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Laurie E. Cohen, MD |
Short stature isn't an illness, but a child who is more than two standard deviations below the expected age-appropriate mean height needs to be assessed for what could be one of several possible underlying conditions. Here, Laurie E. Cohen, MD, director of Children's Hospital Boston's Neuroendocrinology Program, discusses growth hormone deficiency (GHD), one possible cause for short stature.
Generally, a child will have short stature, but GHD can also present as a child who is not short but is falling off of her height percentile. Between about age 3 and prior to the onset of puberty, keep an eye out for a child who is growing less than two inches (five centimeters) a year. However, since 3 percent or more of children will grow below that rate, it doesn't always mean the child has GHD.
Whenever you see a child who is short or not growing well, you have to rule out many other causes before you consider GHD. You can think of those in four categories:
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Normal variation – children who are genetically predisposed to be short and/or going to be late bloomers.
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Children who have intrinsic problems, such as Turner syndrome or other syndromes, or who have been growth-restricted in utero and don't have catch-up growth.
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Systemic illnesses, either due to undernutrition from inadequate caloric intake or gastrointestinal illnesses; or related to disease activity.
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Endocrine disorders, which are generally associated with preserved weight gain or frank obesity despite falling off in height percentile.
We use screening tests when we think a child may have GHD. These include IGF-1 and IGFBP-3 levels. If we then suspect a deficiency, we can also perform stimulation testing, in which we give agents that we know will provoke the pituitary to release GH. Those tests are helpful, but don't necessarily have great predictive value in diagnosing GHD.
Part of the reason it's a complex diagnosis is that there are many different levels in the pathway that can go wrong, both problems leading up to GH secretion, or problems downstream from GH secretion; the latter are expected to be less responsive to GH treatment.
Untreated patients may have life-long decreases in bone mineral density, abnormal body composition, increases in cardiovascular risk factors and decreased energy and quality of life, although there continues to be controversy about the degree of these complications.
A child can have a congenital or acquired deficiency. Often, we don't have an explanation for a congenital deficiency, but it may be due to a mutation in one of the factors in the GH pathway, or that the pituitary didn't develop normally.
Acquired deficiency can occur when there's some sort of lesion in that area, such as a brain tumor in the hypothalamus or pituitary or with diseases that infiltrate the connections between the hypothalamus and the pituitary, such as histiocytosis, germ cell tumors and lymphocytic hypophysitis. We may also see GHD after surgical resection of those tumors or from cranial radiation.
A child wouldn't attain the adult height she is meant to reach. If she's profoundly deficient, she'll end up very short. There would also be long-term ramifications with her bones, cardiovascular health and energy level.
One is using recombinant human GH as a nightly subcutaneous injection. If the child is truly deficient, she'll have a nice response and catch up in her growth, unless she starts therapy close to the end of the period of time when she can grow. For patients who have problems downstream of GH, there's recombinant human IGF-1, a newer treatment reserved for patients who are extremely short and have low levels of IGF-1, but passed their GH stimulation testing.
If she's truly GH deficient without other underlying conditions and is treated with GH, she should attain her natural adult height. Children who are not truly deficient may gain anywhere from nothing to only a few inches. Right now, the safety profile of GH looks good in terms of not having long-term complications, but we don't know what's going to happen to a child decades from now, especially if she wasn't truly deficient when treated. Somebody who is truly deficient may also need GH replacement as an adult.
Children's research includes studying the GH pathway that could be corrected with GH, but might not show up on the kinds of testing that we do now.
People continue to debate GH medication dosing: Do you dose by growth response, body weight or response of IGF-1? Our division has been involved in various trials of GH and IGF-1 treatment.
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