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February 17, 1989, Vol 261, No. 7 >
ARTICLE | February 17, 1989

Ethical Issues in Growth Hormone Therapy FREE

John Lantos, MD; Mark Siegler, MD; Leona Cuttler, MD
[+] Author Affiliations

Reprint requests to Department of Pediatrics, University of Chicago Pritzker School of Medicine, 5841 S Maryland Ave, Chicago, IL 60637 (Dr Cuttler).


JAMA. 1989;261(7):1020-1024. doi:10.1001/jama.1989.03420070070033
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Article
References

Pediatricians face clinical and ethical dilemmas about therapy to augment growth in short children who do not meet classic criteria for growth hormone (GH) deficiency. Biologic norms of health are unhelpful because of the uncertain relationship between stature, GH secretion, health, and disease. Instead, we suggest that GH therapy be evaluated from the perspective of cultural norms. We compare GH therapy for short normal children with currently accepted therapies for non-life-threatening pediatric conditions such as well-child care, cosmetic therapy, treatment of psychological problems, and invasive outpatient therapy for chronic conditions. Based on this analysis, we argue that the burdens of therapy, the uncertainty about long-term risks and benefits, the unclear therapeutic end point, and the implications for child health policy place routine GH therapy for children without documented deficiency of GH secretion outside current pediatric ethical norms. Such therapy is properly administered within a comprehensive clinical research protocol.

(JAMA 1989;461:1020-1024)

REFERENCES

1 +
Glasbrenner K:  Technology spurt resolves growth hormone problem, ends shortage . JAMA 1986;;255:581-584,587.
2 +
Milner RDG:  Growth hormone 1985 . Br Med J 1985;;291:1593-1594.
3 +
Fryklund LM, Bierich JR, Ranke MB:  Recombinant human growth hormone . Clin Endocrinol Metab 1986;;15:511-535.
4 +
Gertner JM, Genel M, Gianfredi SP, et al:  Prospective clinical trial of human growth hormone in short children without growth hormone deficiency . J Pediatr 1984;;104:172-176.
5 +
Van Vliet G, Styne DM, Kaplan SL, et al:  Growth hormone treatment for short stature . N Engl J Med 1983;;309:1016-1022.
6 +
Albertsson-Wikland K:  Growth hormone treatment in short children . Acta Paediatr Scand Suppl 1986;;325:64-70.
7 +
Underwood LE:  Growth hormone treatment for short children . Pediatrics 1984;;104:237-239.
8 +
Dean HJ, Friesen HG:  Growth hormone therapy in Canada: End of one era and beginning of another . Can Med Assoc J 1986;;135:297-301.
9 +
Kolata G:  New growth industry in human growth hormone . Science 1986;;236:22-24.
10 +
Benjamin M, Muyskens J, Saenger P:  Short children, anxious parents: Is growth hormone the answer? Hastings Cent Rep 1984;;14( (April) ):5-9.
11 +
 Ad Hoc Committee on Growth Hormone Usage, The Lawson Wilkens Pediatric Endocrine Society, and Committee on Drugs: Growth hormone in the treatment of children with short stature . Pediatrics 1983;;72:891-894.
12 +
Bercu BB:  Growth hormone treatment and the short child: To treat or not to treat? J Pediatr 1987;;110:991-995.
13 +
Pollitt E, Money J:  Studies in the psychology of dwarfism: I. Intelligence quotient and school achievement . J Pediatr 1964;;63:415-421.
14 +
Gordon M, Crouthamel C, Post E, et al:  Psychosocial aspects of constitutional short stature: Social competence, behavior problems, self-esteem and family functioning . J Pediatr 1982;;101:477-480.
15 +
King LS:  What is disease?  in Caplan AL, Engelhardt HT, McCartney JJ (eds): Concepts of Health and Disease: Interdisciplinary Perspectives . Reading, Mass, Addison-Wesley Publishing Co, 1981;, pp 107-118.
16 +
Kass L:  The end of medicine and the pursuit of health , in Kass L: Toward a More Natural Science . New York, Free Press, 1985;, pp 157-186.
17 +
Siegler M:  The doctor-patient encounter and its relationship to theories of health and disease , in Caplan AL, Engelhardt HT, McCartney JJ (eds): Concepts of Health and Disease: Interdisciplinary Perspectives . Reading, Mass, Addison-Wesley Publishing Co, 1981;, pp 627-644.
18 +
Siegler M:  The doctor-patient accommodation: A central event in clinical medicine . Ann Intern Med 1982;;142:1899.
19 +
Physician's Desk Reference . Oradell, NJ, Medical Economics Co Inc, 1988;, pp 999,1193.
20 +
Frasier SD:  A review of growth hormone stimulation tests in children . Pediatrics 1974;;53:929-939.
21 +
Bercu BB, Shulman D, Root AW, et al:  Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion . J Clin Endocrinol Metab 1986;;63:709-716.
22 +
Schaff-Blass E, Burstein S, Rosenfield RL:  Advances in the diagnosis and treatment of short stature, with special reference to the role of growth hormone . J Pediatr 1984;;104:801-813.
23 +
Reiter EO, Morris AH, MacGillivray MH, et al:  Variable estimates of serum growth hormone concentration by different radioassay systems . J Clin Endocrinol Metab 1988;;66:68-71.
24 +
Spiliotis BE, August GP, Hung W, et al:  Growth hormone neurosecretory dysfunction: A treatable cause of short stature . JAMA 1984;;251: 2223-2230.
25 +
Zadik Z, Chalew SA, Raiti S, et al:  Do short children secrete insufficient growth hormone? Pediatrics 1985;;76:355-360.
26 +
Rose SR, Ross JL, Uriate M, et al:  The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency . N Engl J Med 1988;;319:201-207.
27 +
Evans WS, Faria ACS, Christiansen E, et al:  Impact of intensive venous sampling on characterization of pulsatile GH release . Am J Physiol 1987;;252:E549-E556.
28 +
Bercu BB, Diamond FB:  Growth hormone neurosecretory dysfunction . Clin Endocrinol Metab 1986;;15:537-590.
29 +
Merriam GR:  Methods of characterizing episodic hormone secretion , in Crowley WF, Hofler JG (eds): The Episodic Secretion of Hormones . New York, Churchill Livingstone Inc, 1987;, pp 47-65.
30 +
Van Cauter E:  Estimating false-positive and false-negative errors in analyses of hormone pulsatility . Am J Physiol 1988;;254:E786-E794.
31 +
Brook CGD, Hindmarsh PC, Smith PJ:  Is growth hormone deficiency a useful diagnosis? Acta Paediatr Scand Suppl 1987;;331:70-75.
32 +
Milner RDG:  Which children should have growth hormone therapy? Lancet 1986;;1:483-485.
33 +
Hindmarsh PC, Brook CGD:  Effect of growth hormone on short normal children . Br Med J 1987;;295:573-577.
34 +
Meyer-Bahlburg HFL:  Psychosocial management of short stature , in Shaffer D, Ehrhardt AA, Greenhill LL (eds): The Clinical Guide to Child Psychiatry . New York, Free Press, 1985;, pp 110-144.
35 +
Steinhausen HC, Stahnke N:  Psychoendocrinological studies in dwarfed children and adolescents . Arch Dis Child 1976;;51:778-783.
36 +
Krims MB:  Observations on children who suffer from dwarfism . Psychiatr Q 1968;;42:430-443.
37 +
Lee PDK, Rosenfeld RG:  Psychosocial correlates of short stature and delayed puberty . Pediatr Clin North Am 1987;;34:851-863.
38 +
Wilson DM, Hammer LD, Duncan PM, et al:  Growth and intellectual development . Pediatrics 1986;;78:646-650.
39 +
Rotnem D, Genel M, Hintz RL, et al:  Personality development in children with growth hormone deficiency . J Am Acad Child Adolesc Psychiatry 1977;;16:412-426.
40 +
Law CM:  The disability of short stature . Arch Dis Child 1987;;62:855-859.
41 +
Dean HJ, McTaggart TL, Fish DG, et al:  The educational, vocational, and marital status of growth hormone deficient adults treated with growth hormone during childhood . AJDC 1985;;135: 1105-1110.
42 +
Rotnem D, CohenD, Hintz R, et al: Psychological sequelae of relative `treatment failure' for children receiving human growth hormone replacement . J Am Acad Child Adolesc Psychiatry 1979;;18:505-520.
43 +
Freedman B:  Equipoise and the ethics of clinical research . N Engl J Med 1987;;317:141-145.
44 +
Grumbach MM:  Growth hormone therapy and the short end of the stick . N Engl J Med 1988;; 319:238-240.
45 +
Hinman AR, Koplan JP:  Pertussis and pertussis vaccine . JAMA 1984;;251:3109-3113.
46 +
Underwood LE:  Report of the conference on uses and possible abuses of biosynthetic human growth hormone . N Engl J Med 1984;;311:606-608.
47 +
Watanabe S, Tsunematsu Y, Fujimoto J, et al:  Leukemia in patients treated with growth hormone . Lancet 1988;;1:1159.
48 +
Fisher DA, Job JC, Preece M, et al:  Response to Watanabe et al, leukemia in patients treated with growth hormone . Lancet 1988;;1:1159-1160.
49 +
Gellis SS:  On growth hormone and leukemia . Pediatr Notes 1988;;12:82.
50 +
Herbst AL, Ulfelder H, Poskanzer DC:  Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women . N Engl J Med 1971;;284:878-881.
51 +
Simpson CL, Hemplemann LH, Fuller LM:  Neoplasia in children treated with x-rays in infancy for thymic enlargement . Radiology 1955;;64:840-845.
52 +
Siegler M, Sheldon M:  Paying the price of medical progress: Causation, responsibility, and liability for bad outcomes after innovative medical care , in Siegler M, Toulmin S, Zimrig FE, et al (eds): Medical Innovation and Bad Outcomes: Legal, Social and Ethical Responses . Ann Arbor, Mich, Health Administration Press, 1987;, pp 1-17.
53 +
Copeland L, Wolraich M, Lindgren S, et al:  Pediatricians' reported practices in the assessment and treatment of attention deficit disorders . J Dev Behav Pediatr 1987;;8:191-197.
54 +
Cowart VS:  The Ritalin controversy: What's made this drug's opponents hyperactive? JAMA 1988;;259:2521-2523.
55 +
Summers JA, Caplan PJ:  Lay people's attitudes toward drug treatment for behavioral control depend on which disorder and which drug . Clin Pediatr 1987;;26:258-263.
56 +
Silver LB:  Controversial approaches to treating learning disabilities and attention deficit disorder . AJDC 1986;;140:1045-1052.
57 +
Rapport MD, Stoner G, DuPaul GJ, et al:  Methylphenidate in hyperactive children: Differential effects of dose on academic, learning, and social behavior . J Abnorm Child Psychol 1985;;13:227-234.
58 +
Famular R, Fenton T:  The effect of methylphenidate on school grades in children with attention deficit disorder without hyperactivity: A preliminary report . J Clin Psychiatry 1987;;48:112-114.
59 +
Wilson DM, Duncan PM, Dornbusch SM, et al:  The effects of growth on intellectual function in children and adolescents , in Stabler B, Underwood LE (eds): Slow Grows the Child: Psychosocial Aspects of Growth Delay . Hillsdale, Calif, Lawrence Erlbaum Associates, 1986;, pp 27-45.
60 +
Rozner L:  Facial plastic surgery for Down's syndrome . Lancet 1983;;1:245.
61 +
Gellis SS:  Comment on facial plastic surgery for Down's syndrome . Pediatr Notes 1983;;7:121.
62 +
Robin AA:  Reshaping the psyche: The concurrent improvement in appearance and mental state after rhinoplasty . Br J Psychiatry 1988;;152:539-543.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Glasbrenner K:  Technology spurt resolves growth hormone problem, ends shortage . JAMA 1986;;255:581-584,587.
2 +
Milner RDG:  Growth hormone 1985 . Br Med J 1985;;291:1593-1594.
3 +
Fryklund LM, Bierich JR, Ranke MB:  Recombinant human growth hormone . Clin Endocrinol Metab 1986;;15:511-535.
4 +
Gertner JM, Genel M, Gianfredi SP, et al:  Prospective clinical trial of human growth hormone in short children without growth hormone deficiency . J Pediatr 1984;;104:172-176.
5 +
Van Vliet G, Styne DM, Kaplan SL, et al:  Growth hormone treatment for short stature . N Engl J Med 1983;;309:1016-1022.
6 +
Albertsson-Wikland K:  Growth hormone treatment in short children . Acta Paediatr Scand Suppl 1986;;325:64-70.
7 +
Underwood LE:  Growth hormone treatment for short children . Pediatrics 1984;;104:237-239.
8 +
Dean HJ, Friesen HG:  Growth hormone therapy in Canada: End of one era and beginning of another . Can Med Assoc J 1986;;135:297-301.
9 +
Kolata G:  New growth industry in human growth hormone . Science 1986;;236:22-24.
10 +
Benjamin M, Muyskens J, Saenger P:  Short children, anxious parents: Is growth hormone the answer? Hastings Cent Rep 1984;;14( (April) ):5-9.
11 +
 Ad Hoc Committee on Growth Hormone Usage, The Lawson Wilkens Pediatric Endocrine Society, and Committee on Drugs: Growth hormone in the treatment of children with short stature . Pediatrics 1983;;72:891-894.
12 +
Bercu BB:  Growth hormone treatment and the short child: To treat or not to treat? J Pediatr 1987;;110:991-995.
13 +
Pollitt E, Money J:  Studies in the psychology of dwarfism: I. Intelligence quotient and school achievement . J Pediatr 1964;;63:415-421.
14 +
Gordon M, Crouthamel C, Post E, et al:  Psychosocial aspects of constitutional short stature: Social competence, behavior problems, self-esteem and family functioning . J Pediatr 1982;;101:477-480.
15 +
King LS:  What is disease?  in Caplan AL, Engelhardt HT, McCartney JJ (eds): Concepts of Health and Disease: Interdisciplinary Perspectives . Reading, Mass, Addison-Wesley Publishing Co, 1981;, pp 107-118.
16 +
Kass L:  The end of medicine and the pursuit of health , in Kass L: Toward a More Natural Science . New York, Free Press, 1985;, pp 157-186.
17 +
Siegler M:  The doctor-patient encounter and its relationship to theories of health and disease , in Caplan AL, Engelhardt HT, McCartney JJ (eds): Concepts of Health and Disease: Interdisciplinary Perspectives . Reading, Mass, Addison-Wesley Publishing Co, 1981;, pp 627-644.
18 +
Siegler M:  The doctor-patient accommodation: A central event in clinical medicine . Ann Intern Med 1982;;142:1899.
19 +
Physician's Desk Reference . Oradell, NJ, Medical Economics Co Inc, 1988;, pp 999,1193.
20 +
Frasier SD:  A review of growth hormone stimulation tests in children . Pediatrics 1974;;53:929-939.
21 +
Bercu BB, Shulman D, Root AW, et al:  Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion . J Clin Endocrinol Metab 1986;;63:709-716.
22 +
Schaff-Blass E, Burstein S, Rosenfield RL:  Advances in the diagnosis and treatment of short stature, with special reference to the role of growth hormone . J Pediatr 1984;;104:801-813.
23 +
Reiter EO, Morris AH, MacGillivray MH, et al:  Variable estimates of serum growth hormone concentration by different radioassay systems . J Clin Endocrinol Metab 1988;;66:68-71.
24 +
Spiliotis BE, August GP, Hung W, et al:  Growth hormone neurosecretory dysfunction: A treatable cause of short stature . JAMA 1984;;251: 2223-2230.
25 +
Zadik Z, Chalew SA, Raiti S, et al:  Do short children secrete insufficient growth hormone? Pediatrics 1985;;76:355-360.
26 +
Rose SR, Ross JL, Uriate M, et al:  The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency . N Engl J Med 1988;;319:201-207.
27 +
Evans WS, Faria ACS, Christiansen E, et al:  Impact of intensive venous sampling on characterization of pulsatile GH release . Am J Physiol 1987;;252:E549-E556.
28 +
Bercu BB, Diamond FB:  Growth hormone neurosecretory dysfunction . Clin Endocrinol Metab 1986;;15:537-590.
29 +
Merriam GR:  Methods of characterizing episodic hormone secretion , in Crowley WF, Hofler JG (eds): The Episodic Secretion of Hormones . New York, Churchill Livingstone Inc, 1987;, pp 47-65.
30 +
Van Cauter E:  Estimating false-positive and false-negative errors in analyses of hormone pulsatility . Am J Physiol 1988;;254:E786-E794.
31 +
Brook CGD, Hindmarsh PC, Smith PJ:  Is growth hormone deficiency a useful diagnosis? Acta Paediatr Scand Suppl 1987;;331:70-75.
32 +
Milner RDG:  Which children should have growth hormone therapy? Lancet 1986;;1:483-485.
33 +
Hindmarsh PC, Brook CGD:  Effect of growth hormone on short normal children . Br Med J 1987;;295:573-577.
34 +
Meyer-Bahlburg HFL:  Psychosocial management of short stature , in Shaffer D, Ehrhardt AA, Greenhill LL (eds): The Clinical Guide to Child Psychiatry . New York, Free Press, 1985;, pp 110-144.
35 +
Steinhausen HC, Stahnke N:  Psychoendocrinological studies in dwarfed children and adolescents . Arch Dis Child 1976;;51:778-783.
36 +
Krims MB:  Observations on children who suffer from dwarfism . Psychiatr Q 1968;;42:430-443.
37 +
Lee PDK, Rosenfeld RG:  Psychosocial correlates of short stature and delayed puberty . Pediatr Clin North Am 1987;;34:851-863.
38 +
Wilson DM, Hammer LD, Duncan PM, et al:  Growth and intellectual development . Pediatrics 1986;;78:646-650.
39 +
Rotnem D, Genel M, Hintz RL, et al:  Personality development in children with growth hormone deficiency . J Am Acad Child Adolesc Psychiatry 1977;;16:412-426.
40 +
Law CM:  The disability of short stature . Arch Dis Child 1987;;62:855-859.
41 +
Dean HJ, McTaggart TL, Fish DG, et al:  The educational, vocational, and marital status of growth hormone deficient adults treated with growth hormone during childhood . AJDC 1985;;135: 1105-1110.
42 +
Rotnem D, CohenD, Hintz R, et al: Psychological sequelae of relative `treatment failure' for children receiving human growth hormone replacement . J Am Acad Child Adolesc Psychiatry 1979;;18:505-520.
43 +
Freedman B:  Equipoise and the ethics of clinical research . N Engl J Med 1987;;317:141-145.
44 +
Grumbach MM:  Growth hormone therapy and the short end of the stick . N Engl J Med 1988;; 319:238-240.
45 +
Hinman AR, Koplan JP:  Pertussis and pertussis vaccine . JAMA 1984;;251:3109-3113.
46 +
Underwood LE:  Report of the conference on uses and possible abuses of biosynthetic human growth hormone . N Engl J Med 1984;;311:606-608.
47 +
Watanabe S, Tsunematsu Y, Fujimoto J, et al:  Leukemia in patients treated with growth hormone . Lancet 1988;;1:1159.
48 +
Fisher DA, Job JC, Preece M, et al:  Response to Watanabe et al, leukemia in patients treated with growth hormone . Lancet 1988;;1:1159-1160.
49 +
Gellis SS:  On growth hormone and leukemia . Pediatr Notes 1988;;12:82.
50 +
Herbst AL, Ulfelder H, Poskanzer DC:  Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women . N Engl J Med 1971;;284:878-881.
51 +
Simpson CL, Hemplemann LH, Fuller LM:  Neoplasia in children treated with x-rays in infancy for thymic enlargement . Radiology 1955;;64:840-845.
52 +
Siegler M, Sheldon M:  Paying the price of medical progress: Causation, responsibility, and liability for bad outcomes after innovative medical care , in Siegler M, Toulmin S, Zimrig FE, et al (eds): Medical Innovation and Bad Outcomes: Legal, Social and Ethical Responses . Ann Arbor, Mich, Health Administration Press, 1987;, pp 1-17.
53 +
Copeland L, Wolraich M, Lindgren S, et al:  Pediatricians' reported practices in the assessment and treatment of attention deficit disorders . J Dev Behav Pediatr 1987;;8:191-197.
54 +
Cowart VS:  The Ritalin controversy: What's made this drug's opponents hyperactive? JAMA 1988;;259:2521-2523.
55 +
Summers JA, Caplan PJ:  Lay people's attitudes toward drug treatment for behavioral control depend on which disorder and which drug . Clin Pediatr 1987;;26:258-263.
56 +
Silver LB:  Controversial approaches to treating learning disabilities and attention deficit disorder . AJDC 1986;;140:1045-1052.
57 +
Rapport MD, Stoner G, DuPaul GJ, et al:  Methylphenidate in hyperactive children: Differential effects of dose on academic, learning, and social behavior . J Abnorm Child Psychol 1985;;13:227-234.
58 +
Famular R, Fenton T:  The effect of methylphenidate on school grades in children with attention deficit disorder without hyperactivity: A preliminary report . J Clin Psychiatry 1987;;48:112-114.
59 +
Wilson DM, Duncan PM, Dornbusch SM, et al:  The effects of growth on intellectual function in children and adolescents , in Stabler B, Underwood LE (eds): Slow Grows the Child: Psychosocial Aspects of Growth Delay . Hillsdale, Calif, Lawrence Erlbaum Associates, 1986;, pp 27-45.
60 +
Rozner L:  Facial plastic surgery for Down's syndrome . Lancet 1983;;1:245.
61 +
Gellis SS:  Comment on facial plastic surgery for Down's syndrome . Pediatr Notes 1983;;7:121.
62 +
Robin AA:  Reshaping the psyche: The concurrent improvement in appearance and mental state after rhinoplasty . Br J Psychiatry 1988;;152:539-543.

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