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.


METHODS
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.


METHODS
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 muIU/ml; P = 0.04) and in overweight/obese patients with hypoechogenicity than in those with normal ultrasound pattern (8.5 vs. 6.8 muIU/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 mug/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.
Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy. anna.rapa@med.unipmn.it
Anna
A
Rapa
Alice
A
Monzani
Stefania
S
Moia
Daniela
D
Vivenza
Simonetta
S
Bellone
Antonella
A
Petri
Francesca
F
Teofoli
Alessandra
A
Cassio
Graziano
G
Cesaretti
Andrea
A
Corrias
Vincenzo
V
de Sanctis
Salvatore
S
Di Maio
Cecilia
C
Volta
Malgorzata
M
Wasniewska
Luciano
L
Tatò
Gianni
G
Bona
D000293:Adolescent; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007037:Hypothyroidism / Q000145:classification / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D007223:Infant; D008297:Male; D009154:Mutation; D009765:Obesity / Q000150:complications / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000235:genetics; D012307:Risk Factors; D013960:Thyroid Function Tests
D015415:Biomarkers; D011989:Receptors, Thyrotropin