Regulation of the Pituitary-Thyroid Axis in Adulthood Is Not Related to Birth Weight: Evidence from Extremely Birth Weight–Discordant Monozygotic Danish Twin Pairs

Abstract

Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults. A total of 152 birth weight-discordant monozygotic twin pairs with a median age of 57 years (interquartile range: 33-63) were ascertained from the Danish Twin Registry in 2010. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3) levels were measured. Birth weights were retrieved from midwife records (individuals born before 1973) and the Danish Birth Record Registry (all other participants) Birth weight was inversely associated with serum levels of FT4 (β=-0.48 pmol/[L·kg], p=0.014) and serum T3 (β=-0.09 nmol/[L·kg], p=0.010), but not serum TSH after adjustment for age, sex, and current use of tobacco products, when the twins were investigated as singletons. Serum levels of TSH and T3 were similar in within twin-pair analyses, while serum FT4 was higher in twins with the lowest birth weight (median difference 0.3 mIU/L). When the analyses were repeated in twin pairs (n=46 pairs) characterized by extreme difference in birth weight (>0.5 kg), serum TSH, T3, and FT4 levels were similar in twins with high and low birth weight. The proportion of individuals with serum TSH level >4 mIU/L or <0.3 mIU/L was identical in both groups. No overall evidence of an association between birth weight and adult pituitary-thyroid axis set point, after control for genetic and environmental factors, could be demonstrated.