Days Of Dexamethasone Administration Research Articles

The rapid disappearance of a large intracranial meningioma-like tumor: A case report

The most common “vanishing” central nervous system (CNS) tumor is a primary lymphoma. After steroid administration, patients usually experience partial or complete remission. Importantly, CNS lymphomas are almost entirely intra-axial, and the complete remission of extra-axial tumors is rarely discussed in the literature. We present a unique patient case where a large meningioma-like tumor in the left frontal area disappeared. Initially the tumor was scheduled for resection, but the tumor was absorbed within 10 days of dexamethasone administration. During the follow-up, the patient was diagnosed with multiple myeloma. This case demonstrates that hematological disease should be considered for extra-axial tumors. Keywords: extra-axial tumor; complete remission; multiple myeloma; meningioma.

Effect of dexamethasone on levels of inflammatory factors and EGF mRNA in rabbits suffering from oral ulcers


 
 
 
 Purpose: To investigate the therapeutic effect of dexamethasone on rabbits suffering from oral ulcers, and the underlying mechanism(s) of action.
 Methods: A rabbit model of oral ulcer was established by applying 40 % glacial acetic acid solution to the oral buccal membranes of the animals. Three groups of rabbits were used. Changes in area of the oral ulcer were recorded after dexamethasone administration. Levels of epidermal growth factor (EGF) were assayed using reverse transcription PCR (RT-PCR), while MDA levels and expression levels of IL- 6, IL-8 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Local histopathological changes were examined histologically with the aid of hematoxylin and eosin (H & E) staining.
 Results: There were reductions in ulcer areas in group C on the 2nd, 4th and 7th days of dexamethasone administration, when compared with group B (p < 0.05). The EGF levels in the buccal mucosa of rabbits in groups B and C were significantly higher than those in group A (p < 0.05), while the highest EGF level was in group C (p < 0.05). The levels of MDA, IL-6, IL-8, and TNF-α significantly increased in groups B and C (p < 0.05). Results from H & E staining showed lower levels of inflammatory cells in group C than in group B, with visible proliferation of fibroblast cells and epithelial cells in group C after dexamethasone administration.
 Conclusion: Dexamethasone accelerates healing of oral ulcer by regulating EGF levels. This finding provides a new approach to the treatment of oral ulcers.
 
 
 

Dexamethasone-induced impairment of post-injury skeletal muscle regeneration

BackgroundDue to the routine use of dexamethasone (DEX) in veterinary and human medicine and its negative impact on the rate of wound healing and skeletal muscle condition, we decided to investigate the effect of DEX on the inflammatory and repair phases of skeletal muscle regeneration. In this study, a porcine skeletal muscle injury model was used. The animals were divided into non-treated and DEX-treated (0.2 mg/kg/day) groups. On the 15th day of DEX administration, bupivacaine hydrochloride-induced muscle injury was performed, and the animals were sacrificed in subsequent days. Regeneration was assessed by histopathology and immunohistochemistry. In the inflammatory phase, the presence and degree of extravasation, necrosis and inflammation were evaluated, while in the repair phase, the numbers of muscle precursor cells (MPCs), myotubes and young myofibres were estimated.ResultsIn the inflammatory phase, DEX increased the severity and prolonged extravasation, prolonged necrosis and inflammation at the site of the muscle injury. In the repair phase, DEX delayed and prolonged MPC presence, impaired and prolonged myotube formation, and delayed young myofibre formation. Furthermore, DEX markedly affected the kinetics of the parameters of the inflammatory phase of the skeletal muscle regeneration more than that of the repair phase.ConclusionsDEX impairment of the inflammatory and repair phases of the skeletal muscle regeneration was proven for the first time. The drug appears to affect the inflammatory phase more than the repair phase of regeneration. In light of our results, the possibility of reduction of the regenerative capacity of skeletal muscles should be considered during DEX therapy, and its use should be based on risk–benefit assessment.

Safety of Dexamethasone for Nausea and Vomiting Prophylaxis in Children Receiving Hematopoietic Stem Cell Transplantation.

Many children undergoing hematopoietic stem cell transplantation (HSCT) experience chemotherapy-induced nausea and vomiting (CINV) despite receiving prophylaxis. Guideline-consistent CINV prophylaxis includes dexamethasone, but uncertainty with regard to safety potentially limits the use of dexamethasone in children. We describe immediate adverse events (AEs) attributable to dexamethasone given for CINV prophylaxis to children during HSCT conditioning. Children enrolled in a previous prospective study were retrospectively analyzed. Objective parameters related to specific AEs occurring within 5 days of dexamethasone administration were abstracted from health records and graded according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). Their association to dexamethasone was assessed using the Liverpool Causality Assessment Tool. Forty-six children (median age, 10.2 y) were eligible for analysis. The most frequent AEs attributable to dexamethasone (Liverpool Causality Assessment Tool category of probable or definite) were hyperglycemia (63%; CTCAE v4.03 grade 3: 2%), hypertension (52%; CTCAE v4.03 grade 3: 15%), and bradycardia (46%; CTCAE v4.03 grade 3: 0%). Other AEs included dyspepsia or gastroesophageal reflux disease (24%) and alterations in mood and behavior (9%). No AE exceeded CTCAE v4.03 grade 3 in severity. In children undergoing HSCT who received dexamethasone for CINV prophylaxis, immediate AEs attributable to dexamethasone were most often of minor clinical importance and transient.

Eating behavior during dexamethasone treatment in children with acute lymphoblastic leukemia.

Large prospective studies on dexamethasone-induced changes in eating behavior, energy, and nutrient intake are lacking in pediatric acute lymphoblastic leukemia (ALL). We prospectively studied eating behavior, energy, nutrient intake, and the effect on leptin and adiponectin levels during dexamethasone administration in children with ALL. Parents of patients with ALL (3-16 years) completed a dietary diary for their child during 4 days of dexamethasone (6 mg/m2 ) administration. Energy intake and nutrient intake (energy percentage = E%) were assessed and compared with the recommended intake. The Dutch Eating Behavior Questionnaire for Children was completed before start and after 4 days of dexamethasone administration by patients of 7-12 years of age. Fasting leptin and adiponectin levels were also measured before start and after 4 days of dexamethasone administration. Energy intake per day(kcal) (N = 44) increased significantly during dexamethasone (median day 1: 1,103 (717-1,572) versus day 4: 1,482 (1,176-1,822), P < 0.01), including an increase in total protein, fat, saturated fat, carbohydrate, and sodium intake. Intake of saturated fat (median day 4: 12 E%) and salt (median day 4: 1.9 g/day) exceeded the healthy range for age and gender. With respect to eating behavior, dexamethasone significantly decreased restrained eating (P = 0.04). Leptin levels as well as adiponectin levels increased significantly during the dexamethasone course. Four days of dexamethasone treatment significantly increased energy intake, including excessive saturated fat and salt intake, and changed eating behavior in children with ALL. Nutritional and behavioral interventions during dexamethasone treatment are recommended to stimulate a healthy lifestyle.

Dexamethasone-suppressed corticotropin-releasing hormone stimulation test in morbid obese adults

In order to differentiate between Cushing's syndrome (CS) and Pseudo-Cushing's syndrome, it is customary to use a test that is conducted by cortisol suppression with low-dose dexamethasone, followed by the administration of corticotropin releasing hormone (Dex-CRH test). In children with severe obesity, Dex-CRH test has shown a specificity of 55%. The aim of current study was to evaluate the specificity of Dex-CRH test in morbid obese adults. The study included a total of 19 subjects with a body mass index (BMI) equal or higher than 40kg/m(2). In all subjects Dex-CRH test was performed, and 24h urinary free cortisol was collected prior the test and during the second day of dexamethasone administration (2nd-day-UFC). BMI was 45.1±4.6kg/m(2) and 45.7±3.3kg/m(2) in women and men, respectively. 14 subjects underwent bariatric surgery. No subject had surgical or perioperative complications and surgically treated subjects had mean body weight loss of 46.5±16.6kg. All except for 2 subjects had normal Dex-CRH test, as 15-min cortisol falling below 1.4μg/dl. During follow-up, no subject gained additional weight, neither developed signs of CS. 15-min-cortisol concentration of 1.4μg/dl revealed a specificity of 89% and 2nd-day-UFC of 16μg/24h showed a specificity of 100%. Morbid obesity in adults seems not to comprise a significant confounder in Dex-CRH test, and 15-min-cortisol concentration of 1.4μg/dl had a higher specificity than previously reported in obese children.

Management of Hyperglycemia in Diabetic Patients with Hematologic Malignancies During Dexamethasone Therapy

To compare the response to different insulin regimens for management of hyperglycemia in diabetic patients with hematologic malignancies who are receiving dexamethasone. A retrospective analysis was conducted to determine whether a basal bolus insulin (BBI) regimen with detemir and aspart is superior to a sliding scale regular insulin (SSI) regimen for management of hyperglycemia in hospitalized diabetic patients receiving dexamethasone. Forty patients with hematologic malignancies were treated with intravenous (8 to 12 mg/day) or oral (40 mg/day) dexamethasone for 3 days. The average blood glucose (BG) level was 301 ± 57 mg/dL in the SSI group (n = 28) and 219 ± 51 mg/dL in the BBI group (n = 12) (P <.001). The BBI regimen resulted in an average BG reduction of 52 ± 82 mg/dL throughout the course of dexamethasone therapy, while the SSI regimen produced an increase in the mean daily BG level of 128 ± 77 mg/dL (P <.001). On the last day of dexamethasone administration, the insulin requirement was 49 ± 29 units/day in the SSI group and 122 ± 39 units/day in the BBI group (P <.001). Three patients in the SSI group developed diabetic ketoacidosis or hyperosmolar hyperglycemia during steroid therapy. No hypoglycemia was observed in either group. The length of stay and infection rates were similar between groups. Basal and bolus insulin regimen is an effective and safe approach for managing dexamethasone-induced hyperglycemia in hospitalized patients with hematologic malignancies.

Acute and Subacute Effects of Dexamethasone on the Number of White Blood Cells in Rats

The purpose of this study was to elucidate the effects of dexamethasone, a synthetic glucocorticoid, on the immune system by analyzing the number of white blood cells (WBCs) over the course of hours and days of dexamethasone administration. Dexamethasone was given as either a single dosage [1.0 mg/kg body weight (BW); subcutaneous injection (s.c.)] or as a daily dosage (1.0 mg/kg BW per day; s.c.) for 10 days for the hourly and daily assessment of changes in the number of white blood cells, respectively. A single administration of dexamethasone markedly decreased the number of total WBCs, as well as the number of lymphocyte, monocyte, neutrophil and eosinophil subsets with a nadir at 8 hr post-injection. The number of these cells recovered to the control levels at 24 hr. The numbers of total WBCs, lymphocytes, monocyte, eosinophil and basophil were reduced by the daily administration of dexamethasone. However, the number of neutrophil was significantly higher at days 2 and 8 after the injection. These results suggest that glucocorticoid-mediated immunosuppressions are at least partly attributable to quantitative changes in the number of circulating WBCs.

The Clinical Conundrum of Corticotropin‐independent Autonomous Cortisol Secretion in Patients with Bilateral Adrenal Masses

Management of patients with bilateral adrenal masses and corticotropin (ACTH)-independent Cushing syndrome (CS) or subclinical CS is problematic. We report our experience with adrenal venous sampling (AVS) in the evaluation of 10 patients with bilateral masses who had ACTH-independent CS or subclinical CS. Ten patients (9 women, 1 man, mean age 56.4 years) with bilateral adrenal masses and ACTH-independent CS (n=3) or subclinical CS (n=7) underwent AVS. Autonomous cortisol secretion was documented in all cases with suppressed serum ACTH concentrations and lack of cortisol suppression with dexamethasone administration. Adrenal venous sampling was performed on the second day of dexamethasone administration. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and from a peripheral vein (PV). Mean (+/-SD) maximal diameter of the adrenal masses on computed tomography was 3.3+/-1.3 cm (range: 1.2-6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient>6.5 was consistent with a cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol-secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia. Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients-2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7-123 months), CS or clinically important cortisol secretory autonomy did not recur. Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH-independent CS or subclinical CS in patients with bilateral adrenal masses.

Caspase‐3 and Bcl‐2 Expression in Aging in Adrenal Zona Reticularis After Dexamethasone Administration

Adrenocortical cell death by apoptosis is a common finding when adrenocorticotropic hormone is suppressed. Despite the well-known final structural features exhibited by those cells, data on the mechanisms preceding these final events are lacking. In this study, after 3 days of dexamethasone administration to rats of different ages, rat adrenals were processed for immunocytochemical study. In the zona reticularis, there was evidence of the activation of Bcl-2 and caspase-3 proteins. Beyond a small age-related increase in labeled cells, the number of cells presenting colocalization for both proteins was noteworthy. The results confirm the involvement of Bcl-2 and caspase-3 proteins in the apoptotic pathway and suggest their simultaneous intervention.

Steroid replacement therapy for severe heart failure after Norwood procedure

A 15-day-old neonate demonstrated severe heart failure and capillary leak syndrome after undergoing a Norwood procedure for hypoplastic left heart syndrome. Because she developed severe subcutaneous edema and baseline blood cortisol was low, we suspected relative adrenal insufficiency. After 18 days of dexamethasone administration, her hemodynamics and respiratory function improved, and she was successfully extubated and discharged from hospital. When hemodynamics are unstable in neonates after major cardiac surgery, relative adrenal insufficiency and steroid replacement should be considered.

Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. 6 adult Standardbreds. In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations. Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21. The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.

Biochemical evidence of aldosterone overproduction and abnormal regulation in normotensive individuals with familial hyperaldosteronism type I.

We examined in detail biochemical characteristics of 10 normotensive individuals (6 females; age range, 11-43 yr) with glucocorticoid-suppressible hyperaldosteronism (familial hyperaldosteronism type I) in an attempt to understand the development of hypertension in this disorder. All were normokalemic (median plasma potassium, 3.7 +/- 0.4 mmol/L SD), and upright plasma aldosterone levels (478 +/- 333 pmol/L) were within the normal range (140-1110 pmol/L) in nine subjects. However, upright PRA levels (3.3 +/- 30.5 pmol/L x min) were suppressed (<13 pmol/L x min), and the aldosterone to PRA ratio (169.0 +/- 308.3) was elevated (>65) in all but one subject. All subjects had elevated 24-h urinary levels of 18-oxo-cortisol (34.3 +/- 11.2 nmol/mmol creatinine; normal range, 0.8-6.5 nmol/mmol creatinine). Plasma aldosterone failed to rise by at least 50% during 2 h of upright posture in five of seven subjects, or during a 1-h infusion of angiotensin II (2 ng/kg x min) in each of six subjects so studied. Serial, second-hourly (day-curve) aldosterone levels correlated tightly with cortisol (r = 0.79-0.97, P < 0.01 to 0.001), but not with PRA (r = 0.13-0.40, not significant) levels in each of six subjects, and plasma aldosterone suppressed to less than 110 pmol/L during 4 days of dexamethasone administration (0.5 mg 6 hourly) in each of two studied, consistent with ACTH-regulated aldosterone production. In conclusion, biochemical evidence of excessive, abnormally regulated aldosterone production is present not only in hypertensive individuals with familial hyperaldosteronism type I, but also in those who are normotensive. The absence of hypertension in such individuals, therefore, cannot be attributed to lack of biochemical expression of the hybrid gene.

Insufficient adaptive capability of pancreatic endocrine function in dexamethasone-treated ageing rats.

This study was aimed at exploring the capability of the pancreatic endocrine adaptive mechanisms of ageing Sprague-Dawley rats to counteract the metabolic challenge induced by the prolonged administration of dexamethasone (DEX) (0.13 mg/kg per day for 13 days). DEX treatment induced peripheral insulin resistance in 3-, 18- and 26-month-old rats, as indicated by the significant and persistent rise of plasma insulin levels in each age group (plasma insulin in 3-, 18- and 26-month-old rats from basal values of 4.3+/-0.8, 4.7+/-0.5 and 5.6+/-1.0 ng/ml (means+/-s.e.m.) respectively, rose to 11.9+/-1.7, 29.1+/-5.5 and 27.9+/-2.7 ng/ml respectively, after 9 days of administration). However, plasma glucose concentrations remained unchanged during the treatment in young rats, whereas they increased up to frankly diabetic levels in most 18-month-old and in all 26-month-old animals after a few days of DEX administration. Plasma free fatty acid concentrations increased 2-fold in 3- and 26-month-old rats and 4-fold in 18-month-old rats and could possibly be involved in the glucocorticoid-induced enhancement in insulin resistance, although they showed no significant correlation with glycaemic values. Incubation of pancreatic islets obtained from treated rats showed that DEX administration increased the insulin responsiveness of islets from not only younger but also older donors. However, in the islets of ageing rats, which already showed an age-dependent impairment of the sensitivity to glucose and other secretagogues, this enhancing effect was clearly attenuated with respect to the younger counterpart. Furthermore, DEX treatment depressed significantly the priming effect of glucose in islets isolated from all the three age groups. In conclusion, our results show that ageing rats are unable to counteract effectively a prolonged hyperglycaemic challenge as such induced by DEX administration. This homeostatic defect can be ascribed to the age-dependent failure of the endocrine pancreas to provide enough insulin to overcome the aggravation of an antecedent state of increased peripheral insulin resistance.

Dexamethasone and methylprednisolone affect rat peritoneal phagocyte chemiluminescence after administration in vivo

Production of reactive oxygen compounds by peritoneal monocytes/macrophages was studied in rats exposed to dexamethasone or methylprednisolone in the drinking water. Luminol-amplified chemiluminescence was measured in preparations of peritoneal leukocytes activated ex vivo by serum opsonized zymosan, N-formyl- l-methionyl- l-leucyl- l-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). After dexamethasone administration for 1 day (∼ 0.13 mg/kg per 24 h) a significant reduction in chemiluminescence was found in cells stimulated with serum opsonized zymosan, while responses to fMLP and PMA stimulation were significantly reduced after 2 days. The maximal inhibition obtained after 5–8 days of dexamethasone administration (plasma levels < 5 nM) was 92.0 ± 1.2%, 87.6 ± 0.2% and 84.5 ± 3.1% in cells stimulated with serum opsonized zymosan, fMLP and PMA, respectively. Administration of dexamethasone or methylprednisolone for 48 h gave a dose-dependent reduction of chemiluminescence. ED 50 values of dexamethasone were estimated at 0.06–0.15 mg/kg for the different stimulators (plasma concentrations 5–10 nM). Estimated ED 50 values for methylprednisolone were 35–36 mg/kg. Since the percentage of mononuclear phagocytes in the peritoneal cell population did not change significantly with dose or time of dexamethasone exposure, this study indicates that glucocorticoids have a depressive effect on the monocyte/macrophage ‘respiratory burst’ in vivo. The results are consistent with the hypothesis that these effects are mediated by glucocorticoid receptors. Although the pathway activated by serum opsonized zymosan was more rapidly inhibited than the fMLP- and PMA-activated pathways, the responses induced by the different stimulators were similarly affected, suggesting a modulation of common components in the activation pathways, possibly protein kinase C or the NADPH-oxidase complex, after administration of low pharmacological doses of glucocorticoids in vivo.

Corticotropin-Releasing Hormone Stimulation Following Low-Dose Dexamethasone Administration

The biochemical and phenotypic presentation of mild hypercortisolism in Cushing's syndrome is often indistinguishable from that seen in pseudo-Cushing's states such as depression. Both dexamethasone suppression and corticotropin-releasing hormone (CRH) stimulation tests have been used individually to distinguish these conditions, but neither approach has achieved a diagnostic accuracy greater than 85%. Therefore, we sought to develop a combined dexamethasone-CRH test that would take advantage of the altered sensitivity of patients with Cushing's syndrome to both dexamethasone and CRH and would achieve greater accuracy in the diagnosis of Cushing's syndrome. Prospective cohort study. Tertiary care research hospital. A total of 58 adults referred for evaluation of mild hypercortisolism (urine free cortisol level < 1000 nmol/d). The diagnosis of Cushing's syndrome was confirmed at surgery in 39 patients. The diagnosis of a pseudo-Cushing's state was made in 19 patients on the basis of extended follow-up (mean, 28 months) without progression of cushingoid features. The low-dose dexamethasone suppression test, the CRH stimulation test, and the CRH stimulation test started 2 hours after completion of low-dose dexamethasone suppression (the dexamethasone-CRH test) were performed in all patients. Sensitivity, specificity, and accuracy of the three procedures for diagnosis of Cushing's syndrome were calculated from plasma corticotropin, plasma cortisol, urine free cortisol, and urine 17-hydroxycorticosteroid values. The low-dose dexamethasone suppression test had 74% specificity, 69% sensitivity, and 71% diagnostic accuracy, using the standard criterion (17-hydroxycorticosteroid excretion level > 11.0 mumol/d on the second day of dexamethasone administration). With a urine free cortisol criterion for Cushing's syndrome of greater than 100 nmol/d, the low-dose dexamethasone suppression test had 100% specificity, 56% sensitivity, and 71% diagnostic accuracy. The CRH stimulation test without dexamethasone pretreatment had 100% specificity, 64% sensitivity, and 76% diagnostic accuracy. The diagnostic accuracy of the dexamethasone-CRH test for Cushing's syndrome was significantly greater than the accuracy of either the low-dose dexamethasone test or the CRH test alone (P < .01). A plasma cortisol concentration greater than 38 nmol/L measured 15 minutes after the administration of CRH correctly identified all cases of Cushing's syndrome and all cases of pseudo-Cushing's states (100% specificity, sensitivity, and diagnostic accuracy). The dexamethasone-CRH test is a more accurate test to distinguish Cushing's syndrome from pseudo-Cushing's states in patients with mild hypercortisolism.

Effects of Mifepristone on Rabbit Intraocular Pressure in the Presence and Absence of Dexamethasone

Topical dexamethasone was used to elevate rabbit intraocular pressure in order to study the interaction with a steroid antagonist, mifepristone. Dexamethasone did not cause a consistently significant increase in intraocular pressure. Animals treated with mifepristone followed by dexamethasone showed no apparent increase in intraocular pressure after dexamethasone, indeed mifepristone caused a lower intraocular pressure than seen in other groups whether in the presence or absence of dexamethasone. Reductions of intraocular pressure when mifepristone was given after 14 days of dexamethasone administration were not found. No conclusion can be reached regarding any dexamethasone antagonism by mifepristone, except that intraocular pressure tended to be lower even in the presence of dexamethasone.

Dexamethasone Hypertension in Rats

The effects of dexamethasone (DEX) on systolic blood pressure, sodium balance and the renin-angiotensin system were studied in rats. DEX significantly increased systolic blood pressure within three days of its administration, but this effect of DEX on blood pressure was not enhanced by concurrent use of saline solution. In DEX-treated rats, urine volume was significantly increased and urinary sodium excretion showed a tendency toward a slight increase compared to control rats. On the 8th day of DEX administration, plasma renin substrate (PRS) was significantly elevated compared to control rats, whereas plasma aldosterone concentration (PAC) was not significantly different from that of control rats. These results suggest that hypertension induced by DEX may not be dependent on sodium retention or activation of the renin-angiotensin system.

Correlation of the effects of dexamethasone administration on urinary 17-ketosteroid and serum androgen levels in patients with hirsutism

Total 24 hour urinary 17-ketosteroid and serum testosterone (T), androstenedione (Δ), dehydroepiandrosterone (DHEA), dehydroeplandrosterone sulfate (DS), and cortisol levels were measured before and during four days of dexamethasone administration in 28 hirsute patients and 10 women with normal ovulatory cycles. Both the base-line urinary 17-ketosteroids and serum androgen levels were significantly higher (p < 0.05) in hirsute than in normal subjects. Cortisol levels were similar in the two groups. Dexamethasone administration resulted in a significant suppression (p < 0.05) of all the urinary and serum androgen and cortisol levels in both groups. At the end of suppression the serum DHEA, DS, and cortisol levels were similar, while the urinary 17-ketosteroids and serum T and Δ levels were still significantly higher (p < 0.05) in the hirsute than in normal women. There was poor correlation between total urinary 17-ketosteroid and serum androgen results. These findings suggest there is a dual abnormality of androgen production in hirsute patients. The adrenal glands appear to secrete increased quatities of DHEA and DS, while the ovaries appear to produce elevated amounts of T and Δ.

Transient fall and subsequent return of high aldosterone secretion by adrenal adenoma during continued dexamethasone administration.

Plasma aldosterone concentration was consistently decreased by 50% or more in 6 patients with aldosterone-producing adenoma on the first day of dexamethasone administration, only to rise subsequently with continued use of dexamethasone while plasma cortisol concentration remained suppressed. The secondary rise in plasma aldosterone was not related to measured changes in known stimuli of aldosterone secretion. It is probable that the observations result from intrinsic alteration of aldosterone synthesis in the adenoma during prolonged ACTH suppression.