Inhaled Fluticasone Causes Iatrogenic Cushing’s Syndrome in Patients Treated with Ritonavir

Mahlab-Guri, Keren; Asher, Ilan; Gradstein, Serge; Zung, Amnon; Radian-Sade, Sara; Elbirt, Daniel; Sthoeger, Zev

doi:10.3109/02770903.2011.606580

Cited by 34 publications

(24 citation statements)

References 23 publications

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“…Although the relative contribution of CYP3A5 in drug metabolism remains a debate, it is beyond doubt that both Cyp3A4 and CYP3A5 are involved in metabolism of fluticasone (9), and that the CYP3A4 *1B/*1G genotype results in low enzyme activity (10). Furthermore, similar to our case study, other case studies have been presented in the literature (4), and it has indeed been shown that ritonavir is a potent inhibitor of both CYP3A4 and CYP3A5 (3). …”

Section: Discussionsupporting

confidence: 88%

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Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Berg

Veer²,

Emmen

et al. 2017

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryWe present a case of iatrogenic Cushing’s syndrome, induced by treatment with fluticasone furoate (1–2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i.e. striae of the upper legs, full moon face, increased body and facial hair) within weeks after starting fluticasone furoate therapy, which was exacerbated after increasing the dose to 2 dd because of complaints of unresolved rhinitis. Biochemical analysis fitted iatrogenic Cushing’s syndrome, with a repeatedly low cortisol (<0.03 µM, ref 0.14–0.60 µM) and low ACTH (9 pg/mL, ref 9–52 pg/mL) without signs of adrenal insufficiency. No other biochemical abnormalities that could point to adrenal or pituitary dysfunction were detected; electrolytes, thyroid and gonadal function, and IGF-1 were within the normal range. Pharmacogenetic analysis revealed that the pediatric patient carried the CYP3A4 *1B/*1G and CYP3A5 *3/*3 genotype (associated with a partial and complete loss of enzyme activity, respectively) which is associated with the development of iatrogenic Cushing’s syndrome in patients treated for HIV due to the strong inhibition of CYP3 enzymes by Ritonavir. Upon discontinuation of fluticasone treatment, the pediatric patient improved both clinically and biochemically with normalisation of cortisol and ACTH within a couple of weeks.Learning points:Fluticasone therapy may induce iatrogenic Cushing’s syndrome in a patient treated with anti-retroviral therapy.Pharmacogenetic analysis, in particular CYP3A genotyping, provides useful information in patients treated for HIV with respect to possible future steroid treatment.Fluticasone furoate is not detected in the Siemens Immulite cortisol binding assay.

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Section: Discussionsupporting

confidence: 88%

“…Iatrogenic Cushing as well as adrenal suppression is uncommon upon fluticasone furoate therapy but had been described in patients treated with antiretroviral therapy due to competition for the rate limiting metabolizing enzyme CYP3A (4), we hypothesized that our pediatric patient may have a low level of expression of the gene.…”

Section: Investigationmentioning

confidence: 99%

Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Berg

Veer²,

Emmen

et al. 2017

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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“…Most of these cases were infants with diaper rash or adults with psoriasis necessitating long-term topical steroid use (2). CS following inhaled or nasal steroids is rare and has been mainly reported in AIDS patients on ritonavir (a potent inhibitor of hepatic cytochrome P450) who were simultaneously taking inhaled steroids such as fluticasone for reactive airway disease (3,4). CS following use of ocular administration of steroids (eye drops) has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Iatrogenic Cushing’s Syndrome Following Short-Term Intranasal Steroid Use

Dutta

Ks²,

Ghosh³

et al. 2012

Jcrpe

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Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.Key words: Cushing’s syndrome, eye drops, dexamethasone, epistaxisConflict of interest:None declared.

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“…Current antiretroviral regimens often contain the HIV protease inhibitor ritonavir, and co-administration with topical fl uticasone results in a dramatic increase in the latter bioavailability. This may result in iatrogenic Cushing's syndrome as alerted in increasing number of case reports (Mahlab-Guri et al 2011 ;Kedem et al 2010 ;Valin et al 2009 ;Samaras et al 2005 ). Ironically, in patients treated by ritonavir, older generations of topical glucocorticoids appear to be safer options (Foisy et al 2008 ).…”

Section: General Treatment Of Allergic Rhinitismentioning

confidence: 99%

Nose and Sleep Breathing Disorders

Poirrier

Eloy

Rombaux

2013

Nasal Physiology and Pathophysiology of Nasal Disorders

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• The nose is the input channel for the airfl ow. Its rigid and erectile structures determine the outline and the output of the airfl ow in the upper airway. Nose obstruction, due to reversible or nonreversible factors, produces collapsing forces that are manifest downstream in the collapsible pharynx. Moreover, nose pathologies result in unstable oral breathing, decreased activation of nasalventilatory refl ex and reduced lung nitric oxide. Long-term oral breathing impacts on the craniofacial growth. The management of nose pathologies could be medical, mechanical (nose dilators) or surgical. Nasal management should be integrated in a multimodal approach, considering the involvement of a multilevel obstruction, and truly refl ecting the complexity of sleep disordered breathing.

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Inhaled Fluticasone Causes Iatrogenic Cushing’s Syndrome in Patients Treated with Ritonavir

Cited by 34 publications

References 23 publications

Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Iatrogenic Cushing’s Syndrome Following Short-Term Intranasal Steroid Use

Nose and Sleep Breathing Disorders

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