(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Cushing-Syndrome

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug-drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug-drug interaction in order to suggest options for the clinical management of HIV-positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Child; Child, Preschool; Cushing Syndrome; Drug Interactions; Female; Fluocinolone Acetonide; HIV Protease Inhibitors; HIV Seropositivity; Humans; Infant; Male; Middle Aged; Ritonavir; Young Adult

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Controlled Clinical Trials as Topic; Cushing Syndrome; Delayed-Action Preparations; Double-Blind Method; Fluticasone; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Remission Induction

From the experience above, it may be concluded that corticosteroid therapy in allergic disease has become more effective than ever before. The expected variations in usage of new important pharmacologic agents is seen with special clarity in the use of corticosteroids. The wide acclaim for the "miracle drug of the 1950's", which followed penicillin of the 1940's, soon gave away to anguish about side-effects that threatened to abolish its use entirely in the late 1950's. The 1960's brought alternate day therapy for chronic usage and recognition that short term usage was relatively safe. The 1970's saw proliferation of topically active steroids similar to those so important to the practice of Dermatology in the previous decade. Results in treating asthma and nasal diseases have been excellent and extensive research for adverse effects has been largely unrevealing.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Asthma; Beclomethasone; Cataract; Cushing Syndrome; Humans; Hypersensitivity; Hypersensitivity, Immediate; Long-Term Care; Nasal Polyps; Osteonecrosis; Osteoporosis; Prednisone; Rhinitis; Sleep Initiation and Maintenance Disorders; Stress, Physiological

Since beclomethasone dipropionate (BDP) is a very potent glucocorticoid and since small oral doses (1 mg) seem to be metabolised (possibly in the gut wall or liver) before they reach the systemic circulation, a study was conducted to find out whether patients with inflammatory bowel disease could be treated with enemas containing small doses of BDP without their acquiring Cushing's syndrome or hypothalamic pituitary adrenal (HPA) suppression. The BDP in the 100 ml enemas used was stable and present in a concentration likely to be therapeutic (0.5 mg/dl). Single overnight BDP enemas, unlike conventional betamethasone (5 mg) enemas, did not interfere with the HPA axis in 6 healthy volunteers. In the double-blind randomised part of the study 2-week courses of BDP or betamethasone enemas were assessed in 9 patients having exacerbations of distal inflammatory bowel disease. The clinical and sigmoidoscopic responses as well as adrenocortical function (judged by the 'Cosyntropin' test) were evaluated on the morning after the last day of a course of enemas. Both types of enemas had similar beneficial effects, but only BDP enemas did not interfere with HPA function. Over a prolonged period, a patient with distal ulcerative colitis had been completely dependent on regular treatment with betamethasone enemas to control his symptoms. Substitution with BDP enemas successfully controlled his bowel symptoms, whilst his cushingoid features and HPA suppression regressed.

Topics: Adult; Beclomethasone; Clinical Trials as Topic; Colitis, Ulcerative; Cushing Syndrome; Double-Blind Method; Enema; Female; Humans; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Random Allocation

Topics: Adrenal Cortex; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Cushing Syndrome; Depression, Chemical; Drug Antagonism; Drug Therapy, Combination; Humans; Prednisone; Stimulation, Chemical

We report a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of four commonly prescribed steroid drugs (prednisolone, dexamethasone, betamethasone and beclomethasone dipropionate) while simultaneously measuring 24-h urine free cortisol and cortisone in patients.. Two hundred and fifty microlitre aliquots of urine were spiked with internal standard and extracted with dichloromethane. The MS instrument was operated with positive electrospray and multiple reaction monitoring. Two transitions were monitored for each analyte of interest and the ratio of the intensities of the product ion fragments was established.. The LC-MS/MS method for the measurement of urine free cortisol and cortisone was established. The assay was linear up to 788 nmol/L for cortisol and 777 nmol/L for cortisone, with a limit of quantitation of 5.0 nmol/L for both. Analysis time per sample was seven minutes. Transitions for four synthetic glucocorticoids were included, and they were identified based on the ratio of the intensities of product ion fragments. Analysis of 219 samples collected from 154 patients (55 male and 99 female) revealed the presence of prednisolone in five samples from three patients. Dexamethasone was detected in samples from four patients, and betamethasone was detected in one sample.. This is the first LC-MS/MS method in routine use to combine quantification of urinary cortisol and cortisone and detection of synthetic glucocorticoids in patients being investigated for Cushing's syndrome. Since the most common quoted cause of Cushing's syndrome is steroid treatment, this is a valuable diagnostic tool.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Beclomethasone; Betamethasone; Child; Chromatography, Liquid; Cortisone; Cushing Syndrome; Dexamethasone; Female; Glucocorticoids; Humans; Hydrocortisone; Limit of Detection; Male; Middle Aged; Prednisolone; Reference Standards; Tandem Mass Spectrometry; Young Adult

Adrenal insufficiency (AI) is a potentially life-threatening condition. It is known that high doses of inhaled corticosteroids (ICS) can induce systemic adverse effects. Currently, there are no data on the prevalence of AI associated with the use of ICS. This study aimed to investigate the prevalence and clinical presentation of AI (associated or not associated with exogenous Cushing's syndrome) in patients who were prescribed ICS by French physicians during the period 2000-5.. All metropolitan French paediatricians, endocrinologists, pulmonologists and intensive care physicians (n = 11 783) were mailed questionnaires requesting information regarding cases of AI associated or not associated with exogenous Cushing's syndrome between 2000 and 2005. Data collected included patient demographics, oral corticosteroid or ICS used during the year preceding the diagnosis of AI, underlying condition(s), concomitant treatment(s), presenting clinical signs and symptoms, results of laboratory investigations and outcome. The French pharmacovigilance database was screened for spontaneous reports to determine the frequency of AI associated with the use of ICS, using the capture-recapture method.. Forty-six cases of AI were identified. Twenty-three cases presented with clinical symptoms of AI alone and 23 with exogenous Cushing's syndrome. ICS prescribed were fluticasone propionate (n = 24), budesonide (n = 12) and beclometasone dipropionate (n = 5). In 82% (n = 32) of cases for which data were available, ICS were prescribed at high doses. A potential drug interaction was found in 12 cases. Thirteen cases of AI were identified in the French pharmacovigilance database, one of which was common with the questionnaire survey. The capture-recapture method provided an estimation of 598 (95% CI 551, 648) cases of AI associated with the use of ICS for the 2000-5 period in France.. The results of this study confirm the occurrence of adrenal insufficiency in patients treated with ICS. Although the prevalence of ICS-induced AI reported in this study is low, the likelihood of under-diagnosis underlines the need to consider this risk in patients when prescribing these drugs.

Topics: Administration, Inhalation; Adolescent; Adrenal Insufficiency; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Androstadienes; Beclomethasone; Budesonide; Child; Child, Preschool; Cushing Syndrome; Data Collection; Databases, Factual; Drug Interactions; Female; Fluticasone; France; Glucocorticoids; Humans; Infant; Male; Middle Aged; Prevalence; Young Adult

Topics: Administration, Inhalation; Beclomethasone; Bronchodilator Agents; Budesonide; Cushing Syndrome; Humans; Pregnenediones

Topics: Administration, Inhalation; Beclomethasone; Budesonide; Cushing Syndrome; Glucocorticoids; Humans; Male; Pregnenediones

To report a case of significant systemic side effects from an inhaled glucocorticoid at a reported dose in the upper recommended therapeutic range.. A 25-year-old white man with asthma treated with inhaled glucocorticoid (beclomethasone 1500 micrograms daily), and primary testicular failure with inadequate androgen replacement, was referred with back pain. He was found to have osteoporosis, clinical features of Cushing's syndrome and complete suppression of endogenous adrenocorticotrophic hormone adrenal function.. He was recommended to receive adequate androgen replacement and to use a spacer device with the inhaled beclomethasone, or to change to budesonide via a Turbuhaler (AB Astra, Sweden).. Inhaled glucocorticoids should not be regarded as entirely safe, as serious systemic side effects may occur at doses at the upper level of the recommended therapeutic range.

Topics: Administration, Intranasal; Adult; Asthma; Beclomethasone; Cushing Syndrome; Humans; Male

An asthmatic child is presented who developed a cushingoid appearance with evidence of adrenal suppression and growth impairment while on low dose inhaled topical steroids. When the inhaled steroids were replaced by inhaled sodium cromoglycate his adrenal function recovered while his appearance and growth returned to normal. This report indicates that there are some children who are at risk of developing side-effects on doses of inhaled topical steroids normally considered to be entirely safe.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Child, Preschool; Cromolyn Sodium; Cushing Syndrome; Humans; Male

Topics: Adolescent; Adrenal Glands; Adult; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Cushing Syndrome; Drug Evaluation; Female; Humans; Male; Middle Aged; Stimulation, Chemical

Topics: Adrenal Glands; Aerosols; Animals; Beclomethasone; Cosyntropin; Cushing Syndrome; Dogs; Female; Hydrocortisone; Hypothalamus; Male; Methylprednisolone; Pituitary Gland; Respiratory System