Growth hormone (GH) is a protein made by the pituitary gland and released into the blood in brief pulses. The major way that GH promotes growth is by increasing levels of the hormone, insulin-like growth factor-1 (IGF-1), and its carrier protein, IGF binding protein-3 (IGFBP-3), in the blood. GH and IGF-1 work together on the cartilage cells of the growth plate in long bones to increase bone length leading to increased height.
Growth hormone deficiency (GHD) in children is defined as growth failure associated with inadequate growth hormone production. Growth failure should be evaluated in children whose length or height remains below the normal range (i.e. <3rd percentile) or whose length or height percentile is falling and is crossing major percentile landmarks over time. Before considering growth hormone deficiency as a possible diagnosis, a child with growth failure needs to be evaluated for more common conditions that can impact growth. Growth failure can occur in children who have inflammation (recurrent illnesses, arthritis, inflammatory bowel disease, etc.), poor nutrition (inadequate intake or malabsorption conditions such as celiac disease, cystic fibrosis, etc.), other chronic conditions (psychosocial short stature, chronic renal insufficiency, liver disease, hypothyroidism, etc.) and genetic conditions that impact growth (skeletal dysplasias, familial short stature, Russell-Silver Syndrome, Turner Syndrome, etc.). Children receiving stimulant therapy for attention deficit and hyperactivity disorder may have impairment of growth, particularly if caloric intake is significantly affected. However, stimulant therapy does not cause GHD. Chronic glucocorticoid therapy (inhaled or oral) can cause significant growth failure. Children with constitutional delay of growth and puberty (“late-bloomers”) can have growth failure that may be difficult to separate from GHD.
Screening tests for GHD in children with growth failure with no identified cause include bone age X-ray and serum IGF-1 and IGFBP-3 levels. A delayed bone age is more common in children with GHD. An IGF-1 in the low part of the normal range or below normal increases the likelihood of GHD. An MRI picture of the brain showing a small or ectopic (misplaced) pituitary gland supports a diagnosis of GHD. The gold standard for diagnosing GHD is failure to increase GH levels in a growth hormone stimulation test (GHST). A GHST is performed in children after an overnight fast by giving a medication or medications (such as insulin, clonidine, arginine, glucagon, L-Dopa, etc.) to cause release of growth hormone into the blood and drawing blood frequently. If the highest growth hormone level obtained following two separate stimuli is less than 10 ng/mL, this is diagnostic of GHD. However, GHST is not required for diagnosis of GHD if other clinical parameters are present. Isolated congenital GHD may be associated with low blood sugars in infants and a small penis in male infants. Congenital GHD may be also be associated with multiple other pituitary deficiencies in infants and is increased in children with optic nerve hypoplasia and midline defects including cleft palate.
Diagnosis & Treatment
Children diagnosed with GHD benefit from GH replacement therapy with improved linear growth until the growth plates fuse. rhGH therapy is given by daily subcutaneous injections. Children and their families are taught to self-inject rhGH at home. The rhGH starting dose is based upon the child’s weight and may be adjusted during therapy based upon weight gain, growth response and IGF-1 levels. Children receiving rhGH therapy should be seen by the pediatric endocrinologist every 3 to 6 months for monitoring of growth and adjustment of the rhGH dose. The earlier a child is diagnosed with GHD, the better the final height attained and the higher the likelihood that the child will reach a height that is normal for an adult. Some children with severe GHD will require rhGH therapy as adults due to the metabolic effects of GH.
Contributing Medical Specialist
Bradley S. Miller, MD, PhD
University of Minnesota Masonic Children’s Hospital
Minneapolis, MN 55454
Medical Advisory Committee Member
The MAGIC Foundation
Psychosocial (how children emotionally adapt to social situations) issues of children with extreme short stature can be very traumatic for some children. And theories vary from place to place as to how much of an influence short stature plays in a persons life both physically and psychologically. Psychosocial aspects, influences and family factors all contribute to a healthy child. However, as parents, we all need to be keenly aware of potential problems.
People tend to judge others by what they wear, how they speak, what they know, and by how they look. Part of the judgement about "looks" is the assessment of height. We seem to judge age by height, "He looks like a five year old", people say, "She seems to be about ten years old". Having made this decision people proceed to act toward the other person, particularly if it is a child, as though they are actually as old as they appear.
For most normal statured children this poses no problems. But for short children who are growth delayed, it can make life difficult. It causes two sets of problems; it suggests to the child that he/she is younger than they are and allows for immature behavior. Second, it interferes with social maturation in the child because he/she will tend to behave in a fashion consistent with what adults seem to expect. Therefore, many short growth delayed children have trouble "acting their age". They become silly and prankish, playing the role of a "clown". This tendency to be immature was thought for a long time to be the major psychological difficulty facing short children, but recent studies have shown there may be others.
In the U.S. approximately 4 to 5% of school-age children show significant degrees of underachievement academically each year. Recent studies done in the National Cooperative Growth Study (NCGS) supported by Genentech, Inc., show that short children entering growth hormone treatment have a much higher rate of learning problems and social problems. About 18 to 20% have a learning skill deficit in arithmetic, spelling or reading. Another group has problems in social interactions and show behavioral problems such as shyness, withdrawal or attention deficits. These problems appear in children with different growth diagnoses and therefore cannot be due entirely to the social effects of being short. Parents should carefully consider how they will approach managing these potential difficulties.
There are several ways to help short children cope with their problems.
First, soon after diagnosis you should ask your pediatric endocrinologist or pediatrician who they would recommend to carry out psychological testing on your child. This is essential in order to know if there are problems in intelligence, academic achievement, learning disability, attention deficit disorders or behavior problems. A skilled pediatric or child psychologist, possibly the school psychologist, can evaluate for these types of problems and offer possible solutions. Also being in close touch with your child's school regarding academic progress or signs of social or behavior problems usually helps "head off" problems before they get out of hand.
Second, building your child's self-esteem is very important. Developing a strong positive self-image is every bit as important as building taller stature. Try to use every opportunity to praise and encourage, do not criticize, be sarcastic, or negative. Find your child's strengths and work to build on them. For example, most short children feel sure they can never be involved in sports. This is incorrect. There are many non-contact sports to become involved with, tennis, track, and swimming to name just a few. If your child has a sense of humor, develop it, praise it, and comment positively about it. If your child is creative, a writer, a poet, a musician; spend time supporting and enlarging these gifts. If your child is especially compassionate towards others, notice, report what you see, and admire the quality. Building positive self-esteem will help combat any negative effects brought about because of feeling different or rejected by others.
Finally, be sure you and your child fully understand what is to be expected from growth hormone therapy. Some studies suggest that children and parents have unrealistic expectations for the changes in height that therapy might bring. They expect too much, believing that treatment will make large differences in height immediately. This is not the case and can lead to some disappointments if these misconceptions are not quickly cleared up. Ask your pediatric endocrinologist or nurse about the treatment at each visit, make up a list of issues, be sure your child also has an opportunity to talk and ask questions, even if they seem silly or stupid.
Growth Delayed Children Later In Life
Researchers have followed the academic and vocational careers of several groups of patients who were growth hormone deficient as children, and for some the outlook is not entirely satisfactory.
Some reports on these young people indicate they do not perform well academically, do not go on to college or higher education, live at home with parents for extended periods of time, and may be unhappy in their social and work lives.
Although these problems are not seen in the majority of cases, they occur frequently enough to warrant concern by physicians, nurses and parents. It may be that growth hormone deficiency is associated with a lack of motivation and drive, or with a tendency to be shy and withdrawn. These characteristics could also be related to the problems of academic and social success. Whatever the cause, it is becoming clear that in order to better develop a successful adult life, children undergoing growth hormone treatment should receive support for a better, all-around outcome.
Contributing Medical Specialist
Brian Stabler Ph.D.
Chapel Hill, NC
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