Eur J Pediatr (1990) 149 : 605-607
European Journal of
Pediatrics
9 Springer-Verlag1990
Screening for congenital hypothyroidism in France Misdiagnosed cases: collaborative study of screening centres in France J.Leger Association Fran~aise pour le D6pistage et la Prdvention des Maladies M6taboliques et des Handicaps de l'Enfant, Centre National de Pr6vention Prdnatale, H6tel Dieu, 1, Place de l'H6pital, F-69002 Lyon, France Received April 26, 1988 / Accepted January 10, 1989
Abstract. Misdiagnosed cases of congenital-hypothyroidism (CH) during the first 9 years of the French screening p r o g r a m were analysed. A total of 50 cases were missed (3% of total diagnosed) which represents a severe failure of the system. Failures were caused by technical errors of sample collection or T S H assay (n = 27) or due to normal T S H (n = 22) or T4 (n = 1) concentrations in the newborn blood specimens. We conclude that screening methods should be improved and that physicians should remain alert to clinical signs of hypothyroidism. Key words: Congenital hypothyroidism - Screening errors - Thyrotropin
Screening for congenital hypothyroidism (CH) first began in France in 1978 and covers the whole country. The system is very efficient, with a recovery rate of almost 100%. The screening for C H in France is based on the measurement of T S H in blood samples collected on filter p a p e r during the first 3 - 5 days of life. (Total thyroxine (T4) concentrations were measured in 2 laboratories during the first few months of the screening program.) The policy for recalling infants at risk is as follows: infants with filter p a p e r T S H (FP-TSH) levels below 30 g U / m l are considered normal. Children with values between 30 and 50 ~tU/ml are considered at risk for C H and a second test is requested. Each child with a F P - T S H result > 50 g U / m l is seen by a paediatrician for clinical and laboratory thyroid investigations. The present report concerns those hypothyroid children who were not diagnosed by the screening network during the period 19781987. They represent a severe failure of the system and analysis of the cause should help to improve screening. Offprint requests to: J. Leger, H6pital Robert Debr6, 48, Boulevard Serurier, F-75019 Paris, France Abbreviations: CH = congenital hypothyroidism; FP-TSH =
filter paper TSH; TSH = thyroid stimulating hormone
Materials and methods A total of 6, 893, 941 neonates were screened for CH between 1978 and 1987. We detected 1724 cases of hypothyroidism. The incidence of the disorder was therefore 1/4000, a figure similar to that of other European Centres [1]. False-negative cases are defined by a failure to detect CH by systematic screening, even if a diagnosis has been made early (before 3 weeks of life) by other means. Cases of central hypothyroidism were excluded as they cannot be diagnosed by the screening method employed. This study is based on the annual questionnaire distributed by the Association Frangaise pour le D6pistage et la Pr6vention des Maladies M6taboliques de l'Enfant (A.F.D.M.M.E.) to hospital paediatricians throughout France to ensure collection of all falsenegative cases. The results have been presented annually in several meetings in France in an attempt to ensure continued co-operation. The first part of this work covering the period 1979-1983 has been published [6].
Results As shown in Table 1, a total of 50 false-negative cases were found between 1978 and 1987. During this period 1724 C H cases were correctly diagnosed. False-negative cases represent 3% of all C H cases diagnosed. This is equivalent to one false-negative case per 118,000 tests. The patients are divided into 2 groups according to the causes of the false-negative results. The patients in group I were missed because of technical errors during the collection of filter p a p e r samples or in the T S H assay. The patients in group II were false-negative cases who had normal F P - T S H at screening. The causes of misdiagnosis are shown in Table 1. There was a technical error in 27 cases, either in the collection of the filter p a p e r (n = 15) or in laboratory testing (n = 12). T h e r e were several types of laboratory errors, the most frequent being a misreading of the correct value on the counter sheet. The second major cause of misdiagnosis was a normal F P - T S H (or T4 in one case) value on screening. The clinical data for these 23 cases are given in Table 2. There were 4 cases of athyreosis, 11 of ectopic gland and 7 of entopic gland. One case was not classified. The original filter p a p e r had b e e n found and measured a second time
606 1. Causes of misdiagnosis
Table
Technical errors: n = 27 (54% of the false negative cases)
Table
Cases
2. Clinical data of the 23 cases Aetiology
FP-TSH normal at birth (n = 23) Age at TSH diagnosis (plasma) (months) (gU/ml)
Errors in blood sampling or in forwarding to the laboratory (n = 15): Blood specimen not obtained (n = 5) infants hospitalized as neonates (n = 4) infants leaving the maternity hospital before the age of 5 days
1 2 3 4
Athyreosis Athyreosis Athyreosis Athyreosis
3.5 3.5 23 40
5a 6a 7a 8 9 10 11 12 13 14 15
Ectopic gland Ectopic gland Ectopic gland Ectopic gland Ectopie gland Ectopic gland Ectopic gland Ectopic gland Ectopic gland Ectopic gland Ectopic gland
2 42 18 12 0.75 20 15 2.5 23 17 10
11 130 140 200 200 442 > 50 > 130 999
16a 17a 18 19 20 21 22
Eutopic gland Eutopic gland Eutopic gland Eutopic gland Eutopic gland Eutopic gland Eutopic gland
2 2 2 10 0.2 10 62
160 96 83 22 22 > 50
23
Unclassified
-
(n = l )
Blood specimen lost (n = 10) taken but not sent to the laboratory (n = 4) taken, sent, but never arrived at the laboratory (n = 3) taken and sent after 3 weeks of life (n = 2) - names switched on 2 blood specimens from 2 children who were born in the same maternity ward (n = 1) -
Errors in the laboratory (n = 12) - reading errors (n = 6) - retranscription error (n = 1) - assay error: 2 FP-TSH samples assayed in the same tube
(~ =
1)
abnormal first assay, normal retest (n = 3) - unknown (n = 1)
200 130 60 200
T4 (plasma) (gg/ml)
1 1 0.2 FT4 = 4pmol/1 11 3.5 1 6 6.2 6.9
European Journal of
Pediatrics
9 Springer-Verlag1990
Screening for congenital hypothyroidism in France Misdiagnosed cases: collaborative study of screening centres in France J.Leger Association Fran~aise pour le D6pistage et la Prdvention des Maladies M6taboliques et des Handicaps de l'Enfant, Centre National de Pr6vention Prdnatale, H6tel Dieu, 1, Place de l'H6pital, F-69002 Lyon, France Received April 26, 1988 / Accepted January 10, 1989
Abstract. Misdiagnosed cases of congenital-hypothyroidism (CH) during the first 9 years of the French screening p r o g r a m were analysed. A total of 50 cases were missed (3% of total diagnosed) which represents a severe failure of the system. Failures were caused by technical errors of sample collection or T S H assay (n = 27) or due to normal T S H (n = 22) or T4 (n = 1) concentrations in the newborn blood specimens. We conclude that screening methods should be improved and that physicians should remain alert to clinical signs of hypothyroidism. Key words: Congenital hypothyroidism - Screening errors - Thyrotropin
Screening for congenital hypothyroidism (CH) first began in France in 1978 and covers the whole country. The system is very efficient, with a recovery rate of almost 100%. The screening for C H in France is based on the measurement of T S H in blood samples collected on filter p a p e r during the first 3 - 5 days of life. (Total thyroxine (T4) concentrations were measured in 2 laboratories during the first few months of the screening program.) The policy for recalling infants at risk is as follows: infants with filter p a p e r T S H (FP-TSH) levels below 30 g U / m l are considered normal. Children with values between 30 and 50 ~tU/ml are considered at risk for C H and a second test is requested. Each child with a F P - T S H result > 50 g U / m l is seen by a paediatrician for clinical and laboratory thyroid investigations. The present report concerns those hypothyroid children who were not diagnosed by the screening network during the period 19781987. They represent a severe failure of the system and analysis of the cause should help to improve screening. Offprint requests to: J. Leger, H6pital Robert Debr6, 48, Boulevard Serurier, F-75019 Paris, France Abbreviations: CH = congenital hypothyroidism; FP-TSH =
filter paper TSH; TSH = thyroid stimulating hormone
Materials and methods A total of 6, 893, 941 neonates were screened for CH between 1978 and 1987. We detected 1724 cases of hypothyroidism. The incidence of the disorder was therefore 1/4000, a figure similar to that of other European Centres [1]. False-negative cases are defined by a failure to detect CH by systematic screening, even if a diagnosis has been made early (before 3 weeks of life) by other means. Cases of central hypothyroidism were excluded as they cannot be diagnosed by the screening method employed. This study is based on the annual questionnaire distributed by the Association Frangaise pour le D6pistage et la Pr6vention des Maladies M6taboliques de l'Enfant (A.F.D.M.M.E.) to hospital paediatricians throughout France to ensure collection of all falsenegative cases. The results have been presented annually in several meetings in France in an attempt to ensure continued co-operation. The first part of this work covering the period 1979-1983 has been published [6].
Results As shown in Table 1, a total of 50 false-negative cases were found between 1978 and 1987. During this period 1724 C H cases were correctly diagnosed. False-negative cases represent 3% of all C H cases diagnosed. This is equivalent to one false-negative case per 118,000 tests. The patients are divided into 2 groups according to the causes of the false-negative results. The patients in group I were missed because of technical errors during the collection of filter p a p e r samples or in the T S H assay. The patients in group II were false-negative cases who had normal F P - T S H at screening. The causes of misdiagnosis are shown in Table 1. There was a technical error in 27 cases, either in the collection of the filter p a p e r (n = 15) or in laboratory testing (n = 12). T h e r e were several types of laboratory errors, the most frequent being a misreading of the correct value on the counter sheet. The second major cause of misdiagnosis was a normal F P - T S H (or T4 in one case) value on screening. The clinical data for these 23 cases are given in Table 2. There were 4 cases of athyreosis, 11 of ectopic gland and 7 of entopic gland. One case was not classified. The original filter p a p e r had b e e n found and measured a second time
606 1. Causes of misdiagnosis
Table
Technical errors: n = 27 (54% of the false negative cases)
Table
Cases
2. Clinical data of the 23 cases Aetiology
FP-TSH normal at birth (n = 23) Age at TSH diagnosis (plasma) (months) (gU/ml)
Errors in blood sampling or in forwarding to the laboratory (n = 15): Blood specimen not obtained (n = 5) infants hospitalized as neonates (n = 4) infants leaving the maternity hospital before the age of 5 days
1 2 3 4
Athyreosis Athyreosis Athyreosis Athyreosis
3.5 3.5 23 40
5a 6a 7a 8 9 10 11 12 13 14 15
Ectopic gland Ectopic gland Ectopic gland Ectopic gland Ectopie gland Ectopic gland Ectopic gland Ectopic gland Ectopic gland Ectopic gland Ectopic gland
2 42 18 12 0.75 20 15 2.5 23 17 10
11 130 140 200 200 442 > 50 > 130 999
16a 17a 18 19 20 21 22
Eutopic gland Eutopic gland Eutopic gland Eutopic gland Eutopic gland Eutopic gland Eutopic gland
2 2 2 10 0.2 10 62
160 96 83 22 22 > 50
23
Unclassified
-
(n = l )
Blood specimen lost (n = 10) taken but not sent to the laboratory (n = 4) taken, sent, but never arrived at the laboratory (n = 3) taken and sent after 3 weeks of life (n = 2) - names switched on 2 blood specimens from 2 children who were born in the same maternity ward (n = 1) -
Errors in the laboratory (n = 12) - reading errors (n = 6) - retranscription error (n = 1) - assay error: 2 FP-TSH samples assayed in the same tube
(~ =
1)
abnormal first assay, normal retest (n = 3) - unknown (n = 1)
200 130 60 200
T4 (plasma) (gg/ml)
1 1 0.2 FT4 = 4pmol/1 11 3.5 1 6 6.2 6.9
