Daily Cortisol Research Articles

The circadian rhythm of free cortisol determined by urine sampling at two-hour intervals in normal subjects and in patients with severe obesity or Cushing's syndrome.

ABSTRACT A method for the investigation of the cortisol rhythm, estimating the free cortisol in 2-hr urine samples, is described. In each of 7 normal individuals highly reproducible curves with circadian rhythm could be found. Due to differences in the time of the morning peak the mean curve of the normal individuals resembles the individual curves only after synchronizing them according to the morning peak. In this peak sample the cortisol excretion rate is 2½ times higher than during the remainder of the day. Eight severely obese patients did not differ from the control subjects in their circadian rhythm: the difference in the absolute daily cortisol excretion (obese patients: 29.1 normal subjects: 46.3 μg/24 hr) probably represents the difference between hospitalized and nonhospitalized persons. Six patients with Cushing's syndrome due to bilateral adrenal hyperplasia exhibited a great heterogeneity with the following observations in different patients: very uneven curves without a distinct pattern, di...

The patterns of rna synthesis and induction of glycogenic enzymes in rat liver under continuous cortisol administration

The synthesis of DNA-dependent RNA and of the enzymes of gluconeogenesis was studied under prolonged cortisol administration. Daily cortisol administration to rats for 15–22 days results in significant decrease and even loss of the capacity of liver cells to react to hormone administration by enhanced synthesis of RNA and enzymes of gluconeogenesis. At the same time the cells retain their capacity to insulin induction. Based on experiments on cellular nuclei in vitro it is postulated that because of prolonged cortisol administration changes occur in the chromatin of liver cells leading to the impairment of their capacity to be induced.

Factors affecting alternate pathways of corticosteroid excretion: Possible catabolite repression phenomena in man

By employing a method of sequential extraction of β-glucuronidase hydrolyzed urine it was possible to quantitate the excretion of “less polar” 17-OH, 20, 21-ketols (tetrahydrocortisol and tetrahydrocortisone) and of polar 17-OH, 20, 21-ketols. In normal subjects the excretion of the less polar fraction exceeds the polar fraction by a 2 1 ratio. In a patient with a recent infarction of a pituitary tumor and subsequent removal of the tumor, the urinary excretion pattern was found to be abnormal, with a greater excretion of polar 17-OH, 20, 21-ketols and essentially zero levels of the less polar 17-OH, 20, 21-ketols. While the patient was maintained on replacement dosages of dexamethasone, intermittent measured doses of cortisol were also found to lead to the urinary excretion of more 17-OH, 20, 21-ketols in the polar fraction than in the less-polar fraction. After the patient was given an infusion of glucose and a small amount of insulin it was found that the excretion pattern after ingestion of cortisol became essentially normal. The change was due to a 63 per cent decrease in the polar steroid pathway and a 23 per cent increase in the less-polar steroid pathway. On substitution of daily cortisol for replacement it was found that the excretion pattern was essentially normal. The alternate pathways described are dependent on two different enzyme systems, the pathway to the “less-polar” steroids is dependent on reduction of the Δ 4, 3-ketone structure by a hepatic Δ 4, 5 hydrogenase and a 3α hydrogenase. The formation of the polar metabolites is dependent on certain hepatic microsomal hydroxylases. The glucose effect and the effect of maintenance doses of cortisol on these alternate pathways are discussed in terms of enzyme induction and repression. The possibility that the glucose effect noted here is an example of the “catabolite repression” phenomena affecting corticosteroid metabolism is considered.