Objective: To prospectively evaluate the course of subclinical hypothyroidism (SH) in children and adolescents with no underlying diseases and no risk factors, which might interfere with the progression of SH. Design: Clinical status, thyroid function, and autoimmunity were prospectively evaluated at entry and after 6, 12, and 24 months in 92 young patients (mean age 8.1G3.0 years) with idiopathic SH. Results: During the study, mean TSH levels showed a trend toward a progressive decrease while FT 4 levels remained unchanged. Overall, 38 patients normalized their TSH (group A): 16 patients between 6 and 12 months, and 22 patients between 12 and 24 months. Among the remaining 54 patients, the majority maintained TSH within the baseline values (group B), whereas 11 exhibited a further increase in TSH above 10 mU/l (group C). Baseline TSH and FT 4 levels were similar in the patients who normalized TSH, compared with those with persistent hyperthyrotropinemia. Even in the patients of group C, both TSH and FT 4 at entry were not different with respect to those of groups A and B. No patients showed any symptoms of hypothyroidism during follow-up and no changes in both height and body mass index were observed throughout the observation period. Conclusions: (a) The natural course of TSH values in a pediatric population with idiopathic SH is characterized by a progressive decrease over time; (b) the majority of patients (88%) normalized or maintained unchanged their TSH; and (c) TSH changes were not associated with either FT 4 values or clinical status or auxological parameters.

Objective: To compare the presentation and clinical course of Graves' disease (GD) in two pediatric populations consisting of 28 patients with Down's syndrome (DS) and 109 controls without DS respectively. Design and methods: The evolution over time of GD was determined in both groups according to the clinical changes and the variations in TSH, free thyroxine, and TSH receptor autoantibodies serum levels during the entire follow-up. Results: Female prevalence (50 vs 81.6%; c 2 Z12.0, P!0.0005) and average age at GD presentation (9.9G4.4 vs 11.5G3.5 years, P!0.05) were significantly lower in DS group than in controls. Clinical responsiveness to methimazole therapy was significantly better in DS patients, as demonstrated by both the lower relapse rates after the first cycle withdrawal (7.1 vs 31.2%; c 2 Z7.4, P!0.005) and the higher persistent remission rates after definitive therapy withdrawal (46.4 vs 26.7%; c 2 Z4.1, P!0.05). Moreover, in DS group, no patients needed surgery or radioiodine ablation, whereas nonpharmacological treatment was necessary in 11% of controls (c 2 Z3.8, P!0.05). Antecedents of Hashimoto's thyroiditis (HT) were documented in 21.4% of DS patients and in 3.7% of controls (c 2 Z10.4, P!0.005). Association with other autoimmune diseases was detected in 32.1% of DS cases and in 12.8% of controls (c 2 Z5.94, P!0.025). Conclusions: GD in DS children and adolescents is characterized by several peculiarities: i) earlier presentation; ii) no gender predominance; iii) less severe clinical course; iv) higher frequency of documented HT antecedents; v) more frequent association with other autoimmune diseases.

Background: There are few studies investigating the factors which may affect different biochemical presentations of Hashimoto’s thyroiditis (HT) and these are frequently based on limited pediatric populations. Aims: (1) To assess the frequency of thyroid function patterns at HT diagnosis in 608 children and adolescents, and (2) to analyze the factors that affect thyroid status at diagnosis. Results: At presentation, test results showed euthyroidism in 52.1% of patients (subgroup A), overt or subclinical hypothyroidism in 41.4%, and overt or subclinical hyperthyroidism in 6.5%. The mean age of patients with thyroid dysfunctions (subgroup B) was significantly lower than that of subgroup A, and the rate of children below 10 years of age was significantly greater in subgroup B. Other variables related to thyroid function patterns were prepubertal status; association with either Down or Turner syndromes, which correlated with increased risk of thyroid dysfunctions, and association with other autoimmune diseases, which correlated with decreased risk of thyroid dysfunctions. None of the remaining factors analyzed were associated with increased risk of thyroid dysfunctions. Conclusions: Biochemical thyroid function patterns at HT presentation in childhood and adolescence are mainly conditioned by patients’ age.

Background: The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T₄) versus those receiving no therapy. Objectives: (a) To evaluate thyroid tests under L-T₄ and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Design: Group A children were treated for 24 months and TSH and FT₄ levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. Results: The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. Conclusions: (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH.

Aim: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH). Methods: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed. Results: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001). Conclusions: (a) L-T4 requirements >4.9 µg/kg/day at 12 months or >4.27 µg/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 µg/kg/day at 12 months or <1.45 µg/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland.