congenital hyperthyroidism is super common and if you work with newborn babies at all you are definitely going to end up seeing it in your career it affects about one in 2,000 babies and if untreated its effects can be devastating on the development but if congenital hypothyroidism is caught early and treated adequately then basically those kids are going to be unaffected so it's super important to catch and to treat neonatal hypothyroidism in any baby who may have it hello I'm Dr tala and I've been a neonatologist for 16 years now and today we're going to talk about hypothyroidism or low thyroid levels in babies make sure you stick around to the end so that you can get your homework assignments mostly I'm going to go over the report that was published in 20123 by the AAP and it was published in Pediatrics by roset Al and it just covered the screening and the management of congenital hyperthyroidism we'll also have a few other references and they're all listed below so this is what we're going to be covering today one the function and regulation of the thyroid gland two causes of hyperthyroidism three clinical manifestations of hyperthyroidism four the diagnosis including the importance of newborn screening five the treatment and six the outcomes of infants with hypothyroidism one let's start with a function and regulation of the thyroid gland so the thyroid gland starts developing in babies in the early first trimester and basically it starts developing at the base of the tongue and then slowly tracks down so that it ends up in the anterior neck region which is where our thyroid gland is now the primary function of the thyroid gland as you all know is to produce and secrete the thyroid hormones thyroxine or T4 is the main hormone but really this is considered a pro hormone because the majority of it gets converted in the periphery in the rest of the body to T3 or triiodothyronine most of the T4 and T3 hormones which are circulating Through Blood areound to proteins including T4 binding globulin it's only the fre T4 and the fre T3 the UN bound thyroid hormone that's able to enter the cells and exert its effects so when we're following babies with hyperthyroidism during screening or during treatment we usually follow the free T4 because that's what the baby cells are actually seeing so what tells the thyroid gland how much thyroid hormone it needs to produce well interestingly the brain does and you probably know a lot of this but I I know that you've all really missed my art so specifically in the brain the anterior pituitary secretes thyroid stimulating hormone that thyroid stimulating hormone then travels down in the blood to the thyroid gland and stimulates the thyroid gland to produce more thyroid hormone what's so amazing about this is that it's all on a feedback loop so for example if the thyroid gland is not producing enough thyroid and the thyroid levels are really low then the anterior pituitary recognizes that and start secreting higher and higher levels of thyroid stimulating hormone or TSH the opposite is also true if the thyroid gland is pumping out loads of thyroid hormone then it will go back to the anterior pituitary and tell the anterior pituitary stop just stop producing as much so the TSH level the 3 T4 is really high because of that reason the TSH level will be low the TSH and the thyroid hormones are controlled at an even higher level by the hypothalamus obviously also in the brain which releases thyrotropin releasing hormone we don't follow that one as much clinically but I just want you to know there's also a feedback loop on the TR as well if a baby does have hypothyroidism then generally we can kind of figure out where the problem is based on the TSH and the freet T4 levels if the freet T4 is really low and the TSH is really high then the problem is probably in the thyroid gland if the TSH is super low and the fre4 is really low then maybe it's a problem in the pituitary make sure you understand this so what do the thyroid hormones actually do well anybody who studied medicine at all knows all the various symptoms that we've had to learn in patients with hypothyroidism so fatigue coldness low resting heart heart rate dryness of the skin constipation it obviously affects many many different systems and we'll talk a little bit more about the symptoms of hypothyroidism in a bit but just realize for a hormone to be affecting so many different symptoms it must be very important in lots of different areas of the body but there's one really important thing that you have to realize there's a big difference in developing hypothyroidism as an adult versus being born with it and that is that as babies are growing part of that neurodevelopmental and physical growth is dependent on the thyroid hormone so if an adult develops hyperthyroidism it's not going to affect them cognitively I mean they'll be a bit slower and more tired but if babies have hyperthyroidism then that could seriously affect their neurodevelopmental outcomes the horrible term ketonis used to be used to describe babies with severe physical and mental deficiencies secondary to hyperthyroidism at Birth or during pregnancy two so what causes hyperthyroidism and we kind of went over this a little bit before the vast majority of hyperthyroidism is because there's an abnormality in the thyroid actually producing the hormones only a very small percentage of hypothyroidism is secondary to an abnormality in the pituitary so I'm mostly going to concentrate on abnormalities in the thyroid so just talking about the thyroid gland there are two major causes of hyperthyroidism the first one is is when the thyroid gland wasn't made at all or it was just made very abnormally and this is called thyroid dysgenesis the second problem is if the thyroid gland is actually there but it has an issue maybe with the enzymes or whatever in actually producing the hormones most of these issues are caused by dis Genesis where the thyroid gland just isn't made right or it's small or it didn't migrate all the way down to the anterior neck and so it isn't functioning right that's where the term lingual thyroid comes from so it's still kind of at the base of the tongue and most of the time thyroid dysgenesis is just completely random just bad luck during pregnancy um and growth of the baby there are a few genetic cases of thyroid dis Genesis but this only makes up about 2 to 5% of the cases interestingly the number of babies who have a normal thyroid but just aren't producing enough thyroid hormone has increased considerably in the last 20 years and in this case it's a lot more likely to have a genetic origin also other factors could inhibit the baby's ability to produce thyroid hormone just even transiently so for example if the mother has hyperthyroidism so the mother has high thyroid levels and she's on medication to treat it so for example met hemosol or propy uracil then those medications can cross through the placenta and actually transiently inhibit thyroid production of the babies and this can decrease the baby's thyroid production for 7 to 10 days or the mother has Graves disease and has antibodies to the TSH receptor these antibodies are usually IGG so we know they can cross the placenta and they can go to the baby's TSH and actually block TSH release if a baby is born to a mother with Graves disease then those antibodies may stick around for about 6 months in this case the TSH obviously will be low and therefore the fre T4 will also be low internationally I deficiency is a pretty common cause of hypothyroidism and probably the most preventable cause of intellectual delays in the US it's a lot less likely but still pregnant mothers are encouraged to take a preal vitamin with iodine in it as you all know iodine is needed to actually produce the thyroid hormone so obviously if you're lacking iodine then the thyroid gland isn't able to produce the thyroid hormone that it needs to so just to really really reiterate this point if there is an abnormality with the thyroid gland which we already said is the vast majority of cases of hyperthyroidism whether it's dis Genesis so the thyroid gland wasn't made normally or whether there's an issue with actually producing the hormone then what are we going to see we're going to see a low level of 3et T4 and then what's going to happen here because of the feed back Loop the anterior pituitary is going to see this low level of 34 and start spitting out as much TSH as possible so what you would see classically is a lowf free T4 and a very elevated TSH level and I'm going to reiterate this again sometimes very rarely the cause of the hypothyroidism is Central and when we say Central in medicine basically we mean brain or kind of middle of the body so here it would be an abnormality in the pituitary or the hypothalamus again this is so rare but still I'm just going to say three things about this the first one is is it's a lot more common for the pituitary to have an issue with releasing TSH than for the hypothalamus the second thing is is here if you tested the levels you would see a really low TSH level and a really low fre T4 level so this is kind of a clue that it could be Central a low freet T4 and then instead of this being elevated the TSH is actually really low and the third thing is and honestly this is probably the most important clinically the anterior pituitary doesn't just release TSH it also releases a bunch of other hormones for example growth hormones gonadotropins adrenocorticotropin so generally if there is an abnormality with the anterior pituitary you won't just have a low TSH you'll also have low growth hormone levels the babies may present with hypoglycemia or micropenis and a bunch of other symptoms so it would be unusual to just have isolated low TSH from the anterior pituitary three what about clinical manifestations of hypothyroidism well like we already said the having a low thyroid level affects many systems in the body but there are few things that you specifically have to know the symptoms in neonates in babies like a lot of diseases they have the symptoms might initially be subtle and very non-specific so you really have to be aware of the fact that hypothyroidism should be on your list of differentials and a lot of babies born with hypothyroidism initially might not have any symptoms at all which is why the newborn screen is so important and we'll come back to that in a minute the three most common symptoms that we would see though would be jaundice poor feeds and hypoglycemia so remember those jaundice poor feeds and hypoglycemia other symptoms may be more similar to adults so we could have constipation or Brady cardio or the baby is cold or maybe baby's a little bit emitus then there are classical symptoms associated with really severe congenital hypothyroidism and by the way people that write tests absolutely love these symptoms so make sure that you know them the first one is macroglossia or a really enlarged tongue the second one which we do actually see is an enlarged Fontanel specifically the posterior Fontanel still being open and above 0.5 cm is one thing that you can kind of get tested on and you should be examining and the third one is an umbilical hernia which obviously we see in a lot of babies anyway you won't necessarily notice this in the newborn period but like we said in newborns thyroid hormone also affects growth and development so if a baby is lagging then that might also be a sign of hyperthyroidism four diagnosis so obviously we've kind of touched on this a lot but obviously if you have any even slightly concerning symptoms then make sure that you do actually check thyroid levels however as we said a lot of those symptoms can be really subtle or not there at all which is why we are so reliant on the newborn screen to make the diagnosis of hypothyroidism Universal newborn screening includes testing for hyperthyroidism in the US as well as in most developed countries in the world and in the US at least we should be getting the that screening between 1 to 7even days of life every state does something pretty different if the baby is sick or premature or particularly high risk for example babies with Down Syndrome go watch the video on down syndrome babies then that test has to be repeated at a couple of weeks of life or 36 weeks correct to gestational age the AAP has different guidelines honestly Most states in the US actually get that second newborn screen anyway most State Labs are checking the TSH level because if you think about it that's going to be more sensitive in diagnosing hyperthyroidism than a free T4 level because if the free T4 is just a little bit low then the TSH will carry on cranking itself up trying to squeeze out as much thyroid hormone from the thyroid gland and maybe a really high TSH level will get just to normal levels of the 3 T4 but that high level of TSH is going to indicate that something is going on here some states do actually te check the T4 level but there's usually some sort of reflex stages so a lot of places if the TSH level is High they'll check a T4 if there are abnormalities in the T4 they'll go check the TSH or they do them at the same time I just want to add something here anybody that's worked in the Nik with newborns has had false positive newborn screen results obviously it's a screening test we don't want to miss anybody so there are going to be by definition higher rates of false positives one of the things that can result in a false positive screen because it affects the production of the thyroid hormone is are certain medications and those medications include Heparin dopamine fatty acids lasx or furosine so if your baby in the unit is on any of those drugs there could be a higher chance of getting a positive newborn screen which is a false positive another thing I want to add and I've mentioned this previously on a previous newborn Screen Video it is so important that that Loop is closed if the newborn screen is sent and the thyroid level is elevated and nobody's following up on that result then you might as well not send it so it's important that there's a system in place where the lab calls the primary care provider or the NICU or whatever to make sure that we are doing something about it it's really important that none of these test results fall through the cracks five so how do we manage infants with congenital hyperthyroidism well in the paper that I already mentioned the AAP goes through a beautiful algorithm of how exactly we should treat babies with an abnormal newborn screen or obviously with symptoms that ended up having an elevated TSA if the newborn screen comes back abnormal and there's a risk of hyperthyroidism then preferably within 24 hours you should be sending your own TSH and 3 T4 some State Labs actually release the level of TSH in the newborn screen and the AAP has an algorithm based on what that level of TSH is in the newborn screen if the newborn screen comes back with a TSH level above 40 Mill international units per liter then you should immediately start some thyroid medication even before you get your results back so obviously if you get your results back and it's still above 40 then obviously you should be continuing that medication if like I said the state releases the TSH level and it's less than 40 then you don't automatically have to start the medications but if you send your own son sample and the TSH level is above 20 then you should be starting medications so this is what you have to realize if you are sending your own TSH in free T4 and the TSH is above 20 then you should be starting medications for sure the AAP recommends that all treatment and followup and everything is obviously done in conjunction with a pediatric endocrinologist they're going to end up following these babies anyway in the future like we said earlier we should also be following the free T4 and if you look at the algorithm it wants you to get the TSH and the free4 as well because there are situations where the TSH might be elevated but it's encouraging the thyroid enough to produce enough hormone level so the fre4 could still be normal if this is the case then the least you should be doing it is at least following those labs in the future to make sure that the baby doesn't end up truly being hyperthyroid according to the algorithm the AAP also describes different situations for example if the TSH level is just staying between 5 and 10 but the free T4 is normal what do you do at that point well their answer is just make sure that you're following with a pediatric endocrinologist the important thing is you really don't want anything falling through the cracks so if in doubt at least make sure that you're following the TSH and the fre T4 another really important part obviously of diagnosing babies and treating babies with hypothyroidism is getting a really good physical exam and the history so in the history figure out is there anybody else in the family with hyperthyroidism so you might be thinking there's a genetic component is the mother on any thyroid medications is it possible that the mother has Graves disease even if she hasn't actually been diagnosed with it yet and there are actually antibodies floating around her system too babies don't really need Imaging or anything of the thyroid gland even after the diagnosis but some people argue that if you do an ultrasound and you see that the thyroid gland is completely missing or there's just dis Genesis or it's the back of the tongue or whatever then there's an extremely low likelihood that this baby is going to end up producing thyroid hormone so it's much more likely that the baby will be on thyroid hormone for life versus the thyroid gland is there and maybe it's just some transient issue with actually producing the hormone and this probably goes without saying but I'm going to say it anyway if it's a central cause of hypothyroidism then obviously you're worried about some abnormality in the brain if it's the pituitary or the hypothalamus that isn't actually stimulating the thyroid gland then you should probably be getting an MRI of the brain just to make sure that there aren't any other abnormalities then as you all know if you've chosen to treat hypothyroidism then you treat it with levothyroxine which is the thyroid hormone basically and it can be given IV or po generally we start and this is what the AAP recommends at 10 to 15 microgram per kilo per day this is actually a much higher dose and the baby will probably end up needing but to Aid future development we want to try to correct the TSH and the 34 as quickly as possible our goal if it genuinely is true congenital hyperthyroidism is to start thyroid hormones within 2 weeks so we've got two weeks to make this diagnosis and then we want the labs normalized by 2 to 4 weeks and again to emphasize this again the later the thyroid hormone is started the higher the chance that there are going to be severe neurocognitive delays so time really is of the essence here after the medication is started then you should be following the TSH and the 34 obviously we'd be doing this in the NICU or if the patient has been discharged Pediatric Endocrinology should be doing it the TSH should be completely normalized on the medication and the 34 should be kind of at the upper limit of normal often we're dropping the dose severely after the TSH and the 34 have normalized so initially we should be checking every one to two weeks until everything's normalized and then once it's normalized checking at least the levels at least once a month for the first 6 months it's very important when we're sending babies home from the ncu that have been put on thyroid medication and the niku that they get excellent followup with a pediatric endocrinologist or somebody who feels very confident about making sure that these babies are going to be followed carefully six what about outcomes of infants with congenital hyperthyroidism well the newborn screen has greatly improved the neur developmental outcomes of babies with hyperthyroidism because it means that we've been able to catch those babies much sooner if the diagnosis is made early and the TSH level is normalized by four to 6 weeks of life and obviously then the baby is kept on the correct thyroid medication then those babies should grow up and have completely normal neurocognitive function having said that some Studies have noted that adults have had severe cental hyperthyroidism may have some mild deficits in memory verbal and attention skills the other question that parents always want to know is how how long is the baby going to have to be on the thyroid medications like we already said this really depends on the cause of the hyperthyroidism if the baby has low thyroidism just because the mother has Graves disease then obviously it's not going to be for Life whereas if there truly is thyroid dysgenesis so the thyroid gland is missing or it's really small or still at the base of the tongue or whatever then much more likely the baby is going to have to be on thyroid medication for Life generally babies are retested at about 3 years of age and if it looks like their thyroid gland is functioning normally at that point then they're taken off the medications okay before we finish I've got a little homework assignment for you so the first one is name five symptoms of hypothyroidism the second one is is what lab values would you expect to see in a baby with a small ectopic thyroid gland and the third one is is why should we be starting a very high dose of the thyroid medication at two weeks of life or by two weeks of life okay I hope you learned something if you want the summary of this video then go subscribe to our newsletter if you've reached this far then please like this video And subscribe if you're interested in neonatal educational content thank you so much for being here