Cortisol clearance rate

Synthetic steroid with strong glucocorticoid-agonistic activity. Dexamethasone is over 10 times more potent than cortisol due to a higher binding affinity for glucocorticoid receptor and a decreased clearance rate of the compound. Due to its potency, dexamethasone is widely used in the clinics for the treatment of inflammatory diseases. 

Significant differences in the pharmacokinetics of methyl-prednisolone have been described in black and white renal transplant patients. Black patients had a slower clearance rate and a lower apparent volume of distribution. They had higher cortisol concentrations throughout the day, with higher nadir concentrations. Some of them had glucocorticoid-associated diabetes, and no white patients did. Further studies are needed to define the differences between the races (SEDA-20, 377 404). 

Corticotropin can promote the development of a more or less pronounced Cushingoid state. Corticotropin also increases the metabolic clearance rate of cortisol, aldosterone, and desoxycorticosterone (SEDA-1, 282). 

Chronic liver disease reduces cortisol clearance and the production of urinary metabolites. Cortisol concentrations are elevated by acute ingestion of alcohol. Individuals with alcoholic cirrhosis have normal to elevated basal cortisol concentrations, blunted circadian rhythms, and prolonged clearance rates. 

Starvation is associated with a decrease in both the production and clearance rates of cortisol. In patients with anorexia neiwosa, despite reductions in urinary excretion of cortisol metabolites, plasma concentrations and urhiary excretion of cortisol may be elevated.The responses of cortisol to dexamethasone are blunted in many patients with anorexia nervosa, but cortisol responses to ACTH hi these patients are normal. 

In the serum, progesterone is bound to either cortisol binding globulin or albumin, with only a small fraction being freely available. The metabolic clearance rate for progesterone is 2,100 to 2,500 L/day, for which protein binding has no role. 

Endocrine Enzyme inducing agents, such as phenytoin, can increase the clearance rates of cortisol and synthetic glucocorticoids. 

ACTH administration results in an increased metabolic clearance rate of cortisol. 

In isolated hepatocytes, after maximum induction of tryptophan dioxygenase by glucocorticoids, the uptake of tryptophan into the cells has a control coefficient of 0.75, whereas the control coefficient of tryptophan dioxygenase falls to 0.25. Therefore, the induction of tryptophan dioxygenase has only a limited effect on tryptophan catabolism and NAD synthesis (Salter and Pogson, 1985 Salter et al., 1986). In isolated perfused liver, although cortisol leads to a several-fold increase in tryptophan dioxygenase activity, there is only a relatively small increase in the rate of clearance of tryptophan from the perfusion medium (Kim and Miller, 1969). 

Estrogens increase tlie plasma concentrations of CBG and thus markedly influence total cortisol blood concentrations. The concentration of free cortisol is unaffected the clearance of cortisol and its production rate and concentrations of urinary metabolites are subnormal with estrogen therapy. 

Isotopic studies of steroid metabolism have been frequent since about 1954. The classical isotope dilution method was first introduced in the steroid field, using urinary metabolites, by Pearlman et al. (P5). In 1957 Pearlman (P4) pioneered the method of measuring the steady-state clearance from the blood of an isotopically labeled steroid administered by constant intravenous infusion. If a steady state is achieved, a knowledge of the rate of infusion of the isotopic steroid and its specific radioactivity, and measurement of the specific radioactivity of the steroid in the blood, yields the net flux of endogenous steroid entering the blood, which can usually be equated with its secretion rate. The same concepts were employed by Peterson (P5a, P7) in the investigation of cortisol metabolism. 

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