Click here to view next page of this article Growth DisordersThe highest growth rate that occurs during life occurs in utero. An average birth length is 20 inches, or 51 centimeters, which is achieved in a nine-month period of fetal life, which translates out to 68 centimeters per year were it maintained. After birth the growth rate decreases rapidly over the first four years, such that between the ages of 4 and 10 - regardless of sex. Let’s talk about non-endocrine causes of short stature that fall into the rubric of target tissue defects, and I will break those into two sort of general categories. The first are those associated with intrauterine growth retardation which, if severe or due to certain conditions, may or may not have significant postnatal catch up. It depends. If this is present with asymmetry the condition would be called Russell-Silver syndrome, or dwarfism. I’ll show you a picture of that. Another category would be the general one of bone and cartilage disorders, the most famous one of which is achondroplasia which is the most common and which a number of the dwarfs. This is a child with Russell-Silver syndrome who is about nine-months-old, who had intrauterine and postnatal growth retardation with a relative sparing of the head. That’s why the face has sort of a triangular appearance to it. The brain is growing behind the forehead normally and causes this relative dysmorphism but that’s actually a good thing. But the issue of asymmetry, I think you can see between the legs. Another category of genetic disease, which is very important and actually quite common, is Turner’s syndrome. Here is a female growth chart showing a representative pattern of height drifting away from the 5th percentile period. Hopefully one wouldn’t let that happen, actually. The weights are relatively preserved at the bottom, and then the mid-parental target height is around the 25th percentile. Now here is a classic picture of a stigmatized 16-year-old girl with Turner’s syndrome. I think you can tell she is short. If people put the blood pressure cuff. In words, let me give you a few points about Turner’s syndrome. It’s also characterized by primary ovarian failure, or gonadal dysgenesis, but in most - but not all - subjects it occurs rather commonly, which you may or may not be aware of; 1:2,000 live female births. It is usually associated with non-functioning ovaries, and hence there is no estrogen development or breast development. However, as I mentioned and showed you on the previous slide, 20% of girls may have ovarian function for at least some time, but typically infertility is the rule. Now only half of the patients with Turner’s syndrome have the classic 45 X karyotype. It used to be called 45 XO but technically there is no O chromosome, so we just call it 45 X. The remainder are mosaics, and contrary to popular opinion they are not necessarily less stigmatized. There is certainly no difference in final height outcome between straight 45 X patients and those with mosaics. Now here is a young lady who doesn’t look very happy, and you would probably have trouble telling - and I’m going to give you a better demonstration in the second talk about this - but she happens to have myxedema of her face, which you might not be able to tell, but I show her to you as a representative patient with long-standing acquired primary hypothyroidism. Alternatively, as another endocrine cause, which you could use that growth curve to show, this is a patient with endogenous Cushing’s syndrome. You’ll notice a sort of plethoric round face. There is a buffalo hump on the back that you can’t see. He’s got centralized obesity. Patients glucocorticoid excess certainly can grow poorly in height and that can be due to endogenous forms, which are relatively rare. But much more commonly this is an iatrogenic problem due to the use of high doses of glucocorticoid to save lives of patients. Now here is a young boy with growth hormone deficiency, untreated, who is about 100 cm tall. He’s about six or seven-years-old and he’s got this sort of centralized pot belly here. He’s got some round cheeks. This is the so-called cherubic look of untreated growth hormone deficiency. He also has a micropenis which occurs in boys with this condition. How he lasted so long without getting medical attention just because of this is another question I can’t answer. But the reason the patients with growth hormone deficiency have this little weight excess. Now growth hormone deficiency, if present, can be an isolated phenomenon or a current combination with other pituitary hormone deficiencies. Its etiology is usually a hypothalamic deficiency, which really means that the patients aren’t truly growth hormone deficient; they are deficient in the hypothalamic factor growth hormone releasing hormone which regulates growth hormone. But from a treatment perspective, we use growth hormone because it’s easier to use and hence we say that the patients are growth hormone deficient. This can be idiopathic. If one found growth hormone deficiency and still needed to look further, the MRI is a very beautiful tool. What you see here is the hypothalamic-pituitary stalk, the nose is out here and there is a transection. You see where it is black in the middle and this is where the MRI has helped to find certain forms of congenital growth hormone deficiency that, in the old days with other imaging studies, we could not appreciate. How do you treat short stature? Well, if it’s growth hormone deficiency you give growth hormone and clearly the only kind that is available is the biosynthetic kind. This is FDA approved. This is the only form of growth hormone that we have been using since 1985 and you may remember back then - or you may not because you were in high school - that the pituitary-derived form of growth hormone was found to be associated with the slow viral disease, Creutzfeldt-Jakob disease which is fatal. Growth hormone is also approved for use in Turner’s syndrome. We also will add low dose estrogen ultimately to this growth hormone regimen or instead of growth hormone at the age when girls should be starting puberty. As far as constitutional delay of growth. Let’s look at the opposite situation for just a moment. That being tall stature. Causes of tall stature are as follows: the most common is familial tall stature, just like short parents tend to get short kids, tall parents tend to get tall kids. Another cause, which may not be well known to you, is exogenous obesity. Now I should point out that children who are obese early in childhood tend to be tall early in childhood, but later on they stop growing prematurely and do not typically end up tall. So it’s not a great way to make a tall child permanently. What about endocrinological causes of tall stature? Well, sexual precocity, early production of androgens or estrogens can cause tall stature early on, just like obesity does. But if unregulated, untreated, these children will then end up short. Another entity, which is probably not well appreciated, is hyperthyroidism. At the time of hyperthyroidism in children, especially if it’s been present for awhile, these children tend to be disproportionately tall. With institution of treatment and normalization of thyroid function, then they tend to grow slowly back down. |