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Dr. Cori Cross (Host): This is Pediatric Insights: Advances in Innovations with Children's Health, where we explore the latest in pediatric care and research. I'm your host, Dr. Cori Cross. Today, we'll discuss when primary care providers should refer to an endocrinologist. We are excited to have Dr. Nadia Merchant, who is a pediatric-boarded endocrinologist and geneticist at Children's Health and an Associate Professor at UT Southwestern with us today to give us guidance and to discuss the key skeletal growth signs that signal the need for a pediatric endocrinology referral. Thank you, Dr. Merchant, for being with us today.

Dr. Nadia Merchant: Thank you for having me.

Host: So, Dr. Merchant, as a primary care physician, we start plotting and charting children's growth from the moment they arrive. And we're tracking them and we know if they're on a low curve or we know if they fall from one curve to another. But there's a lot to consider, and sometimes we have a lot of questions from parents as to when to refer. When should a primary care provider think about referring to an endocrinologist?

Dr. Nadia Merchant: So, there are the obvious signs, such as if they look disproportionate in general or slight dysmorphology that may be concerning. But also, I think what we're talking a lot about is a child that has no past medical history looking great, but falling off the growth chart, so maybe decreased growth velocity, falling in percentiles, those are all reasons I would say should refer to endocrinology in general.

Host: So, those are not times where we should say, "Hey, this is constitutional growth delay. Let's give it six months to a year and see if you pop back up." We should be making those referrals quickly. Correct?

Dr. Nadia Merchant: Yes, those are the referrals I think are more necessary as soon as you notice them.

Host: Got it. And now some signs may be more nuanced. Is there anything particularly that we should be looking for or any obvious physical features that may indicate a skeletal or genetic issue that warrants consult?

Dr. Nadia Merchant: One of the signs that I always say is if mom, during her pregnancy, was told the baby's not growing as well, especially if there was small femur length. And that is one I would say should be referred. The other is if you feel the child is disproportionate in one way or the other. So, is it extremities disproportionate or not? And a large head circumference sometimes can make you think of a skeletal dysplasia, and those require more appropriate referrals.

Host: Got it. And so, I'm a pediatrician. And so, I have a question. I was taught that something like constitutional growth delay is just sometimes kids, for whatever reason, genetic or whatnot, just sort of stop growing. And then, there'll be like late bloomers. Is that actually true or is that just an old wives' tale?

Dr. Nadia Merchant: So, constitutional growth delay is true. And I think I like to get a history like when did mom have menarche? Was dad a late bloomer or not? Did he grow after high school? So, those are sometimes signs that I'll say, "Oh, you were a late bloomer." And then, if you see the child's growing slightly off in percentile, but they're relatively on the growth chart, those are more signs that may not need referral if they just have constitutional growth delay.

The other thing I would say is, "Are they still growing?" If you have no growth rate or less than three centimeters per year, then that might require a referral or some lab work that will say there's something going on compared to a child who's growing four to five centimeters a year and maybe not making it on where everybody else is going through puberty, and this kid is not showing signs of puberty.

Host: Got it. Now, have there been changes to really the thought process on treating short stature? So before, it was obviously not treatable. But now, with growth hormone and with puberty blockers, there's the ability to actually change someone's stature. Have there been changes really in the thought process on the endocrine side-- I know there are changes on the parental side-- as to when this is appropriate and not appropriate?

Dr. Nadia Merchant: So if the child is less than maybe Z-score or -2.25 or like less than third percentile, that's what we would call idiopathic short stature. And that is approved indication for growth hormone as such. But that doesn't mean it's always given because we have to put some thought process to it. So, every child is not going to be on growth hormone just because they're slightly shorter. And they don't always have great improvement or even respond to growth hormone. So, there are indications that are specific based on genetic conditions or where they're on the growth chart, or if they have growth hormone deficiency where they don't make enough growth hormone.

Host: Now when you say they don't always respond, is that something that's dose-dependent or is that something that's patient-dependent?

Dr. Nadia Merchant: It's patient-dependent. I have some kids I've put on growth hormone and they did not improve in their growth velocity. Sometimes they started going through puberty, so that improved, but it wasn't the growth hormone that was helping.

Host: Got it. And so, the other thing I wanted to ask is we have become much more sophisticated in our treatment of short stature, whether it's idiopathic or for other reasons. How has that changed? Because I remember that one of the big concerns was the sequela of these medications, the sequela of giving growth hormone. How has that changed as we've become more sophisticated with our dosage and our treatment plans?

Dr. Nadia Merchant: So, we have different dosage that we give based on the indication. So for certain genetic conditions, the dosage may be higher. And for like growth hormone and deficiency, sometimes the kids are on a much lower dose. And then, for what we call idiopathic short stature, the dosage we use has to be higher dosed, but then I'm always concerned am I going to cause side effects by giving too much growth hormone.

Host: And what are those possible side effects?

Dr. Nadia Merchant: So, you can have increased intracranial pressure in a sense like when you give too much, the kids can get headaches. There is always the risk of SCFE, slipped capital femoral epiphysis, where it can happen in any child. But if you give growth hormone, there is a higher risk. And honestly, growth hormone was only even around since the late 1980s. We don't know what the long-term effects are. And so if I don't need to give it to a child, I'm always hesitant to give growth hormone.

Host: And is it associated with any sort of increased risk of stroke or heart disease or cancers later in life, or is that not true?

Dr. Nadia Merchant: There is some maybe data that is there, but I think that it's hard for us to say. And also, we don't follow healthy children that we put on growth hormone into their 40s and 50s. So really, I have a hard time saying will it cause problems in the future. But there are some papers out there that maybe say yes.

Host: So as a pediatrician, if I have a parent who comes to me who says they just don't want their son to be 5'7", I should not refer to endocrinology if that's part of their mid-parental height. And they've had no dropping off the growth curve because we are tinkering with the body.

Dr. Nadia Merchant: I agree. I think that also plotting the child on the growth chart with the mid-parental height. And sometimes even getting a bone age and showing, "Oh look, your child's bone age is fine for your family or they're delayed" can help explain to the family and the child why they are where they are on the growth chart. I think that everybody thinks that they're supposed to be six-foot tall. But if your mid-parental height is around 5'4", I can't make you six-foot tall even if I put you on growth hormone.

Host: That makes sense. So, let's take a moment to discuss the future of what you see on the horizon. Are there any advancements or emerging treatments in this field that you and your team are participating in that you're particularly excited about?

Dr. Nadia Merchant: So now, we have a lot more research, specifically on genetic short stature, which includes what we thought was idiopathic short stature. There's certain genes we've discovered that really lead to short stature, and there've been some new drugs that are in development. One is vosoritide that's been approved by the FDA for achondroplasia and that works at the growth plate level and those drugs are now being clinically trialed for certain genetic causes of short stature, and currently also for idiopathic short stature, which is less than -2.25 standard deviation on the Z-score. And so, we're part of the clinical trials, but I think there's a lot to come in the horizon, because we're doing a lot of genetic testing on kids that are truly short.

Host: That's amazing. And so, what percentage of short stature do you think is actually incorporated in our genetics?

Dr. Nadia Merchant: So, there are what's called genome-wide association studies that have been done. And we know there's a lot of genes that contribute to 1% of our height. So, that's one thing that we've discovered, but then there are certain genes that we don't even realize that can make you on the third percentile or slightly shorter.

And there's genes like IHH and NPR2 that are leading to shorter stature. And there's some great studies coming out. There's some studies coming from Brazil and from the US that are really doing whole genome to see whether or not we can understand what causes short stature compared to just saying it's idiopathic.

Host: That's really amazing and very exciting. So for you, you care for some medically complicated children, and I'm sure that requires a lot of communication between providers. How does your team collaborate with referring providers and specialty clinics to really coordinate care for these children and their parents?

Dr. Nadia Merchant: So, we are starting a skeletal dysplasia multidisciplinary clinic. In the past, if there was a child with achondroplasia, they would go to whichever doctor they needed to go to based on where the patient or the family thought they need to go or which referrals were done. But now, we're trying to make sure that these patients have a ringleader, and that's kind of what we're doing is I'm being the ringleader for my skeletal dysplasia patients and it starts prenatally.

Now, there's advancement in genetic testing, as we have non-invasive prenatal testing now that can diagnose certain skeletal disorders prenatally. So, I do consultations for those. And then, I'll meet with the family before they even have the child and kind of walk them through what to expect. And then, we'll coordinate all the referrals that could include sleep medicine, neurosurgery, MRIs, if there are certain risks that need to be done, ENT.

And so, we're trying to make sure these children optimize their care they're getting. But also, now that there's new trials and there's FDA-approved treatments, we discuss whether or not a family would want to do it, why would they not want to do it, versus using some of these therapies.

Host: That's amazing, because I think as a parent it's so hard to coordinate everything, but then also to make sure that you're not having any of the kids slip through cracks. And there often is a limited time when you can utilize their growth to really get to where you want to go. And if you miss that window, you really can't go back.

Dr. Nadia Merchant: Yes. And with certain skeletal dysplasias, like achondroplasia, there's a much higher risk of sudden infant death, which is due to foramen magnum stenosis. So, I want to see those babies as soon as they're born. And ideally, they would leave the hospital with an appointment with me so that way I can coordinate like they need to make sure their car seat's working properly for this child. They know they get the MRI sleep medicine, because we want to make sure that their foramen magnum stenosis is not so severe. And a lot of the times these kids get diagnosed later, it takes forever to get an appointment. So, the goal is that we're getting the care as early as possible for these children. And there's a lot of other skeletal dysplasias that obviously are there, but the achondroplasia is one that we know is really important during infancy to be managed appropriately.

Host: That's amazing. Dr. Merchant, give us a 30-second wrap-up take-home message for our listeners.

Dr. Nadia Merchant: Growth is such an important part of childhood. The pediatrician is following them since they're born, making sure they're growing appropriately. And poor growth can mean they have a chronic condition or they could have growth hormone deficiency or a skeletal disorder. And so, I think that the general pediatrician is really the person who refers to the appropriate provider. And it could be endocrinology, it could be GI, it could be whoever that is appropriate to make sure that this child's getting the optimal care to make sure they're going to grow as they should.

Host: Thank you, Dr. Merchant. That is such great advice, and thank you for taking the time to speak with us today.

Dr. Nadia Merchant: Thank you for having me today.

Host: If you would like more information about the endocrinology clinic at Children's Health, please visit childrens.com/endocrinology. Thank you so much for your time with us today, and for our audience for listening to Pediatric Insights: Advances and Innovations with Children's Health, where we explore the latest in pediatric care and research. You can find more information at childrens.com. And if you found this podcast helpful, please rate, review and share this episode, and please follow Children's Health on your social channels.