- Email: [email protected]
Jaundice with hypertrophic pyloric stenosis
16 8
Editorial correspondence
Such a conference would be of obvious interest to workers in this field, but we believe also that its findings could be a guide for editors of journals and their referees. We would welcome wider collaboration.
The Journal of Pediatrics July 1990
ter day 60 of gestation began to return to a normal growth pattern, would be supported.
Ken Tokugawa, MD Kohji Ueda, MD Department of Pediatrics, Faculty of Medicine Kyushu University 3-1-1, Maidashi, Higashi-ku, Fukuoka 812, Japan
Lesley Mutch, MD Social Paediatric and Obstetric Research Unit University of Glasgow Glasgow, Scotland
REFERENCE
M. Ann Johnson, MD Oxford Region Child Development Project John Radcliffe Hospital Oxford, England Ruth Morley, MB,BChir Medical Research Council, Dunn Nutrition Unit Cambridge, England
1. Tokugawa K, Ueda K, Fukushige J, Koyanagi T, Hisanaga S. Congenital rubella syndrome and physical growth: a 17-year, prospective, longitudinal follow-up in the Ryukyu Islands. Rev Infect Dis 1986;8:874-83.
Reply
REFERENCES
1. Mutch LMM, Johnson MA, Morley R. Follow-up studies: design, organisation and analysis. Arch Dis Child 1989;64:1394402. 2. International classification of diseases. 9th revision. Geneva: World Health Organization, 1970. 3. International Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Pediatrics 1984;74:127-33. 4. Evans p, Johnson A, Mutch L, Alberman E. A standard form for recording clinical findings in children with a motor deficit of central origin. Dev Med Child Neurol 1989;31:119-27.
Growth in congenital rubella syndrome
To the Editor: We thank Drs. Tokugawa and Ueda for their letter. Our populations differ in a number of ways. First, we did not observe a difference in the mean time of maternal infection between any of our three patient groups with different growth patterns (Group 1, normal growth; group 2, growth consistently less than the 5th percentile channel for height; group 3, initially relatively normal growth followed by early cessation of growth that resulted in final heights less than the 5th percentile channel). Second, we observed cataracts, unilateral or bilateral, in all of our patient groups. Specifically, in group 1, eleven had none, and six had unilateral and two bilateral cataracts. In group 2, four had none, and one had unilateral and nine bilateral cataracts. In group 3, eight had none, and 10 had unilateral and 17 bilateral cataracts. Therefore we cannot confirm Drs. Tokugawa's and Ueda's contention that children with CRS and cataracts grow poorly, whereas those without cataracts show normal catch-up growth.
Sharon E. Oberfield, MD Lenore S. Levine, MD Pediatric Service St. Luke-Roosevelt Hospital Center New York, N Y 10025
To the Editor." We read with interest the article by Chiriboga-Klein et al. entitled "Growth in Congenital Rubella Syndrome and Correlation With Clinical Manifestations" (J PEDIATR 1989; 115:251-5). However, they did not note a similar article that we pub!ished, l We compared the physical growth of our patients with congenital rubella syndrome (CRS) (in the Ryukyu Islands of Japan), grouped according to their clinical manifestations (i.e., cataract, congenital heart diseases, and deafness). Those CRS children who had cataract also had poor physical growth in both height and weight (below the - 1 SD line for standard values); the other CRS children had catch-up growth after school age. Furthermore, all CRS children had microcephaly. We did not note any correlation between mental retardation and physical growth retardation, as ChiribogaKlein et al. pointed out. We wonder whether those children with CRS who had growth consistently below the 5th percentile in the Chiriboga-Klein series were patients who have had cataract? If so, then our postulate that children supposedly exposed to maternal rubella before day 60 of gestation grew most poorly, whereas those supposedly infected af-
Jaundice with hypertrophic pyloric stenosis To the Editor: The article by Labrune et al. (J PEDIATR 1989; 115:93-5) makes a strong case for ascribing the jaundice associated with hypertrophic pyloric stenosis to an early manifestation of Gilbert syndrome, and the reduced hepatic activity of bilirubin uridine diphosphate-glucuronyl transferase seems to strengthen the argument. It would be interesting to attain a further value of this enzyme's activity at a later age (could it mature later?) and to record whether patient 2 ever has unconjugated hyperbilirubinemla in fu-
Volume 117 Number 1, Part I
E d i t o r i a l correspondence
ture years, especially in relation to caloric deprivation. Do we know whether the patients from the early reports in 1959, 1965, and 1966 manifested Gilbert syndrome in second or later decades? W h a t makes me doubt t h e amplifying role of caloric deprivation per se is the observed very prompt (often within 6 hours) reduction in serum bilirubin levels postoperatively, long before adequate calorie intake resumes. If we supply the calories for 24 hours before the pyloromyotomy, can we relieve the jaundice? The heterogenous nature of Gilbert syndrome makes one curious about other explanations in this condition as well. 1
M. M. Lippert, MMed(Paed), D T M & H University o f Pretoria and HF Verwoerd Hospital Pretoria 0002, South Africa REFERENCE
1. Gilbert's syndrome: more questions than answers [Editorial]. Lancet 1987;1:1071.
Reply To the Editor." A later maturation of bilirubin uridine diphosphate-glucuronyl transferase hepatic activity seems unlikely, according to Onishi et al.l; furthermore, attaining a further value of this enzymatic activity would require another liver biopsy, which is ethically unjustified. We do not know whether the patients previously reported manifested Gilbert syndrome later on. W e have not yet evaluated the influence of fasting on our two patients, but we will try to do so when they are older. To the best of our knowledge, no one has ever supplied calories for 24 hours before the pyloromyotomy; however, this hypothesis would certainly be interesting to investigate.
Philippe Labrune, MD Hopital Antoine Beclere 92141 Clamart, France REFERENCE
1. Onishi S, Kawade N, Itoh S, Isobe K, Sugiyama S. Postnatal development of uridine diphosphate-glucuronyl transferase activity towards bilirubin and 2-aminophenol in h u m a n liver. Biochem J 1979;184:705-7.
Thyroid function of infants born to mothers with Graves disease To the Editor: Tamaki et al (J PEDIATR 1989;115:318-21) reported a case of central hypothyroidism in an infant born to a mother with Graves disease and stated that they have found a new type of hypothyroidism in this neonate. The authors stated that "suppression of pituitary T S H [thyroid-stimulating hormone] secretion might have
169
been caused by fetal thyrotoxicosis, but the mother had no detectable TBII [thyrotropin-binding inhibitor immunoglobulin] activity and there was no obvious sign of thyrotoxicosis in utero." Since our initial report of hypopituitary hypothyroidism from fetal thyrotoxicosis, 1 we have found three infants with central hypothyroidism born to mothers with Graves disease. O n e infant manifested hypopituitary hypothyroidism after transient thyrotoxicosis. Two infants were born with hypopituitary hypothyroidism to mothers with inadequately treated Graves disease. 2 In one infant, antithyroid medication was mistakenly not started until 37 weeks of gestation despite the diagnosis of hyperthyroidism at 20 weeks of gestation. 2 In the other infant, the mother was noncompliant with antithyroid medication throughout most of pregnancy. Likewise, in all t 5 mothers with Graves disease reported by M a t s u r a et al. 3 whose infants had low thyroxine (T4), low free T4, and nonelevated T S H levels, hyperthyroidism was uncontrolled during their pregnancies. The mother of the patient reported by Tamaki et at. was not started on antithyroid medication until 27 weeks of gestation. Although there are differences among the patients described above, the similarities are striking. Most mothers have had elevated TBII activity, but some have not. 3 Some infants were known to have fetal thyrotoxicosis, 1 others were presumed to have fetal thyrotoxicosis with advanced bone age, 2 and others had no obvious signs of fetal thyrotoxicosis and no advancement of bone age. 3 However, all infants were either known to have fetal thyrotoxicosis or were born to mothers with uncontrolled hyperthyroidism (at least until late in pregnancy). In addition to finding a positive correlation between TBII and fetal thyroid hormone levels, Momotani et al. 4 found that when mothers with Graves disease were not taking antithyroid medication, the T4 values in the fetuses were virtually identical to those in their thyrotoxic mothers.Thus the authors suggested that the fetal thyroid is under the same stimulatory and inhibitory factors as the maternal thyroid and that the maternal T4 level is a useful index of fetal thyroid status. Animal studies have shown that if fetuses are briefly exposed to elevated thyroid hormone levels during a critical stage in development, prolonged hypopituitary hypothyroidism will result. We hypothesize that infants born to mothers with uncontrolled thyrotoxicosis m a y be exposed to high thyroid hormone levels during fetal life. This exposure, even if not prolonged or severe, may lead to central hypothyroidism. The absence of TBII activity in the mothers of some infants and the absence of obvious signs of fetal thyrotoxicosis in many others do not negate this hypothesis. TBII is not an ideal test to determine fetal thyroid activity, and obvious signs of fetal thyrotoxicosis (tachycardia and advanced bone age) m a y not be present, especially if the mother is started on antithyroid medication late in pregnancy. Although the patient described by Tamaki et al. was not overtly hyperthyroid during fetal life, mild transient thyrotoxicosis cannot be ruled out. We believe that fetal thyrotoxicosis is the most likely explanation for the development of central hypothyroidism in this infant as well as those described by Matsura et al. 3 More important, infants with fetal thyrotoxicosis and those born to mothers
Editorial correspondence
Such a conference would be of obvious interest to workers in this field, but we believe also that its findings could be a guide for editors of journals and their referees. We would welcome wider collaboration.
The Journal of Pediatrics July 1990
ter day 60 of gestation began to return to a normal growth pattern, would be supported.
Ken Tokugawa, MD Kohji Ueda, MD Department of Pediatrics, Faculty of Medicine Kyushu University 3-1-1, Maidashi, Higashi-ku, Fukuoka 812, Japan
Lesley Mutch, MD Social Paediatric and Obstetric Research Unit University of Glasgow Glasgow, Scotland
REFERENCE
M. Ann Johnson, MD Oxford Region Child Development Project John Radcliffe Hospital Oxford, England Ruth Morley, MB,BChir Medical Research Council, Dunn Nutrition Unit Cambridge, England
1. Tokugawa K, Ueda K, Fukushige J, Koyanagi T, Hisanaga S. Congenital rubella syndrome and physical growth: a 17-year, prospective, longitudinal follow-up in the Ryukyu Islands. Rev Infect Dis 1986;8:874-83.
Reply
REFERENCES
1. Mutch LMM, Johnson MA, Morley R. Follow-up studies: design, organisation and analysis. Arch Dis Child 1989;64:1394402. 2. International classification of diseases. 9th revision. Geneva: World Health Organization, 1970. 3. International Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Pediatrics 1984;74:127-33. 4. Evans p, Johnson A, Mutch L, Alberman E. A standard form for recording clinical findings in children with a motor deficit of central origin. Dev Med Child Neurol 1989;31:119-27.
Growth in congenital rubella syndrome
To the Editor: We thank Drs. Tokugawa and Ueda for their letter. Our populations differ in a number of ways. First, we did not observe a difference in the mean time of maternal infection between any of our three patient groups with different growth patterns (Group 1, normal growth; group 2, growth consistently less than the 5th percentile channel for height; group 3, initially relatively normal growth followed by early cessation of growth that resulted in final heights less than the 5th percentile channel). Second, we observed cataracts, unilateral or bilateral, in all of our patient groups. Specifically, in group 1, eleven had none, and six had unilateral and two bilateral cataracts. In group 2, four had none, and one had unilateral and nine bilateral cataracts. In group 3, eight had none, and 10 had unilateral and 17 bilateral cataracts. Therefore we cannot confirm Drs. Tokugawa's and Ueda's contention that children with CRS and cataracts grow poorly, whereas those without cataracts show normal catch-up growth.
Sharon E. Oberfield, MD Lenore S. Levine, MD Pediatric Service St. Luke-Roosevelt Hospital Center New York, N Y 10025
To the Editor." We read with interest the article by Chiriboga-Klein et al. entitled "Growth in Congenital Rubella Syndrome and Correlation With Clinical Manifestations" (J PEDIATR 1989; 115:251-5). However, they did not note a similar article that we pub!ished, l We compared the physical growth of our patients with congenital rubella syndrome (CRS) (in the Ryukyu Islands of Japan), grouped according to their clinical manifestations (i.e., cataract, congenital heart diseases, and deafness). Those CRS children who had cataract also had poor physical growth in both height and weight (below the - 1 SD line for standard values); the other CRS children had catch-up growth after school age. Furthermore, all CRS children had microcephaly. We did not note any correlation between mental retardation and physical growth retardation, as ChiribogaKlein et al. pointed out. We wonder whether those children with CRS who had growth consistently below the 5th percentile in the Chiriboga-Klein series were patients who have had cataract? If so, then our postulate that children supposedly exposed to maternal rubella before day 60 of gestation grew most poorly, whereas those supposedly infected af-
Jaundice with hypertrophic pyloric stenosis To the Editor: The article by Labrune et al. (J PEDIATR 1989; 115:93-5) makes a strong case for ascribing the jaundice associated with hypertrophic pyloric stenosis to an early manifestation of Gilbert syndrome, and the reduced hepatic activity of bilirubin uridine diphosphate-glucuronyl transferase seems to strengthen the argument. It would be interesting to attain a further value of this enzyme's activity at a later age (could it mature later?) and to record whether patient 2 ever has unconjugated hyperbilirubinemla in fu-
Volume 117 Number 1, Part I
E d i t o r i a l correspondence
ture years, especially in relation to caloric deprivation. Do we know whether the patients from the early reports in 1959, 1965, and 1966 manifested Gilbert syndrome in second or later decades? W h a t makes me doubt t h e amplifying role of caloric deprivation per se is the observed very prompt (often within 6 hours) reduction in serum bilirubin levels postoperatively, long before adequate calorie intake resumes. If we supply the calories for 24 hours before the pyloromyotomy, can we relieve the jaundice? The heterogenous nature of Gilbert syndrome makes one curious about other explanations in this condition as well. 1
M. M. Lippert, MMed(Paed), D T M & H University o f Pretoria and HF Verwoerd Hospital Pretoria 0002, South Africa REFERENCE
1. Gilbert's syndrome: more questions than answers [Editorial]. Lancet 1987;1:1071.
Reply To the Editor." A later maturation of bilirubin uridine diphosphate-glucuronyl transferase hepatic activity seems unlikely, according to Onishi et al.l; furthermore, attaining a further value of this enzymatic activity would require another liver biopsy, which is ethically unjustified. We do not know whether the patients previously reported manifested Gilbert syndrome later on. W e have not yet evaluated the influence of fasting on our two patients, but we will try to do so when they are older. To the best of our knowledge, no one has ever supplied calories for 24 hours before the pyloromyotomy; however, this hypothesis would certainly be interesting to investigate.
Philippe Labrune, MD Hopital Antoine Beclere 92141 Clamart, France REFERENCE
1. Onishi S, Kawade N, Itoh S, Isobe K, Sugiyama S. Postnatal development of uridine diphosphate-glucuronyl transferase activity towards bilirubin and 2-aminophenol in h u m a n liver. Biochem J 1979;184:705-7.
Thyroid function of infants born to mothers with Graves disease To the Editor: Tamaki et al (J PEDIATR 1989;115:318-21) reported a case of central hypothyroidism in an infant born to a mother with Graves disease and stated that they have found a new type of hypothyroidism in this neonate. The authors stated that "suppression of pituitary T S H [thyroid-stimulating hormone] secretion might have
169
been caused by fetal thyrotoxicosis, but the mother had no detectable TBII [thyrotropin-binding inhibitor immunoglobulin] activity and there was no obvious sign of thyrotoxicosis in utero." Since our initial report of hypopituitary hypothyroidism from fetal thyrotoxicosis, 1 we have found three infants with central hypothyroidism born to mothers with Graves disease. O n e infant manifested hypopituitary hypothyroidism after transient thyrotoxicosis. Two infants were born with hypopituitary hypothyroidism to mothers with inadequately treated Graves disease. 2 In one infant, antithyroid medication was mistakenly not started until 37 weeks of gestation despite the diagnosis of hyperthyroidism at 20 weeks of gestation. 2 In the other infant, the mother was noncompliant with antithyroid medication throughout most of pregnancy. Likewise, in all t 5 mothers with Graves disease reported by M a t s u r a et al. 3 whose infants had low thyroxine (T4), low free T4, and nonelevated T S H levels, hyperthyroidism was uncontrolled during their pregnancies. The mother of the patient reported by Tamaki et at. was not started on antithyroid medication until 27 weeks of gestation. Although there are differences among the patients described above, the similarities are striking. Most mothers have had elevated TBII activity, but some have not. 3 Some infants were known to have fetal thyrotoxicosis, 1 others were presumed to have fetal thyrotoxicosis with advanced bone age, 2 and others had no obvious signs of fetal thyrotoxicosis and no advancement of bone age. 3 However, all infants were either known to have fetal thyrotoxicosis or were born to mothers with uncontrolled hyperthyroidism (at least until late in pregnancy). In addition to finding a positive correlation between TBII and fetal thyroid hormone levels, Momotani et al. 4 found that when mothers with Graves disease were not taking antithyroid medication, the T4 values in the fetuses were virtually identical to those in their thyrotoxic mothers.Thus the authors suggested that the fetal thyroid is under the same stimulatory and inhibitory factors as the maternal thyroid and that the maternal T4 level is a useful index of fetal thyroid status. Animal studies have shown that if fetuses are briefly exposed to elevated thyroid hormone levels during a critical stage in development, prolonged hypopituitary hypothyroidism will result. We hypothesize that infants born to mothers with uncontrolled thyrotoxicosis m a y be exposed to high thyroid hormone levels during fetal life. This exposure, even if not prolonged or severe, may lead to central hypothyroidism. The absence of TBII activity in the mothers of some infants and the absence of obvious signs of fetal thyrotoxicosis in many others do not negate this hypothesis. TBII is not an ideal test to determine fetal thyroid activity, and obvious signs of fetal thyrotoxicosis (tachycardia and advanced bone age) m a y not be present, especially if the mother is started on antithyroid medication late in pregnancy. Although the patient described by Tamaki et al. was not overtly hyperthyroid during fetal life, mild transient thyrotoxicosis cannot be ruled out. We believe that fetal thyrotoxicosis is the most likely explanation for the development of central hypothyroidism in this infant as well as those described by Matsura et al. 3 More important, infants with fetal thyrotoxicosis and those born to mothers