No effect of variable patterns of infusion of hydrocortisone in subjects with adrenal insufficiency on circadian appearance of leptin levels

Pharmacological doses of glucocorticoids stimulate leptin secretion from the adipocyte and increase levels of leptin in the blood. Therefore it has been suggested that the circadian variation in cortisol levels (high levels in the AM, low levels in the PM) may contribute to circadian variations in serum leptin levels (low in the AM, high in the PM) in humans. To test whether infusions of hydrocortisone designed to vary physiologic patterns of cortisol affects leptin levels in the blood, 7 subjects (3 women) with complete adrenal insufficiency were recruited for this study with a mean (range) of age of 42 (29-67) and BMI of 29 (22-43 kg/m²). 24° prior to admission before each of 3 separate admissions to the CRC, subject's discontinued oral glucocorticoid medication. Upon admission they then received a 48 hour IV infusion of either normal saline (no replacement) or hydrocortisone. Hydrocortisone infusion protocols consisted of either an infusion designed to mimic the normal circadian variation of cortisol, or an infusion that resulted in a reversal of the normal diurnal rhythm (low in AM, high in PM) over each 24 hour period. Blood was sampled every 15 minutes on the second day of infusion and pooled into hourly aliquots for leptin measurements. Although peak PM leptin levels appeared to be somewhat attenuated during infusion with normal saline only (Graph A), variable cortisol infusion protocols had no effect on leptin levels (Graph B - normal circadian infusion shown in black circles and inverse circadian infusion shown in open squares, all times points not significantly different by t-testing). Variation in physiologic patterns of hydrocortisone infusion does not alter the circadian appearance of leptin in humans. (Graph Presented).