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• THE TSH THRESHOLD IN NEONATAL SCREENING FOR CONGENITAL HYPOTHYROIDISM: A VARIABLE SOLUTION
  Jose Ramon Alonso-Fernandez
  Published on: 22 March 2016
• The TSH Threshold in Neonatal Screening for Congenital Hipothyroidism: a Variable Solution
  Jose Ramon Alonso-Fernandez
  Published on: 22 March 2016

• Published on: 22 March 2016

  THE TSH THRESHOLD IN NEONATAL SCREENING FOR CONGENITAL HYPOTHYROIDISM: A VARIABLE SOLUTION

  • Jose Ramon Alonso-Fernandez, Jefe de Seccion

  Dear Editor: In their paper on the TSH threshold in neonatal screening for congenital hypothyroidism (CH), Korada et al. (1) conclude that a threshold of 6 mIU/L for DELFIA-measured TSH in samples collected between days 5 and 8 may be preferable to the 10 mIU/L recommended by the UK Newborn Screening Programme Centre. Our laboratory instituted DELFIA measurements of TSH in 5-8-day paper-borne heelprick samples in 1985. S...

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  Dear Editor: In their paper on the TSH threshold in neonatal screening for congenital hypothyroidism (CH), Korada et al. (1) conclude that a threshold of 6 mIU/L for DELFIA-measured TSH in samples collected between days 5 and 8 may be preferable to the 10 mIU/L recommended by the UK Newborn Screening Programme Centre. Our laboratory instituted DELFIA measurements of TSH in 5-8-day paper-borne heelprick samples in 1985. Since 1998 we have used an accelerated AutoDELFIA(R) method - fully endorsed by the results of external quality control services (DGKL, NEQAS, AECNE) - that takes about 2 h and thus allows follow-up samples to be called for, if necessary, on the same day as the first sample is analysed. Since 2003, heelprick has been performed on day 3 in response to the desire of paediatric endocrinologists to begin the treatment of CH patients as early as possible, even though the typical physiological TSH peak on day 2 reduces the efficiency of screening thresholds; Table 1 summarizes the distribution of TSH levels in the 102,789 newborns screened during this period.

  Having observed significant between-lot variation in TSH assay kits, since November 2004 we recalculate our TSH threshold for every run in the light of two factors: a) the dispersion of the calibration data in the vicinity of 10 mIU/L; and b) measurements of certified control samples with concentrations close to 10 mIU/L that are supplied by Perkin Elmer and, within its Newborn Screening Quality Assurance Program, by the CDC. Defining CV10 as the coefficient of variation of two replicate fluorescence measurements of the calibration standard nearest to 10 mIU/L, expressed as a percentage, factor (a) is assigned the value zero if CV10 < 10, and the value 0.1 x CV10 otherwise. The control samples (C1 and C2, of certified concentrations c1 and c2, respectively) are each measured once; in each case a parameter bi (i = 1,2) is assigned the value zero if the measured value mi is greater than 90% of the certified value, or the value 10 x (ci - mi)/ci otherwise; and the value of factor (b) is defined as the greater of b1 and b2. Finally, the TSH threshold is defined as (10 - x) mIU/L, where x is the larger of factors (a) and (b). This entirely empirical algorithm is displayed in flow-chart form in Fig. 1.

  In the 1171 runs in which the above procedure has been followed, the threshold so determined was > 9 mIU/L in 54.7%, 8-9 mIU/L in 35.3%, 7-8 mIU/L in 8.5%, and < 7 mIU/L in 1.5%. Of the 62 cases of CH that we have detected in this time, three (all with adequate weight at birth) had first-sample TSH levels lower than 10 mIU/L (see Table 2 for details). In paper-borne heelprick blood samples. b In blood samples obtained by venous puncture.

  Cristobal Colon and Jose Ramon Alonso-Fernandez. Metabolopathy Laboratory, Departament of Paediatrics, Clinical Hospital and Universiy of Santiago de Compostela (Spain).

  References

  1) KORADA SM, PEARCE M, PLATT MPW, AVIS E, TURNER S, WASTEL H, CHEETHAM T. Dificulties in selecting an appropriate Neonatal TSH screening threshold. Arch Dis Child (Online First), 12 Aug 2009.

  2) ALONSO-FERNANDEZ JR. V Reunion Nacional de la Sociedad Espanola de Quimica Clinica. Santiago de Compostela 28 y 29 de abril de 1985.

  3) POMBO M, ALONSO-FERNANDEZ JR, BRAVO M, FRAGA JM, PEnA J. Diagnostico Precoz del Hipotiroidismo Congenito y de la deficiencia de Hormona del Crecimiento. An Esp Ped. 1987;27(sup.28):44-47.

  4) COLON C, ALONSO-FERNANDEZ JR. Depistage de L'Hipothiroidie neonatal avec un inmuno-essai marque a l'Europeum. Etude comparative de curbes de calibrage. Proceedings of "Reunion Europeene sur le Depistage Neonatal en 1986. Evian (France). 28-30 de abril de 1986.

  5) ALONSO-FERNANDEZ JR, COLON C, FRAGA JM. Neonatal Screening of Hipotiroidism: A comparative study of RIA Technique and the Non Isotopic Inmunoessay DELFIA System. In BL Therrel; Advances in Neonatal Screening pp 163-164 (1987). Excerpta Medica.

  6) COLON C, ALONSO-FERNANDEZ JR, CASTInEIRAS DE, ROMERO ME, FRAGA JM, PEnA J. Posible Causes of Bordeline TSH: a Summary of our experrience. In F Delange, DA Ficher, D Glinder; Research in congenital Hypothyroidism, pp 316, 1989. Plenum Press.

  7) COLON C.Epidemiological study of thyroid stimulating hormone (TSH) levels in the Galician neonatal population (Estudio epidemiologico de los niveles de hormona estimuladora del tiroides (TSH) en la poblacion neonatal gallega). Microfiche ISBN 13: 978-84-8121-340-9. ISBN 10:84-8121- 340-3. Ed. Universidade de Santiago de Compostela. 1995.

  8) ALONSO-FERNANDEZ JR, CASTInEIRAS DE, CASTInEIRAS C, VILLAR P. Determinacion de TSH Neonatal con el metodo DELFIA reduciendo a dos horas el periodo de Elucion-Incubacion, concentrando el trazador y el analito. Immunoensayo 97. La Habana (Cuba) 14-18 de septiembre de 1997.

  Post date

  In 1985 (2, 3) we propound the adaptation of DELFIA test for seric TSH measurement to the newborn screening sample (DBS). Once (actually) Perkin-Elmer marketed the neonatal screening TSH test, we suggested a calibrate modification, increasing from 3 to 5 points and using the interpolation with logarithmic spline instead linear regression such as made in the procedure for seric and neonatal screening TSH determination (4). It is compared with the RIA test using until then (5). In 1988 we discussed the causes of borderline results (6), one of the main reasons for recall sample. In the PhD thesis of one of us (C. Colon) in 1995 (7), we could verify that the gestational age, the birth weight, and the age of analysis, influence on the TSH values. Also was found the thyroid function alteration due to antiseptic iodine use (effect Wolff-Chaikoff).

  In 1997 we presented (8) a new DELFIA test for neonatal TSH modification; reducing until 2 hours the elution-incubation time, using half buffer volume in the preparation of tracer solution and reducing to 100 microlitres the volume of this solution dispensed in the microtiter plate wells containing the DBS disc. In the next year, using the AutoDELFIA, we introduced another modification, increasing to double the content of second antibody-tracer in the immunochemistry reaction mixture, in this mixture the analyte concentration result is multiplied for 2 and Europium-labelled antibody for 4.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  The TSH Threshold in Neonatal Screening for Congenital Hipothyroidism: a Variable Solution

  • Jose Ramon Alonso-Fernandez, Jefe de Seccion
  • Other Contributors:
    • Cristobal Colon

  THE TSH THRESHOLD IN NEONATAL SCREENING FOR CONGENITAL HYPOTHYROIDISM: A VARIABLE SOLUTION

  Dear Editor:

  In their paper on the TSH threshold in neonatal screening for congenital hypothyroidism (CH), Korada et al. (1) conclude that a threshold of 6 mIU/L for DELFIA-measured TSH in samples collected between days 5 and 8 may be preferable to the 10 mIU/L recommended by the UK Newborn Screening Programme C...

  Show More

  THE TSH THRESHOLD IN NEONATAL SCREENING FOR CONGENITAL HYPOTHYROIDISM: A VARIABLE SOLUTION

  Dear Editor:

  In their paper on the TSH threshold in neonatal screening for congenital hypothyroidism (CH), Korada et al. (1) conclude that a threshold of 6 mIU/L for DELFIA-measured TSH in samples collected between days 5 and 8 may be preferable to the 10 mIU/L recommended by the UK Newborn Screening Programme Centre. Our laboratory instituted DELFIA measurements of TSH in 5-8—day paper-borne heelprick samples in 1985. Since 1998 we have used an accelerated AutoDELFIA(R); method – fully endorsed by the results of external quality control services (DGKL, NEQAS, AECNE) – that takes about 2 h and thus allows follow-up samples to be called for, if necessary, on the same day as the first sample is analysed. Since 2003, heelprick has been performed on day 3 in response to the desire of paediatric endocrinologists to begin the treatment of CH patients as early as possible, even though the typical physiological TSH peak on day 2 reduces the efficiency of screening thresholds; Table 1 summarizes the distribution of TSH levels in the 102,789 newborns screened during this period.

  Having observed significant between-lot variation in TSH assay kits, since November 2004 we recalculate our TSH threshold for every run in the light of two factors: a) the dispersion of the calibration data in the vicinity of 10 mIU/L; and b) measurements of certified control samples with concentrations close to 10 mIU/L that are supplied by Perkin Elmer and, within its Newborn Screening Quality Assurance Program, by the CDC. Defining CV10 as the coefficient of variation of two replicate fluorescence measurements of the calibration standard nearest to 10 mIU/L, expressed as a percentage, factor (a) is assigned the value zero if CV10 < 10, and the value 0.1 x CV10 otherwise. The control samples (C1 and C2, of certified concentrations c1 and c2, respectively) are each measured once; in each case a parameter bi (i = 1,2) is assigned the value zero if the measured value mi is greater than 90% of the certified value, or the value 10 x (ci – mi)/ci otherwise; and the value of factor (b) is defined as the greater of b1 and b2. Finally, the TSH threshold is defined as (10 – j) mIU/L, where j is the larger of factors (a) and (b). This entirely empirical algorithm is displayed in flow-chart form in Fig. 1. In the 1171 runs in which the above procedure has been followed, the threshold so determined was > 9 mIU/L in 54.7%, 8 9 mIU/L in 35.3%, 7-8 mIU/L in 8.5%, and < 7 mIU/L in 1.5%. Of the 62 cases of CH that we have detected in this time, three (all with adequate weight at birth) had first-sample TSH levels lower than 10 mIU/L (see Table 2 for details).

  Cristobal Colon and Jose Ramon Alonso-Fernandez. Metabolopathy Laboratory, Departament of Paediatrics, Clinical Hospital and Universiy of Santiago de Compostela (Spain).

  References 1) KORADA SM, PEARCE M, PLATT MPW, AVIS E, TURNER S, WASTEL H, CHEETHAM T. Dificulties in selecting an appropriate Neonatal TSH screening threshold. Arch Dis Child (Online First), 12 Aug 2009. 2) ALONSO-FERNANDEZ JR. V Reunion Nacional de la Sociedad Española de Química Clínica. Santiago de Compostela 28 y 29 de abril de 1985. 3) POMBO M, ALONSO-FERNANDEZ JR, BRAVO M, FRAGA JM, PEÑA J. Diagnostico Precoz del Hipotiroidismo Congénito y de la deficiencia de Hormona del Crecimiento. An Esp Ped. 1987;27(sup.28):44-47. 4) COLON C, ALONSO-FERNANDEZ JR. Depistage de L’Hipothiroidie neonatal avec un inmuno-essai marque a l’Europeum. Etude comparative de curbes de calibrage. Proceedings of “Reunion Europeene sur le Depistage Neonatal en 1986. Evian (France). 28-30 de abril de 1986. 5) ALONSO-FERNANDEZ JR, COLON C, FRAGA JM. Neonatal Screening of Hipotiroidism: A comparative study of RIA Technique and the Non Isotopic Inmunoessay DELFIA System. In BL Therrel; Advances in Neonatal Screening pp 163-164 (1987). Excerpta Medica. 6) COLON C, ALONSO-FERNANDEZ JR, CASTIÑEIRAS DE, ROMERO ME, FRAGA JM, PEÑA J. Posible Causes of Bordeline TSH: a Summary of our experrience. In F Delange, DA Ficher, D Glinder; Research in congenital Hypothyroidism, pp 316, 1989. Plenum Press. 7) COLON C.Epidemiological study of thyroid stimulating hormone (TSH) levels in the Galician neonatal population (Estudio epidemiologico de los niveles de hormona estimuladora del tiroides (TSH) en la poblacion neonatal gallega). Microfiche ISBN 13: 978-84-8121-340-9. ISBN 10:84-8121- 340-3. Ed. Universidade de Santiago de Compostela. 1995. 8) ALONSO-FERNANDEZ JR, CASTIÑEIRAS DE, CASTIÑEIRAS C, VILLAR P. Determinacion de TSH Neonatal con el método DELFIA reduciendo a dos horas el periodo de Elucion-Incubacion, concentrando el trazador y el analito. Immunoensayo 97. La Habana (Cuba) 14-18 de septiembre de 1997.

  Post date

  In 1985 (2, 3) we propound the adaptation of DELFIA test for seric TSH measurement to the newborn screening sample (DBS). Once Perkin-Elmer marketed the neonatal screening TSH test, we suggested a calibrate modification, increasing from 3 to 5 points and using the interpolation with logarithmic spline instead linear regression such as made in the procedure for seric and neonatal screening TSH determination (4). It is compared with the RIA test using until then (5). In 1988 we discussed the causes of borderline results (6), one of the main reasons for recall sample. In the PhD thesis of one of us (C. Colon) in 1995 (7), we could verify that the gestational age, the birth weight, and the age of analysis, influence on the TSH values. Also was found the thyroid function alteration due to antiseptic iodine use (effect Wolff-Chaikoff).

  In 1997 we presented (8) a new DELFIA test for neonatal TSH modification; reducing until 2 hours the elution-incubation time, using half buffer volume in the preparation of tracer solution and reducing to 100 microlitres the volume of this solution dispensed in the microtiter plate wells containing the DBS disc. In the next year, using the AutoDELFIA, we introduced another modification, increasing to double the content of second antibody-tracer in the immunochemistry reaction mixture, in this mixture the analyte concentration result is multiplied for 2 and Europium-labelled antibody for 4.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top