Suppression Of Plasma Cortisol Levels Research Articles

Effects of high-dose inhaled fluticasone propionate on the hypothalamic-pituitary-adrenal axis in asthmatic patients with severely impaired lung function

The effects of high-dose fluticasone propionate therapy on dynamic cortisol stimulation in severe asthma are unknown. To evaluate the human corticotropin-releasing factor (hCRF)-stimulated plasma cortisol response to fluticasone propionate therapy in severe asthmatic patients with impaired airway caliber (forced expiratory volume in 1 second [FEV1] < 60% of predicted) and in control subjects. Ten severe asthmatic patients (mean FEV1, 47% of predicted) and 10 controls (mean FEV1, 104% of predicted) received fluticasone propionate, 2,000 microg/d, via a 750-mL primed spacer for 2 weeks. Plasma cortisol levels before and after hCRF stimulation and overnight 10-hour urinary cortisol excretion corrected for creatinine concentration (OUCC) were measured at baseline after washout and 12 hours after the last dose of fluticasone propionate. Baseline values before fluticasone propionate use were not significantly different in asthmatic patients vs controls for plasma cortisol before and after hCRF stimulation and OUCC. Comparing values at baseline vs after fluticasone propionate use, there was no significant suppression of plasma cortisol levels before (378.2 vs 357.4 nmol/L) or after (510.5 vs 507.9 nmol/L) hCRF stimulation or OUCC (8.2 vs 7.5 nmoL/mmoL) in asthmatic patients. In controls, all outcomes were significantly suppressed comparing values before vs after fluticasone propionate therapy: plasma cortisol levels before (423.5 vs 200.2 nmol/L; P = .002) and after (503.5 vs 291.1 nmol/L; P = .001) hCRF stimulation and OUCC (6.5 vs 2.4 nmol/mmol; P = .002). Patients with severe persistent asthma and impaired airway caliber seem to be protected from developing systemic adverse effects with high-dose fluticasone propionate therapy, as evaluated by basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity.

Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis

BACKGROUND & AIMS: Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis. METHODS: A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed. RESULTS: Thirty- four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group. CONCLUSIONS: The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation. (Gastroenterology 1996 Jun;110(6):1713-8)

Budesonide

Budesonide is a glucocorticoid with high topical activity, but low systemic bio-availability which results in reduced systemic effects in comparison with other glucocorticoids. To date, it has been evaluated for use in patients with inflammatory bowel disease when administered either orally as a controlled ileal release formulation or rectally as an enema. In comparative trials, daily treatment with budesonide enema 2 mg/100ml for 4 weeks produced endoscopic remission or improvement in 46 to 84% of patients with active distal ulcerative colitis and/or proctitis and histological remission or improvement in 45 to 68%. In general, this regimen was effective as regimens of hydrocortisone, methylprednisolone, prednisolone or mesalazine (5-amino-salicylic acid, mesalamine) enemas, but caused less suppression of plasma cortisol levels than the other glucocorticoids. Oral treatment with controlled release budesonide 9 mg/day for 8 weeks produces clinical remission in 42 to 67% of patients with active Crohn's disease of the ileum, ileocaecal region and/or ascending colon and significantly reduces Crohn's disease activity index scores compared with baseline and placebo. Results of a quality-of-life questionnaire reflected these clinical improvements. Budesonide has similar efficacy to prednisolone. Response to budesonide is maintained after dosage tapering at 8 weeks. Compared with placebo, maintenance treatment with oral budesonide 3 or 6 mg/day increases the duration of remission in patients with Crohn's disease, but does not appear to affect the 1-year relapse rate. Thus, budesonide, administered rectally to patients with distal ulcerative colitis or proctitis or orally to patients with Crohn's disease of the ileum, ileocaecal region and/or ascending colon, is a favourable option for the treatment of acute exacerbations of inflammatory bowel disease. Because of the low incidence of adverse glucocorticoid-related effects associated with oral budesonide, it may also be a useful agent for longer term maintenance therapy if further clinical trials confirm its efficacy in this indication.

Mometasone furoate 0.1% fatty cream once daily versus betamethasone valerate 0.1% cream twice daily in the treatment of patients with atopic and allergic contact dermatitis

The efficacy of mometasone furoate fatty cream was evaluated in a Scandinavian multicenter study of 117 patients with mild to moderate atopic dermatitis compared with betamethasone valerate cream for 3 weeks. Mometasone furoate was applied once daily and betamethasone valerate twice daily. Mometasone valerate was significantly more effective in this single-blind study; in general, a striking effect was noted after 1 week. In 36 patients with allergic contact dermatitis, no significant difference was noted between the two creams. Except for mild signs of skin thinning, only negligible side effects were reported, and no suppression of plasma cortisol levels were registered in the 41 investigated cases.

Adrenal suppression following extradural steroids.

Adrenocortical function was tested in 12 patients following a single lumbar extradural injection of methylprednisolone acetate ('Depo-Medrol') 80 mg as treatment for chronic sciatica. There was no absorption of the corticosteroid into the systemic circulation, but marked suppression of plasma cortisol levels was documented for up to 3 weeks following the injection and the capacity of the adrenal cortex to secrete cortisol in response to synthetic adrenocorticotrophin (ACTH) was diminished. These results suggest that the dose and frequency of extradural steroid administration should be kept to a minimum to prevent suppression of the hypothalamic/pituitary/adrenocortical axis and that patients thus treated should be considered candidates for steroid cover during surgery and other stressful procedures.

The effect on adrenal axis function of topically applied betamethasone valerate ointment 0.1%.

SummaryIt is widely recognized that topical corticosteroids may be absorbed systemically, resulting in suppression of plasma cortisol levels. However, their effect on the true competence of the adrenal axis has not been fully established.Eight adult inpatients with dermatoses of variable type and severity were treated with betamethasone valerate 0.1% ointment without occlusion. In all cases there was some degree of suppression of serum cortisol levels. In five patients adrenal axis stress tests were performed. The Synacthen test was normal in all patients and only one had a clearly abnormal response to insulin‐induced hypoglycaemia, which had returned to normal one month after cessation of treatment.This suggests that despite suppression of serum cortisol levels, adrenal axis competence was either maintained or, if diminished, returned promptly to normal after treatment ceased.

Abnormal suppression of plasma cortisol during the intravenous infusion of dexamethasone to alcoholic patients.

In some cases the oral administration of dexamethasone to alcoholic patients has failed to cause a normal depression of plasma cortisol levels. Although alcoholics often show signs of intestinal malabsorption, the possibility that the dexamethasone was not fully absorbed has not previously been considered. To eliminate any question of malabsorption, ten male alcoholic patients were infused intravenously with dexamethasone (1 mg/h). The plasma cortisol levels in blood samples withdrawn at half-hourly intervals during a 2-h infusion were compared with the values found in ten normal subjects similarly infused. Four of the alcoholics failed to show normal suppression of plasma cortisol levels, thus confirming that in some alcoholics there is a disturbance of pituitary-adrenal function similar to that found in Cushing's disease. In only one of the four cases was failure to suppress normally associated with the presence of clinical signs of Cushing's disease.

Plasma steroid levels after intra-articular injection of prednisolone acetate in patients with rheumatoid arthritis.

Eight patients with rheumatoid arthritis received an intra-articular injection of either 50 mg or 100 mg of prednisolone acetate into the knee joint. After the injection plasma levels of prednisolone were measured by radioimmunoassay and plasma cortisol levels were estimated fluorimetrically. Peak prednisolone levels were reached at between 2 and 4 hours after the intra-articular injection at both dosage levels, though the peak was higher with the larger dose. The 50 mg dose did not have any effect on the plasma cortisol level at 24 or 48 hours, but there was some suppression of plasma cortisol levels for up to 48 hours after the 100 mg dose.