Altered Thyroid and Adrenal Function in Children Born at Term and Preterm, Small for Gestational Age

Abstract

Intrauterine growth retardation may permanently influence the endocrine system by affecting its programming during development. The aim of this study was to evaluate thyroid and adrenal function together with insulin sensitivity in a group of children born small for gestational age (SGA). Forty SGA children (mean age, 6.7 ؎ 1.7 yr) and 35 children born appropriate for gestational age (mean age, 6.5 ؎ 2.2 yr) were selected for the study. TSH, free T 4 , free T 3 (fT 3 ), rT 3 , antithyroid antibodies, cortisol, and dehydroepiandrosterone sulfate (DHEAS) were assessed. Insulin sensitivity was evaluated with the quantitative insulin sensitivity check index (QUICKI). A thyroid ultrasound was also performed in the SGA children. We found that TSH was significantly higher in SGA than in children born appropriate for gestational age [2.9 ؎ 1.1 vs. 1.7 ؎ 0.7 U/ml (mIU/liter); P < 0.001]; furthermore, eight SGA children (20%), seven born preterm and one at term, had TSH levels above the upper limit of normality. fT 3 was also higher in SGA children (4.2 ؎ 0.4 vs. 3.6 ؎ 0.6 pg/ml; 6.4 ؎ 0.6 vs. 5.5 ؎ 0.9 pmol/liter; P < 0.0001), whereas no difference was found for free T 4 , rT 3 , and the fT 3 /rT 3 ratio. Urinary iodine was normal, and antithyroid antibodies were absent. Thyroid ultrasound showed a normal echographic pattern with a normal volume in SGA children. Serum cortisol was similar in both groups, whereas DHEAS was significantly lower in SGA subjects (43 ؎ 18 vs. 65 ؎ 50 g/dl; 1.1 ؎ 0.4 vs. 1.7 ؎ 1.3 mol/liter; P < 0.05). There was no difference in insulin sensitivity between the two groups. Birth length and birth weight were the main determinants of TSH and DHEAS serum levels, respectively.In conclusion, functional thyroid and adrenal changes have been found in children who suffered from intrauterine growth retardation. A larger survey with an appropriate follow-up is, however, required to confirm these findings and to assess their natural evolution. (J Clin Endocrinol Metab 89: 6320 -6324, 2004) R ECENT STUDIES HAVE provided unequivocal evidence of the role played by events occurring in prenatal life in modulating the future development of adult diseases. Intrauterine growth retardation is frequently associated with a higher systolic blood pressure (1, 2), increased cardiovascular mortality (3), elevated plasma cortisol (4), glucose intolerance, hyperinsulinism, type 2 diabetes (5, 6), premature pubarche, and ovarian hyperandrogenism (7-9). Given the significant alterations that thyroid and adrenal glands show in case of severe illness (10 -15) or metabolic derangement (16, 17), we decided to study a group of children born small for gestational age (SGA) to investigate whether fetal growth restriction could induce permanent changes in thyroid and adrenal function. Subjects and MethodsWe studied 40 children (29 female, 11 male) born SGA who, at the time of the investigation, were 6.7 Ϯ 1.7 (2.2-11.5) years old. SGA was defined as weight and length at birth below the 10th centile, according to Lubchenko et al. (18...

Prematurity May Be a Risk Factor for Thyroid Dysfunction in Childhood

“…Moreover, we recently reported that thyroid function is frequently altered in children born small for gestational age (SGA) (8). The aim of the present study was to confirm this finding in a larger number of children and in particular to verify the role played by prematurity per se on thyroid function later on in life.…”

“…In a previous study, in which we examined a group of children of the same age, we found an increased prevalence of thyroid dysfunction in those born SGA (8) and identified in the shorter length at birth the cause for the thyroid alteration. In that study, however, most of the patients were born prematurely, and there was indeed a trend toward a negative correlation between TSH levels and gestational age, which, however, did not reach statistical significance, probably because of the low number of patients examined.…”

ENDOCRINOLOGY IN PREGNANCY: Thyroid antibodies and risk of preterm delivery: a meta-analysis of prospective cohort studies

“…Of these, 16 citations were excluded after the first screening based on the abstracts or titles, mainly because they were overlapping records, not cohort studies, or obviously irrelevant studies. After full-text review of the remaining 17 articles (8,9,10,11,12,13,14,27,28,29,30,31,32,33,34,35,36), three articles were excluded because the exposure was not relevant (32,33,36), two articles were excluded because they were not on preterm delivery (34,35), and one article was excluded because of the nested case-control design (31). Finally, 11 articles involving a total of 35 467 participants were included in our meta-analysis (8,9,10,11,12,13,14,27,28,29,30).…”

Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life

“…Various studies have shown that low birth weight is associated with higher serum DHEAS concentrations, and as a consequence predisposes to an earlier adrenarche and/or an adrenal hyperandrogenic profile in adult life (4)(5)(6)(7), though in other studies, no such association was observed (8,9). An early adrenarche appears to be associated with a higher risk of hyperandrogenism and polycystic ovaries (10,11).…”