Nichols, Nugent, and Tyler (1965) reported that while a small single dose of 0.5 mg. of dexamethasone given at 08.00 or 16.00 hours to normal healthy male subjects caused only temporary suppression of cortisol production, the same dose given at midnight produced virtually complete suppression for 24 hours. This observation was used as the basis of a rapid simple single-dose dexamethasone suppression test for the diagnosis of Cushing's syndrome Pavlatos, Smilo, and Forsham, 1965) We wished to use a single-dose test on patients with chronic congestive cardiac failure in whom we had found a disturbance of the circadian rhythm in plasma cortisol levels and a diminished response to dexamethasone (Connolly and Wills, 1967).In a preliminary study we attempted to find a dose of dexamethasone which, given at midnight, consistently suppressed the plasma cortisol level at 09.00 hours below the lower limits of the normal range for this time of day, not only in healthy controls but also in hospital inpatients. This paper presents our findings.
Subjects and MethodsForty-nine normal subjects were studied. All were members of either the medical or ward staff of this hospital. No modifications of their normal daily routine occurred during the period of study.One hundred and eight patients were studied. They were in the medical and surgical wards, and had either recovered from the acute cause of their admission to hospital or were at None of the patients had any clinical evidence of an endocrine disorder. Patients with chronic heart failure and severe hepatic or renal failure were excluded from the study. The purpose of the investigation was explained to the patients and their permission for the test to be made was obtained. AU the patients studied followed their normal ward routine. Forty-seven were studied again as outpatients. Both control and test blood samples were collected between 09.00 and 10.00 hours. Dexamethasone was given at 23.00 hours the night before the test. In those subjects where more than one dose level response was studied, at least 48 hours was allowed to elapse between the tests.Plasma 1 1-hydroxycorticoids (1 1-OHCS) were measured by a modification of the Mattingly (1962) method. This method measures fluorimetrically both cortisol and corticosterone. As the normal circulating amount of the latter is small, the plasma 1l-OHCS concentration is taken to be essentially a measure of plasma cortisol, though James, Townsend, and Fraser (1967) have found that a variable proportion of the total fluorescence is due to substances other than cortisol.
ResultsEffect of Size of Dose.-In the 49 normal subjects 84 tests were performed to assess the response to a single dose of dexamethasone over the range 0.5-2 mg. The 0.900 hours control plasma 1l-OHCS values of these subjects were in the range 7-31 jug./100 ml., with no significant difference between males (mean 17.7, S.D. 4.4) and females (mean 17.9, S.D. 6.2).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.