr. Handy] Mostly because thyroid-binding globulin levels increase during pregnancy. Total T4 and T3 levels are about 1.5 times higher throughout pregnancy. But the free T4, which is the same or slightly higher at the end of the first trimester, then progressively decreases so that the third trimester values in healthy pregnancies are often below the non-pregnant lower reference cutoff. During pregnancy, subclinical hypothyroidism occurs in about 2% of women, but overt hypothyroidism is present in only 1 in 500. 

[Dr. Wiener] Okay. So that's why option C. is false. 

[Dr. Handy] Yes, and that leads me to option A. Prospective randomized controlled trials have not shown a benefit for universal thyroid disease screening in pregnancy. Targeted TSH testing for hypothyroidism is recommended for women planning a pregnancy for certain patients. So if people have a strong family history of autoimmune thyroid disease or other autoimmune disorders, patients who have infertility or prior pre-term delivery or recurrent miscarriage or signs or symptoms of thyroid disease or are older than 30 years of age, then it can be recommended. 

[Dr. Wiener] Okay. Anything else before we close? 

[Dr. Handy] Yes. One important point. So in women who are already prescribed thyroid replacement for hypothyroidism, thyroid hormone requirements are increased by up to 45% during pregnancy. So these women should be monitored carefully. 

[Dr. Wiener] Great. So the teaching points today are that pregnancy causes changes in thyroid metabolism and alterations in thyroid-related laboratory studies. Routine thyroid screening is not indicated in an uncomplicated pregnancy. Typically, total T3 and total T4 levels increase during pregnancy without a significant change in physiologic free levels. Subclinical hypothyroidism is not common, and clinically significant hypothyroidism is even more uncommon in routine pregnancy. 

[Dr. Handy] And you can find this question and other questions like it in the Harrison's Self-Review book, and you can learn more about this topic in the Harrison's chapter on thyroid gland physiology and testing. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review so we can reach more listeners just like you. Thanks so much for listening. 

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