Maternal-Fetal Thyroid Pathology

00:01 In this discussion, we’ll take a look at the interaction between the mother and the foetus and what may then happen when there is lack of proper thyroid functioning between the two symbiotic relationships.

00:18 Maternal thyroid changes during pregnancy.

00:21 Major alterations in the thyroid system during pregnancy include the following.

00:26 Because of the estrogen, there will be an increase in total binding globulin.

00:30 That increase in total binding globulin is then going to remove or more accurately bind the free T4.

00:40 You will then increase the bound type of T4 which then increases the total.

00:48 When the total T4 increases, remember that the free is going to then communicate with the hypothalamal pituitary axis and therefore making sure that the free is always available in the mother so that the foetus is properly developing.

01:06 This is all perfectly normal during pregnancy with thyroid functioning.

01:11 Also, as you can imagine because now, the hypothalamus, pituitary and the thyroid is increasing its production to normal levels of free there will also be increased demand for iodine.

01:26 Results from an increase in iodide clearance by the kidney due to increased GFR that is also noted in pregnancy and siphoning.

01:35 Meaning to say, the channelling of the iodine from the mother to the foetus for proper thyroid creation.

01:42 The thyroid gland can increase in size during pregnancy called Pregnancy Induced Goiter, perfectly normal especially though in a patient from, let’s say, a developing country in which there is already iodine deficiency… that’s problematic.

02:00 We’re going to walk through this graph in great detail.

02:05 Let’s first dissect the graph like we’ve done with every single one to clearly understand as to what we’re trying to compare.

02:14 On the X-axis would be the weeks of gestation… 10, 20, 30, 40… takes us to all three trimesters.

02:23 And on the Y-axis represents your relative serum concentration for the particular hormones.

02:31 The blue line is characterized by TSH, the red line is then defined as being your hCG and the grey shade represents TBG.

02:44 You can expect during pregnancy and we already discussed over and over again that estrogen that’s abundant in pregnant women then causes increased total binding globulin and that total binding globulin in a separate discussion.

03:00 How it’s going to bind to that free T4 and so, therefore, the pregnant woman is then going to normally have an enlarged thyroid glands so that it can keep up with the free T4 and that’s a different discussion that we’ve had over and over again.

03:14 Here, in this discussion is the fact that we’re going to focus upon hCG and in the first 8 to 10 weeks is when the placenta, the syncytiotrophoblast of the foetus is producing human chorionic gonadotropin.

03:31 Human chorionic gonadotropin apart from working on the LH receptor of the corpus luteum so that you bring out the progesterone for proper foetal development is also working upon or replacing the TSH, isn’t it? And it’s perfectly normal to find a little bit of a drop in TSH during pregnancy, hence the dip that you noticed and the elevation of hCG this whopping interaction.

03:57 Everything’s perfectly normal though.

04:01 Meaning to say, that you have normal production of your T3, T4.

04:05 And then you noticed after 10 weeks, especially after 8 weeks you’re going to start dropping your hCG and the TSH comes back to its normal functioning upon your TSH receptors.

04:19 hCG… let’s read through this now, hCG can weakly turn on the thyroid, but it can be bind and transduce signalling from TSH receptor; hCG and TSH are structurally very similar.

04:34 High circulating hCG levels in the first trimester may result in a slightly low TSH.

04:46 When this occurs TSH will be slightly decreased… not every single pregnant woman, huh? However, those of you that are going into your wards and your shadowing your OB you can expect that TSH in a normal pregnant woman to be highly depressed, but as far as the TSH is concerned that after the first trimester, it comes back to be perfectly normal.

05:13 TSH the blue line, comes back to perfectly normal.

05:17 In the meantime, tell me about that free T4.

05:20 It’s always at normal levels… always at normal level.

05:25 What about the bound? Increased, why? Estrogen working upon the liver to increase TBG.

05:34 What about the total? Increased, why? Total is mostly composed or contributed by the bound.

05:45 So, therefore, total is increased.

05:48 Let’s take a look at pregnancy and all the different changes that are taking place overall.

05:54 It’s a nice little table here to give you a summary of what you can expect in pregnancy with all the different organ systems: thyroid testing, TSH, Total T3, T4.

06:06 Finding first trimester… your TSH could be a little bit depressed, that’s okay discussion here… why? Because of Beta-hCG… we just discussed this previously in that graph.

06:18 Finding of total is increased why, because estrogen then works upon the liver to increase TBG.

06:23 Let’s move on to another system.

06:25 Cortisol… estrogen increases cortisol binding globulin from the liver thus you find your total to be elevated.

06:33 Your cardiovascular system is the following.

06:34 Now, you’ll find this to be fascinating and I said review of your cardiovascular system in pregnancy.

06:41 First, what happens is the fact that you’re going to decrease your peripheral vascular resistance, especially in the first trimester by 50 percent.

06:52 Who’s helping you do this in pregnancy? These hormones include progesterone and substances such as nitric oxide.

07:01 Because of all this increase in plasma volume during pregnancy, you’re going to find an increase in cardiac output.

07:08 Here, once again, you find it to be increased by 50 percent, increase in plasma volume decrease in PVR; a decrease is your after load.

07:18 So, therefore, cardiac output increases as much as 50 percent, the heart rate increases as well.

07:25 Cardiovascular changes that are taking place during pregnancy… the respiratory rate increases, the plasma volume increases as much as 50 percent.

07:34 Now, RBC mass could increase as much as 20 to 30 percent.

07:38 I really want you to focus upon not much… the discussion is a little bit more important here.

07:46 There might be haemodilution, in fact, there is haemodilution because of that increase in plasma volume that we just saw above so even though there was an increase that could be an increase in RBC mass, it’s really the haemodilution that you’re also paying attention to because of that increase in plasma volume.

08:05 Thyroid hormone and the foetal development.

08:08 In the first trimester, the baby’s completely dependent on the mother for the production of thyroid hormone… the first trimester.

08:17 By the end of the first trimester, the baby’s thyroid begins to produce its own thyroid hormones, thus the siphoning of the iodine from the mother to the foetus becomes incredibly important.

08:30 Impact on the mother… in women with subclinical hypothyroidism, what does that mean to you? Subclinical, meaning to say the mother and even before she became pregnant never really had overt hypothyroidism; subclinical would mean that you have a normal free T4, but a high TSH hence subclinical.

08:53 Extra demands of pregnancy can precipitate clinical disease though.

08:56 Is that clear? So, that’s when things become really interesting for you.

09:01 Up until pregnancy, the patient was completely asymptomatic, no bradycardia and no tiredness or fatigue; in fact, the free T4 is perfectly normal.

09:11 Now, she becomes pregnant, there’s increase for demand for iodine, there’s increased demand for thyroid hormones, in general.

09:20 She may then become symptomatic which becomes dangerous for the foetus obviously and for her as well.

09:25 Now, the overt maternal hypothyroidism is typically not significant, the reason for that is if your patient wishes to become pregnant and she has Hashimoto to begin with, there’s every possibility that with overt disease, she’s already infertile.

09:45 So, what I’m saying is the reason that it’s not significant is because pregnancy never took place in overt maternal hypothyroidism.

09:56 Untreated hypothyroidism can lead to anaemia, myopathy, heart failure, pre-eclampsia, placental abnormalities, low birth weight babies, postpartum haemorrhage… all kinds of issues as you would expect with decreased thyroid hormone.

10:12 If that’s the impact on the mother by thyroid hormones, what about the impact on the baby? Thyroid hormone critical for development of everything in the infant, especially during the first two to three years of life.

10:27 So, there’s long term consequences.

10:31 Children with congenital hypothyroidism, no thyroid function can have severe, severe developmental abnormalities; you have to treat this child immediately and promptly.

10:44 These abnormalities can be treated if-if screened which is done in the U.S. diligently within 12 to 30 days after birth early.

10:55 Hence, all newborn babies in U.S. are screened by for congenital hypothyroidism because you have to be prompt with your treatment because the long term sequelae could be disastrous, if not administered properly.

11:10 If untreated, everything goes wrong.

11:15 The child, I showed you cretinism earlier, there’s a protuberant stomach with umbilical hernia, macroglossia, I wanted you to pay attention to that cheek and the mouth, macroglossia.

11:26 IQ severely compromised and the skin is yellow.

11:31 Why? Because of carotene.