ABSTRACT
As an extension of our study on corticosteroid metabolism in essential hypertension, plasma levels of »free«, »polar free«, glucuronide and sulfate conjugated 17-hydroxycorticosteroids (17-OHCS), as well as »total conjugated« 17-OHCS, have been determined in 13 patients with Cushing's syndrome and 56 healthy people, before and after administration of corticotrophin (ACTH). Levels of these steroid fractions were also compared in normal subjects during rest and after intensive work. Furthermore, kinetics of the formation and disposal of each of these steroid fractions were investigated in vivo in 3 normal subjects and 3 patients with Cushing's syndrome, by means of radioisotopic tracer techniques. The results obtained indicated the following: (1) although mean levels of each of the estimated 17-OHCS fractions, both before and after ACTH, were in Cushing's syndrome statistically significantly higher than in normal subjects (exception: 17-OHCS-sulfates after ACTH), many individual values for steroid concentrations in Cushing patients were well below the upper limit of the normal range; (2) levels of conjugated and »polar free« 17-OHCS in these patients were much more often increased above the normal range than those of »free« steroids usually measured; moreover, levels of these steroids in the control specimens constituted a much better index of adrenocortical hyperactivity than those after ACTH administration; (3) arithmetical formulae were construed, taking into account both an absolute increase in steroid levels and a relative increase in levels of conjugated and »polar free« steroids above those of »free« 17-OHCS, which permitted a clear-cut separation of all patients with Cushing's syndrome from normal subjects; (4) in the sulfate conjugated 17-OHCS fraction in Cushing patients, the increase in levels of more polar steroids (extractable with ethyl acetate following solvolysis and removal of less polar steroids with dichloromethane) was statistically significantly greater than that of less polar steroids (extractable with dichloromethane), thus, patients with Cushing's syndrome resembled from this angle patients with essential hypertension; (5) when steroid levels in normal subjects were compared during rest and during intensive work, a proportional increase in all steroid fractions during work was noted; this points to a perfect homeostatic mechanism involving enzyme systems metabolizing cortisol under »normal« stressful conditions; (6) however, after ACTH administration, the increase in the levels of conjugated steroids in normal subjects considerably exceeded that of »free« 17-OHCS; in contrast, in Cushing patients the increase in the conjugated 17-OHCS after ACTH administration was relatively smaller than that of »free« 17-OHCS; this, it is believed, indicates that the level of activity of enzymes metabolizing cortisol is in patients with Cushing's syndrome closer to the upper limit of these enzymes' capacity than in normal subjects, possibly due to a chronic saturation with higher steroid concentrations; (7) the results of the radioisotopic tracer study of the kinetics of formation and disposal of various free and conjugated plasma corticosteroid fractions demonstrated that, under basal conditions: (a) biological halflife of cortisol in Cushing patients is shorter than in normal subjects, (b) rates of formation of conjugated and polar free metabolites are much faster in Cushing patients than in normal subjects; this indicates that patients with Cushing's syndrome develop adaptive mechanisms to metabolize chronically increased loads of cortisol, and explains why plasma levels of »polar free« and conjugated 17-OHCS are a better index of adrenocortical hyperactivity than those of the »free« steroids, usually measured.
ABNORMALITIES IN N15 EXCRETION RATES AFTER INGESTION OF TAGGED GLYCINE IN CUSHING'S SYNDROME AND FOLLOWING ACTH ADMINISTRATION 1