Volume 120 Number 5
REFERENCE
1. Torrado C, Bastian W, Wisniewski KE, Castells S. Treatment of children with Down syndrome and growth retardation with recombinant human growth hormone. J PEDIATR 1991;119:478-83.
To the Editor." Torrado et al. I concluded that it is appropriate to treat children who have Down syndrome with growth hormone (GH) because the authors believe that these children are GH deficient. The evidence for this belief is weak. Of the 13 treated patients, 7 had endogenous serum GH responses > 10 ng/ml in response to at least one provocative test. Such responses do not exclude GH deficiency, nor can they be used to make the diagnosis. The authors based their belief that GH deficiency is present on speculation by Youlton et al. 2 that disparate GH responses might indicate GH deficiency, and on the suggestion by Shulman et al. 3that elonidine might differ from other provocative stimuli by giving false-positive results in some GH-deficient children. Neither of these points is widely accepted as valid. Likewise, "GH neurosecretory dysfunction" is not widely accepted as a definable entity. The guidelines for therapeutic use of GH, suggested in 1983 by the American Academy of Pediatrics and the Lawson Wilkins Pediatric Endocrine Society,4 encourage physicians to doeument GH deficiency before recommending GH therapy. This recommendation was not followed in the study by Torrado et al. The investigators leave the reader with the implication that increased head circumference during GH therapy provides some special benefit to the patient, but they did not show that increased head size related to improved intellectual performance. It is probable that some parents of children with Down syndrome might assume that increased head circumference can be equated with improved intellectual capacity and might pursue GH therapy for their child for inappropriate reasons. It seems likely from the limited information presented that some patients did not meet reasonable criteria (or the criteria proposed by the investigators) for treatment with GH. The mean height standard deviation score was -2.2 _+ 0.8 (SD). The 3rd percentile is approximately -1.8 SD below the mean; the reader must infer that several of the patients were not short. It is inappropriate to use a pretreatment growth velocity that is "less than normal" as a criterion for therapy; the authors should have defined "less than normal" as less than the 50th percentile or less than the 3rd percentile for age. The mean growth velocity of their patients before treatment was 5.4 _+ 1.6 cm/yr, suggesting that some of these children were growing at a normal rate. It is not my purpose to propose that patients with Down syndrome should never be treated with GH. It is important, however, not to Undertake treatments that are difficult and expensive if the patient does not benefit or is harmed. The investigators focus on lack of development of carbohydrate intolerance in their treated patients but fail to express concern about reports of leukemia in GH-deficient children treated with GH. 5 This is particularly pertinent in Down syndrome because these patients have a predisposition to leukemia.
Editorial correspondence
833
Physicians and parents of children with Down syndrome should be wary about treating these children with GH before controlled studies are completed. These studies should include assessment of the child's biologic and psychologic need for GH, the potential benefits to the child, and the potential physical and psychologic risks of treatment, some of which may be unique to patients with Down syndrome. The matter of informed consent is especially pertinent because many of these children are limited in their ability to understand the complex issues involved in GH treatment. We might serve the needs of children with Down syndrome better by questioning the assumption that "taller is more desirable" and by committing the resources that would have been applied toward GH therapy to meeting their other needs.
Louis E. Underwood, MD Professor of Pediatrics University of North Carolina at Chapel Hill Chapel Hill, N C 27599-7220 REFERENCES
1. Torrado C, Bastian W, Wisniewski KE, Castells S. Treatment of children with Down syndrome and growth retardation with recombinant human growth hormone. J PEDIATR 1991; 119:478-83. 2. Youlton R, Kaplan SL, Grumbach MM. Growth and growth hormone. IV. Limitations of the growth hormone response to insulin and arginine and the immunoreactive insulin response to arginine in the assessment of growth hormone deficiency in children. Pediatrics 1969;43:989-1004. 3. Shulman D, Zamanillo J, Lowitt S. Effect of clonidine upon anterior pituitary function and plasma cateeholamine concentrations in short children and adolescents. J Pediatr Endoerinol 1985;4:211-6. 4. Ad Hoc Committee on Growth Hormone Usage, Lawson Wilkins Pediatric Endocrine Society, and Committee on Drugs, American Academy of Pediatrics. Growth hormone in the treatment of children with short stature. Pediatrics 1983; 72:891-4. 5. Fisher DA, Job J-C, Preece M, Underwood LE. Growth hormone deficiency, human growth hormone and the occurrence of leukemia. Lancet 1988;l:1159-60.
Reply To the Editor." Dr. Underwood suggests that the evidence of growth hormone (GH) deficiency in the 13 children whom we treated with recombinant human growth hormone (hGH) is weak. We disagree because we tested all 13 children for hGH deficiency (height
REFERENCE
1. Torrado C, Bastian W, Wisniewski KE, Castells S. Treatment of children with Down syndrome and growth retardation with recombinant human growth hormone. J PEDIATR 1991;119:478-83.
To the Editor." Torrado et al. I concluded that it is appropriate to treat children who have Down syndrome with growth hormone (GH) because the authors believe that these children are GH deficient. The evidence for this belief is weak. Of the 13 treated patients, 7 had endogenous serum GH responses > 10 ng/ml in response to at least one provocative test. Such responses do not exclude GH deficiency, nor can they be used to make the diagnosis. The authors based their belief that GH deficiency is present on speculation by Youlton et al. 2 that disparate GH responses might indicate GH deficiency, and on the suggestion by Shulman et al. 3that elonidine might differ from other provocative stimuli by giving false-positive results in some GH-deficient children. Neither of these points is widely accepted as valid. Likewise, "GH neurosecretory dysfunction" is not widely accepted as a definable entity. The guidelines for therapeutic use of GH, suggested in 1983 by the American Academy of Pediatrics and the Lawson Wilkins Pediatric Endocrine Society,4 encourage physicians to doeument GH deficiency before recommending GH therapy. This recommendation was not followed in the study by Torrado et al. The investigators leave the reader with the implication that increased head circumference during GH therapy provides some special benefit to the patient, but they did not show that increased head size related to improved intellectual performance. It is probable that some parents of children with Down syndrome might assume that increased head circumference can be equated with improved intellectual capacity and might pursue GH therapy for their child for inappropriate reasons. It seems likely from the limited information presented that some patients did not meet reasonable criteria (or the criteria proposed by the investigators) for treatment with GH. The mean height standard deviation score was -2.2 _+ 0.8 (SD). The 3rd percentile is approximately -1.8 SD below the mean; the reader must infer that several of the patients were not short. It is inappropriate to use a pretreatment growth velocity that is "less than normal" as a criterion for therapy; the authors should have defined "less than normal" as less than the 50th percentile or less than the 3rd percentile for age. The mean growth velocity of their patients before treatment was 5.4 _+ 1.6 cm/yr, suggesting that some of these children were growing at a normal rate. It is not my purpose to propose that patients with Down syndrome should never be treated with GH. It is important, however, not to Undertake treatments that are difficult and expensive if the patient does not benefit or is harmed. The investigators focus on lack of development of carbohydrate intolerance in their treated patients but fail to express concern about reports of leukemia in GH-deficient children treated with GH. 5 This is particularly pertinent in Down syndrome because these patients have a predisposition to leukemia.
Editorial correspondence
833
Physicians and parents of children with Down syndrome should be wary about treating these children with GH before controlled studies are completed. These studies should include assessment of the child's biologic and psychologic need for GH, the potential benefits to the child, and the potential physical and psychologic risks of treatment, some of which may be unique to patients with Down syndrome. The matter of informed consent is especially pertinent because many of these children are limited in their ability to understand the complex issues involved in GH treatment. We might serve the needs of children with Down syndrome better by questioning the assumption that "taller is more desirable" and by committing the resources that would have been applied toward GH therapy to meeting their other needs.
Louis E. Underwood, MD Professor of Pediatrics University of North Carolina at Chapel Hill Chapel Hill, N C 27599-7220 REFERENCES
1. Torrado C, Bastian W, Wisniewski KE, Castells S. Treatment of children with Down syndrome and growth retardation with recombinant human growth hormone. J PEDIATR 1991; 119:478-83. 2. Youlton R, Kaplan SL, Grumbach MM. Growth and growth hormone. IV. Limitations of the growth hormone response to insulin and arginine and the immunoreactive insulin response to arginine in the assessment of growth hormone deficiency in children. Pediatrics 1969;43:989-1004. 3. Shulman D, Zamanillo J, Lowitt S. Effect of clonidine upon anterior pituitary function and plasma cateeholamine concentrations in short children and adolescents. J Pediatr Endoerinol 1985;4:211-6. 4. Ad Hoc Committee on Growth Hormone Usage, Lawson Wilkins Pediatric Endocrine Society, and Committee on Drugs, American Academy of Pediatrics. Growth hormone in the treatment of children with short stature. Pediatrics 1983; 72:891-4. 5. Fisher DA, Job J-C, Preece M, Underwood LE. Growth hormone deficiency, human growth hormone and the occurrence of leukemia. Lancet 1988;l:1159-60.
Reply To the Editor." Dr. Underwood suggests that the evidence of growth hormone (GH) deficiency in the 13 children whom we treated with recombinant human growth hormone (hGH) is weak. We disagree because we tested all 13 children for hGH deficiency (height
