Levels of leptin during hydrocortisone infusions that mimic normal and reversed diurnal cortisol levels in subjects with adrenal insufficiency.

Levels of leptin throughout the day follow a circadian pattern, with a trough in the late morning/early afternoon and a peak at midnight. This pattern of appearance of leptin correlates inversely with the circadian appearance of cortisol. Pharmacological doses of cortisol increase leptin messenger RNA expression in vitro and raise plasma leptin levels in animals and humans. To determine whether the circadian appearance of leptin might be accounted for by delayed effects from physiological cortisol secretion on fat cells, seven subjects with confirmed adrenal failure were admitted to the Clinical Research Center, on three separate dates, to receive 48-h infusions of: continuous normal saline (NS), a normal daily amount and diurnal pattern of cortisol (ND), and a normal daily amount but reversed diurnal pattern of cortisol. Blood samples were taken every 15 min during the second 24 h of infusion and pooled for hourly measurements of leptin. The circadian pattern of leptin appearance was unchanged during all of the infusion protocols. Area-under-the-curve analysis showed no differences in the total amount of leptin during the NS and ND protocols (20,565 ng/mL x 24 h vs. 20,637 ng/mL x 24 h during NS and ND protocols, respectively; P = 0.94). Acute changes in physiological levels of cortisol do not affect the circadian appearance of leptin in subjects with adrenal failure, nor is cortisol required to maintain normal leptin levels for up to 72 h. The circadian variation of leptin levels cannot be accounted for by normal activity of the hypothalamic-pituitary-adrenal axis.