Endocrine Abstracts

Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis in men of low birthweight may be an important link between early life events and adult metabolic syndrome. In animal models females are more sensitive to HPA axis programming by manipulations in utero, but whether gender influences susceptibility in humans is unknown.
We studied 106 women aged 67-78 y, from Hertfordshire UK, in whom birthweight was recorded. None had pituitary or adrenal disease or were receiving steroid therapy. Ethical approval was obtained. Negative feedback sensitivity was assessed by overnight low dose (0.25 mg) dexamethasone suppression, and adrenal sensitivity by low dose (1 microgram) ACTH_1-24 stimulation test. Cortisol and its metabolites were analysed in 24h urine.
In women, plasma cortisol levels after dexamethasone were lower (p<0.0001) and peak cortisol and cortisol AUC following ACTH_1-24 were higher (p<0.0001) than in men, suggesting a more dynamic HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH_1-24 (r = -0.19, p=0.05) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from in men; a 1 lb decrease in birthweight was associated with an increment in peak cortisol of 12.6 nmol/l (95% CI 1.4, 23.8) in men, p=0.03 and 14.8 nnol/l (95% CI -0.4, 29.9) in women, p=0.06 (p-value for birthweight x gender interaction p=0.82). In a combined analysis of men and women adjusted for gender (n=302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) increment in peak plasma cortisol, p=0.003.
Thus, men and women with low birthweight have similar increased activity of the HPA axis, supporting the hypothesis that activation of the HPA axis may be an important mechanism underlying the fetal programming of adult disease.