Dexamethasone Ingestion Research Articles

The effect of in vivo dexamethasone on lymphocyte subpopulations: Differential response of EA hu rosette-forming cells

The purpose of this study was to compare the differential effect of dexamethasone on “third population” lymphocytes with its effect on B and T lymphocytes. Five human volunteers were given a single oral dose of dexamethasone (6–8 mg). Samples were evaluated prior to the drug, 5 hr after drug ingestion and 24 hr following the poststeroid sample. Surface marker studies included SIg, EAC rosettes, mouse rosettes, EA hu (Ripley) rosettes, total E-rosette-forming lymphocytes, Tμ lymphocytes, and Tγ lymphocytes. Functional studies included mitogen stimulation with phytohemagglutinin, concanavalin A, and pokeweed and antigen stimulation with herpes simplex virus and Candida albicans. At the nadir of the steroid-induced lymphopenia absolute counts for all B-cell markers were decreased. No differential effects were noted in SIg using polyvalent, IgM, IgG, κ, or λ antisera. Total T lymphocytes decreased 55% ( P < 0.05). There was a differential effect on Tμ and Tγ subsets and the former were significantly decreased. Unlike other lymphocyte subpopulations, cells with high avidity Fc receptors for IgG molecules, i.e., EA hu (Ripley)-rosette-forming and Tγ lymphocytes, were unresponsive to steroid treatment. EA hu (Ripley)-rosette-forming lymphocytes increased from a baseline value of 15 to 28% after dexamethasone ingestion but absolute cell counts remained essentially unchanged with a mean baseline value of 287/μl compared with a poststeroid count of 250/μl. A rebound phenomenon was noted for B, T, Tμ, and Tγ lymphocytes ( P < 0.05). Functional studies of the peripheral blood mixture of lymphocytes at the nadir of the lymphopenia showed significantly suppressed responses to both mitogens and antigens.

Serum cortisol and 11 deoxycortisol by liquid chromatography: clinical studies and comparison with radioimmunoassay.

We describe a liquid-chromatographic procedure for separating and measuring cortisol and 11-deoxycortisol in serum. We quantitated these steroids in patients who were undergoing various tests of pituitary and (or) adrenal function and compared the results with those obtained by two radioimmunoassays done in two different laboratories. Results of 48 tests done in 37 functionally normal humans are presented. Cortisol values for sera collected in the morning as determined by liquid chromatography were (mean +/- SD) 134 +/- 54 micrograms/L. Serum cortisol concentrations increased from 136 +/- 65 to 321 +/- 80 micrograms/L 60 min after injecting synthetic corticotropin and increased from 107 +/- 46 to 242 +/- 31 micrograms/L after insulin-induced hypoglycemia. Serum cortisol decreased from 142 +/- 49 to 26 +/- 20 micrograms/L after oral administration of metyrapone, while 11-deoxycortisol increased from less than 10 to 210 +/- 53 micrograms/L. Serum cortisol measured less than 10 micrograms/L the morning after oral ingestion of dexamethasone. Results of the dynamic tests of adrenal function correlated well with previously reported studies. However, the cortisol values obtained by our technique were generally lower than those obtained by radioimmunoassay, possibly owing to lack of specificity of the latter methods used here for comparison. In contrast, values for 11-deoxycortisol were the same by both methods. The present studies confirm the usefulness of liquid chromatography for measuring these two steroids in serum during tests of pituitary and adrenal function. Future refinements of the technique should continue to increase its clinical applications.

Development of Neutrophilia by serially increasing doses of dexamethasone.

Dexamethasone (4-8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4-6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2-6 h. Dexamethasone-induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.

Suppression of activity of the adrenal cortex by dexamethasone in Cushing's syndrome.

Suppression of the 17-hydroxycorticoids in the urine to 2.5 mg/24 hr during the second day of the ingestion of dexamethasone, 0.5 mg every 6 hr, was thought to be strong evidence against the diagnosis of Cushing's syndrome. Nonetheless, adrenalectomy was advised because of the clinical features and other suggestive data. The diagnosis was confirmed by the finding of enlarged adrenal glands and the subsequent course.