332
E d i t o r i a l correspondence
Oral captopril test in children To the Editor: Cetta et al., 1 in their clinical conference on malignant hypertension, state that the oral captopril test to screen hypertensive patients for renovascular hypertension has not been described in children. This is not true. Daman Willems et al. 2 have found that the hypotensive response 2 hours after an oral dose of 0.7 mg/kg of captopril is an effective screening test for hyperreninemic hypertension in children. This test should be especially useful in institutions without facilities for plasma renin estimation. Kanekal Suresh Gautham, MD Senior Resident, Department o f Pediatrics Postgraduate Institute o f Medical Education and Research Chandigarh-160012, India
REFERENCES
1. Cetta F, Hurley RM, Hatch D, Castelli M. Malignant hypertension. J P~DIATR 1991;118:981-6. 2. Daman Willems CE, Shah V, Uchiyama M, Dillon MJ. The captopril test: an aid to investigation of hypertension. Arch Dis Child 1989;64:229-34.
Reply To the Editor: We thank Dr. Gautham for bringing the Daman Williams article to our attention. This study was an important investigation of the oral captopril test with hypertensive children. We should have referenced this article in our clinical conference article. Frank Cetta, MD R. M. Hurley, MD D. Hatch, MD M. Castelli, MD Department of Pediatrics Loyola University Medical Center Maywood, IL 60153
"Transient" congenital hypoparathyroidism To the Editor: In 1987, we published in THE JOURNALa study of an infant with transient congenital hypoparathyroidismI (TCHP). At that time, we questioned whether TCHP was as transient as its name would indicate: an ethylenediaminetetraacetie acid (EDTA) infusion test to induce hypocalcemia performed after the child was eucalcemic, and after calcium and vitamin D therapy had been discontinued for 5 months, showed that this child did not have an appropriate increase in serum parathyroid hormone (PTH) concentrations af-" ter significant hypocalcemia. We wondered whether TCHP could be a latent situation, rather than a transient one, and whether hypocalcemia might recur. Further, Gidding et al. 2 later showed that the same EDTA test may unmask latent hypoparathyroidism in patients with the DiGeorge syndrome.
The Journal o f Pediatrics February 1992
Four years after cessation of therapy, our patient had a recurrence of hypocalcemia, with serum ionized calcium concentrations of 1.16 to 1. l 7 mmol/L (4.64 to 4.68 mg/dl) (normal adult range in our laboratory: 4.82 to 5.12 mg/dl). Serum phosphorus concentrations were increased at 1.70 to 1.78 mmol/L (5.3 to 5.5 mg/dl) (normal adult range in our laboratory: 2.5 to 4.7 mg/dl). At the same time, serum PTH values have remained inappropriately low (20 to 27 pg/ml; normal adult range in our laboratory, 10 to 60 pg/ml). There was no precipitating factor that we could identify, and the patient has remained free of symptoms. We have restarted her calcium therapy. Recently Kooh and Binet3 published case reports on three children with neonatal hypocaleemia, diagnosed and treated as TCHP for several months to years, who subsequently recovered but who had a recurrence of hypocalcemia and its associated symptoms later in childhood. The authors suggested that hypocalcemia in an otherwise normal neonate should therefore be followed up with determinations of blood calcium levels in childhood and adolescence. Our experience with our patient indicates that routine evaluation for TCHP should possibly be expanded to include an EDTA infusion test (done carefully) during the time of eucalcemia and after the cessation of therapy, thereby allowing identification o f patients at increased risk for recurrence of hypoealcemia and hypoparathyroidism. With this strategy, patients at risk can be followed more closely and therapy can be reinstituted before the development of symptoms. Maria Lourdes Cruz, MD Francis Mimouni, MD Reginald C. Tsang, MD Department o f Pediatrics Division o f Neonatology University o f Cincinnati Medical Center Cincinnati, OH 45267-0541 REFERENCES
1. Bainbridge R, Mughal Z, Mimouni F, Tsang RC. Transient congenital hypoparathyroidism: how transient is it? J PEDIATR 1987;111:866-8. 2. Gidding SS, Miniciotti AL, Langman CB. Unmasking of hypoparathyroidism in familial DiGeorge syndrome by challenge with disodium edetate. N Engl J Meal 1988;319:1589-91. 3. Kooh SW, Binet A. Partial hypoparathyroidism: a variant of transient congenital hypoparathyroidism. Am J Dis Child 1991;145:877-80.
Growth hormone therapy for children with Down syndrome To the Editor." Torrado et al. (J PEDIATR 1991;119:478-83) report impressive evidence of growth hormone (GH) secretory abnormalities and growth acceleration with GH therapy in patients with Down syndrome (DS). Their assertion that the GH responsiveness of these children justifies treatment with GH, however, is oversimplified, and highlights the weakness of invoking specific diagnoses (such as DS) as indications for GH therapy.
Volume 120 Number 2, Part 1
Editorial correspondence
The authors' statement that "DS children are responsive to rhGH [recombinant human GH] treatment, fulfilling the suggested requirements of Allen and Fost I " (for entitlement to GH therapy) obscures a central point. Responsiveness to GH is a necessary but not sufficient criterion for treatment. Evidence that short stature is a disability for a particular individual should also be required. This is problematic in children with DS, where the broad range of intellectual capabilities is accompanied by variability in the importance of attaining an improved adult height. Disability related to height and likelihood of therapeutic benefit (not the child's underlying diagnosis) should guide access to GH therapy for DS (and all short) children. Analysis of risks of GH for children with DS should include the development of leukemia. Although an association between leukemia and GH therapy is extremely tenuous, it might be more significant in a population already at increased risk. Psychologic effects of repeated injections should also be addressed, particularly for children whose understanding of their purpose may be limited. Would benefits of GH therapy for children with DS justify its risks and cost? The goal of GH therapy is not tall stature but, rather, an improved quality of life resulting from having achieved a height within the normal range. Before GH is considered for treatment of short stature in children with DS, information is needed to support the contention that short stature per se impairs the outlook for socialization and employment in this "new generation" of individuals with DS, as it appears to for other extremely short children.
David B. Allen, MD Associate Professor of Pediatrics Endocrinology and Diabetes University of Wisconsin Medical School Madison, WI 53792 REFERENCES
1. Allen DB, Fost NC. Growth hormone therapy for short stature: panacea or Pandora's box? J PEDIATR 1990;117:16-21.
Kawasaki disease and rug shampooing To the Editor." Daniels and Specker's contention that "methodologic limitations" discredit the variable rug shampooing-Kawasaki disease (KD) association (J PEDIA'rR 1991;118:485-8) ignores basic evidence and inappropriately condenses what remains into a paradigm of good versus bad study design. They ignore five critical outbreaks l-s and fail to mention that all the negative studies they cite, and one they do not cite,z,~ came from the 1982-1983 KD pandemic; four nonpandemic studies, and a fifth report of sporadic and clustered cases, 6 show a strong association. Rather than poor methods, might this not suggest different modes of transmission of an agent of KD? Further, the authors' "straw man" argument over studies that they decided to include fails to recognize that there are no accepted standards for judging case-control studies, let alone what is called
333
"the case-control method in outbreak investigations." Equally questionable are the authors' specific criticisms. How could recall bias lead case parents to remember shampooing only 2 to 4 weeks but not up to 2 weeks, before the onset of disease? Exposure clustering at approximately 3 weeks before onset in all four studies noting both an association and a specific time interval, and possibly in three other published studies, argues strongly for the association's validity. Furthermore, alleging both overmatching (which would decrease an apparent shampooing association) and recall bias (which would increase it) is paradoxical; if anything, their less stringent matching would generate spurious case-control differences, a strange suggestion when the rug shampoo association itself might be attributed to an undermatching artifact. Nor is the operation of confounding a novel idea: the 1982 article7 identifying the shampoo association considered it a proxy variable for aerosolization or hydration-activation of an infectious agent. Criticizing "absent biologic understanding of exposure-disease relationships" for a confounded exposure is another "straw man" argument. There may be much to learn from the rug shampoo-KD association, but not from specious arguments about poor methods:
David M. Morens, MD Professor and Head, Section of Epidemiology School of Public Health Professor, Department of Tropical Medicine University of Hawaii School of Medicine Honolulu, HI 96822 REFERENCES
1. Glode MP, Brogden R, Joffe LS, et al. Kawasaki syndrome and house dust mite exposure. Pediatr Infect Dis J 1986;5:644-8. 2. Teixeira OHP, Quinn A. Outbreak of Kawasaki syndrome in Canada. Can J Public Health 1985;76:352-3. 3. Teixeira OHP, Quinn A. Kawasaki syndrome. Am J Dis Child 1986;140:190-1. 4. Ranch AM. Kawasaki syndrome: critical review of U.S. epidemiology. Progr Med Biol 1987;250:33-44. 5. Rauch AM. Kawasaki syndrome: review of new epidemiologic and laboratory developments.Pediatr Infect Dis J 1987;6:101621. 6. Fatica NS, Ichida F, Engle MA, Lesser ML. Rug shampoo and Kawasaki disease. Pediatrics 1989;84:231-4. 7. Patriarca PA, Rogers MF, Morens DM, Schonberger LB, Kaminski R. Kawasaki syndrome: association with the appliCation of rug shampoo. Lancet 1982;2:578-80.
Reply To the Editor: Dr. Morens appears to have misunderstood both the purpose and conclusion of our article on rug shampooing and Kawasaki disease. The purpose was to review critically the case-control studies published in enough detail to evaluate their methods. It is disturbing that Dr. Morens suggests that there are no accepted standards for judging case-control studies. Certainly numerous publications set forth such standards. Without such standards, there would be no way of judging whether or not a study is likely to have reached a valid conclusion. We made no attempt to categorize studies as good
E d i t o r i a l correspondence
Oral captopril test in children To the Editor: Cetta et al., 1 in their clinical conference on malignant hypertension, state that the oral captopril test to screen hypertensive patients for renovascular hypertension has not been described in children. This is not true. Daman Willems et al. 2 have found that the hypotensive response 2 hours after an oral dose of 0.7 mg/kg of captopril is an effective screening test for hyperreninemic hypertension in children. This test should be especially useful in institutions without facilities for plasma renin estimation. Kanekal Suresh Gautham, MD Senior Resident, Department o f Pediatrics Postgraduate Institute o f Medical Education and Research Chandigarh-160012, India
REFERENCES
1. Cetta F, Hurley RM, Hatch D, Castelli M. Malignant hypertension. J P~DIATR 1991;118:981-6. 2. Daman Willems CE, Shah V, Uchiyama M, Dillon MJ. The captopril test: an aid to investigation of hypertension. Arch Dis Child 1989;64:229-34.
Reply To the Editor: We thank Dr. Gautham for bringing the Daman Williams article to our attention. This study was an important investigation of the oral captopril test with hypertensive children. We should have referenced this article in our clinical conference article. Frank Cetta, MD R. M. Hurley, MD D. Hatch, MD M. Castelli, MD Department of Pediatrics Loyola University Medical Center Maywood, IL 60153
"Transient" congenital hypoparathyroidism To the Editor: In 1987, we published in THE JOURNALa study of an infant with transient congenital hypoparathyroidismI (TCHP). At that time, we questioned whether TCHP was as transient as its name would indicate: an ethylenediaminetetraacetie acid (EDTA) infusion test to induce hypocalcemia performed after the child was eucalcemic, and after calcium and vitamin D therapy had been discontinued for 5 months, showed that this child did not have an appropriate increase in serum parathyroid hormone (PTH) concentrations af-" ter significant hypocalcemia. We wondered whether TCHP could be a latent situation, rather than a transient one, and whether hypocalcemia might recur. Further, Gidding et al. 2 later showed that the same EDTA test may unmask latent hypoparathyroidism in patients with the DiGeorge syndrome.
The Journal o f Pediatrics February 1992
Four years after cessation of therapy, our patient had a recurrence of hypocalcemia, with serum ionized calcium concentrations of 1.16 to 1. l 7 mmol/L (4.64 to 4.68 mg/dl) (normal adult range in our laboratory: 4.82 to 5.12 mg/dl). Serum phosphorus concentrations were increased at 1.70 to 1.78 mmol/L (5.3 to 5.5 mg/dl) (normal adult range in our laboratory: 2.5 to 4.7 mg/dl). At the same time, serum PTH values have remained inappropriately low (20 to 27 pg/ml; normal adult range in our laboratory, 10 to 60 pg/ml). There was no precipitating factor that we could identify, and the patient has remained free of symptoms. We have restarted her calcium therapy. Recently Kooh and Binet3 published case reports on three children with neonatal hypocaleemia, diagnosed and treated as TCHP for several months to years, who subsequently recovered but who had a recurrence of hypocalcemia and its associated symptoms later in childhood. The authors suggested that hypocalcemia in an otherwise normal neonate should therefore be followed up with determinations of blood calcium levels in childhood and adolescence. Our experience with our patient indicates that routine evaluation for TCHP should possibly be expanded to include an EDTA infusion test (done carefully) during the time of eucalcemia and after the cessation of therapy, thereby allowing identification o f patients at increased risk for recurrence of hypoealcemia and hypoparathyroidism. With this strategy, patients at risk can be followed more closely and therapy can be reinstituted before the development of symptoms. Maria Lourdes Cruz, MD Francis Mimouni, MD Reginald C. Tsang, MD Department o f Pediatrics Division o f Neonatology University o f Cincinnati Medical Center Cincinnati, OH 45267-0541 REFERENCES
1. Bainbridge R, Mughal Z, Mimouni F, Tsang RC. Transient congenital hypoparathyroidism: how transient is it? J PEDIATR 1987;111:866-8. 2. Gidding SS, Miniciotti AL, Langman CB. Unmasking of hypoparathyroidism in familial DiGeorge syndrome by challenge with disodium edetate. N Engl J Meal 1988;319:1589-91. 3. Kooh SW, Binet A. Partial hypoparathyroidism: a variant of transient congenital hypoparathyroidism. Am J Dis Child 1991;145:877-80.
Growth hormone therapy for children with Down syndrome To the Editor." Torrado et al. (J PEDIATR 1991;119:478-83) report impressive evidence of growth hormone (GH) secretory abnormalities and growth acceleration with GH therapy in patients with Down syndrome (DS). Their assertion that the GH responsiveness of these children justifies treatment with GH, however, is oversimplified, and highlights the weakness of invoking specific diagnoses (such as DS) as indications for GH therapy.
Volume 120 Number 2, Part 1
Editorial correspondence
The authors' statement that "DS children are responsive to rhGH [recombinant human GH] treatment, fulfilling the suggested requirements of Allen and Fost I " (for entitlement to GH therapy) obscures a central point. Responsiveness to GH is a necessary but not sufficient criterion for treatment. Evidence that short stature is a disability for a particular individual should also be required. This is problematic in children with DS, where the broad range of intellectual capabilities is accompanied by variability in the importance of attaining an improved adult height. Disability related to height and likelihood of therapeutic benefit (not the child's underlying diagnosis) should guide access to GH therapy for DS (and all short) children. Analysis of risks of GH for children with DS should include the development of leukemia. Although an association between leukemia and GH therapy is extremely tenuous, it might be more significant in a population already at increased risk. Psychologic effects of repeated injections should also be addressed, particularly for children whose understanding of their purpose may be limited. Would benefits of GH therapy for children with DS justify its risks and cost? The goal of GH therapy is not tall stature but, rather, an improved quality of life resulting from having achieved a height within the normal range. Before GH is considered for treatment of short stature in children with DS, information is needed to support the contention that short stature per se impairs the outlook for socialization and employment in this "new generation" of individuals with DS, as it appears to for other extremely short children.
David B. Allen, MD Associate Professor of Pediatrics Endocrinology and Diabetes University of Wisconsin Medical School Madison, WI 53792 REFERENCES
1. Allen DB, Fost NC. Growth hormone therapy for short stature: panacea or Pandora's box? J PEDIATR 1990;117:16-21.
Kawasaki disease and rug shampooing To the Editor." Daniels and Specker's contention that "methodologic limitations" discredit the variable rug shampooing-Kawasaki disease (KD) association (J PEDIA'rR 1991;118:485-8) ignores basic evidence and inappropriately condenses what remains into a paradigm of good versus bad study design. They ignore five critical outbreaks l-s and fail to mention that all the negative studies they cite, and one they do not cite,z,~ came from the 1982-1983 KD pandemic; four nonpandemic studies, and a fifth report of sporadic and clustered cases, 6 show a strong association. Rather than poor methods, might this not suggest different modes of transmission of an agent of KD? Further, the authors' "straw man" argument over studies that they decided to include fails to recognize that there are no accepted standards for judging case-control studies, let alone what is called
333
"the case-control method in outbreak investigations." Equally questionable are the authors' specific criticisms. How could recall bias lead case parents to remember shampooing only 2 to 4 weeks but not up to 2 weeks, before the onset of disease? Exposure clustering at approximately 3 weeks before onset in all four studies noting both an association and a specific time interval, and possibly in three other published studies, argues strongly for the association's validity. Furthermore, alleging both overmatching (which would decrease an apparent shampooing association) and recall bias (which would increase it) is paradoxical; if anything, their less stringent matching would generate spurious case-control differences, a strange suggestion when the rug shampoo association itself might be attributed to an undermatching artifact. Nor is the operation of confounding a novel idea: the 1982 article7 identifying the shampoo association considered it a proxy variable for aerosolization or hydration-activation of an infectious agent. Criticizing "absent biologic understanding of exposure-disease relationships" for a confounded exposure is another "straw man" argument. There may be much to learn from the rug shampoo-KD association, but not from specious arguments about poor methods:
David M. Morens, MD Professor and Head, Section of Epidemiology School of Public Health Professor, Department of Tropical Medicine University of Hawaii School of Medicine Honolulu, HI 96822 REFERENCES
1. Glode MP, Brogden R, Joffe LS, et al. Kawasaki syndrome and house dust mite exposure. Pediatr Infect Dis J 1986;5:644-8. 2. Teixeira OHP, Quinn A. Outbreak of Kawasaki syndrome in Canada. Can J Public Health 1985;76:352-3. 3. Teixeira OHP, Quinn A. Kawasaki syndrome. Am J Dis Child 1986;140:190-1. 4. Ranch AM. Kawasaki syndrome: critical review of U.S. epidemiology. Progr Med Biol 1987;250:33-44. 5. Rauch AM. Kawasaki syndrome: review of new epidemiologic and laboratory developments.Pediatr Infect Dis J 1987;6:101621. 6. Fatica NS, Ichida F, Engle MA, Lesser ML. Rug shampoo and Kawasaki disease. Pediatrics 1989;84:231-4. 7. Patriarca PA, Rogers MF, Morens DM, Schonberger LB, Kaminski R. Kawasaki syndrome: association with the appliCation of rug shampoo. Lancet 1982;2:578-80.
Reply To the Editor: Dr. Morens appears to have misunderstood both the purpose and conclusion of our article on rug shampooing and Kawasaki disease. The purpose was to review critically the case-control studies published in enough detail to evaluate their methods. It is disturbing that Dr. Morens suggests that there are no accepted standards for judging case-control studies. Certainly numerous publications set forth such standards. Without such standards, there would be no way of judging whether or not a study is likely to have reached a valid conclusion. We made no attempt to categorize studies as good
