Possible Role of Genetic Factors in Thyroid Growth Rate and in the Assessment of Upper Limit of Normal Thyroid Volume in Iodine-Replete Adolescents

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Abstract
The objective of this study was to answer the question whether thyroid volume in adolescent siblings of similar age and a life-long sufficient iodine intake is uniform. If different, it would indicate that genetic or environmental factors unrelated to iodine intake can influence thyroid growth. We measured thyroid volume by ultrasound in: (1) 251 sibling pairs (SP) and 19 sibling triads 10 to 18 years of age. The age range of each SP was less than 24 months and of each triad less than 42 months; (2) 28 monozygotic and 13 dizygotic sets of twins 7 to 18 years of age. The sibling pairs were retrospectively divided into 3 groups irrespective of age (thyroid volume as means ± S.E. mL/m2). Group 1: 159 pairs with low thyroid volume in both siblings; mean thyroid volume of each pair less than 5.00 mL/m2 (3.96 ± 0.05, median 4.08, range 2.07-4.98); group 2: 69 pairs with high thyroid volume in both siblings; mean thyroid volume greater than 5.00 mL/m2 (5.85 ± 0.12, median 5.57, range 5.03-11.02); group 3: 23 pairs with low thyroid volume in 1 sibling (3.53 ± 0.15, median 3.53, range 1.71-4.91) and high thyroid volume in another (7.36 ± 0.23, median 7.18, range 5.96-10.30). The majority of triads, monozygotic, and dizygotic twins resembled group 1, a few resembled group 2, and only 3 triads and 1 set of dizygotic twins resembled group 3. Among monozygotic twins, there was no pair with a strikingly discordant thyroid volume and only 1 such pair was found among dizygotic twins. In monozygotic twins, the thyroid volume was almost identical (mean difference 0.34 ± 0.06 mL/m2) and significantly less {p < 0.012) than in dizygotic twins (0.9 ± 0.25 mL/m2). Among 502 children of 251 sibling pairs the frequency of high thyroid volume (>5.00 mL/m2) was greater in girls (103/279, 36.9%, p < 0.01) than in boys (49/223, 22.0%). The same was true for the frequency of hypoechogenicity (42/279 or 15.0% in girls vs. 12/223 or 5.4% in boys; p < 0.01). The frequency of hypoechogenicity in both sexes of the combined groups 2 and 3 (40/186, 21.5%) was higher (p < 0.001) than in group 1 (14/316, 4.4%). All siblings examined lived in a common household with their parents, eating the same daily meals at home and school. Our results suggest that the observed differences in thyroid volume of siblings were not related to iodine intake, but to other factors, eg, genetic and environmental. It is not clear whether the children with high thyroid volume and increased frequency of hypoechogenicity should be included into the recently recommended range of normal thyroid volume for adolescents.

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