Association of Serum Lipid Concentrations, Insulin Resistance Index and Catch-Up Growth with Serum Cortisol/Cortisone Ratio by Liquid Chromatography Tandem Mass Spectrometry in Children Born Small for Gestational Age

Abstract

Intrauterine growth restriction (IUGR) may influence adrenocortical function, lipid metabolism and glucose tolerance in later life. Both cortisol (F) synthesis and metabolism contribute to serum F concentrations. 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) enzyme converts F to biologically inactive cortisone (E). Decreased 11beta-HSD2 activity has been suggested for a reason to IUGR and to its metabolic consequences. Our aim was to develop a specific liquid chromatography - tandem mass spectrometry (LC-MS/MS) method for analysing serum F and E concentrations, to determine the F/E ratios, and to correlate them with serum lipid concentrations, insulin resistance index (HOMA-IR), and catch-up growth in children born small for gestational age (SGA). The mean serum F and E concentrations, and F/E ratios did not differ between the SGA and their control children at 12 y age. The SGA children in the highest F/E ratio quartile had poorer gain in height between 0-12 y, and higher serum total and LDL cholesterol levels than those with lower F/E ratios. In logistic regression analysis, high LDL cholesterol, high HOMA-IR, and early pubertal stage associated with high F/E ratio in the SGA children. In conclusion, our LC-MS/MS method enables a reliable measurement of both F and E concentrations from a single serum sample. High serum F/E ratio may be associated with IUGR, its metabolic consequences, and poor catch-up growth in a subset of SGA children.