Francesca Calaciura

Childhood IQ measurements in infants with transient congenital hypothyroidism

OBJECTIVE In view of the fact that, during the first period of life, thyroid hormones are critical for brain development, we investigated whether even transient congenital hypothyroidism could affect the long‐term intellectual development of affected infants.

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 (1277(insGGCC)) was present; in two other cases mutations not previously described (1996(G-->T) and 2295(G-->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 (1277(insGGCC)) and the other from the father (1996(G-->T), Glu --> Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)(13)CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.

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.

Epidemiology and clinical characteristics of endemic cretinism in Sicily

In this study we report the prevalence of endemic cretinism in the general population of two iodine deficient areas in Northeastern Sicily that were described more than 10 yr ago. In addition, the individual characteristics of endemic cretins are considered in order to define the typical expressions of this major iodine deficiency disorder in Sicily. Forty-three mental defectives were identified: 22 were living in an area with three bordering and closely connected municipalities within the province of Messina and with a population of 17,485 inhabitants (prevalence= 0.13%). Three out of the 22 were school-age children. The other community, in the province of Catania, was constituted by a unique and mostly agricultural hamlet, and showed a prevalence of cretinism that was 0.68% (21/3,100). Among the 43 mental defectives, 16 (37%) presented prominent neuromotor and neurosensorial disorders, including deafmutism and were euthyroid, thus conforming to the neurological type of cretinism; 13 (30%) were hypothyroid and exhibited stunted growth without significant neuromotor and neurosensorial impairment (myxedematous cretins). In the remaining 14 individuals (33%) neurological disorders were associated with stunted growth and clinical or biochemical hypothyroidism. These data indicate that also in Sicily endemic cretinism is a continuum of a variety of forms: among these the pure neurological and pure myxedematous forms represent the two extremes.Our observations also indicate that endemic cretinism still represents a major public health problem in Sicily.The finding of 3 endemic cretins younger than 13 yr suggests the persistence of this disorder even in the presence of improved economic, social and nutritional conditions.

Personality traits and mental prognosis in patients with congenital hypothyroidism not treated from early life

Congenital hypothyroidism, if not treated in very early life, severely impairs the neuropsychological development of affected subjects. We have carried out a detailed analysis of cognitive functioning and personality traits in 18 congenital hypothyroid patients treated late and/or unproperly. Significant cognitive defects were observed, the most important being a defective learning ability and an impaired capacity to judge socially significant events and to project complex actions in a temporal perspective. A mental retardation (IQ < 70) was observed in 8/18 (44.4%) of these patients, a moderate intellective deficit in 5/18 (27.8%) and an IQ > 85 in the remaining 5 patients (27.8%). These data indicate that the mental defect of congenital hypothyroid patients may be overstimated. The patients personality was characterized by dependence on the mother, worrying about their body, maladjustement and socialization problems. Since the intellective prognosis of these patients may significantly improve when the environmental conditions are optimized, social and psychological help must always be suggested.

Cytogenetic analysis in congenital hypothyroidism

In order to evaluate the possible role of genetic factors in the pathogenesis of congenital hypothyroidism (CH), we investigated the occurrence of chromosome aberrations in a consecutive series of 47 patients with CH and 208 matched healthy controls. No abnormal karyotype was found in CH patients. In 5 CH patients and in 3 healthy controls a number of heterochromatin variants was detected. Although chromosomal variants are devoid of phenotypic effects, the frequency of these variants was higher in CH patients than in the control group (10.6% vs 1.4%, p < 0.005). These findings suggest that the association of congenital hypothyroidism with chromosomal variants may reflect more than chance concurrence.

Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors

To correlate clinical and pathological characteristics at diagnosis with patient long‐term outcomes and to evaluate ongoing risk stratifications in a large series of paediatric differentiated thyroid cancers (DTC).

Nutrizione iodica e ipotiroidismo neonatale

SommarioIl deficit iodico rappresenta la più comune causa di alterazione dello sviluppo neuro-intellettivo prevenibile nel mondo. Lo iodio è fondamentale per la formazione degli ormoni tiroidei, il cui adeguato apporto è indispensabile per la normale maturazione del sistema nervoso fetale e neonatale. Lo screening dell’ipotiroidismo congenito ha consentito l’individuazione di frequenti alterazioni della funzione tiroidea neonatale di durata e gravità variabile, con un’incidenza tanto più elevata quanto più grave è il deficit iodico. Assicurare un adeguato apporto iodico a tutta la popolazione mondiale e, in particolare, ai soggetti più a rischio (bambini e donne in gravidanza) rappresenta un obiettivo da raggiungere.