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.

[Iodine deficiency and iodine prophylaxis experience in Sicily]. / Carenza iodica ed esperienza di iodoprofilassi in Sicilia.

Twenty years ago we described an area of goiter endemia in North-Eastern Sicily. In this area endemic goiter was associated to a variable degree of iodine deficiency and, in some places, also to an increased thiocyanate urine excretion. Our studies have demonstrated a strict relationship between iodine deficiency and congenital hypothyroidism (both permanent and transient), an increased prevalence of autonomously functioning thyroid nodules and an increased prevalence of thyroid cancer (follicular and anaplastic histotypes). A number of cases of endemic cretinism have also been described. An active iodine prophylaxis program has been carried in the town of Troina in the years 1979-87, by iodinating the municipal water supply. This intervention caused the disappearance of goiter in schoolchildren in only five years. In the last 20 years the prevalence of goiter has decreased in all endemic areas probably because of the "silent prophylaxis", due to improved socio-economic conditions and industrial food consumption. Today the persistence of endemic goiter confirms the inadequacy of the silent iodine prophylaxis and the need to immediately introduce an active iodine prophylaxis in Sicily.

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. DESIGN: A case-control study of intellectual development, auxometric parameters and thyroid function performed in late infancy in children with documented transient congenital hypothyroidism or hyperthyrotrophinaemia at birth. PATIENTS: Nine children born in an endemic goitre area who had short-term transient congenital hypothyroidism or hyperthyrotrophinaemia after birth (TCH) were studied and compared to nine matched children born in the same area at the same time but having normal thyroid function at birth (N). MEASUREMENTS: Global, verbal and performance IQs were evaluated on the Wechsler scale. Height, bone age, total and free thyroid hormones, thyroid volume, thyroglobulin, basal and TRH stimulated TSH were also measured. RESULTS: Height and bone age were similar in the two groups. Thyroid function tests were also similar in the two groups except for basal and TRH stimulated serum TSH and serum Tg which were higher in the TCH than in the control group. Global, verbal and performance IQs were systematically lower in the TCH than in the N group. (78.3 +/- 11.1 vs 90.9 +/- 14.2, P < 0.05; 84.4 +/- 15.4 vs 96.2 +/- 14.8, P NS; 75.0 +/- 8.5 vs 89.2 +/- 12.5, P < 0.01 respectively). CONCLUSION: Infants born and living in an academic goitre area, who had biochemical signs of thyroid hypo-function at birth, had a lower intelligence quotient at the age of 7-8 years than matched controls living in the same environmental conditions but with normal thyroid function at birth. The present findings strongly suggest that abnormalities in thyroid function at birth, even when transient, can adversely affect long-term intellectual development.

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.

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 less than 0.005). These findings suggest that the association of congenital hypothyroidism with chromosomal variants may reflect more than chance concurrence.

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 less than 70) was observed in 8/18 (44.4%) of these patients, a moderate intellective deficit in 5/18 (27.8%) and an IQ greater than 85 in the remaining 5 patients (27.8%). These data indicate that the mental defect of congenital hypothyroid patients may be overestimated. The patients personality was characterized by dependence on the mother, worrying about their body, maladjustment 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.