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The Use of Growth Hormone Therapy in Children
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Am Fam Physician. 2000 Mar 1;61(5):1510-1513.
Natural growth hormone is produced by the anterior pituitary gland. Its production is stimulated by growth hormone-releasing factor and inhibited by somatostatin, which are both produced by the hypothalamus. Growth hormone binds to receptors on hepatic tissue and other cells, stimulating the production of insulin-like growth factor I. This compound mediates most, but not all, of the biologic effects of growth hormone. Synthetically produced growth hormone has been available for about 15 years. It is used to treat a variety of conditions in adults and children. Vance and Mauras reviewed current indications for the use of growth hormone in children.
Growth hormone deficiency in children ranges from complete absence of growth hormone to partial deficiency. Children who completely lack endogenous growth hormone will have severe growth retardation. Children with partial deficiency will usually be of slightly short stature. Measuring the response of growth hormone to an insulin stimulus is the standard measurement technique. Obtaining frequent daytime and nocturnal samples of growth hormone is an alternate technique, but it is not more effective. Previously, a diagnosis of growth hormone deficiency was based on a peak serum level of 5 ng per mL (5 μg per L) or less. However, most physicians now consider a peak level of less than 10 ng per mL (10 μg per L) to be abnormal.
Unfortunately, currently available growth hormone assays have not been standardized. Therefore, the authors recommend basing a true diagnosis of growth hormone deficiency on the following criteria: very short height (less than 2.5 standard deviations below the mean height for normal age), poor growth velocity (less than the 25th percentile), delayed bone age and a predicted adult height substantially below the mean parental height. The difficulty for physicians occurs when children meet some, but not all, of these criteria. It is hard to predict which of these patients will respond to growth hormone therapy.
Growth hormone deficiency in children is caused by a variety of conditions. Congenital etiologies include aplasia or hypoplasia of the pituitary gland. A number of genetic causes have been identified. Most of these are related to mutations of the growth hormone gene, but mutations of genes for other pituitary factors and prolactin are also included. Acquired forms of growth hormone deficiency include tumors of the pituitary, hypothalamus and optic nerve. Cranial irradiation for tumors of the central nervous system can result in growth hormone deficiency. Other causes include cranial trauma, hypoxic insult and infiltrative diseases. Treatment with growth hormone will usually result in marked acceleration of linear growth. This is most pronounced in the first two years of therapy. In a study of more than 12,000 children, growth hormone replacement therapy was started at an average age of 9.2 ± 4.1 years and produced an increase in growth velocity from 4.4 cm per year to 10.0 cm per year. In the United States, the current recommended dosage is 0.3 mg per kg per week in daily divided doses. The younger the patient at the initiation of treatment and the more severe the growth deficiency, the better the response to therapy will be.
Chronic renal insufficiency and Turner's syndrome are two other conditions for which growth hormone therapy is labeled by the U.S. Food and Drug Administration. Data show that girls with Turner's syndrome have a greater than predicted final height. However, it is unclear whether the same is true for children with renal disease.
Children with idiopathic short stature (those at or below the 5th percentile for height) constitute about one third of all children currently receiving growth hormone in the United States. Treating these children continues to be a matter of controversy from an efficacy and an ethical point of view. Parental pressure is the reason that physicians start treatment in many of these children. Although growth hormone will accelerate linear growth, most current data have not proved that it increases final attained height. The authors state that growth hormone should only be given to children whose height is more than 2.5 standard deviations below the mean for age, who have a growth velocity of less than the 25th percentile and who have no identifiable cause of growth failure.
Early concerns about adverse effects with growth hormone included the development of Creutzfeldt-Jakob disease, diabetes mellitus, leukemia and solid tumors. However, none of these conditions has been noted in association with growth hormone therapy since the mid-1980s when recombinant growth hormone became available.
Vance ML, Mauras N. Growth hormone therapy in adults and children. N Engl J Med. October 14, 1999;341:1206–15.
Copyright © 2000 by the American Academy of Family Physicians.
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