Dr. Mike (Host): Welcome to Pediatrics in Practice, a CME podcast. I'm Dr. Mike. And joining me today is Dr. Pratibha Rana from Children's Mercy. In this episode, we'll explore caring for patients with short stature. Dr. Rana, welcome to the show.

Pratibha Rana, MD: Hi, Dr. Smith. Thanks for inviting me. I'm really happy to be here.

Host: What are the most common causes of short stature in children? And I guess, also, how can pediatricians differentiate between maybe more benign issues and true pathological growth patterns?

Pratibha Rana, MD: So beyond the first couple years of life, the two most common causes of short stature are familial short stature and constitutional delay of growth and development. And these are really benign growth issues, which are really variants of normal growth, which need to be recognized and differentiated from pathological causes.

So, your familial short stature, there's history of parents heights being low or small. Here, the child is following a familial pattern. They're growing along that low curve, and there's been no slowing of growth. So, it's expected the child will meet the genetic target for height. And here, I might mention that the genetic target is calculated by averaging out the parental height, subtracting and adding two and a half inches, depending on the gender. And the number that you come up with is the mid-parental height or target height. So, it's important also to get accurate heights of parents when you can, because sometimes these can be overestimated.

The other kind is the constitutional delay, which is really a pattern of delayed pubertal maturation with a child temporarily falling behind the curve. And these children experience a slowing down in their linear growth within the first three years of life, which is then followed by a regular phase of growth, but a little lower than their peers. But at the average age of puberty, when the other kids are beginning to take off, the height in these kids begins to move further down away from the growth curve because of the delay.

So, this is that child who looks leaner, younger than the other kids and is your late bloomer. And you get a family history of delayed puberty in about 50-75%, but will eventually catch up. Now, if it gets delayed beyond 14 in boys or 13 in girls, then you need a short course of testosterone or estrogen to jumpstart puberty so that they can achieve their genetic height.

Your other question was about how to differentiate between benign and pathological patterns. So, by looking at the growth chart really, and any growth deceleration is a red flag. It's also important to recognize what are normal patterns and a few things to know about normal growth pattern.

So, for one, the length at birth has little to do with growth hormone. It has to do with maternal nutrition and growth factors. There's very little correlation between birth length and final adult height. And in the first two years of life, there is rapid growth. The growth rate far outpaces any other later phase. After which, there's gradual slowing until about age four. And then, the child enters what I like to call the cruise control phase where there is slower consistent growth until they hit puberty and had that growth spurt. But growth hormone deficiency does not present with linear growth problems in the first two years of life, because it's not the primary driver of growth in this early phase. In fact, the kids that have growth hormone deficiency in this early phase present with hypoglycemia. So, that's an important piece of relevant information when considering the diagnosis.

Host: So when does a general pediatrician say, "Okay, I need help," like, when should they be referring these patients to you, the specialist?

Pratibha Rana, MD: I think the best way to look at it is look at the growth chart because it tells us about the growth problem, the present, the past, and the future. At present, what is the child's height? If it's less than third percentile, they've earned themselves a referral. And in the past, if they've tracked down over the course of the past few years or even recently, then that is the biggest red flag there is. What about the future? If they're traveling at a curve well below the target height that they're trying to get to, then that's another reason to refer out.

Another thing I want to point out here is there is an interesting phenomenon that happens in the first couple of years of life where there is a gradual movement between growth curves in nearly two-thirds of the patients, which is called rechanneling. This is a normal thing. Kids of parents that are small that are born bigger will track down. This is not abnormal. But when they cross two growth percentile curves, then that becomes a concern.

Host: So when a patient is referred to you, can you walk us through your initial workup and what are some of the things you're looking for that should have already been answered by the primary care physician?

Pratibha Rana, MD: Yeah, sure. So, investigating short stature should be geared towards ruling out some chronic conditions, because anything that is chronic in terms of infections, inflammation, kidney or liver disease, malabsorptive disorders or hormonal issues, basically all the causes for pathological short stature need to be investigated.

And so, the basic workup would include a blood count, a sed rate or CRP, which are inflammatory markers, a basic metabolic panel, hepatic function test, free T4, TSH, celiac panel and growth factors. Something to note, growth hormone levels should not be checked randomly because this is secreted in a pulsatile fashion, so it should not be done. Growth factors can be checked to screen for growth hormone deficiency though.

Host: So when you're working up a patient, what are some of the red flags you are looking for that might suggest there's a genetic or endocrine issue here?

Pratibha Rana, MD: Before I go on, I wanted to add that an x-ray, bone age x-ray is an important part of workup. And this can tie in with also your next question about what are some of the red flags. So for endocrine dysfunction, it needs to be considered as a cause in any child with growth deceleration, but a good history is extremely important. History of hypoglycemia at birth, suspicious of poor counter-regulatory response, or if you have a kid with some traumatic brain injury, optic nerve hypoplasia, that could point towards a pituitary dysfunction.

On exam, if you have midline defects like a cleft palate or micropenis, that could prompt consideration of growth hormone deficiency. And if you have advanced or delayed puberty, hypothyroidism, you could have goiter on exam. And a genetic etiology may be considered when there is history of developmental delay. Some dysmorphism syndromic features and severe short stature should certainly be kept in mind when thinking of genetic causes.

Another set of signs could be related to skeletal dysplasias. So if you have like short third or fourth fingers, some disproportionate short stature scoliosis, then you may be looking at something genetic.

Host: So when it comes now to treatment, so you've gone through this workup, you have some diagnosis of short stature. It could be a genetic cause, let's say endocrine cause. How do you. You now approach treatment? What kind of options are you looking at, especially if you're considering growth hormone therapy? How do you go through that decision process?

Pratibha Rana, MD: This has to do with establishing the diagnosis and then, of course, getting insurance approval. So, we're talking about growth hormone therapy, which is approved for not only growth hormone deficiency, but other short stature conditions, which I can talk about. But really, your question is about growth hormone deficiency, where the initial step is doing that screening lab work we talked about, but also addressing any malnutrition or poor weight gain concerns because those need to be ruled out before establishing the diagnosis by a three-hour long growth hormone stimulation test at the clinic.

Now, this has to be scheduled and may have a wait time. Once the testing confirms the diagnosis, we need to get an MRI of the brain down to evaluate pituitary, and then talk about growth hormone therapy. These are shots. These are daily shots and need to be done for as long as the child is still growing and then discuss the side effects of growth hormone, which include pseudotumor cerebri can present as headache, nausea, vomiting, or you could have SCFE, scoliosis. And we also know that growth hormone increases blood sugars. So if diabetes is brewing, it could be unmasked in these children. So, those are the sorts of considerations.

Another thing is that they follow up very frequently every four months at the endocrine clinic. So, that's something very important for the parents to know.

Host: Can you give us an idea? How long does this go on for, the growth hormone therapy? Is it different in each case? Is there a standard length of time you do this for, then you stop and you watch? How does all that work?

Pratibha Rana, MD: Yeah. So, the following every four months up until they're done with growth. And how do you know they're done with growth is when they're getting near the end of puberty and the growth velocity slows down to a certain point, less than two centimeters per year. But we also track their bone age exams. And once that bone age reaches maturity in boy or a girl, then we know they're done. That can be slightly different for different kids. But it's based on the bone age, if it's 16 in a boy and 14 in a girl, then we stop therapy. But this could be years of being on growth hormone.

Host: I think there's a lot of parents out there when they hear growth hormone, and they understand maybe in the immediate time period it's necessary, but do they ever ask questions about the long-term consequences, maybe increase in cancer rates as adults? What kind of things do you see with the long-term consequences?

Pratibha Rana, MD: So, we know that growth hormone therapy may have a permissive role, but not a causative role in cancer. We also know that in kids who've had cancer in the past, they may have a slightly higher rate of recurrence. But as far as the literature we have, it does not increase the incidence of cancer. There is a certain subset of patients who are at a higher risk, certain syndromes like Bloom syndrome or Down Syndrome, where if you are considering growth therapy, then those concerns need to be discussed with the parent.

Host: What kind of role does psychosocial support play in managing children with short stature?

Pratibha Rana, MD: Yeah. Kids with short stature certainly can have impairments and psychosocial impairments. And this comes from just being underestimated by peers, teachers, parents, or experiencing isolation, bullying. I will say parents understand their kids. They can help the child feel good about themselves. Trying to point out your child's strengths and not focusing too much on their height is an important way of the family connecting with the child.

Now, youth will perceive themselves based on social support and coping strategies. So when kids have strong social connections, they often develop healthier coping skills. And so, these parents supporting good, healthy relationships within themselves and with their friends is an important part of this. Primary care physicians are in a unique position to help talk to that child who they may be seeing every year. And having known them well, this really helps. They can reinforce that height is just one aspect and safety, in terms of ruling out a pathological cause, is an even important part of this and that you, the child, are healthy.

But what the child is going through is real for them. So, the support also depends on the diagnosis. For example, growth hormone can be treated, constitutional delay would need reassurance. And in familial short stature, having a realistic view of what their target height is and how parents and other role models have done with similar adult type helps the child see how they can do in the future.

Host: To end our conversation, which has been fantastic, by the way. Are there any recent updates or guidelines in the management of short stature that general pediatricians should be aware of?

Pratibha Rana, MD: To be honest, the guidelines have largely remained the same in terms of approach, workup, and treatment. What may be coming into the future is that the landscape of genetic evaluation is going to change since this may give us better understanding of growth and help individualize care for any genetic conditions.

Host: Dr. Rana, I want to thank you for coming on today. This has been fantastic. A lot of good information. For more information, you can visit cmkc.link/cmepodcast. If you enjoyed this one, share it on your social channels and explore our whole podcast library for more topics of interest. This is Pediatrics in Practice, a CME podcast. I'm Dr. Mike. Thanks for listening.