Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors

It has been suggested that increased activity of the hypothalamic-pituitary -adrenal axis may link low birth weight with subsequent development of card iovascular risk factors and disease. Two hundred and five men, aged 66-77 y r, who were born and still live in East Hertfordshire underwent an overnigh t very low dose (0.25 mg) dexamethasone suppression test followed by a low dose 1-mug ACTH-(1-24) stimulation test. A 24-h urine sample was collected for analysis of cortisol metabolites by gas chromatography/electron impact mass spectrometry. Men with lower birth weight had enhanced responses of pl asma cortisol to ACTH-(1-24) (P = 0.03), increased total urinary cortisol m etabolite excretion (after adjustment for confounding effects of increased obesity and lean body mass in high birth weight men; P = 0.04), but no diff erence in plasma cortisol after dexamethasone. Features of the metabolic sy ndrome were independently associated with enhanced adrenal responsiveness t o ACTH-(1-24) (raised blood pressure, P = 0.02; glucose intolerance, P = 0. 09; hypertriglyceridemia, P = 0.02), with trends to increased urinary corti sol metabolite excretion, but not with differences in plasma cortisol after dexamethasone. Men with low birth weight and/or the metabolic syndrome hav e increased activity of the hypothalamic-pituitary-adrenal axis. This may b e an important mechanism underpinning the effects of events in early life o n later cardiovascular disease.