Subclinical hypothyroidism in children and adolescents: a wide range of clinical, biochemical and genetic factors involved.

Objective: To examine clinical characteristics, biochemical parameters and TSH-R gene variations in children and adolescents with subclinical hypothyroidism (SH) in order to evaluate their pattern of distribution in SH. Patients: We enrolled 88 patients, each having at least two TSH measurements above the upper limit of the reference range with normal free thyroid hormones and negative thyroid-autoantibodies. Main Outcome Measures: Clinical characteristics included height, weight, family history of thyroid diseases, thyroid volume and echogenicity at ultrasonography. Biochemical parameters included TSH, free thyroid hormones, thyroid-autoantibodies and adjusted daily urinary iodine excretion (UIE). Genetic variations in the TSH-R gene were assessed. Results: The prevalence of overweight/obesity, positive family history of thyroid diseases and thyroid hypoechogenicity was 28.4%, 45.5% and 22.7%, respectively. Median TSH was higher in overweight/obese patients than in normal weight ones (7.4 vs. 5.7 μUI/ml, p=0.04) and in overweight/obese patients with hypoechogenicity than in those with normal ultrasound pattern (8.5 vs.5 6.8 μUI/ml, p=0.04). Adjusted daily UIE was lower in subjects without than in those with a positive family history of thyroid diseases (81 vs. 120 μg/day, p=0.001). The prevalence of a positive family history of thyroid diseases was 1.9-fold higher in patients with non-synonymous mutations in the TSH-R gene than in patients without any mutation (80% vs. 42%, p=0.03). A novel mutation at position 1559 in exon 10 (W520X) was detected in one child. Conclusions: Overweight/obesity, thyroid hypoechogenicity and non-synonymous mutations in the TSH-R gene are characterizing features of a large portion of SH children.