fluticasone and Adrenal-Insufficiency

Highly effective antiretroviral treatment has improved the life expectancy of human immunodeficiency virus (HIV) infected patients, but has led to an increase in the comorbidities related to aging, such as the chronic obstructive pulmonary disease (COPD). All this implies the need for a greater number of drugs and an increasing risk of drugs interactions with antiretroviral treatment, particularly protease inhibitors.. We report a case of iatrogenic adrenal insufficiency interaction secondary to ritonavir and inhaled fluticasone in an HIV-infected patient with COPD. A review was made of the cases reported in adults in the medical literature (Medline) up to December 2012.. A total of 34 cases were reported. The mean age was 4 years. The mean dose of ritonavir was 187 mg/day, while the fluticasone dose was 866 μg/day. The average time of the interaction between ritonavir and fluticasone was 8 months. In 85% of cases fluticasone was discontinued at the time of diagnosis of adrenal insufficiency/Cushing syndrome. Almost all (90%) patients had a complete resolution of the symptoms after changing the treatment.. HIV-infected patients on antiretroviral therapy with protease inhibitor boosted with ritonavir which requires the use of inhaled corticosteroids, beclomethasone would be the best treatment option.

Topics: Administration, Inhalation; Adrenal Insufficiency; Aged; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Ritonavir

Inhaled corticosteroids (ICS) are drugs of choice for persistent asthma. Less than 500 µg/d of fluticasone are believed to be safe. We found 92 cases of adrenal suppression in PubMed; among these cases there were 13 children who took 500 µg/d or less of fluticasone. Adrenal insufficiency was diagnosed in a 7-year-old boy on 460 µg ICS for 16 months, with a diagnosis of chronic persistent asthma. A random cortisol was nondetectable as was an early morning cortisol. ICS have greatly improved the day-to-day lives of children with chronic persistent asthma. Parents of children younger than 12 years, who use at least 400 µg of inhaled fluticasone (or bioequivalent), must be given oral and written instructions about warning symptoms of hypocortisolism. Major stress such as surgery, gastrointestinal, bronchopulmonary, or other systemic infections, and heat stress may mandate a written plan of action for use by hospital physicians.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocortisone; Male; Off-Label Use

The dose-response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear. The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose-response studies of >or=4 weeks' duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range. Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses >1,000 mug were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-microg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01-1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 microg.day(-1). In conclusion, for routine prescribing within the established therapeutic dose-response range (50-500 microg.day(-1)), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate >1,000 mug and by the considerable individual variability in the response.

Topics: Adrenal Insufficiency; Adult; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans

For the vast majority of asthmatic children, treatment with inhaled glucocorticoids is safe and effective. Mild impairment of adrenal function of doubtful clinical significance is known to occur in some children inhaling > or = 400 micro g/day budesonide and beclomethasone or > or = 200 micro g fluticasone. Recent reports of life-threatening adrenal failure in asthmatic children inhaling glucocorticoids, some of whom were prescribed licensed doses, have prompted the recommendation that the use of high-dose inhaled glucocorticoids, particularly fluticasone, should be avoided. However, the importance of correctly diagnosing asthma, of using the minimum dose of inhaled glucocorticoid required for symptom control and of regular growth-velocity assessment cannot be over-emphasised. Appropriate asthma management including the early introduction of steroid-sparing agents such as a long-acting beta-agonist or leukotriene antagonist may reduce the morbidity associated with inhaled glucocorticoid use but some children, for reasons as yet unknown, may exhibit increased sensitivity to the systemic effects of inhaled glucocorticoid treatment. Possible explanations for this, with reference to the pharmacology and molecular mechanisms of glucocorticoid action, are accompanied in this review by a summary of the recent case reports and discussion of assessment of adrenal function.

Topics: Administration, Topical; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Child; Dehydroepiandrosterone Sulfate; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Receptors, Glucocorticoid

To establish the prevalence of adrenal insufficiency (AI) in children with eosinophilic esophagitis treated with swallowed fluticasone propionate (FP) or budesonide.. Children treated with FP or budesonide for ≥ 6 months underwent a low-dose adrenocorticotropin stimulation test. Patients using systemic, inhaled, intranasal, or topical glucocorticoids were excluded. The primary outcome is AI, defined as peak serum cortisol <18 μg/dL (≤ 495 nmol/L).. Of 58 patients (81% male), 67% were on FP (median age 13.7 years [range 4.3-19.1], dose 1320 μg/d [440-1760], treatment duration 4.0 years [0.6-13.5]). Thirty-three percent were on budesonide (median age 10.7 years [range 3.2-17.2], dose 1000 μg/d [500-2000], treatment duration 3.4 years [0.6-7.7]). The overall prevalence of abnormal peak cortisol response (≤ 20 μg/dL) was 15% (95% CI 6%-25%) (indeterminate [18-20 μg/dL] 5% [n = 3] vs AI [<18 μg/dL] 10% [n = 6]). All patients on budesonide had a normal response vs only 77% of patients on FP (P = .02), all of whom were taking FP at a dose >440 μg/d.. AI was present in 10% of children treated with swallowed glucocorticoids for ≥ 6 months and was found only in those treated with FP >440 μg/d. We recommend low-dose adrenocorticotropin stimulation testing in children treated long term with high dose FP to allow early detection of AI.

Topics: Administration, Oral; Adolescent; Adrenal Insufficiency; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Eosinophilic Esophagitis; Female; Fluticasone; Follow-Up Studies; Humans; Male; Prevalence; Prospective Studies; Treatment Outcome; Young Adult

To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels.. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min.. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%.. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Circadian Rhythm; Cortisone; Cosyntropin; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Saliva

To assess the effect of inhaled fluticasone propionate on (i) systemic blood pressure, and (ii) the need for volume expanders (crystalloids and colloids) and inotropes for blood pressure support in preterm, very low birth weight (VLBW) infants.. Ventilated VLBW infants, less than 32 weeks of gestation, with respiratory distress syndrome were randomised to receive a 14-day course of either fluticasone propionate (500 microg/puff, 2 puffs every 12 h; n=27) or placebo (n=26) with a metered dose inhaler-spacer device. The response of treatment was assessed by comparing the use of volume expanders, inotropes, and the average and the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups.. There were no significant differences in the average or the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. However, the total volume of crystalloids and colloids requirement was significantly greater in control than in treated infants (p=0.03). There was also a trend towards greater consumption of the total cumulative dose of dopamine in the control infants (p=0.10).. Fluticasone-treated infants required significantly less volume of crystalloids and colloids for blood pressure support compared with control infants. Further larger scale studies are required to determine whether inhaled corticosteroids could minimise the use of volume replacement therapy and inotropes in the treatment of hypotension in preterm infants in the early postnatal period.

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Blood Pressure; Blood Volume; Colloids; Crystalloid Solutions; Diastole; Dobutamine; Dopamine; Fluticasone; Gestational Age; Humans; Hypotension; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Isotonic Solutions; Placebos; Plasma Substitutes; Respiratory Distress Syndrome, Newborn; Systole

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 microg/L 73 m2) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33-77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200-900 microg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200-600 microg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6-7.9 microg/dL, p < 0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p < 0.01; evening: 67.3 to 72.1%, both p < 0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p < 0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.

Topics: Administration, Inhalation; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal Function Tests

Exposure to any form of glucocorticoid preparation is associated with a risk of adrenal insufficiency (AI).. To establish the contribution of oral corticosteroid (OCS) and inhaled corticosteroid (ICS) exposure to the risk of AI in a cohort of patients (n = 80) with severe, uncontrolled asthma.. We compiled individualized cumulative OCS and ICS exposure data using a combination of health care records and electronic inhaler monitoring using an Inhaler Compliance Assessment device and estimated the risk of AI for each participant using a morning serum cortisol concentration.. The predicted prevalence of AI based on morning cortisol concentrations was 25% (20 of 80). Participants on maintenance OCS therapy had the highest risk of AI at 60% (6 of 10) compared with 17% (11 of 65) in those with no recent OCS exposure. Morning serum cortisol correlated negatively with both OCS exposure (mg/kg prednisolone) (r = -0.4; P < .0002) and ICS exposure (mg/kg fluticasone propionate) (r = -0.26; P = .019). Logistic regression of risk of AI against the number of standard treatment courses of OCS demonstrated a positive relationship although this did not reach statistical significance (odds ratio, 1.41; 95% CI, 0.97-2.05; P = .073). Logistic regression analysis, categorizing patients as high-risk AI (cortisol <130 nmol/L) or not (cortisol >130 nmol/L), showed that cumulative ICS exposure remained a significant predictor of AI, even when exposure to OCS was controlled for (odds ratio, 2.17 per 1 mg/kg increase in cumulative fluticasone propionate exposure; 95% CI, 1.06-4.42; P = .033).. Our data suggest that AI is common among patients with asthma and highlights that the risk of AI is associated with both high-dose ICS therapy and intermittent treatment courses of OCS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Anti-Asthmatic Agents; Asthma; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Prednisolone

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Child; Eosinophilic Esophagitis; Fluticasone; Humans; Steroids

Topics: Adrenal Insufficiency; Adult; Aged; Comorbidity; Cushing Syndrome; Drug Interactions; Female; Fluticasone; HIV Infections; Humans; Iatrogenic Disease; Male; Middle Aged; Ritonavir; Steroids; Triamcinolone; Young Adult

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Eosinophilic Esophagitis; Fluticasone; Humans

Ritonavir is a powerful inhibitor of the cytochrome P450 3A4 (CYP3A4) isoenzyme. It is used as a pharmaceutical enhancer in the management of HIV-positive patients. However, when co-administered with other drugs that are metabolised via the CYP3A4 pathway, ritonavir can potentially cause serious drug-drug interactions. Inhaled fluticasone propionate, which is used to treat asthma and chronic obstructive airway disease, is particularly prone to such interactions due to its physiological attributes. We report a HIV-positive 48-year-old male patient who presented to Al Nahdha Hospital, Muscat, Oman, in 2012 with weight loss, generalised weakness and fatigue and diagnosed with secondary adrenal insufficiency as a result of concomitant ritonavir and inhaled fluticasone.

Topics: Administration, Inhalation; Adrenal Insufficiency; Asthma; Bronchodilator Agents; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Oman; Ritonavir

Topics: Adrenal Insufficiency; Aged; Antifungal Agents; Asthma; Bronchodilator Agents; Drug Interactions; Fatigue; Female; Fluid Therapy; Fluticasone; Glucocorticoids; Humans; Itraconazole; Pulmonary Aspergillosis; Treatment Outcome

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Budesonide; Deglutition; Eosinophilic Esophagitis; Fluticasone; Humans

Topics: Adrenal Insufficiency; Adult; Androstadienes; Anti-Inflammatory Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Ritonavir

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Androstadienes; Carbamates; Cobicistat; Drug Interactions; Enzyme Inhibitors; Fluticasone; Humans; Hydrocortisone; Iatrogenic Disease; Male; Thiazoles

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Albuterol; Androstadienes; Asthma; Child; Child, Preschool; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Growth; Humans; Hydrocortisone; Male

A 52-year-old man with well-controlled HIV infection taking ritonavir and increasing doses of inhaled fluticasone for chronic bronchitis developed thrush. Within days of discontinuing fluticasone and initiating fluconazole, he presented with fatigue, malaise, lower-extremity oedema and orthostasis. Testing confirmed exogenous Cushing's syndrome and secondary adrenal insufficiency. Although ritonavir-fluticasone interactions have been previously reported as a cause for adrenal insufficiency, we propose that fluconazole increased the rapidity of onset and severity of symptoms through synergistic inhibition of the adrenal axis.

Topics: Adrenal Insufficiency; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Bronchitis; Drug Interactions; Fluconazole; Fluticasone; HIV Infections; Humans; Male; Middle Aged; Ritonavir

A 3-year-old boy was treated for asthmatic symptoms with fluticasone inhalations. Due to a flattening growth curve Cushing's syndrome was suspected and the dosage of fluticasone was gradually decreased after which the boy became less active and his appetite decreased. Another patient, a 7-year-old boy with asthma was also treated with fluticasone inhalations. For 6 months he felt tired, nauseous and had abdominal pain. A third patient, an 8-year-old boy with asthma being treated with fluticasone inhalations was presented at the emergency department because he could not be roused; for the preceding few days he had been nauseous and pyrexic. Further laboratory tests showed that all three patients had adrenal cortex insufficiency (addisonism) due to exogenic glucocorticoids in the form of inhaled corticosteroids. This condition is difficult to recognize as its symptoms are aspecific and may resemble those that accompany inadequately treated asthma; furthermore, inhaled corticosteroids may mask the symptoms. On long-term use of inhaled corticosteroids accompanied by aspecific symptoms, the possibility of adrenal cortex insufficiency should be considered. In addition, it is important to prescribe the lowest possible dosage of inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Fluticasone; Humans; Male

To report the rapid onset of adrenal insufficiency and subsequent development of Cushing syndrome precipitated by a CYP3A4-mediated drug-drug interaction that may have been enhanced by the presence of cystic fibrosis (CF)-related liver disease.. A 9-year-old girl with CF and cirrhosis experienced a decline in lung function that led to a diagnosis of asthma. After initiation of asthma therapy with inhaled fluticasone 110 μg/actuation, the patient experienced improvement in lung function to baseline. Seven weeks after the initiation of inhaled fluticasone, she developed vaginal candidiasis and was prescribed fluconazole 100 mg/day, a CYP3A4 inhibitor. Three days after starting fluconazole, she developed polyuria and polydipsia and was found to have severe hyperglycemia, which led to the diagnosis of Cushing syndrome. Fluticasone was discontinued, and the patient's adrenal function normalized.. Patients with CF are commonly prescribed complex medication regimens that may affect drug metabolism. CYP3A4 inhibitors may significantly decrease metabolic clearance in patients using chronic inhaled corticosteroids. Iatrogenic Cushing syndrome has been reported in patients with CF treated concomitantly, and for extended duration, with inhaled corticosteroids and CYP3A4 inhibitors. This case highlights rapid onset of adrenal insufficiency in a patient with CF-related liver disease treated briefly with a moderate CYP3A4 inhibitor. Use of the Horn drug interaction probability scale indicates that the interaction between fluticasone and fluconazole was probable.. CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Antifungal Agents; Asthma; Candidiasis, Vulvovaginal; Chemical and Drug Induced Liver Injury, Chronic; Child; Cushing Syndrome; Cystic Fibrosis; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Enzyme Inhibitors; Female; Fluconazole; Fluticasone; Humans; Treatment Outcome

Symptomatic adrenal insufficiency secondary to the use of inhaled corticosteroids is a rare condition. We present a case in which a 16 year-old male patient with asthma treated with high dose fluticasone (1,000 microgram/d) was admitted with septicaemia and concomitant adrenal insufficiency. Further investigations revealed isolated adrenocorticotropic hormone deficiency most probably caused by inhalation of fluticasone. The diagnosis was initially delayed because of treatment of the underlying infection. The case serves as a memento that adrenal insufficiency should always be borne in mind when it comes to patients treated with corticosteroids in any form.

Topics: Administration, Inhalation; Adolescent; Adrenal Insufficiency; Androstadienes; Bronchodilator Agents; Fluticasone; Humans; Male

To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP).. Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of > or =500 microg and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables.. Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests.. The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Reproducibility of Results

We report a 12 year-old asthmatic girl with adrenal insufficiency during inhaled corticosteroid treatment. Symptoms, investigations and treatment are discussed.

Topics: Administration, Inhalation; Adrenal Insufficiency; Adrenergic beta-Agonists; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans

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: Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Consensus; Fluticasone; Health Policy; Humans; Hydrocortisone; Prednisolone

To document previously unreported acute effects of adrenal insufficiency.. We describe two siblings who presented acutely with hyponatraemia and cerebral oedema following prolonged treatment with high dose inhaled fluticasone.. A girl aged 5.5 years presented with vomiting, headache, visual impairment and seizures. She was hyponatraemic but not hypoglycaemic. Her conscious level continued to deteriorate and she died, post mortem examination showing small adrenal glands and cerebral oedema. Four weeks later her 7-year-old brother presented with similar symptoms. Assessment showed hyponatraemia with cerebral oedema. His illness responded to intensive care. A diagnosis of adrenal insufficiency was made retrospectively in both cases. The siblings had been receiving Fluticasone propionate (FP) in doses of up to 2000 microg/day for several years.. We believe that the hyponatraemia and cerebral oedema was related to cortisol deficiency, leading to impaired excretion of water. We emphasize the need for careful cerebral monitoring in acute adrenal insufficiency presenting with impaired consciousness.

Topics: Administration, Inhalation; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Brain Edema; Child; Fatal Outcome; Female; Fluticasone; Glucocorticoids; Humans; Hyponatremia; Male; Siblings

Topics: Adrenal Insufficiency; Androstadienes; Bronchodilator Agents; Child; Child, Preschool; Drug Administration Schedule; Drug and Narcotic Control; Drug Industry; Fluticasone; Humans

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Child; Fluticasone; Humans; Patient Compliance

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible.

Topics: Adolescent; Adrenal Insufficiency; Albuterol; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Atazanavir Sulfate; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; Humans; Hydrocortisone; Oligopeptides; Pyridines; Ritonavir; Salmeterol Xinafoate

A number of previous studies have suggested that adrenal suppression occurs in asthmatic children treated with high-doses of inhaled glucocorticoids (IGC). This study was designed to determine the frequency of adrenal suppression in children with severe asthma treated with recommended doses of IGC: namely 500-1,000 microg/day of fluticasone propionate or the equivalent of budesonide (1,000-2,000 microg/day) for a period of at least 12 months.. Early morning cortisol (F) and ACTH serum levels were measured in 27 severe asthmatics aged 6-16 years old. The children underwent a low dose ACTH test (1 microg/1.73 m2) with a parallel glucose measurement. Twenty-four hour urine collection was performed before examination for free F (UfF) and creatinine levels. There were no clinical manifestations of adrenal hypofunction in the analyzed children.. Of the 27 patients, 22 had normal basal and post-stimulatory levels of F and normal UfF, and the other five (18.5%) had basal serum F levels of <400 nmol/l. Four of the five also had normal post-stimulatory levels of F and normal UfF. One child had a subnormal peak F value of 484 nmol/l during the ACTH test. None of the patients had a suppressed serum ACTH level, but an elevated ACTH level was found in four children. This study provided biochemical evidence of suboptimal adrenal function in one child in the examined group (3.7%) and a good response to stimulation in all the others, even in those with slightly reduced basal cortisol levels.. This study showed that the use of fluticasone in doses of up to 1,000 microg/day (or the equivalent of budesonide) as long-term treatment of children with severe asthma did not substantially affect their adrenal function.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Asthma; Blood Glucose; Budesonide; Child; Female; Fluticasone; Humans; Hydrocortisone; Male

Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose.. Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l).. A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day.. Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluticasone; Humans; Hydrocortisone

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

We present 2 cases of Cushing syndrome with secondary adrenal insufficiency from concomitant use of ritonavir and inhaled corticosteroids in children with human immunodeficiency virus infection. These cases highlight the need for special consideration when treatment with an inhaled/intranasal corticosteroid is indicated in children receiving antiretroviral therapy.

Topics: Administration, Inhalation; Adolescent; Adrenal Insufficiency; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir; Salmeterol Xinafoate

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Cerebrospinal Fluid Pressure; Fluticasone; Headache; Humans; Hydrocortisone; Intracranial Hypertension; Magnetic Resonance Imaging; Male; Spinal Puncture; Tomography, X-Ray Computed

Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (

Topics: Administration, Inhalation; Adrenal Insufficiency; Adult; Androstadienes; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Male; Middle Aged; Osteoporosis; Ritonavir

Topics: Administration, Inhalation; Adrenal Insufficiency; Adrenocorticotropic Hormone; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Hydrocortisone; Long-Term Care; Male

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Humans; Middle Aged

Topics: Adrenal Insufficiency; Androstadienes; Bronchodilator Agents; Canada; Diphosphonates; Eye Diseases; Fluticasone; Humans; Vision Disorders

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Cushing Syndrome; Diagnosis, Differential; Fluticasone; Humans

International guidelines recommend prescription of inhaled corticosteroids to improve asthma control. Chronic secondary adrenal suppression due to inhaled corticosteroids has been described. We report a case of acute adrenal suppression due to drug interaction between Fluticasone and antiretroviral therapy in a HIV patient. Seeing an increased prevalence of hyperresponsiveness among HIV-infected men, we conclude that coprescription of Fluticasone and highly active antiretroviral therapy must be carefully controlled.

Topics: Acute Disease; Administration, Inhalation; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Androstadienes; Anti-Inflammatory Agents; Antiretroviral Therapy, Highly Active; Asthma; Fluticasone; HIV Infections; Humans; Hydrocortisone; Male

Topics: Acute Disease; Administration, Inhalation; Adrenal Insufficiency; Adult; Androstadienes; Anti-Asthmatic Agents; Child; Fluticasone; Glucocorticoids; Humans; Infant

Although widely used, the effects of steroid "bursts" on the hypothalamic-pituitary-adrenal axis, especially with long-term, concomitant topical steroids use, have not been studied.. To examine the effect of a prednisone burst, long-term intranasal steroids, and inhaled fluticasone propionate on the suppression and recovery of adrenal function.. Adult patients taking long-term intranasal steroids, either moderate-dose (440 microg/d) or high-dose (880 microg/d) inhaled fluticasone propionate, underwent a low-dose cosyntropin stimulation test (LDCST) before and 2 days after a prednisone burst. Suppressed adrenal responses were monitored with a weekly LDCST. Persistent abnormal LDCST results were confirmed by 8-hour cosyntropin infusion. Inhaled fluticasone dosages were decreased; adrenal recovery was evaluated by a monthly LDCST. Adverse effects of steroids were monitored by questionnaires.. Sixty-three patients participated in the study. Three of 31 patients not taking inhaled steroids and 1 of 13 patients taking moderate-dose fluticasone had abnormal LDCST results on day 2 after the prednisone burst, which normalized by the second week. In the high-dose fluticasone group, 14 of 19 patients had suppressed LDCST responses on day 2 and adrenal function recovered in 10 of 19 patients by the fourth week. These patients complained significantly of decreased libido (P = 0.02), listlessness (P = 0.03), and weight loss (P = 0.05). High-dose fluticasone (r = 0.66, P < 0.001) and duration of use (r = 0.32, P = 0.01) were statistically correlated with adrenal impairment. Of the 4 patients with persistent adrenal impairment, 3 patients successfully reduced dosages of inhaled fluticasone and adrenal function recovered in 2 to 10 months.. Prednisone bursts induce brief adrenal impairment. Intranasal steroids and moderate-dose fluticasone had no effect on adrenal function. High-dose, inhaled fluticasone caused mild-to-significant adrenal suppression and delayed the recovery after a steroid burst. Avoiding or limiting the duration of high-dose inhaled steroids would minimize systemic adverse effects.

Topics: Administration, Intranasal; Adrenal Glands; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Cosyntropin; Female; Fluticasone; Humans; Male; Middle Aged; Prednisone; Respiratory Tract Diseases

Four cases of asthma (one adult, three children) developing acute adrenal crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7-9 yrs, had been prescribed inhaled fluticasone, dosage 500-2,000 microg x day(-1) and duration 5 months-5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3-1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000-2,000 microg x day(-1) for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute adrenal crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-adrenal axis suppression were excluded.

Topics: Acute Disease; Adrenal Insufficiency; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Female; Fluticasone; Humans; Male

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Asthma; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocortisone

Topics: Administration, Topical; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Fluticasone; Glucocorticoids; Humans

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenal Insufficiency; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Fluticasone; Glucocorticoids; Humans

Topics: Administration, Inhalation; Administration, Topical; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Fluticasone; Glucocorticoids; Humans

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Fluticasone; Growth Disorders; Humans

Topics: Acute Disease; Administration, Inhalation; Administration, Topical; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans; Hypoglycemia

Topics: Administration, Inhalation; Administration, Topical; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Fluticasone; Glucocorticoids; Humans; Hypoglycemia

Symptomatic adrenal insufficiency, presenting as hypoglycaemia or poor weight gain, may occur on withdrawal of corticosteroid treatment but has not previously been reported during inhaled corticosteroid treatment. This case series illustrates the occurrence of clinically significant adrenal insufficiency in asthmatic children while patients were on inhaled corticosteroid treatment and the unexpected modes of presentation. General practitioners and paediatricians need to be aware that this unusual but acute serious complication may occur in patients treated with inhaled corticosteroids.

Topics: Administration, Inhalation; Administration, Topical; Adrenal Insufficiency; Adrenocorticotropic Hormone; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Female; Fluticasone; Humans; Hydrocortisone; Male

Topics: Administration, Inhalation; Adrenal Insufficiency; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Aspergillosis; Asthma; Fluticasone; Humans; Lung Diseases, Fungal; Male

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Fluticasone; Humans; Infant; Male

Topics: Acute Disease; Adrenal Insufficiency; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Budesonide; Child; Female; Fluticasone; Humans; Nebulizers and Vaporizers

Inhaled glucocorticoids are the medical treatment of choice in many of patients with asthma. Fluticasone propionate is an inhaled glucocorticoid with little systemic bioavailability via the oral route and infrequent association with systemic adverse effects at the recommended dosage.. To report a case of adrenal suppression and exogenous glucocorticoid excess from inhaled fluticasone propionate.. A 9-year-old girl with a previous history of episodic asthma was placed on 550 microg of fluticasone propionate daily for severe labile asthma diagnosed by history and methacholine challenge. The patient returned 6 months later with complaints of increased appetite, nausea, and feeling "hot and flushed." On physical exam she had stigmata of Cushing's syndrome. The patient subsequently developed orthostatic hypotension and moderate dehydration following a viral illness. After a long taper of fluticasone propionate the patient' s adrenal function returned to normal and she had no acute or chronic exacerbations of her asthma.. Her 8 AM cortisol was undetectable with an ACTH of 21 pg/mL. The serum prolactin, TSH, free thyroxine, insulin-like growth factor I, and renin activity were all normal. An MRI study of her head was also normal. Repeat methacholine challenges while receiving a much smaller dose fluticasone propionate showed a significant decrease in airway reactivity.. Adrenal suppression can occur from inhaled fluticasone propionate at a dosage less than has been previously reported.

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Anti-Allergic Agents; Child; Depression, Chemical; Female; Fluticasone; Forced Expiratory Volume; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Time Factors