Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates. Objectives: To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH. Design and Patients: Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH. Results: Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors. Conclusions: This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

Neonatal Screening for Congenital Hypothyroidism: What Can We Learn from Discordant Twins / E. Medda, M.C. Vigone, A. Cassio, F. Calaciura, P. Costa, G. Weber, T. De Filippis, G. Gelmini, M. Di Frenna, S. Caiulo, R. Ortolano, D. Rotondi, M. Bartolucci, R. Gelsomino, S. De Angelis, M. Gabbianelli, L. Persani, A. Olivieri. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 104:12(2019), pp. 5765-5779. [10.1210/jc.2019-00900]

Neonatal Screening for Congenital Hypothyroidism: What Can We Learn from Discordant Twins

M.C. Vigone
Secondo
;
G. Weber;G. Gelmini;L. Persani
Penultimo
;
2019

Abstract

Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates. Objectives: To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH. Design and Patients: Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH. Results: Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors. Conclusions: This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.
thyroid-stimulating hormone; monozygotic twins; preterm birth; diagnosis; infants; serum; concordance; mutations; prevalence; management
Settore MED/13 - Endocrinologia
Settore MED/38 - Pediatria Generale e Specialistica
2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/706230
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