Single Dose Of Dexamethasone Research Articles

Dissociation between plasma bioactive and immunoactive ACTH concentrations in depressed patients

Previous studies have reported dissociations between plasma cortisol and immunoactive adrenocorticotropic hormone (ACTH) concentrations in both normal controls and in patients with major depression. In order to investigate this issue further, placebo and dexamethasone (DEX) were administered to normal controls and depressed patients at 11 pm, and plasma cortisol and ACTH were measured the following morning at 7 am. Plasma ACTH concentrations were quantitated by both immunoassay (I-ACTH) and by bioassay (B-ACTH). In 10 normal controls, DEX (0.25, 0.5, and 1.0 mg, PO, elixir) produced a dose-related suppression of cortisol, I-ACTH and B-ACTH, with all three hormones significantly suppressed by DEX (0.5 and 1.0 mg) (p ≤ 0.01). In 20 depressed patients, 7 am plasma ACTH and cortisol concentrations were assessed following a single dose of DEX (0.5 mg). Fifteen patients were classified as suppressors and five as escapers, as reflected by mean (±SEM) cortisol concentration of 19.9 ± 3.0 ng/ml and 81.2 ± 7.0 ng/ml, respectively. Mean I-ACTH concentrations were comparable in both the escapers (8.6 ± 1.6 pg/ml) and in the suppressors (7.0 ± 1.0 pg/ml). In contrast, the mean B-ACTH concentration was more than two-fold higher in the escapers (4.5 ± 0.5 pg/ml) than in the suppressors (2.2 ± 0.3 pg/ml) (p ≤ 0.0013. Eleven of the 20 patients received both placebo and DEX (0.5 mg) on two separate occasions. Although DEX significantly suppressed both cortisol (p ≤ 0.0001) and B-ACTH (p ≤ 0.01) concentrations, I-ACTH was not significantly reduced. The dissociations between postDEX plasma cortisol and I-ACTH replicates and extends previous observations, and suggests that the disparity between plasma concentrations of these hormones could be caused, at least in part, by the procedure used to quantitate ACTH.

Rapid increase of blood pressure in extremely low birth weight infants after a single dose of dexamethasone.

Blood pressure was retrospectively studied in all 22 extremely low birth weight infants (ELBW) (birth weight median 720 g, range 450-1020 g) who were admitted between July 1989 and October 1991 and received dexamethasone on days 2-25 (median 10) because of bronchopulmonary dysplasia or since lung function had not improved after installation of bovine surfactant. The average blood pressure during the 4 h before dexamethasone increased significantly (median individual increase 8 mmHg, P = 0.0005) until 8-12h thereafter. In addition to the lung disease, ten infants showed severe arterial hypotension with prolonged capillary refilling time ( > 3s) and oliguria and needed continuous infusion of epinephrine to increase blood pressure and urinary flow after treatment with colloids, dopamine and dobutamine had proved ineffective. Epinephrine infusion could be stopped in eight infants 8 h after dexamethasone administration. In ELBW infants blood pressure rose 8-12 h after a single dose of 0.25 mg/kg dexamethasone. In ELBW infants suffering from arterial hypotension who do not respond to infusion of colloids and catecholamines, dexamethasone may represent a new therapeutic tool.

Single-dose i.v. dexamethasone?an effective anti-emetic in cancer chemotherapy

We conducted a randomised, single-blind, placebo-controlled crossover study to assess the efficacy of a single i.v. dose of 20 mg dexamethasone as an anti-emetic in 31 patients receiving cancer chemotherapy. Patients receiving dexamethasone experienced significantly less nausea and vomiting (P less than 0.001 and P less than 0.01, respectively), and appetite and activity were normal in a majority of the treated group. Side effects were insignificant. We conclude that single-dose dexamethasone given i.v. at a dose of 20 mg is a safe and effective anti-emetic for patients receiving cancer chemotherapy excluding cisplatin.

Transient inhibition of RU 486 Antiglucocorticoid Action by Dexamethasone

RU 486 antagonizes both progesterone and glucocorticoids at the receptor level. To study the duration of RU 486 antiglucocorticoid activity on corticotropic function and to establish the means of overcoming it with dexamethasone, plasma corticolipotropic hormones and cortisol were measured in 10 healthy male patients during the 3 days after intake, at 2200 h, of a single 400-mg dose of RU 486, alone or combined with a single dexamethasone dose (1, 2, or 4 mg) given at 2400 h. On the first day after RU 486 alone, ACTH, lipotropin, and cortisol plasma levels were significantly higher than basal values. The 1-mg dose of dexamethasone totally abolished the stimulatory effect of RU 486, and higher doses of dexamethasone (2 and 4 mg) further depressed hormone levels. During the succeeding days, antiglucocorticoid activity of RU 486 alone was still present 34 h after administration, while on the third day all hormone levels returned to normal. After the combined administration, the RU 486 effect reappeared as early as the first day with the 1-mg dose of dexamethasone, while it was delayed until the third day with the higher doses. These results showed that a single 400-mg dose of RU 486 induced a response that lasted at least 34 h. Thus, a dose-dependent competition between RU 486 and dexamethasone was demonstrated. However, the suppressive effect of dexamethasone was only transient, after which the antiglucocorticoid activity of RU 486 reappeared.

Different sensitivity to the dexamethasone treatment of the lymphoid organs of Rana perezi in two different seasons

Adult female frogs ( Rana perezi) have been used to analyze structural and morphometrical changes which affect lymphoid organs after treatment with a single dose of dexamethasone (DX). Special attention was given to the distinct sensitivity observed during two different periods of the year. Morphological differences were found between adult control frogs sacrificed in November and February. In February, frogs showed degenerated thymic reticular epithelial cells but lesser numbers of cortical pycnotic and mitotic thymocytes than in November. Splenic lymphoid tissue was clearly less well developed in February. No significant variations were found in the morphometrical parameters of jugular bodies whereas the number of lymphocytes of both peripheral blood and bone marrow was significantly higher in February than in November. In contrast, frogs sacrificed in February exhibited less drastic variations as well as a more delayed response to DX-treatment than those of November. The reported differential changes could be attributed to possible distinct levels of circulating sexual and nonsexual steroids during both seasonal periods.

Direct radioimmunoassay procedure for plasma dexamethasone with a sensitivity at the picogram level.

A simple radioimmunoassay (RIA) for the direct quantitation of plasma dexamethasone (DEX) at the picogram level has been developed. An antiserum with high specificity and avidity was obtained by the immunization of a carefully synthesized dexamethasone-21-succinyl-thyroglobulin with a high incorporation ratio. As little as 1 pg of DEX in 50 microL of plasma sample can be detected directly by this RIA without extraction and other purification procedures. Intra- and interassay coefficients of variation were 2.1 and 3.3% for plasma levels at 2.93 ng/mL or 2.3 and 7.2% for plasma levels at 0.88 ng/mL. Blank values for plasma of normal or pre-DEX patients were always under the detection limit (20 pg/mL). Excellent linearity (r = 0.9991-0.9999) was demonstrated between the serial dilutions of six plasma samples and their corresponding DEX concentrations. In single-dose DEX (0.25-1 mg) pharmacokinetic studies, plasma DEX was consistently detectable up to 24 h post dose. Compared with existing methods, this direct RIA demonstrates superior performance with regard to simplicity, sensitivity, specificity, and reproducibility. It also enables high sample throughput and has proven robust in our hands. This assay should be readily transferable to other laboratories for clinical or research purposes.

A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis

To determine whether a single dose of dexamethasone (0.6 mg/kg) is useful in the treatment of acute laryngotracheitis (croup), 29 hospitalized patients with acute laryngotracheitis were randomly assigned in a double-blind fashion to receive either parenterally administered dexamethasone (n = 16) or a saline placebo (n = 13). Severity of the illness was assessed by a clinical croup score based on retractions, stridor, air entry, cyanosis, and level of consciousness. Twelve hours from the time of injection, the patients receiving the dexamethasone had a statistically significant decline in median croup score from 4.5 to 1.0 (p less than 0.001), whereas the patients receiving the placebo did not. By 24 hours, a decline of two or more points in the total croup score was noted in 85% of the patients in the dexamethasone group compared with 33% of the patients in the placebo group (p = 0.027). During this same period, only 19% of patients receiving dexamethasone required two or more racemic epinephrine treatments in comparison with 62% of patients who received the placebo (p less than 0.05). There was no statistical difference between the two groups in improvement in oxygen saturation, respiratory rates, or duration of hospitalization. We conclude that dexamethasone is beneficial in reducing the overall severity of moderate to severe acute laryngotracheitis during the first 24 hours after injection.

Diagnostic Value of Growth Hormone‐Releasing Hormone Tests in Short Children

The growth hormone-releasing hormone (GHRH) test was applied to more than 230 children. Twenty-five out of 61 patients with proven growth hormone (GH) deficiency responded to GHRH with a GH increase of greater than 10 ng/ml. In most of the patients with idiopathic GH deficiency, a priming procedure using daily injections of GHRH improved the secretory response to GHRH. Nearly all children with familial shortness of stature showed a prompt increase in GH levels, with a mean peak level of 34.9 ng/ml (range 0.5-144 ng/ml). A second test was performed in five children with familial short stature because of failure to respond to the first test. Children with constitutional delay of growth and development did not differ in their GH response from patients with familial shortness of stature. Ten girls with Ullrich-Turner's syndrome responded with a mean increase of 22 ng/ml GH (range 10.1-34.0 ng/ml). Therapy with glucocorticoids, as well as endogenous hypersecretion of cortisol, suppressed the responsiveness of the pituitary gland to GHRH. Suppression was also observed following a single dose of dexamethasone during the steroid-suppression test in eight obese children. Low responsiveness of the pituitary gland was also seen in patients with thalassaemia and transfusion-induced haemosiderosis. It is concluded that it is not possible to detect GH deficiency with a single GHRH test. A full endocrinological evaluation is necessary to prove the diagnosis.

17OH-progesterone response to acute dexamethasone administration in congenital adrenal hyperplasia.

Glucocorticoid-related changes in 17OH-progesterone (17P) concentrations were studied in 13 patients receiving treatment for 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH). Blood spot and saliva 17P levels were elevated, with or without loss of diurnal rhythm, within 24 h of stopping maintenance glucocorticoid therapy. A single dose of dexamethasone (0.01 mg/kg) given either intravenously or orally at 09.00 h resulted in rapid onset of complete pituitary-adrenal suppression characterised by a prompt and exponential fall in 17P levels (first-order elimination half-life, mean 2.87 h, range 1.98-3.98 h). Concentrations of 17P remained low throughout the day until the onset of an abrupt nocturnal rise, which occurred between 24.00 and 05.00 h. There were individual differences in both the rate of fall and the timing of the nocturnal rise in 17P levels which may partly explain the need to vary individual steroid requirements in the treatment of CAH.

Analgésie postopératoire : injection péridurale de phosphate sodique de dexaméthasone

Epidural administration of steroids has been suggested for the prevention of postoperative epidural fibrosis after lumbar lamino-arthrectomy. In order to assess the efficacy of this technique on pain occurring after such surgery, the demand of pentazocine during the first 24 postoperative hours was studied in 39 patients randomly assigned to two groups. Pain intensity was assessed by a five-point verbal scale (0 : none ; 1 : poor ; 2 : moderate ; 3 : severe ; 4 : very severe) at five intervals (0–4, 5–8, 9–12, 13–16 and 17–24 h). The patients in group T (n = 20) did not receive any steroid, whereas those in group C (n = 19) were given, just after the end of surgery, a single dose of dexamethasone (4 mg) via an epidural lumbar catheter previously inserted by the surgeon. In group T, 18 patients required one or several intramuscular injections of pentazocine, whereas only three patients of group C (p < 0.001) did so. Patients in group T expressed more severe pain (4 moderate, 12 severe, 3 unbearable) than those patients who had received steroids (1 moderate, 1 severe, 1 unbearable). As a consequence, they requested more pain killer (30 injections vs 8 injections, respectively ; p < 0.001) and sooner than patients of the steroid group (8 h vs 12 h ; p < 0.05). It was concluded that epidural administration of dexamethasone was helpful in preventing postoperative pain after lumbar lamino-arthrectomy.

Effects of dexamethasone on the lymphoid organs of [formula omitted

Owing to the possible importance of steroids in the mutual neuroendocrine-immune influences found in lower vertebrates, we study the structural and morphometrical changes induced by a single dose of dexamethasone, a synthetic corticosteroid, on the lymphoid organs of the frog Rana perezi . The dexamethasone treatment produces thymic involution with massive destruction of cortical lymphocytes, intense peripheral lymphopenia with lymphocyte redistribution to the bone marrow from peripheral blood and spleen. The effects on the spleen were less dramatic than in the thymus, but, the proportion of white pulp underwent a significant decrease and the size of splenic lymphoid follicles diminished. Our results demonstrate that Rana perezi is a corticosensitive species although the induced corticosteroid effects were less drastic than those described in other vertebrates, mainly mammals.

Simultaneous autoradiographic and histochemical analysis of bone formed in vitro.

The simultaneous histochemical demonstration of alkaline phosphatase activity and autoradiographic demonstration of [3H]-thymidine uptake is valuable for study of bone cell kinetics in vivo or in vitro. By use of this technique, it has been possible to detect changes induced by a single dose of dexamethasone (10(-7) M) in the time course of alkaline phosphatase activity, the number of alkaline phosphatase-positive cells, and [3H]-thymidine labeling in bone formed in vitro.

Single dose dexamethasone suppression test in children: dose relationship to body size.

We have performed an overnight single dose dexamethasone suppression test in 15 children at different dosages to determine the minimum dose required to suppress the 0800 h serum cortisol level. With a dexamethasone dose of 0.1 mg/m2 two of seven children showed suppression. When the dose was increased to 0.3 mg/m2 all of six patients showed suppression as did three given dexamethasone 0.5 mg/m2. We recommend that doses of dexamethasone should be calculated in terms of body surface area when assessing the hypothalamo-pituitary axis in children and that a dose of 0.3 mg/m2 should be used for suppression tests.

Glucocorticoid activation of Na+/H+ exchange in renal brush border vesicles: kinetic effects

Administration of the synthetic glucocorticoid dexamethasone to adrenalectomized rats increased Na+/H+ exchange activity in isolated renal brush border membrane vesicles. Treatment altered the initial rate of Na+ uptake by increasing Vmax (19.90 +/- 2.17 vs. 27.32 +/- 1.50 nmol.mg protein-1.5 s-1) and not the apparent affinity KNa+ (8.33 +/- 1.11 vs. 7.94 +/- 1.60 mM). Dexamethasone treatment resulted in a proportional increase in 1 mM Na+ uptake at every intravesicular pH measured. When these data were analyzed by the Hill equation, it was found that dexamethasone treatment did not change the apparent number of H+ binding sites (1.24 vs. 1.26) or the [H+]0.5 (0.33 vs. 0.32 microM) but increased the apparent Vmax (0.98 vs. 0.55 nmol.mg protein-1.2 s-1). It was also found that dexamethasone injections of 60 micrograms/100 g body wt resulted in maximum stimulation of exchange activity and that a significant increase in amiloride-sensitive Na+ uptake was detected within 12 h after a single dose of dexamethasone.

Plasma Cortisol and urinary melatonin in obese patients after a single dose of dexamethasone

Previous studies have indicated that cortisol hypersecretion and abnormal cortisol responses to dexamethasone (DEX) could be both associated with low levels of plasma melatonin (MT). In this study, the possible relationship between urinary MT excretion (8 PM-8 AM) and the CRF-ACTH-Cortisol axis was investigated. 39 children and adolescents whose weight for age was above the 97th percentile received 2 mg of DEX at 8 PM. Plasma cortisol levels were determined at 8 AM and 5 PM before, and at 8 AM after DEX administration. 15 patients with a normal cortisol cycle (12.1±1.4 and 3.1±0.5 μg/100ml), and levels below 1.0 after DEX, showed a highly significant increase in MT excretion during the night following DEX administration (63.8±5.6 ng/12h vs 33.1±3.0 for the control night, p<.001). In a second group of 14 patients with mean cortisol levels similar at 8 AM and 5 PM (10.7±1.3 and 9.3±1.5), but with a normal cortisol decrease after DEX, nocturnal MT excretion increased from 21.5±2.2 to 34.7±5.6 (p<0.02). A third group of 10 patients with both poor cortisol cycles (16.1±2.5 and 10.8±2.4) and abnormal cortisol suppression after DEX (7.6±2.1), showed no increase in MT excretion (24.2±2.7 and 24.9±3.7). The reciprocal changes in plasma cortisol and MT excretion in obese subjects suggest a relationship between the CRF-ACTH adrenal axis and the pineal gland.

Control in congenital adrenal hyperplasia monitored by frequent saliva 17OH-progesterone measurements.

Treatment in a group of 19 patients with congenital adrenal hyperplasia (CAH) has been monitored by frequent, serial measurements of saliva 17OH-progesterone (17OHP) concentrations. Detailed 17OHP profiles were obtained during consecutive weekend days and every 1-2 h over a separate 24-hour period. Patients showed a marked diurnal rhythm in 17OHP levels, particularly when treated with hydrocortisone. In some patients, 10 mg/m2/day of hydrocortisone was sufficient glucocorticoid replacement to produce adequate control, although there was considerable individual variation. Saliva 17OHP profiles provided valuable information on the efficacy of hydrocortisone, cortisone acetate, prednisolone and dexamethasone as glucocorticoid suppressive regimes in the treatment of CAH. Preliminary results suggest that hydrocortisone given in two divided doses during the day, supplemented by a small dose of prednisolone at bedtime, is suitable treatment for CAH patients who are still growing. In the patient who has completed statural growth, single daily dose dexamethasone therapy ensures adequate adrenal suppression and is convenient in the longterm.

Antiemetic Efficacy of Dexamethasone Therapy in Patients Receiving Cancer Chemotherapy

To assess the value of high-dose dexamethasone therapy in preventing the gastrointestinal (GI) side effects of chemotherapy, a randomized double-blind study was conducted in women receiving outpatient therapy for breast cancer. Single-dose dexamethasone sodium phosphate (10 mg) or placebo was administered intravenously in 57 trials in 22 women immediately before chemotherapy. Questionnaires (administered before therapy and 24 hours later) were compared for evidence of nausea, vomiting, and anorexia produced by chemotherapy. No GI intolerance to chemotherapy was noted in 24 (83%) of the 29 dexamethasone trials v 16 (57%) of the 28 placebo trials. Dexamethasone trials produced the following results: no side effects in 50% (14/29), insomnia the night after chemotherapy in 21% (6/29), an increase in energy levels in 24% (7/29), and an improvement in mood in 14% (4/29). High-dose dexamethasone therapy has useful application in alleviating the emetic effects of cancer chemotherapy.

Mood, vegetative disturbance, and dexamethasone suppression test after stroke.

Assessments of mood disturbance and "vegetative" (appetite or sleep) disturbance as well as a single-dose dexamethasone suppression test (DST) were carried out in 25 randomly selected stroke patients and in 13 nonstroke control patients hospitalized in a rehabilitation center. Prevalence rates of moderate-to-serve depression of mood and vegetative disturbance were significantly higher in stroke patients than controls (48% and 52% versus 0% and 8%, respectively), as was the prevalence of abnormal DST results (52% versus 8%). Abnormal DST results were associated with the occurrence of moderate to severe mood, appetite, and sleep disturbances among all patients. in 2 stroke patients, repeated DST results paralleled the clinical course. The DST may be useful as an adjunct to the diagnosis and in monitoring the progress of the common and potentially reversible mood and vegetative disturbances occurring after stroke.

Menarche and subsequent ovarian function in girls with congenital adrenal hyperplasia (CAH)

Chronological age, body weight and plasma steroid concentrations at menarche, and subsequent ovarian function in relation to plasma/saliva steroid concentrations and glucocorticoid therapy were reviewed in 6 girls with 21-hydroxylase deficiency (3 salt-losers). Mean age at menarche was 13.6 yr (12.6-14.5); body weight varied from 45 to 66 kg. Menarche did not occur with plasma testosterone (T) levels of 5-6 nmol/L. Normal female plasma T levels occurred on changing from hydrocortisone to single dose dexamethasone (dex) given as 0.25 to 0.75 mg/day. The potency of dex relative to cortisol was 80:1 based on adrenal suppression effect. Regular menses occurred with plasma T levels in the normal female range. Ovulatory cycles were documented using menstrual profiles of saliva progesterone (P) performed at a post-menarchal age of 3.0-3.4 yr. Some showed the characteristic rise in luteal levels of saliva 17P indicating previous ovulation; one 16 yr old girl became pregnant. Anovulatory cycles also occurred in well-controlled girls. Preliminary data on controls showed absence of ovulatory cycles for at least 2 yr post-menarche. Conclusions: in CAH, 1) Menarche is not usually delayed. 2) Ovulatory cycles may be delayed but further control data is needed. 3) Normal plasma T levels are required for regular menses. 4) This can be achieved using single dose dex. therapy.

Effect of dexamethasone on the neonatal adrenal medulla.

Newborn male rats were injected with a single dose of dexamethasone on the first day of life. Controls received only the diluent. Two to ten days later the experimental and control animals were sacrificed, and the adrenal medullae were processed for electron microscopy and for histochemical demonstration of catecholamines. Rats that received dexamethasone, as compared to controls showed (1) an earlier appearance of the catecholamine reactions, and (2) a pronounced development of Golgi complex. These results are further indication that glucocorticoid stimulates the maturation of the chromaffin complex. The Golgi apparatus may play some role in this inductive mechanism.