A 6-year-old boy was brought to the clinic to be evaluated for GH deficiency. The boy's height is between 2 and 3 standard deviations below the average height for his age. Initial physical examination rules out head trauma, chronic illness, and malnutrition. The patient's family history does not suggest similar short stature in immediate relatives. Thyroid hormones are normal.
1. Why would the doctor order a blood test for levels of IGFBP3 and IGF-I?
2. The levels of IGFBP3 and IGF-I are below the normal range in this patient. What does this finding suggest?
3. What is GH resistance, and what measurements would support the presence of this problem?
5. Why is resistance to insulin action a potential adverse effect of giving extremely high pharmacological doses of GH for a long time?
1. GH is released in a pulsatile manner; between pulses of GH secretion the blood concentration may be undetectable in normal individuals. GH induces the synthesis and secretion of IGF-I and IGFBP3, both of which are easily detectable in the serum. Low IGF-I and IGFBP3 levels would indicate insufficient GH secretion.
2. In most cases, low levels of IGF-I and IGFBP3 in the blood would indicate insufficient GH release. However, low levels of IGF-I and IGFBP3 could also be due to a defect in the GH receptor, resulting in GH resistance.
3. GH resistance is characterized by impaired growth as a result of low levels of IGF-I and IGFBP3 in the blood. However, the blood concentration of GH is high. Defects in the GH receptor, which prevent GH from stimulating the production of IGF-I and IGFBP3, are a common cause of GH resistance.
Measurement of a GH in the blood should detect the extremely high levels of the hormone to confirm diagnosis.
4. GH and IGF-I stimulate the epiphyseal growth plate of the long bones to grow. The epiphyseal plate fuses several years after puberty, at which time GH and IGF-I can no longer stimulate the growth of the bone. Therefore, the earlier GH therapy is initiated, the greater will be the chance of achieving normal adult height before long bone growth stops.
5. GH has diabetogenic actions, which oppose the actions of insulin. Thus, chronic, high doses of GH can impair the actions of insulin. Insulin resistance is a condition in which tissues in the body do not respond very well to insulin (see Chapter 35).
Grumbach MM, Bin-Abbas BS, Kaplan SL. The growth hormone cascade: progress and long-term results of growth hormone treatment in growth hormone deficiency. Horm Res 1998;49(Suppl 2):41-57.
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