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 T4, free T3 (fT3), rT3, 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 microU/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. fT3 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 T4, rT3, and the fT3/rT3 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 microg/dl; 1.1 +/- 0.4 vs. 1.7 +/- 1.3 micromol/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.