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

Objective: The aim of the study was 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 μIU/ml; P = 0.04) and in overweight/obese patients with hypoechogenicity than in those with normal ultrasound pattern (8.5 vs. 6.8 μIU/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/d; P = 0.001). The prevalence of a positive family history of thyroid diseases was 1.9-fold higher in patients with nonsynonymous 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 nonsynonymous mutations in the TSH-R gene are characterizing features of a large portion of SH children.