School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement

OBJECTIVE—To determine the feasibility of annual hypothyroid screening of children with Down''s syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children.DESIGN—Establishment of a register of school children with Down''s syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre.SUBJECTS—All school age children with Down''s syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8.RESULTS—200 of 214 school children with Down''s syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto''s thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is ? 8.9%.CONCLUSION—Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down''s syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

Thyroid dysfunction in Down's syndrome and screening for hypothyroidism in children and adolescents using capillary TSH measurement

Thyroid dysfunction is more common in individuals with Down's syndrome (DS) than in the general population, whose clinical features can mask the presenting signs and symptoms of hypothyroidism. Biochemical screening is necessary; however, venepuncture may be difficult. AIMS: To assess the prevalence of thyroid dysfunction in children and adolescents with DS and the feasibility of screening for hypothyroidism using capillary dried blood spot thyroid stimulating hormone (TSH) from infancy. METHODS: 394 children (217 boys, 177 girls) were clinically assessed for thyroid dysfunction and 305 children (aged 4 months to 18.9 years) were screened for hypothyroidism by capillary whole blood TSH sample. RESULTS: Thyroid dysfunction was detected in 4.6%, with 50% unscreened since neonatal screening. Parents reported minimal distress by fingerprick screening. CONCLUSION: DS is associated with an increased prevalence of thyroid dysfunction, particularly in preschool children. Biochemical screening is essential and capillary whole blood TSH sampling for hypothyroidism is feasible, less invasive and acceptable.     

Analysis of failures of screening for congenital hypothyroidism by the assay of TSH in capillary blood

Screening for congenital hypothyroidism was started in France in 1979. The system was rapidly extended to the whole country and works very efficiently. The number of children who escaped the system is very small. However, these children represent a severe failure of the system. From 1980 to 1983, 32 cases escaped the screening. Retrospective analysis of these cases should help in improving the present system.     

Umbilical cord blood TSH levels in term neonates: a screening tool for congenital hypothyroidism

This study was conducted to find normative values for thyroid stimulating hormone (TSH) in 1200 cord blood samples of term babies whose mothers were not on any thyroid medications. TSH was estimated within 24 hrs by enzyme immunoassay. A full thyroid profile, viz, T3, T4, TSH, fT3 and fT4 was done at 7-10 days of age in all babies with cord TSH >20 mIU/L. The mean, median and standard deviation for the TSH values for the cohort were 6.13 mIU/L, 5.8 mIU/L and 4.523 respectively. 22 babies with TSH values >20 mIU/L were given repeat tests. Hypothyroidism was confirmed in two of these babies. We conclude that a cut off value of TSH >20 mIU/L is adequate for neonatal thyroid screening in Indian settings.     

Maternal TSH-receptor antibodies and TSH antibodies in screening for congenital hypothyroidism

Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyperthyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.     

Neonatal screening for cystic fibrosis by dried blood spot trypsin assay. Results in 47 127 newborn infants from a homogeneous population

47 127 newborn infants from the Emilia-Romagna region were screened for cystic fibrosis by dried blood spot trypsin assay. In the initial 12 099 subjects screened with a non-standardized method, two children with cystic fibrosis were observed. Of the remaining 35 028 newborn infants, 299 showed high immunoreactive trypsin values; retesting revealed persistent elevation in 11. Sweat testing confirmed cystic fibrosis in 6 subjects and was normal in 5. Clinical monitoring of these 5 children has, as yet, shown no pathological signs. No false-negative test results have yet been identified. In our region, cystic fibrosis frequency would appear to be 1 case every 5 890 newborn infants. Our study confirms that elevated immunoreactive trypsin is characteristic of newborn infants with cystic fibrosis and that screening by determination of immunoreactive trypsin is of great benefit since it allows early diagnosis and a rational approach to therapy.     

Early detection of neonatal hypothyroidism by serial TSH determination in dried blood. Six months experience with a reliable, efficient and inexpensive method

Mass newborn screening for primary hypothyroidism was introduced in Switzerland on January 1st, 1977, using a radioimmunoassay of TSH in dried blood spotted on filter paper. After incubation for 38 h at 20 degrees C, bound and free TSH is separated by double antibody precipitation. The filter paper discs of 6.5 mm diameter remain in the test tubes. At present, one TSH determination costs approx. SFr. 4.40. All reagents used are commercially available and their costs amount to not more than 15% of the total expenses. During the first 8 months of 1977, of 21862 newborns tested routinely on day 5 (together with the Guthrie-test), 7 infants with primary hypothyroidism were discovered owing to blood TSH values of greater than 100 muU/ml. Diagnosis was not recognized clinically although all of the infants showed some symptoms. Thyroxin therapy was started within the second week of life. The incidence of about 1 in 3000 newborns is higher than reported so far. It has to be shown whether this is due to genetic or geographic factors, to the occurrence of transitory forms, or to a higher efficiency of screening by the TSH (versus T4) assay.     

Raised serum TSH in hypothyroidism.

It is desirable to detect early hypothyroidism of the mildest degree even before conventional tests of thyroid function become abnormal. Serum TSH levels (normal: undetectable to 4 muU/ml) rise in patients with mild hypothyroidism long before serum T4 and T3 levels fall. In the patient described the serum TSH level was 310 muU/ml, while other tests of thyroid function gave normal results. After treatment with thyroxine, serum TSH returned to normal. It should now be accepted that patients with mild hypothyroidism have a raised serum TSH and that thyroid insufficiency can be confidently excluded if the serum TSH concentration is normal. It is thus important to assay serum TSH when suspicion of hypothyroidism is aroused.