The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country

The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance.

The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are described.The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are describe

Genetics of specific phenotypes of congenital hypothyroidism: A population-based approach

Congenital hypothyroidism (CH) may cause severe and irreversible neurologic and developmental abnormalities when not recognized early. Many millions of newborns have now been screened and many thousands of patients with CH have been identified. Approximately 80%-85% have defects of thyroid gland development, while 15%-20% have congenital errors of thyroid hormone biosynthesis. An entire population screened for CH over a long period of time, was studied in the present report, using a population-based approach. In particular, two CH phenotypes, both presenting with in situ thyroid gland (patients with either goiter or with thyroid gland volume ranging from normal to hypoplasic) were analyzed. Mutations were searched in some of the most likely candidate genes: thyroperoxidase (TPO) in patients with CH goiter, Pax8 and thyrotropin receptor (TSHR) in the other group. In the former group (n = 8), four TPO gene mutations were identified in three patients. One patient was a compound heterozygous. In two cases an already described mutation (1277insGGCC) was present; in two other cases mutations not previously described (1996G → T and 2295G → A), which induced aminoacid variations with a Glu → Stop and Val → Ile changes, respectively, were identified. In all patients mutations were inherited from one of the parents. In the case of the compound heterozygous patient, one mutation was inherited from the mother (1277insGGCC) and the other from the father (1996G → T, Glu → Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)13CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene

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

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

Risk factors for congenital hypothyroidism: results of a population case-control study (1997-2003).

none26noneMedda E; Olivieri A; Stazi MA; Grandolfo ME; Fazzini C; Baserga M; Burroni M; Cacciari E; Calaciuria F; Cassio A; Chiovato L; Costa P; Leopardi D; Martucci M; Moschini L; Pagliardini S; Parlato G; Pignoro A; Pinchera A; Sala D; Sava L; Stoppioni V; Tancredi F; Valentini F; Vigneri R; Sorcini M;Medda E; Olivieri A; Stazi MA; Grandolfo ME; Fazzini C; Baserga M; Burroni M; Cacciari E; Calaciuria F; Cassio A; Chiovato L; Costa P; Leopardi D; Martucci M; Moschini L; Pagliardini S; Parlato G; Pignoro A; Pinchera A; Sala D; Sava L; Stoppioni V; Tancredi F; Valentini F; Vigneri R; Sorcini M