Independence of circadian rhythm of endogenous cortisol production and diurnal fluctuations of fibrinolysis in hospitalized patients

Summary Prolonged treatment of rats with high doses of dexamethasone decreases blood fibrinolysis by increasing the plasma level of the inhibitor of plasminogen activators PAI-1. We investigated, in man, the effects of a short term treatment with a low dose of dexamethasone (2 mg/d for 2 consecutive days), as performed in the so-called ‘low-dose dexamethasone suppression test’ which is used for the investigation of the pituitary adrenal axis. Fibrinolysis (PAI activity, PAI-1 antigen and t-PA antigen) was measured in the blood of 9 women sampled at 08:00, 12:00 and 16:00, before and after this dexamethasone test. The main result was that dexamethasone suppressed the daytime fluctuations of PAI, thereby decreasing its morning values. To investigate whether the circadian rhythm of endogenous cortisol and fibrinolysis could be interrelated, we examined in a group of 14 other patients the effects on fibrinolysis of metyrapone, an agent which inhibits 11-β-hydroxylase and suppresses endogenous cortisol production. Metyrapone did not change fibrinolysis at any time-point and diurnal fluctuations remained unaffected, indicating that the circadian rhythm of cortisol plays no role in fibrinolysis fluctuation.